@article {pmid38700207,
year = {2024},
author = {Keeley, O and Coyne, AN},
title = {Nuclear and degradative functions of the ESCRT-III pathway: implications for neurodegenerative disease.},
journal = {Nucleus (Austin, Tex.)},
volume = {15},
number = {1},
pages = {2349085},
pmid = {38700207},
issn = {1949-1042},
mesh = {Humans ; *Endosomal Sorting Complexes Required for Transport/metabolism ; *Neurodegenerative Diseases/metabolism/pathology/genetics ; Animals ; Cell Nucleus/metabolism ; Frontotemporal Dementia/metabolism/pathology/genetics ; Endosomes/metabolism ; },
abstract = {The ESCRT machinery plays a pivotal role in membrane-remodeling events across multiple cellular processes including nuclear envelope repair and reformation, nuclear pore complex surveillance, endolysosomal trafficking, and neuronal pruning. Alterations in ESCRT-III functionality have been associated with neurodegenerative diseases including Frontotemporal Dementia (FTD), Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease (AD). In addition, mutations in specific ESCRT-III proteins have been identified in FTD/ALS. Thus, understanding how disruptions in the fundamental functions of this pathway and its individual protein components in the human central nervous system (CNS) may offer valuable insights into mechanisms underlying neurodegenerative disease pathogenesis and identification of potential therapeutic targets. In this review, we discuss ESCRT components, dynamics, and functions, with a focus on the ESCRT-III pathway. In addition, we explore the implications of altered ESCRT-III function for neurodegeneration with a primary emphasis on nuclear surveillance and endolysosomal trafficking within the CNS.},
}

Humans
*Endosomal Sorting Complexes Required for Transport/metabolism
*Neurodegenerative Diseases/metabolism/pathology/genetics
Animals
Cell Nucleus/metabolism
Frontotemporal Dementia/metabolism/pathology/genetics
Endosomes/metabolism

@article {pmid38697975,
year = {2024},
author = {Tsitkov, S and Valentine, K and Kozareva, V and Donde, A and Frank, A and Lei, S and , and E Van Eyk, J and Finkbeiner, S and Rothstein, JD and Thompson, LM and Sareen, D and Svendsen, CN and Fraenkel, E},
title = {Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {3606},
pmid = {38697975},
issn = {2041-1723},
support = {RF1 AG057331/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; *Induced Pluripotent Stem Cells/metabolism ; *Motor Neurons/metabolism/pathology ; Male ; Female ; Middle Aged ; Case-Control Studies ; Chromatin/metabolism/genetics ; Aged ; Epigenomics/methods ; Chromatin Immunoprecipitation Sequencing/methods ; Disease Progression ; Epigenesis, Genetic ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing. Once these covariates are corrected for, we are able to identify ALS-specific signals in the data. Additionally, we find that the ATAC-seq data is able to predict ALS disease progression rates with similar accuracy to methods based on biomarkers and clinical status. These results suggest that iPSC-derived motor neurons recapitulate important disease-relevant epigenomic changes.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
*Induced Pluripotent Stem Cells/metabolism
*Motor Neurons/metabolism/pathology
Male
Female
Middle Aged
Case-Control Studies
Chromatin/metabolism/genetics
Aged
Epigenomics/methods
Chromatin Immunoprecipitation Sequencing/methods
Disease Progression
Epigenesis, Genetic

@article {pmid38697285,
year = {2024},
author = {Tuerxun, K and Tang, RH and Abudoumijiti, A and Yusupu, Z and Aikebaier, A and Mijiti, S and Ibrahim, I and Cao, YL and Yasheng, A and Wu, YQ},
title = {Comparative proteomics analysis of samples from hepatic cystic echinococcosis patients using data-independent acquisition approach.},
journal = {Journal of proteomics},
volume = {},
number = {},
pages = {105191},
doi = {10.1016/j.jprot.2024.105191},
pmid = {38697285},
issn = {1876-7737},
abstract = {Cystic echinococcosis is a zoonotic disease resulting from infection caused by the larval stage of Echinococcus granulosus. This study aimed to assess the specific proteins that are potential candidates for the development of a vaccine against E. granulosus. The data-independent acquisition approach was employed to identify differentially expressed proteins (DEPs) in E. granulosus samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to identify several noteworthy proteins. Results: The DEPs in E. granulosus samples were identified (245 pericystic wall vs. parasite-free yellowish granuloma (PYG, 1725 PY vs. PYG, 2274 PN vs. PYG). Further examination of these distinct proteins revealed their predominant enrichment in metabolic pathways, amyotrophic lateral sclerosis, and neurodegeneration-associated pathways. Notably, among these DEPs, SH3BGRL, MST1, TAGLN2, FABP5, UBE2V2, and RARRES2 exhibited significantly higher expression levels in the PYG group compared with the PY group (P < 0.05). The findings may contribute to the understanding of the pathological mechanisms underlying echinococcosis, providing valuable insights into the development of more effective diagnostic tools, treatment modalities, and preventive strategies. SIGNIFICANCE: CE is a major public health hazard in the western regions of China, Central Asia, South America, the Mediterranean countries, and eastern Africa. Echinococcus granulosus is responsible for zoonotic disease through infection Our analysis focuses on the proteins in various samples by data-dependent acquisition (DIA) for proteomic analysis. The importance of this research is to develop new strategies and targets to protect against E. granulosus infections in humans.},
}

@article {pmid38697002,
year = {2024},
author = {Su, T and Gan, Y and Ma, S and Wu, H and Lu, S and Zhi, M and Wang, B and Lu, Y and Yao, J},
title = {Graves' disease and the risk of five autoimmune diseases: A Mendelian randomization and colocalization study.},
journal = {Diabetes & metabolic syndrome},
volume = {18},
number = {5},
pages = {103023},
doi = {10.1016/j.dsx.2024.103023},
pmid = {38697002},
issn = {1878-0334},
abstract = {BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD).

OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases.

METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations.

RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases.

CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.},
}

@article {pmid38696744,
year = {2024},
author = {},
title = {Variation in Resting Metabolic Rate Affects Identification of Metabolic Change in Geographically Distinct Cohorts of Patients With ALS.},
journal = {Neurology},
volume = {102},
number = {10},
pages = {e209407},
doi = {10.1212/WNL.0000000000209407},
pmid = {38696744},
issn = {1526-632X},
}

@article {pmid38696153,
year = {2024},
author = {Chugunov, DA and Shmilovich, AA and Larina, MR and Goncharenko, SN and Moiseeva, TV and Ryauzova, ES and Fedorova, EV and Bukinich, AA},
title = {[Clinical and psychometric characteristics of cognitive and negative disorders in schizophrenia].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {124},
number = {4. Vyp. 2},
pages = {64-71},
doi = {10.17116/jnevro202412404264},
pmid = {38696153},
issn = {1997-7298},
mesh = {Humans ; Male ; Female ; Adult ; *Schizophrenia/diagnosis/complications ; *Psychometrics ; Middle Aged ; *Schizophrenic Psychology ; Cognition ; Neuropsychological Tests ; Cognition Disorders/diagnosis/etiology ; },
abstract = {OBJECTIVE: To establish the characteristics of clinical manifestations and cognitive tests in patients with schizophrenia, with a predominance of cognitive and negative disorders.

MATERIAL AND METHODS: We examined 76 patients, 66 in the main group, 10 in the comparison group, who were treated in Psychiatric Hospital No. 1 and Psychiatric Hospital No. 4 (Moscow). Clinical-psychopathological, psychometric and statistical methods were used. Features of cognitive functioning were studied using the Frontal Assessment Battery (FAB) and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS). Emotional intelligence scores were assessed using the Ekman Face Emotion Recognition (EFER) test.

RESULTS: Patients with schizophrenia showed dominance of one of 3 types of deficit symptoms: cognitive, emotional, and volitional. Cognitive functions were significantly reduced in patients with schizophrenia when compared with the comparison group (mean FAB score (M±SD) 13.44±2.97 in patients with schizophrenia vs. 16.10±1.70 in the comparison group; t=4.10; p<0.001). Cognitive functions were particularly reduced in patients with volitional deficit (mean EFER total score 42.40±9.0 in patients with volitional deficit vs. 47.21±633 in patients with cognitive deficit; t=2.12; p=0.039; mean FAB score 12.83±3.29 in patients with volitional deficit vs. 16.10±1.70 in the comparison group; t=4.24; p<0.001; mean ECAS score specific to ALS 78.80±9.07 in patients with volitional deficit vs. 84.50±6.71 in the comparison group; t=2.18; p=0.034).

CONCLUSION: The greatest contribution to the development of cognitive disorders in schizophrenia is made by dysfunction of frontal (especially) and temporal cortex. Executive functions, speech skills and verbal fluency are most severely damaged.},
}

Humans
Male
Female
Adult
*Schizophrenia/diagnosis/complications
*Psychometrics
Middle Aged
*Schizophrenic Psychology
Cognition
Neuropsychological Tests
Cognition Disorders/diagnosis/etiology

@article {pmid38695966,
year = {2024},
author = {Mendes Ferreira, V and Caetano, A and Santos, L and Fernandes, M},
title = {FIG4-associated disease manifesting as rapidly progressive amyotrophic lateral sclerosis.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {38695966},
issn = {1590-3478},
}

@article {pmid38695638,
year = {2024},
author = {Fullam, T and Hunt, SL and Han, M and Denesia, J and Chandrashekhar, S and Jawdat, O and Piccione, E and Fernandes, JA and Statland, J},
title = {Outcomes after intervention for enteral nutrition in patients with amyotrophic lateral sclerosis in multidisciplinary clinics.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.28103},
pmid = {38695638},
issn = {1097-4598},
support = {10.13039/100000002/NH/NIH HHS/United States ; },
abstract = {INTRODUCTION/AIMS: Patients with amyotrophic lateral sclerosis (ALS) are susceptible to malnutrition, with appropriate management of nutritional interventions an active area of investigation. We sought to determine the impact of gastrostomy tube placement in ALS patients, exploring the correlation between forced vital capacity (FVC), malnutrition, and perioperative complications.

METHODS: A retrospective review was performed of clinically diagnosed ALS patients treated at two multidisciplinary clinics (University of Kansas, University of Nebraska) from January 2009 to September 2020 who were referred for gastrostomy. Data collected included demographics, disease characteristics, and key gastrostomy related dates/outcomes.

RESULTS: Two hundred thirty-nine patients were included with a median age of 65 years and median of 589 days from symptom onset to gastrostomy (interquartile range, 404-943). The population was predominantly Non-Hispanic White with bulbar-onset ALS. 30-day mortality was 4% and 30-day morbidity was 13%. Weight loss, body mass index, and predicted FVC at placement showed no increased 30-day morbidity or mortality association. Bulbar-onset ALS patients exhibited higher overall mortality postplacement than limb onset (odds ratio: 1.85, 95% confidence interval: 1.03-3.33). There was a 5% incidence of symptoms suggestive of refeeding syndrome.

DISCUSSION: Rates of major/minor complications and 30-day mortality related to gastrostomy placement in our population were similar compared with prior studies in ALS. The lack of difference in outcomes based on FVC at procedure may suggest this is not predictive of outcome, or perhaps, high-quality perioperative respiratory management. Alternative reasons may account for the increased morbidity and mortality of gastrostomy placement in the ALS population.},
}

@article {pmid38694387,
year = {2024},
author = {Arora, H and Javed, B and Kutikuppala, LVS and Chaurasia, M and Khullar, K and Kannan, S and Golla, V},
title = {ST2 levels and neurodegenerative diseases: is this a significant relation?.},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {5},
pages = {2812-2817},
pmid = {38694387},
issn = {2049-0801},
abstract = {Interleukin-33 (IL-33), belonging to the interleukin-1 cytokine family, has a decoy receptor soluble ST2 (sST2). IL-33 is found in oligodendrocytes and astrocytes and is involved in central nervous system healing and repair, whereas ST2 is found in microglia and astrocytes. Some studies have found a link between changes in the IL-33/ST2 pathway and neurodegenerative disorders. This review article investigates the relationship between the interleukin-33 (IL-33)/ST2 pathway and neurodegenerative disorders. It was discovered that soluble st2 levels were increased. Furthermore, IL-33 levels were found to be lower in many neurodegenerative diseases such as Alzheimer's and amyotrophic lateral sclerosis (ALS). The association with other disorders, such as ankylosing spondylitis, multiple sclerosis, and systemic lupus erythematosus (SLE), was also observed. Various studies suggest that ST2/IL-33 signalling may be pivotal in the disease modulation of neurodegenerative disorders. The serum sST2 level test can be useful in determining the inflammatory status and severity of illness in many neurodegenerative disorders. In this review, we will discuss recent findings concerning the interleukin-33 (IL-33)/ST2 pathway and its role in the diagnosis and treatment of diseases with neurodegeneration.},
}

@article {pmid38694349,
year = {2024},
author = {Amjadi, N and Mohammadi, S and Paybast, S and Dadkhah, P and Talayeh, M and Asemi, Z},
title = {A pregnant woman with amyotrophic lateral sclerosis from Iran: a case report.},
journal = {Annals of medicine and surgery (2012)},
volume = {86},
number = {5},
pages = {3013-3015},
pmid = {38694349},
issn = {2049-0801},
abstract = {INTRODUCTION AND IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease, which is extremely rare during pregnancy. The severity of the disease affects the pregnancy outcome. The present study reports the first Iranian case of a woman with ALS overlapping pregnancy.

CASE PRESENTATION: The 27-year-old lady in her second pregnancy was admitted to the emergency department with labor pain at the 37th gestation week. Following a multidisciplinary team meeting, including a neurologist, maternal-fetal medicine specialist, and anesthesiologist, a decision was made for an emergent cesarean section under spinal anesthesia. The delivery was successful without any maternal or fetal complications. A 5-month follow-up revealed the stable neurologic status of the mother.

CLINICAL DISCUSSION: The combination of ALS and pregnancy is very rare because the disease is more common in elderly men. ALS management involves a multidisciplinary approach. Riluzole is a drug that can increase the survival of the patients. ALS does not affect on motor and sensory nerves of the uterus, so vaginal delivery might be possible. The main cause of cesarean section in patients with ALS is respiratory compromise, but four patients with uncomplicated vaginal deliveries have been reported. The neonatal outcome of most cases resulted in normal healthy infants.

CONCLUSION: Management of ALS in pregnancy is challenging because of respiratory concerns, so multidisciplinary team management is important.},
}

@article {pmid38692734,
year = {2024},
author = {Tartwijk, FWV and Wunderlich, LCS and Mela, I and Makarchuk, S and Jakobs, MAH and Qamar, S and Franze, K and Schierle, GSK and George-Hyslop, PHS and Lin, JQ and Holt, CE and Kaminski, CF},
title = {Mutation of the ALS/FTD-associated RNA-binding protein FUS affects axonal development.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.2148-23.2024},
pmid = {38692734},
issn = {1529-2401},
abstract = {Aberrant condensation and localisation of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organisation and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease. We use two reported Xenopus models of ALS/FTD (of either sex), the ALS-associated mutant FUS(P525L) and a mimic of hypomethylated FUS, FUS(16R). Both mutants strongly reduced axonal complexity in vivo. We also observed an axon looping defect for FUS(P525L) in the target area, which presumably arises due to errors in stop cue signalling. To assess whether loss of axon complexity also had a cue-independent component, we assessed axonal cytoskeletal integrity in vitro Using a novel combination of fluorescence and atomic force microscopy, we found that mutant FUS reduced actin density in the growth cone, altering its mechanical properties. Therefore, FUS mutants may induce defects during early axonal development.Significance statement This study demonstrates that mutation of the ALS/FTD (amyotrophic lateral sclerosis/frontotemporal dementia)-associated RNA-binding protein Fused in Sarcoma (FUS) can result in changes in axonal development. These changes occur both axon-autonomously in cytoskeletal organisation during axon extension and context-dependently during axonal branching. This indicates pre-symptomatic, developmental changes in axonal organisation may occur in familial disease variants.},
}

@article {pmid38691665,
year = {2024},
author = {Singh, P and Belliveau, P and Towle, J and Neculau, AE and Dima, L},
title = {Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.},
journal = {American journal of therapeutics},
volume = {31},
number = {3},
pages = {e258-e267},
doi = {10.1097/MJT.0000000000001742},
pmid = {38691665},
issn = {1536-3686},
mesh = {*Edaravone/administration & dosage/pharmacology/therapeutic use ; Humans ; *Amyotrophic Lateral Sclerosis/drug therapy ; *Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects ; Administration, Oral ; Suspensions ; Biological Availability ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.

MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.

PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.

CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.

THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.},
}

*Edaravone/administration & dosage/pharmacology/therapeutic use
Humans
*Amyotrophic Lateral Sclerosis/drug therapy
*Neuroprotective Agents/administration & dosage/therapeutic use/adverse effects
Administration, Oral
Suspensions
Biological Availability

@article {pmid38689650,
year = {2024},
author = {Swindell, WR},
title = {Meta-analysis of differential gene expression in lower motor neurons isolated by laser capture microdissection from post-mortem ALS spinal cords.},
journal = {Frontiers in genetics},
volume = {15},
number = {},
pages = {1385114},
pmid = {38689650},
issn = {1664-8021},
abstract = {INTRODUCTION: ALS is a fatal neurodegenerative disease for which underlying mechanisms are incompletely understood. The motor neuron is a central player in ALS pathogenesis but different transcriptome signatures have been derived from bulk analysis of post-mortem tissue and iPSC-derived motor neurons (iPSC-MNs).

METHODS: This study performed a meta-analysis of six gene expression studies (microarray and RNA-seq) in which laser capture microdissection (LCM) was used to isolate lower motor neurons from post-mortem spinal cords of ALS and control (CTL) subjects. Differentially expressed genes (DEGs) with consistent ALS versus CTL expression differences across studies were identified.

RESULTS: The analysis identified 222 ALS-increased DEGs (FDR <0.10, SMD >0.80) and 278 ALS-decreased DEGs (FDR <0.10, SMD < -0.80). ALS-increased DEGs were linked to PI3K-AKT signaling, innate immunity, inflammation, motor neuron differentiation and extracellular matrix. ALS-decreased DEGs were associated with the ubiquitin-proteosome system, microtubules, axon growth, RNA-binding proteins and synaptic membrane. ALS-decreased DEG mRNAs frequently interacted with RNA-binding proteins (e.g., FUS, HuR). The complete set of DEGs (increased and decreased) overlapped significantly with genes near ALS-associated SNP loci (p < 0.01). Transcription factor target motifs with increased proximity to ALS-increased DEGs were identified, most notably DNA elements predicted to interact with forkhead transcription factors (e.g., FOXP1) and motor neuron and pancreas homeobox 1 (MNX1). Some of these DNA elements overlie ALS-associated SNPs within known enhancers and are predicted to have genotype-dependent MNX1 interactions. DEGs were compared to those identified from SOD1-G93A mice and bulk spinal cord segments or iPSC-MNs from ALS patients. There was good correspondence with transcriptome changes from SOD1-G93A mice (r ≤ 0.408) but most DEGs were not differentially expressed in bulk spinal cords or iPSC-MNs and transcriptome-wide effect size correlations were weak (bulk tissue: r ≤ 0.207, iPSC-MN: r ≤ 0.037).

CONCLUSION: This study defines a robust transcriptome signature from LCM-based motor neuron studies of post-mortem tissue from ALS and CTL subjects. This signature differs from those obtained from analysis of bulk spinal cord segments and iPSC-MNs. Results provide insight into mechanisms underlying gene dysregulation in ALS and highlight connections between these mechanisms, ALS genetics, and motor neuron biology.},
}

@article {pmid38689506,
year = {2024},
author = {Parvizi, T and Klotz, S and Keritam, O and Caliskan, H and Imhof, S and König, T and Haider, L and Traub-Weidinger, T and Wagner, M and Brunet, T and Brugger, M and Zimprich, A and Rath, J and Stögmann, E and Gelpi, E and Cetin, H},
title = {Clinical heterogeneity within the ALS-FTD spectrum in a family with a homozygous optineurin mutation.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.52075},
pmid = {38689506},
issn = {2328-9503},
abstract = {OBJECTIVE: Mutations in the gene encoding for optineurin (OPTN) have been reported in the context of different neurodegenerative diseases including the amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum. Based on single case reports, neuropathological data in OPTN mutation carriers have revealed transactive response DNA-binding protein 43 kDa (TDP-43) pathology, in addition to accumulations of tau and alpha-synuclein. Herein, we present two siblings from a consanguineous family with a homozygous frameshift mutation in the OPTN gene and different clinical presentations.

METHODS: Both affected siblings underwent (i) clinical, (ii) neurophysiological, (iii) neuropsychological, (iv) radiological, and (v) laboratory examinations, and (vi) whole-exome sequencing (WES). Postmortem histopathological examination was conducted in the index patient, who deceased at the age of 41.

RESULTS: The index patient developed rapidly progressing clinical features of upper and lower motor neuron dysfunction as well as apathy and cognitive deterioration at the age of 41. Autopsy revealed an ALS-FTLD pattern associated with prominent neuronal and oligodendroglial TDP-43 pathology, and an atypical limbic 4-repeat tau pathology reminiscent of argyrophilic grain disease. The brother of the index patient exhibited behavioral changes and mnestic deficits at the age of 38 and was diagnosed with behavioral FTD 5 years later, without any evidence of motor neuron dysfunction. WES revealed a homozygous frameshift mutation in the OPTN gene in both siblings (NM_001008212.2: c.1078_1079del; p.Lys360ValfsTer18).

INTERPRETATION: OPTN mutations can be associated with extensive TDP-43 pathology and limbic-predominant tauopathy and present with a heterogeneous clinical phenotype within the ALS-FTD spectrum within the same family.},
}

@article {pmid38687737,
year = {2024},
author = {Lumi, R and Petri, S and Siwy, J and Latosinska, A and Raad, J and Zürbig, P and Skripuletz, T and Mischak, H and Beige, J},
title = {Small peptide CSF fingerprint of amyotrophic lateral sclerosis.},
journal = {PloS one},
volume = {19},
number = {4},
pages = {e0302280},
pmid = {38687737},
issn = {1932-6203},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Female ; Male ; Middle Aged ; Aged ; *Peptides/cerebrospinal fluid ; Proteomics/methods ; Adult ; Biomarkers/cerebrospinal fluid ; Case-Control Studies ; Tandem Mass Spectrometry ; Chromatography, Liquid ; },
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by abnormal protein aggregation in the motor neurons. Present and earlier proteomic studies to characterize peptides in cerebrospinal fluid (CSF) associated with motoneuron pathology did not target low molecular weight proteins and peptides. We hypothesized that specific changes in CSF peptides or low molecular weight proteins are significantly altered in ALS, and that these changes may support deciphering molecular pathophysiology and even guide approaches towards therapeutic interventions.

METHODS: Cerebrospinal fluid (CSF) from 50 ALS patients and 50 non-ALS controls was collected, centrifuged immediately after collection, aliquoted into polypropylene test tubes, frozen within 30-40 min after the puncture, and stored at -80°C until use. Peptides were sequenced using capillary electrophoresis or liquid chromatography/mass spectrometry (CE-MS/MS or LC-MS/MS).

FINDINGS: In the CSF of 50 patients and 50 non-ALS controls 33 peptides were found, of which 14 could be sequenced using a non-lytic single-pot proteomic detection method, CE/MS. ALS deregulated peptides vs. controls included Integral membrane protein 2B, Neurosecretory protein VGF, Osteopontin, Neuroendocrine protein 7B2 (Secretogranin-V), EGF-containing fibulin-like extracellular matrix protein 1, Xylosyltransferase 1 XT-1, Chromogranin-A, Superoxide dismutase SOD-1, Secretogranin-1 (Chromogranin B), NR2F2 Nuclear Receptor Subfamily 2 Group F Member 2 and Collagen alpha-1(VII) chain.

INTERPRETATION: Most striking deregulations in CSF from ALS patients were found in VGF, Osteopontin, SOD-1 and EFEMP1 peptides. No associations of disease severity, duration and region of onset with sequenced peptides were found.},
}

Humans
*Amyotrophic Lateral Sclerosis/cerebrospinal fluid
Female
Male
Middle Aged
Aged
*Peptides/cerebrospinal fluid
Proteomics/methods
Adult
Biomarkers/cerebrospinal fluid
Case-Control Studies
Tandem Mass Spectrometry
Chromatography, Liquid

@article {pmid38686337,
year = {2024},
author = {Felix, C and Johnston, JD and Owen, K and Shirima, E and Hinds, SR and Mandl, KD and Milinovich, A and Alberts, JL},
title = {Explainable machine learning for predicting conversion to neurological disease: Results from 52,939 medical records.},
journal = {Digital health},
volume = {10},
number = {},
pages = {20552076241249286},
pmid = {38686337},
issn = {2055-2076},
abstract = {OBJECTIVE: This study assesses the application of interpretable machine learning modeling using electronic medical record data for the prediction of conversion to neurological disease.

METHODS: A retrospective dataset of Cleveland Clinic patients diagnosed with Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, or Parkinson's disease, and matched controls based on age, sex, race, and ethnicity was compiled. Individualized risk prediction models were created using eXtreme Gradient Boosting for each neurological disease at four timepoints in patient history. The prediction models were assessed for transparency and fairness.

RESULTS: At timepoints 0-months, 12-months, 24-months, and 60-months prior to diagnosis, Alzheimer's disease models achieved the area under the receiver operating characteristic curve on a holdout test dataset of 0.794, 0.742, 0.709, and 0.645; amyotrophic lateral sclerosis of 0.883, 0.710, 0.658, and 0.620; multiple sclerosis of 0.922, 0.877, 0.849, and 0.781; and Parkinson's disease of 0.809, 0.738, 0.700, and 0.651, respectively.

CONCLUSIONS: The results demonstrate that electronic medical records contain latent information that can be used for risk stratification for neurological disorders. In particular, patient-reported outcomes, sleep assessments, falls data, additional disease diagnoses, and longitudinal changes in patient health, such as weight change, are important predictors.},
}

@article {pmid38685454,
year = {2024},
author = {Gadri, Y and Avneri, A and Peleg, Z},
title = {Induced mutation in the SiALS gene offers new weed management opportunities for sesame crop.},
journal = {Plant science : an international journal of experimental plant biology},
volume = {},
number = {},
pages = {112104},
doi = {10.1016/j.plantsci.2024.112104},
pmid = {38685454},
issn = {1873-2259},
abstract = {Weeds are the primary biotic constraint affecting sesame growth and production. Here, we applied EMS mutagenesis to an elite sesame cultivar and discovered a novel point mutation in the sesame SiALS gene conferring resistance to imidazolinone, a group of acetolactate-synthase (ALS)-inhibitors. The mutant line exhibited high resistance to imazamox, an ALS-inhibitor, with hybrid plants displaying an intermediate response. Field-based validation confirmed the mutant line's substantial resistance, leading to a significantly higher yield under imazamox treatment. Under pre-emergence application of imazapic, the mutant plants sustained growth, whereas wild-type and weed were effectively controlled. Field trials using s-metolachlor and imazapic combined resulted in weed-free plots compared to untreated controls. Consequently, this treatment showed a significantly greater yield (2280 vs. 880 Kg ha[-1]) than the commercial practice (s-metolachlor). Overall, our study unveils the potential of utilizing this point mutation in sesame breeding programs, offering new opportunities for integrated weed management strategies for sesame cultivation. Developing herbicide-resistant crop plants holds promise for supporting sustainable production and addressing the challenges of weed infestations in sesame farming.},
}

@article {pmid38685248,
year = {2024},
author = {Chtourou, M and Osuna, MD and Vázquez-García, JG and Lozano-Juste, J and De Prado, R and Torra, J and Souissi, T},
title = {Pro197Ser and the new Trp574Leu mutations together with enhanced metabolism contribute to cross-resistance to ALS inhibiting herbicides in Sinapis alba.},
journal = {Pesticide biochemistry and physiology},
volume = {201},
number = {},
pages = {105882},
doi = {10.1016/j.pestbp.2024.105882},
pmid = {38685248},
issn = {1095-9939},
mesh = {*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Sinapis/drug effects/genetics ; *Malathion/pharmacology ; *Mutation ; Plant Proteins/genetics/metabolism ; Arylsulfonates/pharmacology ; Molecular Docking Simulation ; Imidazoles/pharmacology ; },
abstract = {White mustard, (Sinapis alba), a problematic broadleaf weed in many Mediterranean countries in arable fields has been detected as resistant to tribenuron-methyl in Tunisia. Greenhouse and laboratory studies were conducted to characterize Target-Site Resistance (TSR) and the Non-Target Site Resistance (NTSR) mechanisms in two suspected white mustard biotypes. Herbicide dose-response experiments confirmed that the two S. alba biotypes were resistant to four dissimilar acetolactate synthase (ALS)-pinhibiting herbicide chemistries indicating the presence of cross-resistance mechanisms. The highest resistance factor (>144) was attributed to tribenuron-methyl herbicide and both R populations survived up to 64-fold the recommended field dose (18.7 g ai ha[-1]). In this study, the metabolism experiments with malathion (a cytochrome P450 inhibitor) showed that malathion reduced resistance to tribenuron-methyl and imazamox in both populations, indicating that P450 may be involved in the resistance. Sequence analysis of the ALS gene detected target site mutations in the two R biotypes, with amino acid substitutions Trp574Leu, the first report for the species, and Pro197Ser. Molecular docking analysis showed that ALS[Pro197Ser] enzyme cannot properly bind to tribenuron-methyl's aromatic ring due to a reduction in the number of hydrogen bonds, while imazamox can still bind. However, Trp574Leu can weaken the binding affinity between the mutated ALS enzyme and both herbicides with the loss of crucial interactions. This investigation provides substantial evidence for the risk of evolving multiple resistance in S. alba to auxin herbicides while deciphering the TSR and NTSR mechanisms conferring cross resistance to ALS inhibitors.},
}

*Acetolactate Synthase/genetics/metabolism/antagonists & inhibitors
*Herbicides/pharmacology
*Herbicide Resistance/genetics
*Sinapis/drug effects/genetics
*Malathion/pharmacology
*Mutation
Plant Proteins/genetics/metabolism
Arylsulfonates/pharmacology
Molecular Docking Simulation
Imidazoles/pharmacology

@article {pmid38685231,
year = {2024},
author = {Deng, W and Yao, S and Li, Y and Yin, H and Yang, Q and Yuan, S},
title = {An Asp376Glu substitution and P450s-involved metabolism endow resistance to ALS inhibitors in an Ammannia auriculata Willd. Population.},
journal = {Pesticide biochemistry and physiology},
volume = {201},
number = {},
pages = {105911},
doi = {10.1016/j.pestbp.2024.105911},
pmid = {38685231},
issn = {1095-9939},
mesh = {*Acetolactate Synthase/genetics/antagonists & inhibitors ; *Herbicides/pharmacology ; *Herbicide Resistance/genetics ; *Cytochrome P-450 Enzyme System/genetics/metabolism ; Malathion/pharmacology ; Sulfonylurea Compounds/pharmacology ; Plant Weeds/drug effects/genetics ; Amino Acid Substitution ; },
abstract = {Ammannia auriculata Willd. is a noxious broadleaf weed, commonly infesting rice ecosystems across southern China. A putative resistant A. auriculata population (AHSC-5) was sampled from a rice field of Anhui Province, where bensulfuron-methyl (BM) was unable to control its occurrence. This study aimed to determine the sensitivities of the AHSC-5 population to common-use herbicides, and to investigate the underlying resistance mechanisms. The bioassays showed that the AHSC-5 population was 138.1-fold resistant to BM, compared with the susceptible population (JSGL-1). Pretreatment of malathion reduced the resistance index to 19.5. ALS sequencing revealed an Asp376Glu substitution in the AHSC-5 population, and in vitro ALS activity assays found that 50% activity inhibition (I50) of BM in AHSC-5 was 75.4 times higher than that of JSGL-1. Moreover, the AHSC-5 population displayed cross-resistance to pyrazosulfuron-ethyl (10.6-fold), bispyribac‑sodium (3.6-fold), and imazethapyr (2.2-fold), and was in the process of evolving multiple resistance to synthetic auxin herbicides fluroxypyr (2.3-fold) and florpyrauxifen-benzyl (3.1-fold). This study proved the BM resistance in A. auriculata caused by the Asp376Glu mutation and P450-regulated metabolism. This multi-resistant population can still be controlled by penoxsulam, MCPA, bentazone, and carfentrazone-ethyl, which aids in developing targeted and effective weed management strategies.},
}

*Acetolactate Synthase/genetics/antagonists & inhibitors
*Herbicides/pharmacology
*Herbicide Resistance/genetics
*Cytochrome P-450 Enzyme System/genetics/metabolism
Malathion/pharmacology
Sulfonylurea Compounds/pharmacology
Plant Weeds/drug effects/genetics
Amino Acid Substitution

@article {pmid38684907,
year = {2024},
author = {Nelson, AT and Cicardi, ME and Markandaiah, SS and Han, JY and Philp, NJ and Welebob, E and Haeusler, AR and Pasinelli, P and Manfredi, G and Kawamata, H and Trotti, D},
title = {Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {38684907},
issn = {1469-3178},
support = {RF1-AG057882//HHS | NIH | National Institute on Aging (NIA)/ ; R21-NS090912//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; RO1-NS109150//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; F31-NS118838//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; RF1-NS114128//HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)/ ; W81XWH-21-1-0134//DOD | USA | MEDCOM | MRDC | U.S. Army Medical Research Acquisition Activity (USAMRAA)/ ; 628389//Muscular Dystrophy Association (MDA)/ ; },
abstract = {The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)n nucleotide repeat expansion (NRE) occurring in the first intron of the C9orf72 gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, but its role in disease pathogenesis is unknown. Here, we show alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We find that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also show that one of the arginine-rich DPRs (PR) could directly contribute to glucose metabolism and metabolic stress by inhibiting glucose uptake in neurons. Our findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model with potential opportunities for therapeutic intervention.},
}

@article {pmid38683778,
year = {2024},
author = {Brennan, MR and Keast, DH and Bain, K and Bain, M and Lorentsen, B and Ayoub, N},
title = {Defining wound bed conformability: a new testing methodology to assess the relative swelling rise of foam dressings.},
journal = {Journal of wound care},
volume = {33},
number = {5},
pages = {312-323},
doi = {10.12968/jowc.2024.33.5.312},
pmid = {38683778},
issn = {0969-0700},
mesh = {Humans ; *Wound Healing ; *Bandages ; Reproducibility of Results ; Exudates and Transudates ; Materials Testing ; Wounds and Injuries/therapy ; },
abstract = {OBJECTIVE: Using a dressing that expands and conforms to the wound bed upon exudate absorption is one of the best ways to promote wound healing. While many products claim wound bed conformability, no externally replicated or verified test methodology had been developed to quantify a wound dressing's ability to conform to the wound bed. The Relative Swelling Rise (RSR) test methodology was developed to measure the relative swelling rise of foam dressings upon fluid absorption, and offers a quantifiable and easily replicated method to measure wound bed conformability.

METHOD: The RSR test method was developed, validated and reliability tested by Coloplast A/S, Denmark. External replication was provided by ALS Odense, Denmark (previously DB Lab). Circular fences provide a fixed diameter to apply and contain the fluid and prevent horizontal spreading in the test set-up. The swelling height is quantified relative to the fence's inner diameter, i.e., the ratio alpha (α), and allows evaluation of a material's ability to conform to the wound bed.

RESULTS: Biatain Silicone foam products (n=3, Coloplast A/S, Denmark) were tested, all afforded an average α-ratio from 0.30 to 0.60. The relative standard deviations were between 1-3%, demonstrating the strength of the test. Robustness of the methodology was demonstrated through the internal validation study, the reliability study, and both an internal and external replication study, as well as a systematic literature review and expert review of the construct, content, criterion and generalisability of the method.

CONCLUSION: Having a validated, effective and easily replicable testing method to quantify wound bed conformability of foam dressings is an important step towards achieving better healing outcomes.},
}

Humans
*Wound Healing
*Bandages
Reproducibility of Results
Exudates and Transudates
Materials Testing
Wounds and Injuries/therapy

@article {pmid38683209,
year = {2024},
author = {Wohnrade, C and Seeliger, T and Gingele, S and Bjelica, B and Skripuletz, T and Petri, S},
title = {Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38683209},
issn = {1432-1459},
abstract = {OBJECTIVE: To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN).

METHODS: This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden's index), and correlations with demographic characteristics were calculated.

RESULTS: Neurofilament concentrations were significantly higher in MND compared to MMN (p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman's rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease.

CONCLUSION: Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.},
}

@article {pmid38682649,
year = {2024},
author = {Zhou, Q and Jiang, X and Zhang, X and Wang, D and Yang, G and Zhou, H and Wu, Y and Guo, F and Chen, M and Diao, G and Ni, L},
title = {Polyoxomolybdate-Based Metal-Organic Framework-Derived Cu-Embedded Molybdenum Dioxide Hybrid Nanoparticles as Highly Efficient Electrocatalysts for Al-S Batteries.},
journal = {ChemSusChem},
volume = {},
number = {},
pages = {e202400424},
doi = {10.1002/cssc.202400424},
pmid = {38682649},
issn = {1864-564X},
abstract = {High-performance rechargeable aluminum-sulfur batteries (RASB) have great potential for various applications owing to their high theoretical capacity, abundant sulfur resources, and good safety. Nevertheless, the practical application of RASB still faces several challenges, including the polysulfide shuttle phenomenon and low sulfur utilization efficiency. Here, we first developed a synergistic copper heterogeneous metal oxide MoO2 derived from polymolybdate-based metal-organic framework as an efficient catalyst for mitigating polysulfide diffusion. This composite enhances sulfur utilization and electrical conductivity of the cathode. DFT calculations and experimental results reveal the catalyst Cu/MoO2@C not only effectively anchors aluminum polysulfides (AlPSs) to mitigate the shuttle effect, but also significantly promotes the catalytic conversion of AlPSs on the sulfur cathode side during charging and discharging. The unique nanostructure contains abundant electrocatalytic active sites of oxide nanoparticles and Cu clusters, resulting in excellent electrochemical performance. Consequently, the established RASB exhibits an initial capacity of 875 mAh g-1 at 500 mA g-1 and maintains a capacity of 967 mAh g-1 even at a high temperature of 50 °C.},
}

@article {pmid38682227,
year = {2024},
author = {Mohammadi, S and Ghaderi, S and Mohammadi, M and Najafi Asli Pashaki, Z and Khatyal, R and Mohammadian, F and Mohammadjani, S},
title = {Thalamic Alterations in Motor Neuron Diseases: A Systematic Review of MRI Findings.},
journal = {Journal of integrative neuroscience},
volume = {23},
number = {4},
pages = {77},
doi = {10.31083/j.jin2304077},
pmid = {38682227},
issn = {0219-6352},
mesh = {Humans ; *Thalamus/diagnostic imaging/pathology/physiopathology ; *Motor Neuron Disease/diagnostic imaging/pathology/physiopathology ; *Magnetic Resonance Imaging ; Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology ; },
abstract = {BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes.

METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale.

RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs.

CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.},
}

Humans
*Thalamus/diagnostic imaging/pathology/physiopathology
*Motor Neuron Disease/diagnostic imaging/pathology/physiopathology
*Magnetic Resonance Imaging
Amyotrophic Lateral Sclerosis/diagnostic imaging/pathology/physiopathology

@article {pmid38682222,
year = {2024},
author = {Huang, Q and Li, Q and Guo, JH},
title = {Causal Relationship between Sex Hormones and Risk of Developing Common Neurodegenerative Diseases: A Mendelian Randomization Study.},
journal = {Journal of integrative neuroscience},
volume = {23},
number = {4},
pages = {78},
doi = {10.31083/j.jin2304078},
pmid = {38682222},
issn = {0219-6352},
support = {2021ZD0201801//Science and Technology Innovation 2030 - Major program of "Brain Science and Brain-like Research"/ ; },
mesh = {Humans ; *Mendelian Randomization Analysis ; *Neurodegenerative Diseases/epidemiology/genetics ; *Sex Hormone-Binding Globulin/analysis/metabolism ; Testosterone/blood ; Alzheimer Disease/epidemiology/genetics ; Estradiol/blood ; Amyotrophic Lateral Sclerosis/epidemiology/genetics ; Parkinson Disease/genetics/epidemiology ; Gonadal Steroid Hormones/blood/metabolism ; Female ; Male ; },
abstract = {BACKGROUND: Neurodegenerative diseases are a group of unexplained disorders of the central nervous system, and studies have shown that a large number of genetic and environmental factors are associated with these diseases. Since these diseases show significant gender differences in epidemiology, sex hormones are thought to be strongly associated with these diseases. In this study, we used Mendelian randomization to explore the causal relationship between sex hormones and the risk of developing neurodegenerative diseases.

METHODS: We obtained genetic instrumental variables for sex hormones (sex hormone-binding globulin [SHBG], estradiol levels [EL], and bioavailable testosterone [BT]) separately through the Integrative Epidemiology Unit (IEU) database (https://gwas.mrcieu.ac.uk/). We analyzed the causal relationship of each with the risk of developing neurodegenerative diseases (Amyotrophic Lateral Sclerosis [ALS], Parkinson's disease [PD], and Alzheimer's disease [AD]) using inverse variance weighted (IVW) in Mendelian randomization. Data were then analyzed for sensitivity.

RESULTS: BT was negatively associated with the risk of developing ALS (odds ratio [OR] = 0.794; 95% confidence interval [95% CI] = 0.672-0.938; p = 0.006). EL and SHBG were not associated with a risk for developing neurodegenerative diseases (ALS, PD, AD).

CONCLUSIONS: Elevated BT is associated with a reduced risk of developing ALS. Further research is needed to investigate the underlying mechanisms of action for this correlation and how it can be used as a potential target of action to reduce the risk of developing ALS.},
}

Humans
*Mendelian Randomization Analysis
*Neurodegenerative Diseases/epidemiology/genetics
*Sex Hormone-Binding Globulin/analysis/metabolism
Testosterone/blood
Alzheimer Disease/epidemiology/genetics
Estradiol/blood
Amyotrophic Lateral Sclerosis/epidemiology/genetics
Parkinson Disease/genetics/epidemiology
Gonadal Steroid Hormones/blood/metabolism
Female
Male

@article {pmid38681726,
year = {2024},
author = {Grzanka, M and Joniec, A and Rogulski, J and Sobiech, Ł and Idziak, R and Loryś, B},
title = {Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control.},
journal = {Open life sciences},
volume = {19},
number = {1},
pages = {20220868},
pmid = {38681726},
issn = {2391-5412},
abstract = {Delayed sowing of winter cereals or unfavorable weather conditions in autumn may make it impossible to carry out herbicide treatment in autumn. In such cases, weed control should be started in the spring. During this time, the plantation should be protected as effectively as possible because the weeds are at an advanced stage of growth. Therefore, they are less sensitive to applied herbicides. In the treatment, it is worth using a mixture of different mechanisms of action. Studies were conducted to evaluate the effectiveness of a band of tribenuron-methyl, and MCPA applied as soluble granules in spring control of dicotyledonous in winter cereals. The biological efficacy of herbicides was estimated in the 25 field experiments on winter cereals in Poland. Postemergence, a spring application of tribenuron-methyl + MCPA, effectively controls the majority of weed species present in spring: Anthemis arvensis, Brassica napus, Capsella bursa-pastoris, Centaurea cyanus, Lamium purpureum, Matricaria chamomilla, Tripleurospermum inodorum, Stellaria media and Thlaspi arvense. Satisfactory control was confirmed for Veronica persica, Viola arvensis, and Galium aparine. Tribenuron-methyl with MCPA is recommended for application to winter cereals in spring. To prevent the development of resistance in weeds, it is advantageous to combine two active substances.},
}

@article {pmid38679739,
year = {2024},
author = {Pérez Compte, D and Etourneau, L and Hesse, AM and Kraut, A and Barthelon, J and Sturm, N and Borges, H and Biennier, S and Courçon, M and de Saint Loup, M and Mignot, V and Costentin, C and Burger, T and Couté, Y and Bruley, C and Decaens, T and Jaquinod, M and Boursier, J and Brun, V},
title = {Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients.},
journal = {Biomarker research},
volume = {12},
number = {1},
pages = {44},
pmid = {38679739},
issn = {2050-7771},
support = {[ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-10-INBS-08]//ProFI project/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-17-EURE-0003]//Chemistry Biology Health (CBH) Graduate School at University Grenoble Alpes/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-15-IDEX-02]//LIFE project/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; [ANR-19-P3IA-0003]//MIAI @ Grenoble Alpes/ ; },
abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world's population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy - an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages.

METHODS: A discovery study was performed on 158 plasma samples from histologically-characterised MASLD patients using mass spectrometry (MS)-based quantitative proteomics. Differentially abundant proteins were selected for verification by ELISA in the same cohort. They were subsequently validated in an independent MASLD cohort (n = 200).

RESULTS: From the 72 proteins differentially abundant between patients with early (F0-2) and advanced fibrosis (F3-4), we selected Insulin-like growth factor-binding protein complex acid labile subunit (ALS) and Galectin-3-binding protein (Gal-3BP) for further study. In our validation cohort, AUROCs with 95% CIs of 0.744 [0.673 - 0.816] and 0.735 [0.661 - 0.81] were obtained for ALS and Gal-3BP, respectively. Combining ALS and Gal-3BP improved the assessment of advanced liver fibrosis, giving an AUROC of 0.796 [0.731. 0.862]. The {ALS; Gal-3BP}
model surpassed classic fibrosis panels in predicting advanced liver fibrosis.

CONCLUSIONS: Further investigations with complementary cohorts will be needed to confirm the usefulness of ALS and Gal-3BP individually and in combination with other biomarkers for diagnosis of liver fibrosis. With the availability of ELISA assays, these findings could be rapidly clinically translated, providing direct benefits for patients.},
}

@article {pmid38679111,
year = {2024},
author = {Thulasidharan, A and Garg, L and Tendulkar, S and Ratnaparkhi, GS},
title = {Age-dependent dynamics of neuronal VAPB[ALS] inclusions in the adult brain.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {106517},
doi = {10.1016/j.nbd.2024.106517},
pmid = {38679111},
issn = {1095-953X},
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a relentlessly progressive and fatal disease, caused by the degeneration of upper and lower motor neurons within the brain and spinal cord in the ageing human. The dying neurons contain cytoplasmic inclusions linked to the onset and progression of the disease. Here, we use a Drosophila model of ALS8 (VAP[P58S]) to understand the modulation of these inclusions in the ageing adult brain. The adult VAP[P58S] fly shows progressive deterioration in motor function till its demise 25 days post-eclosion. The density of VAP[P58S]-positive brain inclusions is stable for 5-15 days of age. In contrast, adding a single copy of VAP[WT] to the VAP[P58S] animal leads to a large decrease in inclusion density with concomitant rescue of motor function and lifespan. ER stress, a contributing factor in disease, shows reduction with ageing for the disease model. Autophagy, rather than the Ubiquitin Proteasome system, is the dominant mechanism for aggregate clearance. We explored the ability of Drosophila Valosin-containing protein (VCP/TER94), the ALS14 locus, which is involved in cellular protein clearance, to regulate age-dependent aggregation. Contrary to expectation, TER94 overexpression increased VAP[P58S] punctae density, while its knockdown led to enhanced clearance. Expression of a dominant positive allele, TER94[R152H], further stabilised VAP[P58S] puncta, cementing roles for an ALS8-ALS14 axis. Our results are explained by a mechanism where autophagy is modulated by TER94 knockdown. Our study sheds light on the complex regulatory events involved in the neuronal maintenance of ALS8 aggregates, suggesting a context-dependent switch between proteasomal and autophagy-based mechanisms as the larvae develop into an adult. A deeper understanding of the nucleation and clearance of the inclusions, which affect cellular stress and function, is essential for understanding the initiation and progression of ALS.},
}

@article {pmid38678262,
year = {2024},
author = {Xu, C and Mei, Y and Yang, R and Luo, Q and Zhang, J and Kou, X and Hu, J and Wang, Y and Li, Y and Chen, R and Zhang, Z and Yao, Y and Sima, J},
title = {Edaravone Dexborneol mitigates pathology in animal and cell culture models of Alzheimer's disease by inhibiting neuroinflammation and neuronal necroptosis.},
journal = {Cell & bioscience},
volume = {14},
number = {1},
pages = {55},
pmid = {38678262},
issn = {2045-3701},
support = {82173804//National Natural Science Foundation of China/ ; 82001144//National Natural Science Foundation of China/ ; 3150120042//High-Level Talents Start-up Funding of China Pharmaceutical University/ ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with limited disease-modifying treatments. Drug repositioning strategy has now emerged as a promising approach for anti-AD drug discovery. Using 5×FAD mice and Aβ-treated neurons in culture, we tested the efficacy of Y-2, a compounded drug containing the antioxidant Edaravone (Eda), a pyrazolone and (+)-Borneol, an anti-inflammatory diterpenoid from cinnamon, approved for use in amyotrophic lateral sclerosis patients.

RESULTS: We examined effects of Y-2 versus Eda alone by i.p. administered in 8-week-old 5×FAD mice (females) for 4 months by comparing cognitive function, Aβ pathologies, neuronal necroptosis and neuroinflammation. Using primary neurons and astrocytes, as well as neuronal and astrocytic cell lines, we elucidated the molecular mechanisms of Y-2 by examining neuronal injury, astrocyte-mediated inflammation and necroptosis. Here, we find that Y-2 improves cognitive function in AD mice. Histopathological data show that Y-2, better than Eda alone, markedly ameliorates Aβ pathologies including Aβ burden, astrogliosis/microgliosis, and Tau phosphorylation. In addition, Y-2 reduces Aβ-induced neuronal injury including neurite damage, mitochondrial impairment, reactive oxygen species production and NAD[+] depletion. Notably, Y-2 inhibits astrocyte-mediated neuroinflammation and attenuates TNF-α-triggered neuronal necroptosis in cell cultures and AD mice. RNA-seq further demonstrates that Y-2, compared to Eda, indeed upregulates anti-inflammation pathways in astrocytes.

CONCLUSIONS: Our findings infer that Y-2, better than Eda alone, mitigates AD pathology and may provide a potential drug candidate for AD treatment.},
}

@article {pmid38677733,
year = {2024},
author = {Keul, J and Sperling, S and Rohde, V and Mielke, D and Ninkovic, M},
title = {Riluzole Reverses a Number of Undesirable Effects of Dexamethasone in Glioblastoma Cells.},
journal = {Anticancer research},
volume = {44},
number = {5},
pages = {1829-1835},
doi = {10.21873/anticanres.16984},
pmid = {38677733},
issn = {1791-7530},
mesh = {*Riluzole/pharmacology ; Humans ; *Glioblastoma/drug therapy/pathology/metabolism ; *Dexamethasone/pharmacology ; *Cell Movement/drug effects ; Cell Line, Tumor ; Brain Neoplasms/drug therapy/pathology/metabolism ; Cell Survival/drug effects ; },
abstract = {BACKGROUND/AIM: Glioblastoma multiforme (GBM)-induced oedema is a major cause of morbidity and mortality among patients with GBM. Dexamethasone (Dex) is the most common corticosteroid used pre-operatively to control cerebral oedema in patients with GBM. Dex is associated with many side effects, and shorter overall survival and progression-free survival of patients with GBM. These negative effects of Dex highlight the need for combinational therapy. Riluzole (Ril), a drug used to treat amyotrophic lateral sclerosis (ALS), is thought to have potential as a treatment for various cancers, with clinical trials underway. Here, we investigated whether Ril could reverse some of the undesirable effects of Dex.

MATERIALS AND METHODS: The effect of Dex, Ril, and Ril-Dex treatment on cell migration was monitored using the xCELLigence system. Cell viability assays were performed using 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide (MTT). The expression of genes involved in migration, glucose metabolism, and stemness was examined using real-time polymerase chain reaction (PCR).

RESULTS: Pre-treating GBM cells with Ril reduced Dex-induced cell migration and altered Dex-induced effects on cell invasion, stem cell, and glucose metabolism markers. Furthermore, Ril remained effective in killing GBM cells in combination with Dex.

CONCLUSION: Ril, which acts as an anti-tumorigenic drug, mediates some of the negative effects of Dex; therefore, it could be a potential drug to manage the side effects of Dex therapy in GBM.},
}

*Riluzole/pharmacology
Humans
*Glioblastoma/drug therapy/pathology/metabolism
*Dexamethasone/pharmacology
*Cell Movement/drug effects
Cell Line, Tumor
Brain Neoplasms/drug therapy/pathology/metabolism
Cell Survival/drug effects

@article {pmid38677657,
year = {2024},
author = {Ko, VI and Ong, K and Cleveland, DW and Yu, H and Ravits, JM},
title = {CK1δ/ε kinases regulate TDP-43 phosphorylation and are therapeutic targets for ALS-related TDP-43 hyperphosphorylation.},
journal = {Neurobiology of disease},
volume = {196},
number = {},
pages = {106516},
doi = {10.1016/j.nbd.2024.106516},
pmid = {38677657},
issn = {1095-953X},
abstract = {Hyperphosphorylated TAR DNA-binding protein 43 (TDP-43) aggregates in the cytoplasm of neurons is the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and a group of neurodegenerative diseases collectively referred to as TDP-43 proteinopathies that includes frontotemporal dementia, Alzheimer's disease, and limbic onset age-related TDP-43 encephalopathy. The mechanism of TDP-43 phosphorylation is poorly understood. Previously we reported casein kinase 1 epsilon gene (CSNK1E gene encoding CK1ε protein) as being tightly correlated with phosphorylated TDP-43 (pTDP-43) pathology. Here we pursued studies to investigate in cellular models and in vitro how CK1ε and CK1δ (a closely related family sub-member) mediate TDP-43 phosphorylation in disease. We first validated the binding interaction between TDP-43 and either CK1δ and CK1ε using kinase activity assays and predictive bioinformatic database. We utilized novel inducible cellular models that generated translocated phosphorylated TDP-43 (pTDP-43) and cytoplasmic aggregation. Reducing CK1 kinase activity with siRNA or small molecule chemical inhibitors resulted in significant reduction of pTDP-43, in both soluble and insoluble protein fractions. We also established CK1δ and CK1ε are the primary kinases that phosphorylate TDP-43 compared to CK2α, CDC7, ERK1/2, p38α/MAPK14, and TTBK1, other identified kinases that have been implicated in TDP-43 phosphorylation. Throughout our studies, we were careful to examine both the soluble and insoluble TDP-43 protein fractions, the critical protein fractions related to protein aggregation diseases. These results identify CK1s as critical kinases involved in TDP-43 hyperphosphorylation and aggregation in cellular models and in vitro, and in turn are potential therapeutic targets by way of CK1δ/ε inhibitors.},
}

@article {pmid38676932,
year = {2024},
author = {Oppegaard, KR and Mayo, SJ and Armstrong, TS and Dokiparthi, V and Melisko, M and Levine, JD and Olshen, AB and Anguera, JA and Roy, R and Paul, S and Cooper, B and Conley, YP and Hammer, MJ and Miaskowski, C and Kober, KM},
title = {Neurodegenerative disease pathways are perturbed in patients with cancer who self-report cognitive changes and anxiety: A pathway impact analysis.},
journal = {Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/cncr.35336},
pmid = {38676932},
issn = {1097-0142},
support = {T32NR016920/NR/NINR NIH HHS/United States ; CA134900/CA/NCI NIH HHS/United States ; CA233774/CA/NCI NIH HHS/United States ; CA082103/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: Cancer-related cognitive impairment (CRCI) and anxiety co-occur in patients with cancer. Little is known about mechanisms for the co-occurrence of these two symptoms. The purposes of this secondary analysis were to evaluate for perturbed pathways associated with the co-occurrence of self-reported CRCI and anxiety in patients with low versus high levels of these two symptoms and to identify potential mechanisms for the co-occurrence of CRCI and anxiety using biological processes common across any perturbed neurodegenerative disease pathways.

METHODS: Patients completed the Attentional Function Index and the Spielberger State-Trait Anxiety Inventory six times over two cycles of chemotherapy. Based on findings from a previous latent profile analysis, patients were grouped into none versus both high levels of these symptoms. Gene expression was quantified, and pathway impact analyses were performed. Signaling pathways for evaluation were defined with the Kyoto Encyclopedia of Genes and Genomes database.

RESULTS: A total of 451 patients had data available for analysis. Approximately 85.0% of patients were in the none class and 15.0% were in the both high class. Pathway impact analyses identified five perturbed pathways related to neurodegenerative diseases (i.e., amyotrophic lateral sclerosis, Huntington disease, Parkinson disease, prion disease, and pathways of neurodegeneration-multiple diseases). Apoptosis, mitochondrial dysfunction, oxidative stress, and endoplasmic reticulum stress were common biological processes across these pathways.

CONCLUSIONS: This study is the first to describe perturbations in neurodegenerative disease pathways associated with CRCI and anxiety in patients receiving chemotherapy. These findings provide new insights into potential targets for the development of mechanistically based interventions.},
}

@article {pmid38676818,
year = {2024},
author = {Kubat, GB and Picone, P},
title = {Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {38676818},
issn = {1590-3478},
abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.},
}

@article {pmid38676672,
year = {2024},
author = {Kutlubaev, MA},
title = {[Promising approaches to the pathogenetic therapy of amyotrophic lateral sclerosis].},
journal = {Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova},
volume = {124},
number = {4},
pages = {13-21},
doi = {10.17116/jnevro202412404113},
pmid = {38676672},
issn = {1997-7298},
mesh = {*Amyotrophic Lateral Sclerosis/drug therapy/therapy ; Humans ; *Neuroprotective Agents/therapeutic use ; Genetic Therapy ; Antioxidants/therapeutic use ; Stem Cell Transplantation ; Gastrointestinal Microbiome ; Immunologic Factors/therapeutic use ; Immunomodulating Agents/therapeutic use ; },
abstract = {Amyotrophic lateral sclerosis is a severe incurable disease of the nervous system. Currently only methods of palliative care for the patients with this disease are available. Few medications for the pathogenetic therapy are registered in some countries, i.e. riluzole, edaravon, sodium phenylbutyrate/taurursodiol as well as tofersen (conditionally). Their efficacy is relatively low. The main directions in the development of pathogenetic therapy of ALS include gene therapy, use of stem cells, immunomodulators, agents affecting gut microbiota. A search is also underway for low-molecular compounds with neuroprotective and antioxidant properties. Perspective direction is prevention of ALS. This will be possible when biomarkers for identification of patients in pre-manifest/prodromal stage are detected.},
}

*Amyotrophic Lateral Sclerosis/drug therapy/therapy
Humans
*Neuroprotective Agents/therapeutic use
Genetic Therapy
Antioxidants/therapeutic use
Stem Cell Transplantation
Gastrointestinal Microbiome
Immunologic Factors/therapeutic use
Immunomodulating Agents/therapeutic use

@article {pmid38676626,
year = {2024},
author = {Dash, BP and Freischmidt, A and Weishaupt, JH and Hermann, A},
title = {An integrative miRNA-mRNA expression analysis identifies miRNA signatures associated with SOD1 and TARDBP patient-derived motor neurons.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddae072},
pmid = {38676626},
issn = {1460-2083},
support = {//Hermann and Lilly Schilling-Stiftung für medizinische Forschung im Stifterverband/ ; //Professorinnenprogramm III (University of Rostock) of the German/ ; },
abstract = {MicroRNAs (miRNAs) are a subset of small non-coding single-stranded RNA molecules involved in the regulation of post-transcriptional gene expression of a variety of transcript targets. Therefore altered miRNA expression may result in the dysregulation of key genes and biological pathways that has been reported with the onset and progression of neurodegenerative diseases, such as Amyotrophic lateral sclerosis (ALS). ALS is marked by a progressive degeneration of motor neurons (MNs) present in the spinal cord, brain stem and motor cortex. Although the pathomechanism underlying molecular interactions of ALS remains poorly understood, alterations in RNA metabolism, including dysregulation of miRNA expression in familial as well as sporadic forms are still scarcely studied. In this study, we performed combined transcriptomic data and miRNA profiling in MN samples of the same samples of iPSC-derived MNs from SOD1- and TARDBP (TDP-43 protein)-mutant-ALS patients and healthy controls. We report a global upregulation of mature miRNAs, and suggest that differentially expressed (DE) miRNAs have a significant impact on mRNA-level in SOD1-, but not in TARDBP-linked ALS. Furthermore, in SOD1-ALS we identified dysregulated miRNAs such as miR-124-3p, miR-19b-3p and miR-218 and their potential targets previously implicated in important functional process and pathogenic pathways underlying ALS. These miRNAs may play key roles in the neuronal development and cell survival related functions in SOD1-ALS. Altogether, we provide evidence of miRNA regulated genes expression mainly in SOD1 rather than TDP43-ALS.},
}

@article {pmid38676602,
year = {2024},
author = {Presotto, A and Hernández, F and Vercellino, RB and Kruger, RD and Fontana, ML and Ureta, MS and Crepy, M and Auge, G and Caicedo, A},
title = {Introgression from local cultivars is a driver of agricultural adaptation in Argentinian weedy rice.},
journal = {Molecular ecology},
volume = {},
number = {},
pages = {e17368},
doi = {10.1111/mec.17368},
pmid = {38676602},
issn = {1365-294X},
support = {IOS-1032023//Division of Integrative Organismal Systems/ ; PICT 2019-00581//Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación/ ; },
abstract = {Weedy rice, a pervasive and troublesome weed found across the globe, has often evolved through fertilization of rice cultivars with little importance of crop-weed gene flow. In Argentina, weedy rice has been reported as an important constraint since the early 1970s, and, in the last few years, strains with herbicide-resistance are suspected to evolve. Despite their importance, the origin and genetic composition of Argentinian weedy rice as well its adaptation to agricultural environments has not been explored so far. To study this, we conducted genotyping-by-sequencing on samples of Argentinian weedy and cultivated rice and compared them with published data from weedy, cultivated and wild rice accessions distributed worldwide. In addition, we conducted a phenotypic characterization for weedy-related traits, a herbicide resistance screening and genotyped accessions for known mutations in the acetolactate synthase (ALS) gene, which confers herbicide resistance. Our results revealed large phenotypic variability in Argentinian weedy rice. Most strains were resistant to ALS-inhibiting herbicides with a high frequency of the ALS mutation (A122T) present in Argentinian rice cultivars. Argentinian cultivars belonged to the three major genetic groups of rice: japonica, indica and aus while weeds were mostly aus or aus-indica admixed, resembling weedy rice strains from the Southern Cone region. Phylogenetic analysis supports a single origin for aus-like South American weeds, likely as seed contaminants from the United States, and then admixture with local indica cultivars. Our findings demonstrate that crop to weed introgression can facilitate rapid adaptation to agriculture environments.},
}

@article {pmid38676303,
year = {2024},
author = {Zhao, W and Wang, R and Chen, M},
title = {Clinical analysis of air-leak syndrome following allogeneic hematopoietic stem cell transplantation in pediatric patients.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e31008},
doi = {10.1002/pbc.31008},
pmid = {38676303},
issn = {1545-5017},
abstract = {BACKGROUND: Air-leak syndrome (ALS) is considered as an independent risk factor for poor prognosis in adult patients who had received hematopoietic stem cell transplantation (HSCT), and the 5-year overall survival (OS) of ALS is less than 30%. However, the clinical features of ALS among post-transplant pediatric patients have rarely been explored.

PROCEDURES: We retrospectively reviewed 2206 pediatric patients who had received an allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in prognosis following HSCT.

RESULTS: In our research, ALS was divided into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). Following treatment of the ALS, 18 patients survived (18/28, 64.3%), and 10 patients died of respiratory failure or infection (10/28, 35.7%).

CONCLUSIONS: The OS of ALS in Hebei Yanda Lu Daopei Hospital is significantly higher than others, and they were cited to be related to early diagnosis and timely FAM treatment in previous reports.},
}

@article {pmid38675428,
year = {2024},
author = {Calenda, S and Catarzi, D and Varano, F and Vigiani, E and Volpini, R and Lambertucci, C and Spinaci, A and Trevisan, L and Grieco, I and Federico, S and Spalluto, G and Novello, G and Salmaso, V and Moro, S and Colotta, V},
title = {Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {17},
number = {4},
pages = {},
pmid = {38675428},
issn = {1424-8247},
support = {RICATEN2021-2023Colotta//University of Florence/ ; 2017MT3993_004//Italian Ministry of University and Research-PRIN2017/ ; },
abstract = {Protein kinase CK1δ (CK1δ) is a serine-threonine/kinase that modulates different physiological processes, including the cell cycle, DNA repair, and apoptosis. CK1δ overexpression, and the consequent hyperphosphorylation of specific proteins, can lead to sleep disorders, cancer, and neurodegenerative diseases. CK1δ inhibitors showed anticancer properties as well as neuroprotective effects in cellular and animal models of Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis. To obtain new ATP-competitive CK1δ inhibitors, three sets of benzimidazole-2-amino derivatives were synthesized (1-32), bearing different substituents on the fused benzo ring (R) and diverse pyrazole-containing acyl moieties on the 2-amino group. The best-performing derivatives were those featuring the (1H-pyrazol-3-yl)-acetyl moiety on the benzimidazol-2-amino scaffold (13-32), which showed CK1δ inhibitor activity in the low micromolar range. Among the R substituents, 5-cyano was the most advantageous, leading to a compound endowed with nanomolar potency (23, IC50 = 98.6 nM). Molecular docking and dynamics studies were performed to point out the inhibitor-kinase interactions.},
}

@article {pmid38674921,
year = {2024},
author = {Wang, W and Pan, D and Liu, Q and Chen, X and Wang, S},
title = {L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.},
journal = {Nutrients},
volume = {16},
number = {8},
pages = {},
pmid = {38674921},
issn = {2072-6643},
mesh = {Humans ; *Carnitine/therapeutic use ; *Nervous System Diseases/drug therapy ; *Mental Disorders/drug therapy ; Dietary Supplements ; },
abstract = {OBJECTIVE: L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.

METHODS: A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.

RESULTS: A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.

CONCLUSION: In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.},
}

Humans
*Carnitine/therapeutic use
*Nervous System Diseases/drug therapy
*Mental Disorders/drug therapy
Dietary Supplements

@article {pmid38674548,
year = {2024},
author = {Bai, L and Li, X and Guo, X and Chen, J and Yu, H and Cui, H},
title = {Distribution and Mechanism of Japanese Brome (Bromus japonicus) Resistance to ALS-Inhibiting Herbicides in China.},
journal = {Plants (Basel, Switzerland)},
volume = {13},
number = {8},
pages = {},
pmid = {38674548},
issn = {2223-7747},
support = {2023YFD1400501//National Key Research and Development Program of China and Technology Innovation Project, Chinese Academy of Agricultural Sciences./ ; },
abstract = {Bromus japonicus is a common monocot weed that occurs in major winter wheat fields in the Huang-Huai-Hai region of China. Pyroxsulam is a highly efficient and safe acetolactate synthase (ALS)-inhibiting herbicide that is widely used to control common weeds in wheat fields. However, B. japonicus populations in China have evolved resistance to pyroxsulam by different mutations in the ALS gene. To understand the resistance distribution, target-site resistance mechanisms, and cross-resistance patterns, 208 B. japonicus populations were collected from eight provinces. In the resistant population screening experiment, 59 populations from six provinces showed different resistance levels to pyroxsulam compared with the susceptible population, of which 17 B. japonicus populations with moderate or high levels of resistance to pyroxsulam were mainly from the Hebei (4), Shandong (4) and Shanxi (9) Provinces. Some resistant populations were selected to investigate the target site-resistance mechanism to the ALS-inhibiting herbicide pyroxsulam. Three pairs of primers were designed to amplify the ALS sequence, which was assembled into the complete ALS sequence with a length of 1932 bp. DNA sequencing of ALS revealed that four different ALS mutations (Pro-197-Ser, Pro-197-Thr, Pro-197-Phe and Asp-376-Glu) were found in 17 moderately or highly resistant populations. Subsequently, five resistant populations, QM21-41 with Pro-197-Ser, QM20-8 with Pro-197-Thr and Pro-197-Phe, and QM21-72, QM21-76 and QM21-79 with Asp-376-Glu mutations in ALS genes, were selected to characterize their cross-resistance patterns to ALS inhibitors. The QM21-41, QM20-8, QM21-72, QM21-76 and QM21-79 populations showed broad-spectrum cross-resistance to pyroxsulam, mesosulfuron-methyl and flucarbazone-sodium. This study is the first to report evolving cross-resistance to ALS-inhibiting herbicides due to Pro-197-Phe mutations in B. japonicus.},
}

@article {pmid38674431,
year = {2024},
author = {Shahim, P and Norato, G and Sinaii, N and Zetterberg, H and Blennow, K and Chan, L and Grunseich, C},
title = {Neurofilaments in Sporadic and Familial Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis.},
journal = {Genes},
volume = {15},
number = {4},
pages = {},
pmid = {38674431},
issn = {2073-4425},
mesh = {*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid ; Humans ; *Neurofilament Proteins/blood/cerebrospinal fluid ; Biomarkers/blood/cerebrospinal fluid ; Intermediate Filaments/metabolism/genetics ; Prognosis ; },
abstract = {BACKGROUND: Neurofilament proteins have been implicated to be altered in amyotrophic lateral sclerosis (ALS). The objectives of this study were to assess the diagnostic and prognostic utility of neurofilaments in ALS.

METHODS: Studies were conducted in electronic databases (PubMed/MEDLINE, Embase, Web of Science, and Cochrane CENTRAL) from inception to 17 August 2023, and investigated neurofilament light (NfL) or phosphorylated neurofilament heavy chain (pNfH) in ALS. The study design, enrolment criteria, neurofilament concentrations, test accuracy, relationship between neurofilaments in cerebrospinal fluid (CSF) and blood, and clinical outcome were recorded. The protocol was registered with PROSPERO, CRD42022376939.

RESULTS: Sixty studies with 8801 participants were included. Both NfL and pNfH measured in CSF showed high sensitivity and specificity in distinguishing ALS from disease mimics. Both NfL and pNfH measured in CSF correlated with their corresponding levels in blood (plasma or serum); however, there were stronger correlations between CSF NfL and blood NfL. NfL measured in blood exhibited high sensitivity and specificity in distinguishing ALS from controls. Both higher levels of NfL and pNfH either measured in blood or CSF were correlated with more severe symptoms as assessed by the ALS Functional Rating Scale Revised score and with a faster disease progression rate; however, only blood NfL levels were associated with shorter survival.

DISCUSSION: Both NfL and pNfH measured in CSF or blood show high diagnostic utility and association with ALS functional scores and disease progression, while CSF NfL correlates strongly with blood (either plasma or serum) and is also associated with survival, supporting its use in clinical diagnostics and prognosis. Future work must be conducted in a prospective manner with standardized bio-specimen collection methods and analytical platforms, further improvement in immunoassays for quantification of pNfH in blood, and the identification of cut-offs across the ALS spectrum and controls.},
}

*Amyotrophic Lateral Sclerosis/genetics/blood/diagnosis/cerebrospinal fluid
Humans
*Neurofilament Proteins/blood/cerebrospinal fluid
Biomarkers/blood/cerebrospinal fluid
Intermediate Filaments/metabolism/genetics
Prognosis

@article {pmid38672445,
year = {2024},
author = {Esperante, IJ and Meyer, M and Banzan, C and Kruse, MS and Lima, A and Roig, P and Guennoun, R and Schumacher, M and De Nicola, AF and Gonzalez Deniselle, MC},
title = {Testosterone Reduces Myelin Abnormalities in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.},
journal = {Biomolecules},
volume = {14},
number = {4},
pages = {},
pmid = {38672445},
issn = {2218-273X},
support = {PICT 2019 Nº 3292//Ministerio de Ciencia, Tecnología e Innovación/ ; PIP 2022-2024 #11220210100091CO//CONICET/ ; },
mesh = {Animals ; Mice ; *Myelin Sheath/metabolism/drug effects ; *Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Male ; *Disease Models, Animal ; *Testosterone/pharmacology ; Spinal Cord/metabolism/drug effects/pathology ; Excitatory Amino Acid Transporter 2/metabolism/genetics ; Microglia/drug effects/metabolism/pathology ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The Wobbler (WR) mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male WRs display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in WRs in the absence or presence of the aromatase inhibitor, anastrozole (A). We studied myelin by using luxol-fast-blue (LFB) staining, semithin sections, electron microscopy and myelin protein expression, density of IBA1[+] microglia and mRNA expression of inflammatory factors, and the glutamatergic parameters glutamine synthetase (GS) and the transporter GLT1. Controls and WR + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than WRs and WR + T + A, and groups showing the rupture of myelin lamellae. WRs showed increased IBA1[+] cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR1 and P2Y12R) vs. controls or WR + T. IBA1[+] cells, and CD11b were not reduced in WR + T + A, but inflammatory factors' mRNA remained low. A reduction of GS[+] cells and GLT-1 immunoreactivity was observed in WRs and WR + T + A vs. controls and WR + T. Clinically, WR + T but not WR + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation.},
}

Animals
Mice
*Myelin Sheath/metabolism/drug effects
*Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology
Male
*Disease Models, Animal
*Testosterone/pharmacology
Spinal Cord/metabolism/drug effects/pathology
Excitatory Amino Acid Transporter 2/metabolism/genetics
Microglia/drug effects/metabolism/pathology

@article {pmid38672428,
year = {2024},
author = {Cox, SN and Lo Giudice, C and Lavecchia, A and Poeta, ML and Chiara, M and Picardi, E and Pesole, G},
title = {Mitochondrial and Nuclear DNA Variants in Amyotrophic Lateral Sclerosis: Enrichment in the Mitochondrial Control Region and Sirtuin Pathway Genes in Spinal Cord Tissue.},
journal = {Biomolecules},
volume = {14},
number = {4},
pages = {},
pmid = {38672428},
issn = {2218-273X},
support = {UNIBA148- project code C1A93B75-CUP H94I20000410008//Research for Innovation (REFIN)-POR PUGLIA FESR-FSE 2014/2020/ ; CN_00000013//National Research Centers: "High Performance Computing, Big Data and Quantum Computing"/ ; CN_00000041//National Research Centers: "Gene Therapy and Drugs based on RNA Technology"/ ; PE_0000006//National Research Centers-Extended Partnerships: MNESYS/ ; IR0000010//ELIXIR-IT ELIXIRNextGenIT/ ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/metabolism ; Humans ; *Spinal Cord/metabolism/pathology ; *DNA, Mitochondrial/genetics ; *Sirtuins/genetics/metabolism ; Male ; Female ; Middle Aged ; Mitochondria/genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Aged ; Exome Sequencing ; },
abstract = {Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS.},
}

*Amyotrophic Lateral Sclerosis/genetics/metabolism
Humans
*Spinal Cord/metabolism/pathology
*DNA, Mitochondrial/genetics
*Sirtuins/genetics/metabolism
Male
Female
Middle Aged
Mitochondria/genetics/metabolism
Cell Nucleus/genetics/metabolism
Aged
Exome Sequencing

@article {pmid38672416,
year = {2024},
author = {Cheslow, L and Snook, AE and Waldman, SA},
title = {Biomarkers for Managing Neurodegenerative Diseases.},
journal = {Biomolecules},
volume = {14},
number = {4},
pages = {},
pmid = {38672416},
issn = {2218-273X},
support = {1R01 CA204881, 1R01 CA206026, 1R21 1NS130388, 1R01 DK1388341/NH/NIH HHS/United States ; },
mesh = {Humans ; *Biomarkers/metabolism ; *Neurodegenerative Diseases/metabolism/diagnosis/therapy ; *Alzheimer Disease/metabolism/diagnosis/therapy ; Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis ; Parkinson Disease/metabolism/diagnosis/therapy ; Animals ; },
abstract = {Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).},
}

Humans
*Biomarkers/metabolism
*Neurodegenerative Diseases/metabolism/diagnosis/therapy
*Alzheimer Disease/metabolism/diagnosis/therapy
Amyotrophic Lateral Sclerosis/metabolism/therapy/diagnosis
Parkinson Disease/metabolism/diagnosis/therapy
Animals

@article {pmid38672412,
year = {2024},
author = {Lachén-Montes, M and Cartas-Cejudo, P and Cortés, A and Anaya-Cubero, E and Peral, E and Ausín, K and Díaz-Peña, R and Fernández-Irigoyen, J and Santamaría, E},
title = {Involvement of Glucosamine 6 Phosphate Isomerase 2 (GNPDA2) Overproduction in β-Amyloid- and Tau P301L-Driven Pathomechanisms.},
journal = {Biomolecules},
volume = {14},
number = {4},
pages = {},
pmid = {38672412},
issn = {2218-273X},
support = {0011-1411-2020-000028 and 0011-1411-2023-000028//Gobierno de Navarra/ ; PID2019-110356RB-I00/AEI/10.13039/501100011033//Spanish Ministry of Science, Innovation and Universities/ ; },
mesh = {Humans ; Animals ; *Zebrafish/metabolism ; *Amyloid beta-Peptides/metabolism ; *tau Proteins/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics/pathology ; Animals, Genetically Modified ; Aldose-Ketose Isomerases/metabolism/genetics ; Cell Proliferation ; Epithelial Cells/metabolism ; Proteomics ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route.},
}

Humans
Animals
*Zebrafish/metabolism
*Amyloid beta-Peptides/metabolism
*tau Proteins/metabolism/genetics
*Alzheimer Disease/metabolism/genetics/pathology
Animals, Genetically Modified
Aldose-Ketose Isomerases/metabolism/genetics
Cell Proliferation
Epithelial Cells/metabolism
Proteomics

@article {pmid38671434,
year = {2024},
author = {Ohlenburg, H and Arnemann, PH and Hessler, M and Görlich, D and Zarbock, A and Friederichs, H},
title = {Flipped Classroom: Improved team performance during resuscitation training through interactive pre-course content - a cluster-randomised controlled study.},
journal = {BMC medical education},
volume = {24},
number = {1},
pages = {459},
pmid = {38671434},
issn = {1472-6920},
mesh = {Humans ; *Patient Care Team ; *Resuscitation/education ; Female ; Male ; *Curriculum ; Germany ; Clinical Competence ; Problem-Based Learning ; Students, Medical ; Education, Medical, Undergraduate/methods ; Adult ; Educational Measurement ; Simulation Training ; },
abstract = {BACKGROUND: Resuscitation is a team effort, and it is increasingly acknowledged that team cooperation requires training. Staff shortages in many healthcare systems worldwide, as well as recent pandemic restrictions, limit opportunities for collaborative team training. To address this challenge, a learner-centred approach known as flipped learning has been successfully implemented. This model comprises self-directed, asynchronous pre-course learning, followed by knowledge application and skill training during in-class sessions. The existing evidence supports the effectiveness of this approach for the acquisition of cognitive skills, but it is uncertain whether the flipped classroom model is suitable for the acquisition of team skills. The objective of this study was to determine if a flipped classroom approach, with an online workshop prior to an instructor-led course could improve team performance and key resuscitation variables during classroom training.

METHODS: A single-centre, cluster-randomised, rater-blinded study was conducted on 114 final year medical students at a University Hospital in Germany. The study randomly assigned students to either the intervention or control group using a computer script. Each team, regardless of group, performed two advanced life support (ALS) scenarios on a simulator. The two groups differed in the order in which they completed the flipped e-learning curriculum. The intervention group started with the e-learning component, and the control group started with an ALS scenario. Simulators were used for recording and analysing resuscitation performance indicators, while professionals assessed team performance as a primary outcome.

RESULTS: The analysis was conducted on the data of 96 participants in 21 teams, comprising of 11 intervention groups and 10 control groups. The intervention teams achieved higher team performance ratings during the first scenario compared to the control teams (Estimated marginal mean of global rating: 7.5 vs 5.6, p < 0.01; performance score: 4.4 vs 3.8, p < 0.05; global score: 4.4 vs 3.7, p < 0.001). However, these differences were not observed in the second scenario, where both study groups had used the e-learning tool.

CONCLUSION: Flipped classroom approaches using learner-paced e-learning prior to hands-on training can improve team performance.

TRIAL REGISTRATION: German Clinical Trials Register (https://drks.de/search/de/trial/DRKS00013096).},
}

Humans
*Patient Care Team
*Resuscitation/education
Female
Male
*Curriculum
Germany
Clinical Competence
Problem-Based Learning
Students, Medical
Education, Medical, Undergraduate/methods
Adult
Educational Measurement
Simulation Training

@article {pmid38671062,
year = {2024},
author = {Angrick, M and Luo, S and Rabbani, Q and Candrea, DN and Shah, S and Milsap, GW and Anderson, WS and Gordon, CR and Rosenblatt, KR and Clawson, L and Tippett, DC and Maragakis, N and Tenore, FV and Fifer, MS and Hermansky, H and Ramsey, NF and Crone, NE},
title = {Online speech synthesis using a chronically implanted brain-computer interface in an individual with ALS.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {9617},
pmid = {38671062},
issn = {2045-2322},
support = {NS114439/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Brain-Computer Interfaces ; *Amyotrophic Lateral Sclerosis/physiopathology/therapy ; Male ; *Speech/physiology ; Middle Aged ; Electrodes, Implanted ; Electrocorticography ; },
abstract = {Brain-computer interfaces (BCIs) that reconstruct and synthesize speech using brain activity recorded with intracranial electrodes may pave the way toward novel communication interfaces for people who have lost their ability to speak, or who are at high risk of losing this ability, due to neurological disorders. Here, we report online synthesis of intelligible words using a chronically implanted brain-computer interface (BCI) in a man with impaired articulation due to ALS, participating in a clinical trial (ClinicalTrials.gov, NCT03567213) exploring different strategies for BCI communication. The 3-stage approach reported here relies on recurrent neural networks to identify, decode and synthesize speech from electrocorticographic (ECoG) signals acquired across motor, premotor and somatosensory cortices. We demonstrate a reliable BCI that synthesizes commands freely chosen and spoken by the participant from a vocabulary of 6 keywords previously used for decoding commands to control a communication board. Evaluation of the intelligibility of the synthesized speech indicates that 80% of the words can be correctly recognized by human listeners. Our results show that a speech-impaired individual with ALS can use a chronically implanted BCI to reliably produce synthesized words while preserving the participant's voice profile, and provide further evidence for the stability of ECoG for speech-based BCIs.},
}

Humans
*Brain-Computer Interfaces
*Amyotrophic Lateral Sclerosis/physiopathology/therapy
Male
*Speech/physiology
Middle Aged
Electrodes, Implanted
Electrocorticography

@article {pmid38670927,
year = {2024},
author = {Quinn, C and Baer, M and Amado, DA and Kelley, M and Elman, L},
title = {A single ALS center experience with clinical use of sodium phenylbutyrate-taurursodiol.},
journal = {Muscle & nerve},
volume = {},
number = {},
pages = {},
doi = {10.1002/mus.28096},
pmid = {38670927},
issn = {1097-4598},
abstract = {INTRODUCTION/AIMS: The aim of this study was to examine clinical utilization and discontinuation rates of sodium phenylbutyrate-taurursodiol (PB-TURSO) in a single Amyotrophic Lateral Sclerosis (ALS) center. PB-TURSO was approved by the United States Food and Drug Administration (FDA) in September 2022. Prior experience has been limited to clinical trials or expanded access protocols. In this manuscript, we discuss insurance approval rates, patient uptake, and discontinuation of PB-TURSO in a large academic center.

METHODS: Records of patients seen for clinical visits between January 2022 and May 2023 were reviewed. Demographic and clinical characteristics of our clinic population and those initiating PB-TURSO were obtained from our clinical database.

RESULTS: A total of 228 patients were seen during the observation period and 122 requested PB-TURSO prescriptions. 77% (94) were approved by insurance. 66% (65) of those who were approved or received free drug chose to start medication. 51% (34) of those who initiated PB-TURSO continued to take it through the end of the observation period. Four patients discontinued due to death during the observation period. Of the 29 patients who survived and discontinued, the main reasons for discontinuation were GI symptoms (17, 58.6%) and taste (8, 29.6%).

DISCUSSION: PB-TURSO was approved by insurance for most patients. The discontinuation rate was high and was driven largely by GI side effects and taste. Future considerations would include deeper examination of demographic trends, patient costs, side effects, and potential benefits in clinical practice.},
}

@article {pmid38670433,
year = {2024},
author = {Sitruk-Ware, R and Sussman, H and Brinton, R and Schumacher, M and Singer, P and Kumar, N and De Nicola, AF and El-Etr, M and Guennoun, R and V Borlongan, C},
title = {Nestorone (segesterone acetate) effects on neuroregeneration.},
journal = {Frontiers in neuroendocrinology},
volume = {},
number = {},
pages = {101136},
doi = {10.1016/j.yfrne.2024.101136},
pmid = {38670433},
issn = {1095-6808},
abstract = {Nestorone® (segesterone acetate) is a progestin with a chemical structure closely related to progesterone with high affinity and selectivity for the progesterone receptor without significant interaction with other steroid receptors. It has been developed for female and male contraception and is FDA-approved in a first long-acting contraceptive vaginal system for female contraception. Its safety has been extensively demonstrated in both preclinical and clinical studies for contraceptive indications. Nestorone was found to display neuroprotective and neuroregenerative activity in animal models of various central nervous system diseases, including multiple sclerosis, stroke, and amyotrophic lateral sclerosis. Reviewed herein are neuroprotective and myelin- regenerating properties of Nestorone in various animal models and its translational potential as a therapeutic agent for debilitating neurological diseases for which limited therapeutic options are available (Table 1).},
}

@article {pmid38668754,
year = {2024},
author = {Dogan, M and Teralı, K and Eroz, R and Kılıç, H and Gezdirici, A and Gönüllü, B},
title = {Discovery of a novel homozygous SOD1 truncating variant bolsters infantile SOD1 deficiency syndrome.},
journal = {Molecular biology reports},
volume = {51},
number = {1},
pages = {580},
pmid = {38668754},
issn = {1573-4978},
mesh = {Humans ; *Superoxide Dismutase-1/genetics ; Male ; *Homozygote ; Female ; *Pedigree ; *Phenotype ; *Exome Sequencing/methods ; Amyotrophic Lateral Sclerosis/genetics ; Child, Preschool ; Infant ; Turkey ; Child ; },
abstract = {OBJECTIVE: Superoxide dismutase 1 (SOD1) is an important antioxidant enzyme whose main function is to neutralise superoxide free radicals in the cytoplasm. Heterozygous variants in SOD1 are responsible for a substantial percentage of familial amyotrophic lateral sclerosis (ALS) cases. Recently, several reports have shown that biallelic loss of SOD1 function results in a novel phenotype called infantile SOD1 deficiency syndrome, which is consistent with a recessive pattern of inheritance and can be distinguished from typical (adult-onset) ALS.

METHODS: We documented detailed family histories and clinical data, followed by whole-exome sequencing and family co-segregation analysis through Sanger sequencing. To facilitate comparisons, relevant data from fifteen previously reported patients with SOD1-related neurodevelopmental disorders were included.

RESULTS: This study presents a new Turkish family with two affected children exhibiting severe delayed motor development, infancy-onset loss of motor skills, axial hypotonia, tetraspasticity, and impaired cognitive functions. Genetic analysis revealed a novel homozygous frameshift variant in SOD1 (c.248dupG [p.Asp84Argfs*8]), with computational biochemical studies shedding light on the mechanistic aspects of SOD1 dysfunction.

CONCLUSIONS: Our findings contribute an affirmative report of a fourth biallelic variant resulting in a severe clinical phenotype, reminiscent of those induced by previously identified homozygous loss-of-function SOD1 variants. This research not only advances our understanding of the pathogenesis of this debilitating neurological syndrome but also aligns with ongoing intensive efforts to comprehend and address SOD1-linked ALS.},
}

Humans
*Superoxide Dismutase-1/genetics
Male
*Homozygote
Female
*Pedigree
*Phenotype
*Exome Sequencing/methods
Amyotrophic Lateral Sclerosis/genetics
Child, Preschool
Infant
Turkey
Child

@article {pmid38667292,
year = {2024},
author = {Ruffo, P and De Amicis, F and La Bella, V and Conforti, FL},
title = {Investigating Repeat Expansions in NIPA1, NOP56, and NOTCH2NLC Genes: A Closer Look at Amyotrophic Lateral Sclerosis Patients from Southern Italy.},
journal = {Cells},
volume = {13},
number = {8},
pages = {},
pmid = {38667292},
issn = {2073-4409},
support = {ex60%//Ministry for Instruction, University and Research/ ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics ; Italy ; Female ; Male ; Middle Aged ; Aged ; DNA Repeat Expansion/genetics ; Adult ; Nuclear Proteins/genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; },
abstract = {The discovery of hexanucleotide repeats expansion (RE) in Chromosome 9 Open Reading frame 72 (C9orf72) as the major genetic cause of amyotrophic lateral sclerosis (ALS) and the association between intermediate repeats in Ataxin-2 (ATXN2) with the disorder suggest that repetitive sequences in the human genome play a significant role in ALS pathophysiology. Investigating the frequency of repeat expansions in ALS in different populations and ethnic groups is therefore of great importance. Based on these premises, this study aimed to define the frequency of REs in the NIPA1, NOP56, and NOTCH2NLC genes and the possible associations between phenotypes and the size of REs in the Italian population. Using repeat-primed-PCR and PCR-fragment analyses, we screened 302 El-Escorial-diagnosed ALS patients and compared the RE distribution to 167 age-, gender-, and ethnicity-matched healthy controls. While the REs distribution was similar between the ALS and control groups, a moderate association was observed between longer RE lengths and clinical features such as age at onset, gender, site of onset, and family history. In conclusion, this is the first study to screen ALS patients from southern Italy for REs in NIPA1, NOP56, and NOTCH2NLC genes, contributing to our understanding of ALS genetics. Our results highlighted that the extremely rare pathogenic REs in these genes do not allow an association with the disease.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics
Italy
Female
Male
Middle Aged
Aged
DNA Repeat Expansion/genetics
Adult
Nuclear Proteins/genetics
Case-Control Studies
Genetic Predisposition to Disease

@article {pmid38667285,
year = {2024},
author = {Alzahrani, FA and Riza, YM and Eid, TM and Almotairi, R and Scherschinski, L and Contreras, J and Nadeem, M and Perez, SE and Raikwar, SP and Jha, RM and Preul, MC and Ducruet, AF and Lawton, MT and Bhatia, K and Akhter, N and Ahmad, S},
title = {Exosomes in Vascular/Neurological Disorders and the Road Ahead.},
journal = {Cells},
volume = {13},
number = {8},
pages = {},
pmid = {38667285},
issn = {2073-4409},
mesh = {*Exosomes/metabolism ; Humans ; Animals ; Neurodegenerative Diseases/metabolism/pathology ; Vascular Diseases/metabolism/pathology ; Nervous System Diseases/metabolism/pathology ; },
abstract = {Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.},
}

*Exosomes/metabolism
Humans
Animals
Neurodegenerative Diseases/metabolism/pathology
Vascular Diseases/metabolism/pathology
Nervous System Diseases/metabolism/pathology

@article {pmid38666827,
year = {2024},
author = {Ismail, M and Großmann, D and Hermann, A},
title = {Increased Vulnerability to Ferroptosis in FUS-ALS.},
journal = {Biology},
volume = {13},
number = {4},
pages = {},
pmid = {38666827},
issn = {2079-7737},
support = {NA//Hermann und Lilly Schilling-Stiftung/ ; },
abstract = {Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exists, e.g., in Parkinson's disease or Alzheimer's disease, there are only a few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disease characterized by progressive motor neuron degeneration. Interestingly, initial studies have suggested that ferroptosis might be significantly involved in ALS. Key features of ferroptosis include oxidative stress, glutathione depletion, and alterations in mitochondrial morphology and function, mediated by proteins such as GPX4, xCT, ACSL4 FSP1, Nrf2, and TfR1. Induction of ferroptosis involves small molecule compounds like erastin and RSL3, which disrupt system Xc[-] and GPX4 activity, respectively, resulting in lipid peroxidation and cellular demise. Mutations in fused in sarcoma (FUS) are associated with familial ALS. Pathophysiological hallmarks of FUS-ALS involve mitochondrial dysfunction and oxidative damage, implicating ferroptosis as a putative cell-death pathway in motor neuron demise. However, a mechanistic understanding of ferroptosis in ALS, particularly FUS-ALS, remains limited. Here, we investigated the vulnerability to ferroptosis in FUS-ALS cell models, revealing mitochondrial disturbances and increased susceptibility to ferroptosis in cells harboring ALS-causing FUS mutations. This was accompanied by an altered expression of ferroptosis-associated proteins, particularly by a reduction in xCT expression, leading to cellular imbalance in the redox system and increased lipid peroxidation. Iron chelation with deferoxamine, as well as inhibition of the mitochondrial calcium uniporter (MCU), significantly alleviated ferroptotic cell death and lipid peroxidation. These findings suggest a link between ferroptosis and FUS-ALS, offering potential new therapeutic targets.},
}

@article {pmid38666665,
year = {2024},
author = {Forsberg, K and Karlsborg, M and Salvesen, L and Svenstrup, K and Winroth, I and Berntsson, H and M Andersen, P},
title = {[SOD1 gene therapy delays ALS disease progression].},
journal = {Lakartidningen},
volume = {121},
number = {},
pages = {},
pmid = {38666665},
issn = {1652-7518},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy ; *Superoxide Dismutase-1/genetics ; *Genetic Therapy ; *Disease Progression ; Male ; Middle Aged ; Mutation ; Oligonucleotides, Antisense/therapeutic use/administration & dosage ; Oligonucleotides/therapeutic use/administration & dosage ; },
abstract = {We present a patient with familial amyotrophic lateral sclerosis caused by an aggressive A4S mutation in the SOD1 gene. In 2020, the patient was enrolled in the VALOR SOD1 gene therapy phase-3 trial. At screening, the ALSFRS-R score was 41 (48 is normal) and the level of CSF-neurofilament L (an indicator of ongoing neuronal damage) was 11 000 ng/L (ref <650 ng/L). In the four years following enrollment, the patient received monthly intrathecal treatment with tofersen, an antisense oligonucleotide compound that inhibits SOD1 protein expression and hence lowers the synthesis of toxic SOD1 protein species. Side effects have been minimal and mostly attributed to the spinal taps. The patient remains ambulatory with an active social lifestyle. The ALSFRS-R score has in the past 18 months stabilized around 35-37, CSF-NfL is 1 290 ng/L and plasma-NfL is 12 (reference <13). This is the first documented arresting intervention in a patient with ALS in Sweden.},
}

Humans
*Amyotrophic Lateral Sclerosis/genetics/drug therapy/therapy
*Superoxide Dismutase-1/genetics
*Genetic Therapy
*Disease Progression
Male
Middle Aged
Mutation
Oligonucleotides, Antisense/therapeutic use/administration & dosage
Oligonucleotides/therapeutic use/administration & dosage

@article {pmid38666601,
year = {2024},
author = {Officer, L and Armon, C and Barkhaus, P and Beauchamp, M and Benatar, M and Bertorini, T and Bowser, R and Bromberg, M and Brown, A and Carbunar, OM and Carter, GT and Crayle, J and Denson, K and Feldman, E and Fullam, T and Heiman-Patterson, T and Jackson, C and Jhooty, S and Levinson, D and Li, X and Linares, A and Mallon, E and Mascias Cadavid, J and Mcdermott, C and Mushannen, T and Ostrow, L and Patel, R and Pattee, G and Ratner, D and Sun, Y and Sladky, J and Wicks, P and Bedlack, R},
title = {ALSUntangled #75: Portable neuromodulation stimulator therapy.},
journal = {Amyotrophic lateral sclerosis & frontotemporal degeneration},
volume = {},
number = {},
pages = {1-5},
doi = {10.1080/21678421.2024.2346825},
pmid = {38666601},
issn = {2167-9223},
abstract = {Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.},
}

@article {pmid38665232,
year = {2024},
author = {Yao, Y and Liu, H and Gu, Y and Xu, X and Zhang, X},
title = {A causal association between amyotrophic lateral sclerosis and atrial fibrillation: a two-sample Mendelian randomization study.},
journal = {Frontiers in cardiovascular medicine},
volume = {11},
number = {},
pages = {1351495},
pmid = {38665232},
issn = {2297-055X},
abstract = {OBJECTIVES: To look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR).

METHODS: Two-sample MR was performed using genetic information from genome-wide association studies (GWAS). Genetic variants robustly associated with ALS and AF were used as instrumental variables. GWAS genetic data for ALS (n = 138,086, ncase = 27,205) and AF (n = 1,030,836, ncase = 60,620), publicly available from IEU Open. The specific MR protocols were Inverse variance-weighted (IVW), Simple mode, MR Egger, Weighted mode, and Weight median estimator (WME). Subsequently, the MR-Egger intercept and Cochran Q examine were used to evaluate instrumental variables (IVs)' heterogeneity and multiplicative effects (IVs). In addition, MR-PRESSO analysis was conducted to exclude any potential pleiotropy.

RESULTS: The IVW method demonstrated that ALS positively affected AF [OR: 1.062, 95% CI (1.004-1.122); P = 0.035]. Indeed, other MR methods were in accordance with the tendency of the IVW method (all OR > 1), and sensitivity testing verified the reliability of this MR result.

CONCLUSIONS: This MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.},
}

@article {pmid38664831,
year = {2024},
author = {Sirtori, R and J Gregoire, M and M Potts, E and Collins, A and Donatelli, L and Fallini, C},
title = {LINC complex alterations are a key feature of sporadic and familial ALS/FTD.},
journal = {Acta neuropathologica communications},
volume = {12},
number = {1},
pages = {69},
pmid = {38664831},
issn = {2051-5960},
support = {R01NS116143/NS/NINDS NIH HHS/United States ; P20GM103430/GM/NIGMS NIH HHS/United States ; },
mesh = {*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism ; Humans ; *C9orf72 Protein/genetics/metabolism ; *Frontotemporal Dementia/genetics/pathology/metabolism ; Male ; Motor Neurons/pathology/metabolism ; Spinal Cord/pathology/metabolism ; Nuclear Envelope/metabolism/pathology ; Female ; Induced Pluripotent Stem Cells/metabolism/pathology ; Middle Aged ; Aged ; Motor Cortex/pathology/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that primarily affects motor neurons, leading to progressive muscle weakness and loss of voluntary muscle control. While the exact cause of ALS is not fully understood, emerging research suggests that dysfunction of the nuclear envelope (NE) may contribute to disease pathogenesis and progression. The NE plays a role in ALS through several mechanisms, including nuclear pore defects, nucleocytoplasmic transport impairment, accumulation of mislocalized proteins, and nuclear morphology abnormalities. The LINC complex is the second biggest multi-protein complex in the NE and consists of the SUN1/2 proteins spanning the inner nuclear membrane and Nesprin proteins embedded in the outer membrane. The LINC complex, by interacting with both the nuclear lamina and the cytoskeleton, transmits mechanical forces to the nucleus regulating its morphology and functional homeostasis. In this study we show extensive alterations to the LINC complex in motor and cortical iPSC-derived neurons and spinal cord organoids carrying the ALS causative mutation in the C9ORF72 gene (C9). Importantly, we show that such alterations are present in vivo in a cohort of sporadic ALS and C9-ALS postmortem spinal cord and motor cortex specimens. We also found that LINC complex disruption strongly correlated with nuclear morphological alterations occurring in ALS neurons, independently of TDP43 mislocalization. Altogether, our data establish morphological and functional alterations to the LINC complex as important events in ALS pathogenic cascade, making this pathway a possible target for both biomarker and therapy development.},
}

*Amyotrophic Lateral Sclerosis/genetics/pathology/metabolism
Humans
*C9orf72 Protein/genetics/metabolism
*Frontotemporal Dementia/genetics/pathology/metabolism
Male
Motor Neurons/pathology/metabolism
Spinal Cord/pathology/metabolism
Nuclear Envelope/metabolism/pathology
Female
Induced Pluripotent Stem Cells/metabolism/pathology
Middle Aged
Aged
Motor Cortex/pathology/metabolism

@article {pmid38664109,
year = {2024},
author = {Hastings, RL and Valdez, G},
title = {Origin, identity, and function of terminal Schwann cells.},
journal = {Trends in neurosciences},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.tins.2024.03.007},
pmid = {38664109},
issn = {1878-108X},
abstract = {The highly specialized nonmyelinating glial cells present at somatic peripheral nerve endings, known collectively as terminal Schwann cells (TSCs), play critical roles in the development, function and repair of their motor and sensory axon terminals and innervating tissue. Over the past decades, research efforts across various vertebrate species have revealed that while TSCs are a diverse group of cells, they share a number of features among them. In this review, we summarize the state-of-knowledge about each TSC type and explore the opportunities that TSCs provide to treat conditions that afflict peripheral axon terminals.},
}

@article {pmid38663103,
year = {2024},
author = {Nozal, V and Fernández-Gómez, P and García-Rubia, A and Martínez-González, L and Cuevas, EP and Carro, E and Palomo, V and Martínez, A},
title = {Designing multitarget ligands for neurodegenerative diseases with improved permeability trough PLGA nanoencapsulation.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {175},
number = {},
pages = {116626},
doi = {10.1016/j.biopha.2024.116626},
pmid = {38663103},
issn = {1950-6007},
abstract = {Multitarget ligands (MTLs) have emerged as an interesting alternative for addressing complex multifactorial pathologies such as neurodegenerative diseases. However, a common challenge associated with these compounds is often their high molecular weight and low solubility, which becomes a hurdle when trying to permeate over the blood-brain barrier (BBB). In this study, we have designed two new MTLs that modulate three pharmacological targets simultaneously (tau, beta-amyloid and TAR DNA-binding protein 43). To enhance their brain penetration, we have formulated organic polymeric nanoparticles using poly(lactic-co-glycolic acid). The characterization of the formulations, evaluation of their permeability through an in vitro BBB model, and assessment of their activity on disease-representative cellular models, such as Alzheimer's disease and amyotrophic lateral sclerosis, have been conducted. The results demonstrate the potential of the new MTLs and their nanoparticle encapsulation for the treatment of neurodegenerative diseases.},
}

@article {pmid38663099,
year = {2024},
author = {Polverino, A and Troisi Lopez, E and Liparoti, M and Minino, R and Romano, A and Cipriano, L and Trojsi, F and Jirsa, V and Sorrentino, G and Sorrentino, P},
title = {Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {163},
number = {},
pages = {14-21},
doi = {10.1016/j.clinph.2024.04.003},
pmid = {38663099},
issn = {1872-8952},
abstract = {OBJECTIVE: To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture.

METHODS: We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches.

RESULTS: ALS patients presented higher values of the nodal strength in both cortical and sub-cortical brain areas. This parameter correlated directly with disease duration.

CONCLUSIONS: In this work, we provide a deeper characterization of neuronal avalanches propagation in ALS, describing their spatio-temporal trajectories and identifying the brain regions most likely to be involved in the process. This makes it possible to recognize the brain areas that take part in the pathogenic mechanisms of ALS. Furthermore, the nodal strength of the involved regions correlates directly with disease duration.

SIGNIFICANCE: Our results corroborate the clinical relevance of aperiodic, fast large-scale brain activity as a biomarker of microscopic changes induced by neurophysiological processes.},
}

@article {pmid38662803,
year = {2024},
author = {Martín-Rivada, Á and Martos-Moreno, GÁ and Guerra-Cantera, S and Campillo-Calatayud, A and Oxvig, C and Frystyk, J and Chowen, JA and Barrios, V and Argente, J},
title = {Prepubertal children with obesity have high free IGF-1 levels and accelerated growth despite reduced pappalysin levels.},
journal = {The Journal of clinical endocrinology and metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1210/clinem/dgae288},
pmid = {38662803},
issn = {1945-7197},
abstract = {BACKGROUND: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation and changes in the GH-IGF axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity.

OBJECTIVE: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1 and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system.

PATIENTS AND METHODS: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls.

RESULTS: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I (fIGF-I), intact IGFBP-3, ALS, IGF-II and insulin levels, with no difference in the free/total IGF-I ratio. Neither the standardized BMI nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2 and PAPP-A were observed after weight loss.

CONCLUSION: Increased circulating total and free IGF-I, insulin and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.},
}

@article {pmid38662766,
year = {2024},
author = {Stikvoort García, DJL and Goedee, HS and van Eijk, RPA and van Schelven, LJ and van den Berg, LH and Sleutjes, BTHM},
title = {Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awae131},
pmid = {38662766},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurones. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients. Measures derived directly from a nerve excitability recording are frequently used as study endpoints, even though their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation, but are only reliable when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared to clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a novel pattern-analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed novel compound measures of excitability that facilitate the implementation of this approach in clinical settings We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared to controls (n = 50, age-gender matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K + -currents), slow potassium- and sodium-currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium-channels was associated with, and predictive of, the disease's progression rate on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside of this study. Our findings demonstrate that nerve excitability changes in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function may play a role in the rate of disease progression. The magnitudes of these patterns, quantified using either a similar approach or our novel composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design.},
}

@article {pmid38661683,
year = {2024},
author = {LaForge, JR},
title = {A Poem About ALS.},
journal = {The American journal of nursing},
volume = {124},
number = {5},
pages = {10},
doi = {10.1097/01.NAJ.0001016304.08449.3a},
pmid = {38661683},
issn = {1538-7488},
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/nursing ; Poetry as Topic ; },
}

Humans
*Amyotrophic Lateral Sclerosis/nursing
Poetry as Topic

@article {pmid38661532,
year = {2024},
author = {Li, A and Yi, J and Li, X and Dong, L and Ostrow, LW and Ma, J and Zhou, J},
title = {Distinct transcriptomic profile of satellite cells contributes to preservation of neuromuscular junctions in extraocular muscles of ALS mice.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {38661532},
issn = {2050-084X},
support = {R01NS105621/NH/NIH HHS/United States ; R01NS129219/NH/NIH HHS/United States ; R01AG071676/NH/NIH HHS/United States ; },
mesh = {Animals ; *Neuromuscular Junction/metabolism ; *Amyotrophic Lateral Sclerosis/genetics/metabolism ; Mice ; *Satellite Cells, Skeletal Muscle/metabolism ; *Disease Models, Animal ; *Transcriptome ; Mice, Transgenic ; Oculomotor Muscles/innervation/metabolism ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by progressive weakness of almost all skeletal muscles, whereas extraocular muscles (EOMs) are comparatively spared. While hindlimb and diaphragm muscles of end-stage SOD1G93A (G93A) mice (a familial ALS mouse model) exhibit severe denervation and depletion of Pax7[+]satellite cells (SCs), we found that the pool of SCs and the integrity of neuromuscular junctions (NMJs) are maintained in EOMs. In cell sorting profiles, SCs derived from hindlimb and diaphragm muscles of G93A mice exhibit denervation-related activation, whereas SCs from EOMs of G93A mice display spontaneous (non-denervation-related) activation, similar to SCs from wild-type mice. Specifically, cultured EOM SCs contain more abundant transcripts of axon guidance molecules, including Cxcl12, along with more sustainable renewability than the diaphragm and hindlimb counterparts under differentiation pressure. In neuromuscular co-culture assays, AAV-delivery of Cxcl12 to G93A-hindlimb SC-derived myotubes enhances motor neuron axon extension and innervation, recapitulating the innervation capacity of EOM SC-derived myotubes. G93A mice fed with sodium butyrate (NaBu) supplementation exhibited less NMJ loss in hindlimb and diaphragm muscles. Additionally, SCs derived from G93A hindlimb and diaphragm muscles displayed elevated expression of Cxcl12 and improved renewability following NaBu treatment in vitro. Thus, the NaBu-induced transcriptomic changes resembling the patterns of EOM SCs may contribute to the beneficial effects observed in G93A mice. More broadly, the distinct transcriptomic profile of EOM SCs may offer novel therapeutic targets to slow progressive neuromuscular functional decay in ALS and provide possible 'response biomarkers' in pre-clinical and clinical studies.},
}

Animals
*Neuromuscular Junction/metabolism
*Amyotrophic Lateral Sclerosis/genetics/metabolism
Mice
*Satellite Cells, Skeletal Muscle/metabolism
*Disease Models, Animal
*Transcriptome
Mice, Transgenic
Oculomotor Muscles/innervation/metabolism

@article {pmid38658168,
year = {2024},
author = {Jaroszynska, N and Salzinger, A and Tsarouchas, TM and Becker, CG and Becker, T and Lyons, DA and MacDonald, RB and Keatinge, M},
title = {C9ORF72 deficiency results in neurodegeneration in the zebrafish retina.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1523/JNEUROSCI.2128-23.2024},
pmid = {38658168},
issn = {1529-2401},
abstract = {Hexanucleotide repeat expansions within the gene C9ORF72 are the most common cause of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FTD). This disease-causing expansion leads to a reduction in C9ORF72 expression levels in patients, suggesting loss of C9ORF72 function could contribute to disease. To further understand the consequences of C9ORF72 deficiency in vivo, we generated a c9orf72 mutant zebrafish line. Analysis of the adult female spinal cords revealed no appreciable neurodegenerative pathology such as loss of motor neurons, or increased levels of neuroinflammation. However, detailed examination of adult female c9orf72[-/-] retinas showed prominent neurodegenerative features, including a decrease in retinal thickness, gliosis, and an overall reduction in neurons of all subtypes. Analysis of rod and cone cells within the photoreceptor layer showed a disturbance in their outer segment structure and rhodopsin mis-localisation from rod outer segments to their cell bodies and synaptic terminals. Thus, C9ORF72 may play a previously unappreciated role in retinal homeostasis and suggests C9ORF72 deficiency can induce tissue specific neuronal loss.Significance statement Hexanucleotide expansions in the gene C9ORF72 are the most common cause of the Amyotrophic lateral sclerosis (ALS)/ Frontotemporal dementia (FTD) disease spectrum. The expansion reduces expression of C9ORF72 and so may play a role in neuronal loss. However, C9ORF72 loss of function has been comparatively understudied in vivo. Using the zebrafish as a model of C9ORF72 deficiency, we demonstrate that loss of C9ORF72 results in marked inflammation and neuronal loss in the aged adult zebrafish retina. Development of the retina is unaffected regardless of C9ORF72 status. This demonstrates that C9ORF72 loss of function can cause spontaneous neurodegeneration in vivo and highlights a novel role of C9ORF72 in retinal homeostasis.},
}

@article {pmid38657911,
year = {2024},
author = {Liguori, F and Alberti, F and Amadio, S and Angelini, DF and Pilesi, E and Vitale, G and Tesoriere, G and Borsellino, G and Vernì, F and Volonté, C},
title = {Pan-neuronal expression of human mutant SOD1 in Drosophila impairs survival and motor performance, induces early neuroinflammation and chromosome aberrations.},
journal = {Biochimica et biophysica acta. Molecular basis of disease},
volume = {},
number = {},
pages = {167192},
doi = {10.1016/j.bbadis.2024.167192},
pmid = {38657911},
issn = {1879-260X},
abstract = {Several mutations in the SOD1 gene encoding for the antioxidant enzyme Superoxide Dismutase 1, are associated with amyotrophic lateral sclerosis, a rare and devastating disease characterized by motor neuron degeneration and patients' death within 2-5 years from diagnosis. Motor neuron loss and related symptomatology manifest mostly in adult life and, to date, there is still a gap of knowledge on the precise cellular and molecular events preceding neurodegeneration. To deepen our awareness of the early phases of the disease, we leveraged two Drosophila melanogaster models pan-neuronally expressing either the mutation A4V or G85R of the human gene SOD1 (hSOD1[A4V] or hSOD1[G85R]). We demonstrate that pan-neuronal expression of the hSOD1[A4V] or hSOD1[G85R] pathogenic construct impairs survival and motor performance in transgenic flies. Moreover, protein and transcript analysis on fly heads indicates that mutant hSOD1 induction stimulates the glial marker Repo, up-regulates the IMD/Toll immune pathways through antimicrobial peptides and interferes with oxidative metabolism. Finally, cytological analysis of larval brains demonstrates hSOD1-induced chromosome aberrations. Of note, these parameters are found modulated in a timeframe when neurodegeneration is not detected. The novelty of our work is twofold: we have expressed for the first time hSOD1 mutations in all neurons of Drosophila and confirmed some ALS-related pathological phenotypes in these flies, confirming the power of SOD1 mutations in generating ALS-like phenotypes. Moreover, we have related SOD1 pathogenesis to chromosome aberrations and antimicrobial peptides up-regulation. These findings were unexplored in the SOD1-ALS field.},
}

@article {pmid38657488,
year = {2024},
author = {Rezaee Semnani, M and Mirzaasgari, Z and Ariaei, A and Haghi Ashtiani, B},
title = {Evaluation of carotid Intima-Media Thickness (IMT) in amyotrophic lateral sclerosis disease using ultrasonography.},
journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia},
volume = {124},
number = {},
pages = {67-72},
doi = {10.1016/j.jocn.2024.04.019},
pmid = {38657488},
issn = {1532-2653},
abstract = {BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with multi-mechanisms as; inflammation, oxidative stress, glutamate excitotoxicity, protein aggregation, etc. This study aimed to evaluate the carotid Intima-Media Thickness (IMT) in ALS and healthy groups, as a possible indicator of these mechanisms.

METHODS: 42 patients with ALS along with 53 normal age and body mass index (BMI) matched participants were recruited from the Firoozgar hospital. Carotid IMT values of the participants were measured using B-mode ultrasonography. Using Pearson correlation and logistic regression adjusting with age, BMI, and gender, the IMT values were assessed.

RESULTS: The mean right and left carotid IMT values of the ALS patients (0.66 ± 0.09) were significantly higher than normal participants (0.45 ± 0.10) (p < 0.001). In addition, the IMT values were highly correlated with the age (r = 0.632; p < 0.001) and the age of ALS onset (r = 0.595; p < 0.001), in contrast to the BMI. Moreover, the higher value of IMT was associated with an increasing risk of ALS with an odd ratio (OR) of 1.483 (95 % Confidence interval [1.026-2.144]). Eventually, evaluating IMT by classifying ALS patients based on the ALS Health State Scale (ALSHSS) from early to late stage revealed a non-linear increase in the OR (1.372, 1.898, 2.172, and 3.403).

CONCLUSION: The increased value of the carotid IMT independent of BMI in ALS could be assessed through ultrasonography as a convenient tool to evaluate the disease severity or possible systemic inflammation.},
}

@article {pmid38657132,
year = {2024},
author = {Washington, KT and Mechling, CA and Pitzer, KA and Maiser, S and Mehta, AK},
title = {Identifying the Unmet Needs of People Living With Amyotrophic Lateral Sclerosis: A National Survey to Inform Interdisciplinary Palliative Care.},
journal = {The American journal of hospice & palliative care},
volume = {},
number = {},
pages = {10499091241248653},
doi = {10.1177/10499091241248653},
pmid = {38657132},
issn = {1938-2715},
abstract = {Introduction/Aims: This national survey builds on previous qualitative research examining potential palliative care needs among people living with ALS (pALS) by quantifying and investigating relationships among pALS' stage of illness progression; physical, emotional, social, spiritual, and intimacy-related concerns; advance care planning behaviors; perceptions of feeling heard and understood by healthcare providers; and overall quality of life. Methods: Researchers partnered with national organizations to recruit pALS to participate in a one-time survey comprising items from validated instruments (eg, the ALS Specific Quality of Life Instrument-Revised) and researcher-generated measures. Data were analyzed using logistic and linear regression. Results: Among pALS (n = 112), many respondents indicated they had discussed their wishes for end-of-life care with family or friends, shared their wishes with providers, and documented their wishes in writing (79.5%, 49.1%, and 63.4%, respectively). Mean (M) quality of life scores were moderate (M ≈ 6 of 10). Illness stage was associated with documentation of end-of-life care wishes but not with having discussed these wishes with others or with overall quality of life. Reported emotional intimacy received was comparable to that desired (difference = .01 of 10); however, a greater desire for physical intimacy relative to that received was indicated (difference = 1.75 of 10). Discussion: Interdisciplinary palliative care teams may enhance ALS care by promoting advance care planning behaviors (particularly discussing one's wishes with healthcare providers), providing interventions to improve quality of life, and supporting pALS in navigating challenges related to physical intimacy.},
}

@article {pmid38655803,
year = {2024},
author = {Temkin-Greener, H and Hua, Y and Cai, S},
title = {Assisted living residents with dementia: Disparities in mental health services pre and during COVID-19.},
journal = {Journal of the American Geriatrics Society},
volume = {},
number = {},
pages = {},
doi = {10.1111/jgs.18926},
pmid = {38655803},
issn = {1532-5415},
support = {RF1AG063811/AG/NIA NIH HHS/United States ; RF1AG073052/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: Little is known about mental health among Medicare beneficiaries with Alzheimer's disease or related dementias (ADRD) who reside in assisted living (AL) communities. The COVID-19 pandemic may have curtailed ambulatory care access for these residents, but telehealth may have expanded it. We examined in-person and telehealth use of ambulatory mental health visits among AL residents with ADRD, pre and during the COVID pandemic, focusing on race/ethnicity and Medicare/Medicaid dual status.

METHODS: A CY2018 cohort of AL residents with ADRD was identified. Outcome was any quarterly in-person or telemedicine mental health visit based on national CY2019-2020 Medicare claims. Key independent variables were individual race/ethnicity and dual status and the AL-level proportion of dual residents. We estimated a linear probability model with random effects and robust standard errors. Quarterly indicators captured service use before and after the onset of the pandemic.

RESULTS: The study included 102,758 fee-for-service Medicare beneficiaries with ADRD in 13,400 ALs. One in five residents had any mental health visits prior to the COVID-19 pandemic. Black residents, and those with dual Medicare/Medicaid eligibility, were significantly less likely to use mental health services prior to and during the pandemic. There were no significant differences in visits via telemedicine by race/ethnicity or individual dual status. Residents in AL communities with a higher proportion of duals had a lower likelihood of visits before and during the pandemic.

CONCLUSIONS/IMPLICATIONS: Mental health service use among AL residents with ADRD was low and declining prior to the pandemic. Telehealth allowed for mental health visits to continue during the pandemic, albeit at a lower level. Residents in ALs with a higher proportion of duals were less likely to have in-person or telehealth visits. The results suggest that some ALs may find it difficult to assure mental health service provision to this vulnerable population.},
}

@article {pmid38655443,
year = {2024},
author = {Zubair, AS and Saab, L and Scharer, K and Khokhar, B},
title = {Patients' experiences with methylcobalamin injections in amyotrophic lateral sclerosis.},
journal = {Brain circulation},
volume = {10},
number = {1},
pages = {60-66},
pmid = {38655443},
issn = {2455-4626},
abstract = {BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with no definitive treatment. Vitamin B12 is not a Food and Drug Administration-approved treatment in the United States, although it has been prescribed off-label as ultra-high-dose methylcobalamin, which has been shown to be safe and effective in slowing functional decline in patients with ALS. This study evaluates the impact of Vitamin B12 injections on the quality of life of five patients.

METHODS: Semi-structured interviews were conducted with the patients and caregivers. The data was carefully read, coded, and organized into themes and sub-themes by two independent researchers.

RESULTS: The study found four themes and 11 subthemes from the data, including initial circumstances, administration of the injection, subjective experience with Vitamin B12, and outcomes and expectations. All participants recognized some benefits from Vitamin B12 injections, specifically increased energy, reduced fatigue, and improved balance. However, some patients had difficulty monitoring its specific effect due to the progressive nature of the disease.

DISCUSSION: The flexibility offered by this intervention is beneficial for patients with declining mobility and strength who wish to adapt their treatment to their schedule. This work is a modest call to fill the existing gap in the literature and push for more randomized controlled trials investigating and clarifying the effects of Vitamin B12 injections on disease progression, muscle function, and quality of life in a small but diverse pool of patients with ALS.},
}

@article {pmid38654338,
year = {2024},
author = {Li, Y and Hu, Q and Wang, Q and Liu, T and Gao, M},
title = {Real-time ultrasound-guided sacral plexus block combined with mild sedation for hemorrhoidectomy and hemorrhoidal artery ligation in a patient with amyotrophic lateral sclerosis: a case report.},
journal = {Journal of medical case reports},
volume = {18},
number = {1},
pages = {205},
pmid = {38654338},
issn = {1752-1947},
mesh = {Humans ; Female ; Middle Aged ; *Amyotrophic Lateral Sclerosis/complications ; *Ultrasonography, Interventional ; *Hemorrhoidectomy/methods ; Ligation ; *Nerve Block/methods ; *Dexmedetomidine/administration & dosage ; *Lumbosacral Plexus/diagnostic imaging ; Hemorrhoids/surgery ; Hypnotics and Sedatives/administration & dosage ; Treatment Outcome ; },
abstract = {BACKGROUND: Patients with amyotrophic lateral sclerosis present perioperative challenges for clinical anesthesiologists for anesthesia-associated complications.

CASE PRESENTATION: A 54-year-old Han woman with a 2-year history of amyotrophic lateral sclerosis was scheduled for hemorrhoidectomy and hemorrhoidal artery ligation. We performed real-time ultrasound-guided sacral plexus block with dexmedetomidine under standard monitoring. The anesthesia method met the surgical demands and avoided respiratory complications during the procedures. There was no neurological deterioration after the surgery and 3 months after, the patient was discharged.

CONCLUSIONS: Real-time ultrasound-guided sacral plexus block combined with mild sedation may be an effective and safe technique in patients with amyotrophic lateral sclerosis undergoing hemorrhoidectomy and hemorrhoidal artery ligation.},
}

Humans
Female
Middle Aged
*Amyotrophic Lateral Sclerosis/complications
*Ultrasonography, Interventional
*Hemorrhoidectomy/methods
Ligation
*Nerve Block/methods
*Dexmedetomidine/administration & dosage
*Lumbosacral Plexus/diagnostic imaging
Hemorrhoids/surgery
Hypnotics and Sedatives/administration & dosage
Treatment Outcome

@article {pmid38652017,
year = {2024},
author = {Rahman, MU and Bano, S and Hong, X and Gu, RX and Chen, HF},
title = {Early Aggregation Mechanism of SOD128-38 Based on Force Field Parameter of 5-Cyano-Tryptophan.},
journal = {Journal of chemical information and modeling},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jcim.4c00289},
pmid = {38652017},
issn = {1549-960X},
abstract = {The aggregation of superoxide dismutase 1 (SOD1) results in amyloid deposition and is involved in familial amyotrophic lateral sclerosis, a fatal motor neuron disease. There have been extensive studies of its aggregation mechanism. Noncanonical amino acid 5-cyano-tryptophan (5-CN-Trp), which has been incorporated into the amyloid segments of SOD1 as infrared probes to increase the structural sensitivity of IR spectroscopy, is found to accelerate the overall aggregation rate and potentially modulate the aggregation process. Despite these observations, the underlying mechanism remains elusive. Here, we optimized the force field parameters of 5-CN-Trp and then used molecular dynamics simulation along with the Markov state model on the SOD128-38 dimer to explore the kinetics of key intermediates in the presence and absence of 5-CN-Trp. Our findings indicate a significantly increased probability of protein aggregate formation in 5CN-Trp-modified ensembles compared to wildtype. Dimeric β-sheets of different natures were observed exclusively in the 5CN-Trp-modified peptides, contrasting with wildtype simulations. Free-energy calculations and detailed analyses of the dimer structure revealed augmented interstrand interactions attributed to 5-CN-Trp, which contributed more to peptide affinity than any other residues. These results explored the key events critical for the early nucleation of amyloid-prone proteins and also shed light on the practice of using noncanonical derivatives to study the aggregation mechanism.},
}

@article {pmid38648781,
year = {2024},
author = {Ikegawa, Y and Fukuma, R and Sugano, H and Oshino, S and Tani, N and Tamura, K and Iimura, Y and Suzuki, H and Yamamoto, S and Fujita, Y and Nishimoto, S and Kishima, H and Yanagisawa, T},
title = {Text and image generation from intracranial electroencephalography using an embedding space for text and images.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/ad417a},
pmid = {38648781},
issn = {1741-2552},
abstract = {Invasive brain-computer interfaces (BCIs) are promising communication devices for severely paralyzed patients. Recent advances in intracranial electroencephalography (iEEG) coupled with natural language processing have enhanced communication speed and accuracy. It should be noted that such a speech BCI uses signals from the motor cortex. However, BCIs based on motor cortical activities may experience signal deterioration in users with motor cortical degenerative diseases such as amyotrophic lateral sclerosis (ALS). An alternative approach to using iEEG of the motor cortex is necessary to support patients with such conditions. Approach: In this study, a multimodal embedding of text and images was used to decode visual semantic information from iEEG signals of the visual cortex to generate text and images. We used contrastive language-image pretraining (CLIP) embedding to represent images presented to 17 patients implanted with electrodes in the occipital and temporal cortexes. A CLIP image vector was inferred from the high-γ power of the iEEG signals recorded while viewing the images. Main results: Text was generated by CLIPCAP from the inferred CLIP vector with better-than-chance accuracy. Then, an image was created from the generated text using StableDiffusion with significant accuracy. Significance: The text and images generated from iEEG through the CLIP embedding vector can be used for improved communication. .},
}

@article {pmid38648089,
year = {2024},
author = {Maglione, R and Ciotola, M and Cadieux, M and Toussaint, V and Laforest, M and Kembel, SW},
title = {Winter rye cover crops shelter competent squash phyllosphere bacteria to reduce Pseudomonas syringae pv. lachrymans growth and angular leaf spot symptoms.},
journal = {Phytopathology},
volume = {},
number = {},
pages = {},
doi = {10.1094/PHYTO-08-22-0291-R},
pmid = {38648089},
issn = {0031-949X},
abstract = {Cover crops, a soil conservation practice, can contribute to reducing disease pressure caused by Pseudomonas syringae, considered one of the most important bacterial plant pathogens. We recently demonstrated that phyllosphere (leaf surface) bacterial community structure changed when squash (Cucurbita pepo) was grown with a rye (Secale cereale) cover crop treatment, followed by a decrease of angular leaf spot (ALS) disease symptoms on squash caused by P. syringae pv. lachrymans. Application of biocontrol agents is a known agricultural practice to mitigate crop losses due to microbial disease. In this study, we tested the hypothesis that some phyllosphere bacteria promoted when squash are grown on cover crops could be isolated and used as a biocontrol agent to decrease ALS symptoms. We grew squash during a two-year field experiment using four agricultural practices: bare soil, cover crops, chemically terminated cover crops, and plastic cover. We sampled squash leaves at 3 different dates each year and constructed a collection of cultivable bacterial strains isolated from squash leaves and rye cover crop material. Each isolated strain was identified by 16S rRNA gene sequencing and used in in vitro (Petri dish) pathogen growth and in vivo (greenhouse) symptom control assays. Four bacterial isolates belonging to the genera Pseudarthrobacter, Pseudomonas, Delftia and Rhizobium were shown to inhibit P. syringae pv. lachrymans growth and ALS symptom development. Strikingly, the symptom control efficacy of all strains was stronger on older leaves. This study sheds light on the importance of bacterial isolation from cover crops sources to promote disease control.},
}

@article {pmid38647433,
year = {2024},
author = {Mousavi, H and Rimaz, M and Zeynizadeh, B},
title = {Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.4c00055},
pmid = {38647433},
issn = {1948-7193},
abstract = {Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2[(G2019S)], hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.},
}

@article {pmid38647181,
year = {2024},
author = {Zejlon, C and Sennfält, S and Finnsson, J and Connolly, B and Petersson, S and Granberg, T and Ingre, C},
title = {Motor band sign is specific for amyotrophic lateral sclerosis and corresponds to motor symptoms.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.52066},
pmid = {38647181},
issn = {2328-9503},
support = {20190565//Region Stockholm and Karolinska Institutet through ALF Medicine/ ; 976444//Region Stockholm and Karolinska Institutet through ALF Medicine/ ; //Neuroförbundet/ ; //Svenska Frimurarorden/ ; //Ulla-Carin Lindquists stiftelse för ALS-forskning/ ; },
abstract = {OBJECTIVE: Magnetic resonance imaging can detect neurodegenerative iron accumulation in the motor cortex, called the motor band sign. This study aims to evaluate its sensitivity/specificity and correlations to symptomatology, biomarkers, and clinical outcome in amyotrophic lateral sclerosis.

METHODS: This prospective study consecutively enrolled 114 persons with amyotrophic lateral sclerosis and 79 mimics referred to Karolinska University Hospital, and also 31 healthy controls. All underwent 3-Tesla brain susceptibility-weighted imaging. Three raters independently assessed motor cortex susceptibility with total and regional motor band scores. Survival was evaluated at a median of 34.2 months after the imaging.

RESULTS: The motor band sign identified amyotrophic lateral sclerosis with a sensitivity of 59.6% and a specificity of 91.1% versus mimics and 96.8% versus controls. Higher motor band scores were more common with genetic risk factors (p = 0.032), especially with C9orf72 mutation, and were associated with higher neurofilament light levels (std. β 0.22, p = 0.019). Regional scores correlated strongly with focal symptoms (medial region vs. gross motor dysfunction, std. β -0.64, p = 0.001; intermediate region vs. fine motor dysfunction, std. β -0.51, p = 0.031; lateral region vs. bulbar symptoms std. β -0.71, p < 0.001). There were no associations with cognition, progression rate, or survival.

INTERPRETATION: In a real-life clinical setting, the motor band sign has high specificity but relatively low sensitivity for identifying amyotrophic lateral sclerosis. Associations with genetic risk factors, neurofilament levels and somatotopic correspondence to focal motor weakness suggest that the motor band sign could be a suitable biomarker for diagnostics and clinical trials in amyotrophic lateral sclerosis.},
}

@article {pmid38646691,
year = {2024},
author = {Flynn, MB and Flynn, JF and Palacios, AM},
title = {Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.},
journal = {International journal of social determinants of health and health services},
volume = {},
number = {},
pages = {27551938241247778},
doi = {10.1177/27551938241247778},
pmid = {38646691},
issn = {2755-1946},
abstract = {Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.},
}

@article {pmid38646235,
year = {2024},
author = {Hagino, T and Ochiai, S and Hagino, T and Furuya, N and Wako, M and Haro, H},
title = {Impacts of Segond Fractures on Anterior Cruciate Ligament Reconstruction Outcomes.},
journal = {Cureus},
volume = {16},
number = {3},
pages = {e56542},
pmid = {38646235},
issn = {2168-8184},
abstract = {INTRODUCTION: Segond fractures, characterized by avulsion injuries at the lateral tibial condyle's anterolateral structure (ALS) attachment, often coincide with anterior cruciate ligament (ACL) injuries, potentially leading to knee instability. However, the influence of Segond fractures on knee stability after ACL reconstruction remains uncertain. Despite documented ALS reconstructions, there is a lack of consensus regarding the assessment of ALS failure and the criteria for surgical interventions. This study aimed to determine if Segond fracture presence impacts ACL reconstruction outcomes, utilizing patient-reported subjective assessments and healthcare providers' objective evaluations.

MATERIALS AND METHODS: This retrospective study encompassed 639 patients (328 males, 311 females; mean age 26.9 years) who underwent ACL reconstruction, with a follow-up of at least one year. Subjects were divided into two groups: Segond fractures diagnosed through radiographic findings (Group S+, n = 17) and no Segond fractures (Group S-, n = 622). Clinical evaluation included the 36-item Short Form Survey (SF-36), Lysholm score, visual analog scale (VAS) for knee pain, knee injury and osteoarthritis outcome score (KOOS), and knee instability assessment via Telos SE (Telos Japan, Tokyo, Japan). Statistical comparisons were performed between the two groups.

RESULTS: At the final follow-up, all SF-36 subscales improved in all eight subscales compared to before surgery, reaching national standard scores; no significant inter-group differences were evident. Lysholm scores were 93.0 ± 12.1 (Group S+) and 91.7 ± 10.9 (Group S-) (P = 0.62), VAS for knee pain was 10.0 ± 18.0 (Group S+) and 11.9 ± 16.9 (Group S-) (P = 0.62), total KOOS was 89.0 ± 17.4 (Group S+) and 90.7 ± 9.9 (Group S-) (P = 0.39), and anterior tibial translation differences were 2.8 ± 3.0 mm (Group S+) and 2.7 ± 2.9 mm (Group S-) (P = 0.73). All these values represent postoperative measurements. No significant discrepancies existed between groups across evaluation methods.

CONCLUSIONS: This study's results suggest that Segond fractures have minimal impact on clinical ACL reconstruction outcomes, as assessed through both patient-reported subjective evaluations and objective healthcare provider evaluations. Segond fractures' significance in postoperative outcomes questions the necessity of ALS reconstruction.},
}

@article {pmid38645254,
year = {2024},
author = {Card, NS and Wairagkar, M and Iacobacci, C and Hou, X and Singer-Clark, T and Willett, FR and Kunz, EM and Fan, C and Vahdati Nia, M and Deo, DR and Srinivasan, A and Choi, EY and Glasser, MF and Hochberg, LR and Henderson, JM and Shahlaie, K and Brandman, DM and Stavisky, SD},
title = {An accurate and rapidly calibrating speech neuroprosthesis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {38645254},
abstract = {Brain-computer interfaces can enable rapid, intuitive communication for people with paralysis by transforming the cortical activity associated with attempted speech into text on a computer screen. Despite recent advances, communication with brain-computer interfaces has been restricted by extensive training data requirements and inaccurate word output. A man in his 40's with ALS with tetraparesis and severe dysarthria (ALSFRS-R = 23) was enrolled into the BrainGate2 clinical trial. He underwent surgical implantation of four microelectrode arrays into his left precentral gyrus, which recorded neural activity from 256 intracortical electrodes. We report a speech neuroprosthesis that decoded his neural activity as he attempted to speak in both prompted and unstructured conversational settings. Decoded words were displayed on a screen, then vocalized using text-to-speech software designed to sound like his pre-ALS voice. On the first day of system use, following 30 minutes of attempted speech training data, the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. On the second day, the size of the possible output vocabulary increased to 125,000 words, and, after 1.4 additional hours of training data, the neuroprosthesis achieved 90.2% accuracy. With further training data, the neuroprosthesis sustained 97.5% accuracy beyond eight months after surgical implantation. The participant has used the neuroprosthesis to communicate in self-paced conversations for over 248 hours. In an individual with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore naturalistic communication after a brief training period.},
}

@article {pmid38645132,
year = {2024},
author = {Caggiano, C and Morselli, M and Qian, X and Celona, B and Thompson, M and Wani, S and Tosevska, A and Taraszka, K and Heuer, G and Ngo, S and Steyn, F and Nestor, P and Wallace, L and McCombe, P and Heggie, S and Thorpe, K and McElligott, C and English, G and Henders, A and Henderson, R and Lomen-Hoerth, C and Wray, N and McRae, A and Pellegrini, M and Garton, F and Zaitlen, N},
title = {Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.04.08.24305503},
pmid = {38645132},
abstract = {Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.},
}

@article {pmid38644973,
year = {2024},
author = {Gonzalez, D and Cuenca, X and Allende, ML},
title = {Knockdown of tgfb1a partially improves ALS phenotype in a transient zebrafish model.},
journal = {Frontiers in cellular neuroscience},
volume = {18},
number = {},
pages = {1384085},
pmid = {38644973},
issn = {1662-5102},
abstract = {Amyotrophic lateral sclerosis (ALS) corresponds to a neurodegenerative disorder marked by the progressive degeneration of both upper and lower motor neurons located in the brain, brainstem, and spinal cord. ALS can be broadly categorized into two main types: sporadic ALS (sALS), which constitutes approximately 90% of all cases, and familial ALS (fALS), which represents the remaining 10% of cases. Transforming growth factor type-β (TGF-β) is a cytokine involved in various cellular processes and pathological contexts, including inflammation and fibrosis. Elevated levels of TGF-β have been observed in the plasma and cerebrospinal fluid (CSF) of both ALS patients and mouse models. In this perspective, we explore the impact of the TGF-β signaling pathway using a transient zebrafish model for ALS. Our findings reveal that the knockdown of tgfb1a lead to a partial prevention of motor axon abnormalities and locomotor deficits in a transient ALS zebrafish model at 48 h post-fertilization (hpf). In this context, we delve into the proposed distinct roles of TGF-β in the progression of ALS. Indeed, some evidence suggests a dual role for TGF-β in ALS progression. Initially, it seems to exert a neuroprotective effect in the early stages, but paradoxically, it may contribute to disease progression in later stages. Consequently, we suggest that the TGF-β signaling pathway emerges as an attractive therapeutic target for treating ALS. Nevertheless, further research is crucial to comprehensively understand the nuanced role of TGF-β in the pathological context.},
}

@article {pmid38644578,
year = {2024},
author = {Yao, Q and Long, C and Yi, P and Zhang, G and Wan, W and Rao, X and Ying, J and Liang, W and Hua, F},
title = {C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.},
journal = {CNS neuroscience & therapeutics},
volume = {30},
number = {4},
pages = {e14721},
pmid = {38644578},
issn = {1755-5949},
support = {jxsq2019201023//Jiangxi Province "Double Thousand Plan"/ ; 82060219//National Natural Science Foundation of China/ ; 82271234//National Natural Science Foundation of China/ ; 20212ACB216009//Natural Science Foundation of Jiangxi Province/ ; 20212BAB216048//Natural Science Foundation of Jiangxi Province/ ; 2019YNTD12003//Youth Team Project of the Second Affiliated Hospital of Nanchang University/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics ; *Disease Progression ; Animals ; Amyloid beta-Peptides/metabolism ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder distinguished by a swift cognitive deterioration accompanied by distinctive pathological hallmarks such as extracellular Aβ (β-amyloid) peptides, neuronal neurofibrillary tangles (NFTs), sustained neuroinflammation, and synaptic degeneration. The elevated frequency of AD cases and its proclivity to manifest at a younger age present a pressing challenge in the quest for novel therapeutic interventions. Numerous investigations have substantiated the involvement of C/EBPβ in the progression of AD pathology, thus indicating its potential as a therapeutic target for AD treatment.

AIMS: Several studies have demonstrated an elevation in the expression level of C/EBPβ among individuals afflicted with AD. Consequently, this review predominantly delves into the association between C/EBPβ expression and the pathological progression of Alzheimer's disease, elucidating its underlying molecular mechanism, and pointing out the possibility that C/EBPβ can be a new therapeutic target for AD.

METHODS: A systematic literature search was performed across multiple databases, including PubMed, Google Scholar, and so on, utilizing predetermined keywords and MeSH terms, without temporal constraints. The inclusion criteria encompassed diverse study designs, such as experimental, case-control, and cohort studies, restricted to publications in the English language, while conference abstracts and unpublished sources were excluded.

RESULTS: Overexpression of C/EBPβ exacerbates the pathological features of AD, primarily by promoting neuroinflammation and mediating the transcriptional regulation of key molecular pathways, including δ-secretase, apolipoprotein E4 (APOE4), acidic leucine-rich nuclear phosphoprotein-32A (ANP32A), transient receptor potential channel 1 (TRPC1), and Forkhead BoxO (FOXO).

DISCUSSION: The correlation between overexpression of C/EBPβ and the pathological development of AD, along with its molecular mechanisms, is evident. Investigating the pathways through which C/EBPβ regulates the development of AD reveals numerous multiple vicious cycle pathways exacerbating the pathological progression of the disease. Furthermore, the exacerbation of pathological progression due to C/EBPβ overexpression and its molecular mechanism is not limited to AD but also extends to other neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple sclerosis (MS).

CONCLUSION: The overexpression of C/EBPβ accelerates the irreversible progression of AD pathophysiology. Additionally, C/EBPβ plays a crucial role in mediating multiple pathways linked to AD pathology, some of which engender vicious cycles, leading to the establishment of feedback mechanisms. To sum up, targeting C/EBPβ could hold promise as a therapeutic strategy not only for AD but also for other degenerative diseases.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*CCAAT-Enhancer-Binding Protein-beta/metabolism/genetics
*Disease Progression
Animals
Amyloid beta-Peptides/metabolism

@article {pmid38644373,
year = {2024},
author = {Niccolai, E and Pedone, M and Martinelli, I and Nannini, G and Baldi, S and Simonini, C and Di Gloria, L and Zucchi, E and Ramazzotti, M and Spezia, PG and Maggi, F and Quaranta, G and Masucci, L and Bartolucci, G and Stingo, FC and Mandrioli, J and Amedei, A},
title = {Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules.},
journal = {Journal of neurology},
volume = {},
number = {},
pages = {},
pmid = {38644373},
issn = {1432-1459},
support = {Grant-No. RF-2016-02361616//Ministero della Salute/ ; Grant no. B008-P00634//University of Florence/ ; },
abstract = {Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons' pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments.},
}

@article {pmid38643758,
year = {2024},
author = {Aiello, EN and Solca, F and Torre, S and Colombo, E and Maranzano, A and De Lorenzo, A and Patisso, V and Treddenti, M and Curti, B and Morelli, C and Doretti, A and Verde, F and Ferrucci, R and Barbieri, S and Ruggiero, F and Priori, A and Silani, V and Ticozzi, N and Poletti, B},
title = {Longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in non-demented ALS patients.},
journal = {European neurology},
volume = {},
number = {},
pages = {},
doi = {10.1159/000538828},
pmid = {38643758},
issn = {1421-9913},
abstract = {INTRODUCTION: The present study aimed at testing the longitudinal feasibility of the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented amyotrophic lateral sclerosis (ALS) patients.

METHODS: N=39 non-demented ALS patients were followed-up at a 5-to-10-month interval (M=6.8; SD=1.4) with the MoCA and the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Practice effects, test-retest reliability and predictive validity (against follow-up ECAS scores) were assessed. Reliable change indices (RCIs) were derived via a regression-based approach by accounting for retest interval and baseline confounders (i.e., demographics, disease duration and severity and progression rate).

RESULTS: At retest, 100% and 69.2% of patients completed the ECAS and the MoCA, respectively. Patients who could not complete the MoCA showed a slightly more severe and fast-progressing disease. The MoCA was not subject to practice effects (t(32)=-.80; p=.429) and was reliable at retest (ICC=.82). Moreover, baseline MoCA scores predicted the ECAS at retest. RCIs were successfully derived - with baseline MoCA scores being the only significant predictor of retest performances (ps<.001).

CONCLUSIONS: As long as motor disabilities do not undermine its applicability, the MoCA appears to be longitudinally feasible at a 5-to-10-month interval in non-demented ALS patients. However, ALS-specific screeners - such as the ECAS - should be preferred whenever possible.},
}

@article {pmid38643177,
year = {2024},
author = {Jeszka, J and Hummel, D and Woźniewicz, M and Morinaka, T and Sone, Y and Crews, DE},
title = {Allostatic load and frailty do not covary significantly among older residents of Greater Poland.},
journal = {Journal of physiological anthropology},
volume = {43},
number = {1},
pages = {12},
pmid = {38643177},
issn = {1880-6805},
mesh = {Male ; Humans ; Female ; Aged ; *Allostasis/physiology ; *Frailty/epidemiology ; Poland/epidemiology ; Biomarkers ; Cohort Studies ; },
abstract = {BACKGROUND: Physiological dysregulation/allostatic load and the geriatric syndrome frailty increase with age. As a neurophysiological response system, allostasis supports survival by limiting stressor-related damage. Frailty reflects decreased strength, endurance, and physical abilities secondary to losses of muscle and bone with age. One suggestion, based on large cohort studies of person's ages 70 + years, is that frailty contributes to allostatic load at older ages. However, small community-based research has not confirmed this specific association.

METHODS: To further explore possible associations between allostatic load and frailty, we enrolled 211 residents of Greater Poland aged 55-91 years living in a small village (Nekla, N = 104) and an urban center and capital of Greater Poland (Poznan, N = 107). For each, we recorded age, self-reported sex, and residence and estimated a 10-biomarker allostatic load score (ALS) and an 8-biomarker frailty index. We anticipated the following: higher ALS and frailty among men and rural residents; for frailty but not ALS to be higher at older ages; significant associations of ALS with sex and place of residence, but not with age or frailty. The significance of observed associations was evaluated by t-tests and multivariate regression.

RESULTS: ALS did not vary significantly between men and women nor between Nekla and Poznan residents overall. However, women showed significantly higher frailty than men. Nekla men showed significantly higher ALS but not frailty, while Nekla women showed nonsignificantly higher ALS and lower frailty than Poznan. In multivariate analyses, neither age, nor sex, nor residence was associated with ALS. Conversely, age, sex, and residence, but not ALS, are associated significantly with frailty. In Nekla, both age and sex, but in Poznan only age, are associated with ALS. Among women, both age and residence, but among men, neither associated with ALS. In no case did ALS associate significantly with frailty.

CONCLUSION: In this sample, lifestyle factors associated with residence, age, and sex influence stress-related physiology, less so in women, while ALS and frailty do not covary, suggesting their underlying promoters are distinct. Similar complex associations of physiological dysregulation with frailty, age, sex, and residence likely exist within many local settings. Knowledge of this variation likely will aid in supporting health and healthcare services among seniors.},
}

Male
Humans
Female
Aged
*Allostasis/physiology
*Frailty/epidemiology
Poland/epidemiology
Biomarkers
Cohort Studies

@article {pmid38643019,
year = {2024},
author = {Guo, J and You, L and Zhou, Y and Hu, J and Li, J and Yang, W and Tang, X and Sun, Y and Gu, Y and Dong, Y and Chen, X and Sato, C and Zinman, L and Rogaeva, E and Wang, J and Chen, Y and Zhang, M},
title = {Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awae123},
pmid = {38643019},
issn = {1460-2156},
abstract = {Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. Spatial architecture of cell types and gene expression is the basis of cell-cell interactions, biological function and disease pathology, but is not well investigated in human motor cortex, a key ALS relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, it remains largely unclear what is the brain regional vulnerability of ALS-associated genes, and what is the genetic link between region-specific genes and ALS risk. Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics (ST). We benchmarked SpatialE against another enrichment tool (Multimodal Intersection Analysis, MIA) using ST data from both human and mouse brain tissues. To investigate regional vulnerability, we analyzed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function (LOF) variants detected by whole-genome sequencing in ALS patients and controls, and then analyzed differential gene expression in the TargetALS RNA-seq dataset. SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than MIA in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogenous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 (L5) motor cortex, with abundant expression of upper motor neurons and L5 excitatory neurons. Burden analyses of rare LOF variants in L5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6,814 ALS patients and 3,324 controls (P = 0.029). Gene expression analyses in central nervous system tissues revealed down-regulation of NOMO1 in ALS, which is consistent with a LOF disease mechanism. In conclusion, our integrated ST and genomic analyses identified regional brain vulnerability in ALS and the association of a L5 gene (NOMO1) with ALS risk.},
}

@article {pmid38643008,
year = {2024},
author = {Zheng, Q and Zeng, Z and Tang, X and Ma, L},
title = {Impact of an ICU bed capacity optimisation method on the average length of stay and average cost of hospitalisation following implementation of China's open policy with respect to COVID-19: a difference-in-differences analysis based on information management system data from a tertiary hospital in southwest China.},
journal = {BMJ open},
volume = {14},
number = {4},
pages = {e078069},
pmid = {38643008},
issn = {2044-6055},
mesh = {Humans ; *COVID-19/epidemiology ; Length of Stay ; Tertiary Care Centers ; Hospitalization ; Intensive Care Units ; China/epidemiology ; Information Management ; },
abstract = {OBJECTIVES: Following the implementation of China's open policy with respect to COVID-19 on 7 December 2022, the influx of patients with infectious diseases has surged rapidly, necessitating hospitals to adopt temporary requisition and modification of ward beds to optimise hospital bed capacity and alleviate the burden of overcrowded patients. This study aims to investigate the effect of an intensive care unit (ICU) bed capacity optimisation method on the average length of stay (ALS) and average cost of hospitalisation (ACH) after the open policy of COVID-19 in China.

DESIGN AND SETTING: A difference-in-differences (DID) approach is employed to analyse and compare the ALS and ACH of patients in four modified ICUs and eight non-modified ICUs within a tertiary hospital located in southwest China. The analysis spans 2 months before and after the open policy, specifically from 5 October 2022 to 6 December 2022, and 7 December 2022 to 6 February 2023.

PARTICIPANTS: We used the daily data extracted from the hospital's information management system for a total of 5944 patients admitted by the outpatient and emergency access during the 2-month periods before and after the release of the open policy in China.

RESULTS: The findings indicate that the ICU bed optimisation method implemented by the tertiary hospital led to a significant reduction in ALS (HR -0.6764, 95% CI -1.0328 to -0.3201, p=0.000) and ACH (HR -0.2336, 95% CI -0.4741 to -0.0068, p=0.057) among ICU patients after implementation of the open policy. These results were robust across various sensitivity analyses. However, the effect of the optimisation method exhibits heterogeneity among patients admitted through the outpatient and emergency channels.

CONCLUSIONS: This study corroborates a significant positive impact of ICU bed optimisation in mitigating the shortage of medical resources following an epidemic outbreak. The findings hold theoretical and practical implications for identifying effective emergency coordination strategies in managing hospital bed resources during sudden public health emergency events. These insights contribute to the advancement of resource management practices and the promotion of experiences in dealing with public health emergencies.},
}

Humans
*COVID-19/epidemiology
Length of Stay
Tertiary Care Centers
Hospitalization
Intensive Care Units
China/epidemiology
Information Management

@article {pmid38642323,
year = {2024},
author = {Ferrari, V and Conti, M and Bovenzi, R and Cerroni, R and Pierantozzi, M and Mercuri, NB and Stefani, A},
title = {Rare association between spinocerebellar ataxia and amyotrophic lateral sclerosis: a case series.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {},
number = {},
pages = {},
pmid = {38642323},
issn = {1590-3478},
abstract = {INTRODUCTION: In this work, we describe a new case of association between SCA2 and MND.

CASE REPORT: A 58-year-old man who was diagnosed with spinocerebellar ataxia type 2 presented dysphagia and a significant decline in his ability to walk, with a reduction in autonomy and the need to use a wheelchair. We performed electromyography and electroneurography of the four limbs and of the cranial district and motor-evoked potentials to study upper and lower motor neurons. Referring to the revised El Escorial criteria of 2015, ALS diagnosis was made.

DISCUSSION: Considering different cases described in literature over the years, SCA2 could represent an important risk factor for developing ALS. In particular, the presence of alleles of ATXN2 with 27 and 28 CAG repeats seems to slightly decrease the risk of developing the disease, which would instead be progressively increased by the presence of alleles with 29, 30, 31, 32, and 33 repeats. The exact physiopathological mechanism by which the mutation increases the risk of developing the disease is currently unknown. Transcriptomic studies on mouse models have demonstrated the involvement of several pathways, including the innate immunity regulation by STING and the biosynthesis of fatty acid and cholesterol by SREBP.

CONCLUSION: CAG repeat expansions in the ATXN2 gene have been associated with variable neurological presentations, which include SCA2, ALS, Parkinsonism, or a combination of them. Further research is needed to understand the relationship between SCA2 and ALS better and explore molecular underlying mechanisms.},
}

@article {pmid38641715,
year = {2024},
author = {Udine, E and DeJesus-Hernandez, M and Tian, S and das Neves, SP and Crook, R and Finch, NA and Baker, MC and Pottier, C and Graff-Radford, NR and Boeve, BF and Petersen, RC and Knopman, DS and Josephs, KA and Oskarsson, B and Da Mesquita, S and Petrucelli, L and Gendron, TF and Dickson, DW and Rademakers, R and van Blitterswijk, M},
title = {Abundant transcriptomic alterations in the human cerebellum of patients with a C9orf72 repeat expansion.},
journal = {Acta neuropathologica},
volume = {147},
number = {1},
pages = {73},
pmid = {38641715},
issn = {1432-0533},
support = {R35 NS097273/NS/NINDS NIH HHS/United States ; R35 NS097261/NS/NINDS NIH HHS/United States ; R21 NS110994/NS/NINDS NIH HHS/United States ; P01 NS084974/NS/NINDS NIH HHS/United States ; R01 AG037491/AG/NIA NIH HHS/United States ; UG3 NS103870/NS/NINDS NIH HHS/United States ; R01 NS121125/NS/NINDS NIH HHS/United States ; RF1 NS123052/NS/NINDS NIH HHS/United States ; RF1 NS120992/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; *Amyotrophic Lateral Sclerosis/pathology ; Transcriptome ; C9orf72 Protein/genetics/metabolism ; DNA Repeat Expansion/genetics ; *Frontotemporal Dementia/pathology ; Cerebellum/pathology ; *Frontotemporal Lobar Degeneration/pathology ; Gene Expression Profiling ; },
abstract = {The most prominent genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is a repeat expansion in the gene C9orf72. Importantly, the transcriptomic consequences of the C9orf72 repeat expansion remain largely unclear. Here, we used short-read RNA sequencing (RNAseq) to profile the cerebellar transcriptome, detecting alterations in patients with a C9orf72 repeat expansion. We focused on the cerebellum, since key C9orf72-related pathologies are abundant in this neuroanatomical region, yet TDP-43 pathology and neuronal loss are minimal. Consistent with previous work, we showed a reduction in the expression of the C9orf72 gene and an elevation in homeobox genes, when comparing patients with the expansion to both patients without the C9orf72 repeat expansion and control subjects. Interestingly, we identified more than 1000 alternative splicing events, including 4 in genes previously associated with ALS and/or FTLD. We also found an increase of cryptic splicing in C9orf72 patients compared to patients without the expansion and controls. Furthermore, we demonstrated that the expression level of select RNA-binding proteins is associated with cryptic splice junction inclusion. Overall, this study explores the presence of widespread transcriptomic changes in the cerebellum, a region not confounded by severe neurodegeneration, in post-mortem tissue from C9orf72 patients.},
}

Humans
*Amyotrophic Lateral Sclerosis/pathology
Transcriptome
C9orf72 Protein/genetics/metabolism
DNA Repeat Expansion/genetics
*Frontotemporal Dementia/pathology
Cerebellum/pathology
*Frontotemporal Lobar Degeneration/pathology
Gene Expression Profiling

@article {pmid38640582,
year = {2024},
author = {Ceccanti, M and Libonati, L and Moret, F and D'Andrea, E and Gori, MC and Bersani, FS and Inghilleri, M and Cambieri, C},
title = {Emotion recognition in amyotrophic lateral sclerosis in a dynamic environment.},
journal = {Journal of the neurological sciences},
volume = {460},
number = {},
pages = {123019},
doi = {10.1016/j.jns.2024.123019},
pmid = {38640582},
issn = {1878-5883},
abstract = {OBJECTIVE: The aim of our study was to measure the ability of ALS patients to process dynamic facial expressions as compared to a control group of healthy subjects and to correlate this ability in ALS patients with neuropsychological, clinical and neurological measures of the disease.

METHODS: Sixty-three ALS patients and 47 healthy controls were recruited. All the ALS patients also underwent i) the Geneva Emotion Recognition Test (GERT) in which ten actors express 14 types of dynamic emotions in brief video clips with audio, ii) the Edimburgh Cognitive and Behavioral ALS Screen (ECAS) test; iii) the ALS Functional Rating Scale Revised (ALSFRS-R) and iv) the Medical Research Council (MRC) for the evaluation of muscle strength. All the healthy subjects enrolled in the study underwent the GERT.

RESULTS: The recognition of irritation and pleasure was significantly different between ALS patients and the control group. The amusement, despair, irritation, joy, sadness and surprise had been falsely recognized differently between the two groups. Specific ALS cognitive impairment was associated with bulbar-onset phenotype (OR = 14,3889; 95%CI = 3,96-52,16). No association was observed between false emotion recognition and cognitive impairment (F(1,60)=,56,971, p=,45,333). The number of categorical errors was significantly higher in the ALS patients than in the control group (27,66 ± 7,28 vs 17,72 ± 5,29; t = 8723; p = 0.001).

CONCLUSIONS: ALS patients show deficits in the dynamic processing of a wide range of emotions. These deficits are not necessarily associated with a decline in higher cognitive functions: this could therefore lead to an underestimation of the phenomenon.},
}

@article {pmid38638511,
year = {2024},
author = {Finsel, J and Rosenbohm, A and Peter, RS and Bäzner, H and Börtlein, A and Dempewolf, S and Schabet, M and Hecht, M and Kohler, A and Opherk, C and Nägele, A and Sommer, N and Lindner, A and Rothenbacher, D and Ludolph, AC and Nagel, G and Lulé, DE},
title = {Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.},
journal = {Frontiers in psychology},
volume = {15},
number = {},
pages = {1361767},
pmid = {38638511},
issn = {1664-1078},
abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing.

METHODS: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded.

RESULTS: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS.

CONCLUSION: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.},
}

@article {pmid38638178,
year = {2023},
author = {Fotouhi, M and Worrall, D and Ayoubi, R and Southern, K and McPherson, PS and Laflamme, C and , and , },
title = {A guide to selecting high-performing antibodies for RNA-binding protein TIA1 for use in Western Blot, immunoprecipitation and immunofluorescence.},
journal = {F1000Research},
volume = {12},
number = {},
pages = {745},
pmid = {38638178},
issn = {2046-1402},
mesh = {T-Cell Intracellular Antigen-1/genetics ; *RNA-Binding Proteins ; Blotting, Western ; Fluorescent Antibody Technique ; Immunoprecipitation ; },
abstract = {A member of the RNA-binding protein family, T-cell intracellular antigen-1 (TIA1) regulates mRNA translation and splicing as well as cellular stress by promoting stress granule formation. Variants of the TIA1 gene have implications in neurogenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Reproducible research on TIA1 would be enhanced with the availability of high-quality anti-TIA1 antibodies. In this study, we characterized twelve TIA1 commercial antibodies for Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. We identified many high-performing antibodies and encourage readers to use this report as a guide to select the most appropriate antibody for their specific needs.},
}

T-Cell Intracellular Antigen-1/genetics
*RNA-Binding Proteins
Blotting, Western
Fluorescent Antibody Technique
Immunoprecipitation

@article {pmid38636451,
year = {2024},
author = {Khalil, B and Da Cruz, S},
title = {14-3-3θ, a novel player in TDP-43 pathophysiology: Implications for ALS/FTD.},
journal = {Neuron},
volume = {112},
number = {8},
pages = {1197-1199},
doi = {10.1016/j.neuron.2024.03.025},
pmid = {38636451},
issn = {1097-4199},
mesh = {Mice ; Animals ; *Amyotrophic Lateral Sclerosis/pathology ; *Frontotemporal Dementia/genetics ; DNA-Binding Proteins/genetics ; *TDP-43 Proteinopathies/genetics ; Neurons/pathology ; Mice, Transgenic ; },
abstract = {In this issue of Neuron, Ke et al.[1] report a novel non-canonical interaction between 14-3-3θ and TDP-43 that impacts loss-of-function and gain-of-toxic pathology in TDP-43 proteinopathies. The authors further provide proof of principle for a 14-3-3θ-targeted gene therapy to reduce TDP-43-induced deficits in transgenic TDP-43 mutant mice.},
}

Mice
Animals
*Amyotrophic Lateral Sclerosis/pathology
*Frontotemporal Dementia/genetics
DNA-Binding Proteins/genetics
*TDP-43 Proteinopathies/genetics
Neurons/pathology
Mice, Transgenic

@article {pmid38330934,
year = {2024},
author = {Yang, L and Li, Y and Zhang, S and Qian, H and Xu, W and Yu, J},
title = {Efficacy of Acupuncture Combined with Traditional Chinese Medicine Fumigation Therapy in Sequelae of Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {175-186},
doi = {10.1159/000536101},
pmid = {38330934},
issn = {2504-2106},
abstract = {BACKGROUND AND OBJECTIVE: Acupuncture combined with traditional Chinese medicine fumigation is increasingly being used in treating sequelae of pelvic inflammatory disease (SPID). However, there is a lack of meta-analysis on the effectiveness of acupuncture combined with traditional Chinese medicine fumigation in treating SPID. The aim of this study was to assess the feasibility of combining acupuncture with traditional Chinese medicine fumigation in the treatment of SPID.

METHODS: We searched eight databases for studies on acupuncture combined with traditional Chinese medicine fumigation for the treatment of SPID from the date of establishment to October 29, 2022. We assessed the quality of included studies by using the Cochrane bias risk tool. Pooled results were expressed as risk ratios (RRs), with a 95% confidence interval (CI). In addition, we identified sources of heterogeneity by sensitivity analysis, assessed publication bias by Egger's test, and assessed the quality of the evidence by Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). All statistical analyses were performed by Review Manager 5.3 and Stata 14.

RESULTS: Finally, seven studies with a total of 663 participants were included. We found a significant difference in the total effective rate in the acupuncture combined with the fumigation group compared with the acupuncture group in the treatment of SPID (RR = 1.17, 95% CI [1.09, 1.25], p = 0.0001 < 0.05; I2 = 0%; 6 trials), and a significant difference in the total effective rate in the acupuncture combined with fumigation group compared with the fumigation group in the treatment of SPID (RR = 1.42, 95% CI [1.21, 1.66], p = 0.0001 < 0.05; 5 trials).

CONCLUSION: The clinical efficacy of acupuncture combined with herbal fumigation in the treatment of SPID is relatively good. Larger scale studies are needed in the future.

UNLABELLED: Akupunktur in Kombination mit Fumigation, einem Verfahren der Traditionellen Chinesischen Medizin, wird zunehmend in der Behandlung von Folgeerscheinungen von Beckenentzündungen (SPID; sequelae of pelvic inflammatory disease) eingesetzt. Es mangelt jedoch an Metaanalysen zur Wirksamkeit der Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID. Das Ziel dieser Studie ist die Beurteilung der Machbarkeit der Kombination aus Akupunktur und Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von SPID.Wir durchsuchten acht Datenbanken nach Studien zur Akupunktur in Kombination mit Fumigation gemäß der Traditionellen Chinesischen Medizin in der Behandlung von Folgeerscheinungen von SPID von der Einrichtung bis zum 29. Oktober 2022. Wir beurteilten die Qualität der eingeschlossenen Studien mit dem Cochrane-Tool zur Bewertung des Bias-Risikos. Die gepoolten Ergebnisse wurden als Risikoquotient (RR; risk ratio) mit 95%-Konfidenzintervall (KI) ausgedrückt. Zusätzlich identifizierten wir Quellen für Heterogenität mittels Sensitivitätsanalyse, beurteilten den Publikations-Bias mittels Egger-Test und bewerteten die Qualität der Evidenz nach Grad der Empfehlungsstärke, Beurteilung, Entwicklung und Evaluierung (GRADE). Alle statistischen Analysen erfolgten mit Review Manager 5.3 und Stata 14.Im Endeffekt wurden 7 Studien mit insgesamt 663 Teilnehmern eingeschlossen. Wir fanden einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Akupunkturgruppe (RR = 1,17; 95%-KI [1,09; 1,25]; p = 0,0001 < 0,05; I2-Wert = 0%; 6 Studien), und einen signifikanten Unterschied in der Gesamt-Effektivitätsrate bei der Gruppe, die zur Behandlung von SPID Akupunktur in Kombination mit Fumigation erhielt, im Vergleich zur reinen Fumigationsgruppe (RR = 1,42; 95%-KI [1,21; 1,66]; p = 0,0001 < 0,05; 5 Studien).Die klinische Wirksamkeit der Akupunktur in Kombination mit Kräuter-Fumigation zur Behandlung von SPID ist relativ gut. Zukünftig sind größere Studien erforderlich.},
}

@article {pmid38330929,
year = {2024},
author = {Fronczek, M and Kopacz, K and Kopacz, Ł and Padula, G},
title = {The Role of Objective Movement Analysis in the Control of Yoga Asanas: A Case Study.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {201-209},
doi = {10.1159/000535312},
pmid = {38330929},
issn = {2504-2106},
abstract = {INTRODUCTION: Yoga is classified as a form of complementary and alternative medicine. It can be used in many disciplines including physiotherapy, medicine, and sport. The objective of the study was to identify possible biomechanical problems during yoga practice and to minimize the risk of injury.

CASE PRESENTATION: Objective evaluation of the symmetry of asanas, balance, stability, and muscle tension was provided in case of a 37-year-old woman, practicing mainly aerial and Hatha yoga for 6 years. The bigger body tilt and deviations in center of pressure (COP) parameters were observed in tadasana during forward examinations. In tadasana, the highest muscle activity was observed in the rectus femoris. In case of forward tadasana observation, the highest activity was found in the gastrocnemius and in the lumbar portion of the erector spinae. During backward tadasana trial, the most active were the tibialis anterior and rectus femoris muscles. In garudasana and natarajasana, the symmetry of the trunk position in relation to the lower limbs was observed, regardless of the supporting limb. In the same way, COP parameters in garudasana were similar regardless of the supporting limb. However, in natarajasana, the higher COP displacement parameters were observed in the case of the nondominant supporting limb. As for the electromyographic evaluation of garudasana and natarajasana, the highest muscle activity was observed in the lumbar portion of the erector spinae. In chakrasana, a slightly greater angle of the hip extension was observed in the left hip. A higher muscle activity in chakrasana was observed in the lumbar portion of the right erector spinae. In sirsasana, no significant displacements of the cervical spine were observed, but a higher activity of the left sternocleidomastoid muscle was found.

CONCLUSION: With the use of objective movement analysis, possible biomechanical problems were identified. Attention should be paid to the normalization of the tension in the lumbar part of the right erector spinae and the right sternocleidomastoid muscle, as well as to the balance training in positions on the nondominant lower limb. Objective movement analysis can be a useful tool for instructors or physiotherapists to adjust yoga programs and correct asanas in order to avoid future injuries.

UNLABELLED: Yoga gilt als Form der Komplementär- und Alternativmedizin. Es ist in vielen Disziplinen einsetzbar, von Physiotherapie über Medizin bis Sport. Das Ziel dieser Studie war es, mögliche biomechanische Probleme bei der Ausübung von Yoga zu identifizieren, um das Verletzungsrisiko zu minimieren.Eine objektive Beurteilung der Symmetrie der Asanas, des Gleichgewichts, der Stabilität und der Muskelspannung erfolgte bei einer 37-jährigen Frau, die seit 6 Jahren hauptsächlich Aerial- und Hatha-Yoga praktiziert. Stärkere Körperneigung und Abweichungen bei Druckmittelpunkt-Parametern wurden in Tadasana bei der Vorwärts-Beobachtung festgestellt. In Tadasana wurde die höchste Muskelaktivität im Rectus femoris beobachtet. Bei der Tadasana-Vorwärts-Beobachtung war die höchste Aktivität im Gastrocnemius und im lumbalen Anteil des Erector spinae zu verzeichnen. Während der Tadasana-Rückwärts-Übung waren die aktivsten Muskeln der Tibialis anterior und Rectus femoris. In Garudasana und Natarajasana wurde die Symmetrie der Rumpfposition im Verhältnis zu den unteren Gliedmaßen unabhängig von der belasteten Gliedmaße beobachtet. Ebenso waren die Parameter des Druckmittelpunkts (DMP) in Garudasana unabhängig von der belasteten Gliedmaße vergleichbar. In Natarajasana wurden jedoch höhere Parameter der DMP-Verschiebung bei der nicht-dominanten belasteten Gliedmaße beobachtet. Bei der elektromyografischen Auswertung von Garudasana und Natarajasana wurde die höchste Muskelaktivität im lumbalen Anteil des Erector spinae beobachtet. In Chakrasana wurde ein etwas größerer Winkel der Hüftstreckung im linken Hüftgelenk beobachtet. Eine höhere Muskelaktivität in Chakrasana wurde im lumbalen Anteil des rechten Erector spinae beobachtet. In Sirsasana wurden keine signifikanten Verschiebungen der Halswirbelsäule beobachtet, jedoch war eine höhere Aktivität des linken Sternocleidomastoideus zu verzeichnen.Mit Hilfe einer objektiven Bewegungsanalyse wurden mögliche biomechanische Probleme identifiziert. Mit besonderer Aufmerksamkeit sollte auf die Normalisierung der Spannung im lumbalen Anteil des rechten Erector spinae und des rechten Sternocleidomastoideus sowie auf die Schulung des Gleichgewichts in Positionen auf der nicht-dominanten unteren Extremität geachtet werden. Die objektive Bewegungsanalyse kann ein nützliches Instrument für Instruktoren oder Physiotherapeuten sein, um Yoga-Programme anzupassen und Asanas zu korrigieren, um Verletzungen vorzubeugen.},
}

@article {pmid38330924,
year = {2024},
author = {Leedasawat, P and Sangvatanakul, P and Tungsukruthai, P and Kamalashiran, C and Phetkate, P and Patarajierapun, P and Sriyakul, K},
title = {The Efficacy and Safety of Chinese Eye Exercise of Acupoints in Dry Eye Patients: A Randomized Controlled Trial.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {149-159},
doi = {10.1159/000536516},
pmid = {38330924},
issn = {2504-2106},
abstract = {INTRODUCTION: Dry eye disorder (DED) is a growing global issue linked to excessive digital screen time. Chinese eye exercise of acupoint (CEA), a set of self-massages on shared Chinese acupuncture (CA), has been used to reduce visual-related ocular symptoms and possibly as an alternative treatment for DED. This study aimed to assess the efficacy and safety of CEA.

METHODS: A single-blind randomized controlled trial was conducted at Thammasat University Hospital in Thailand, recruiting 56 participants aged 20-60 years, equally divided into two groups: the treatment group with CEA and the control group with standard lid hygiene treatment (STD). The intervention program lasted 12 weeks.

MAIN OUTCOME MEASURES: Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Schirmer-I test (SIT), corneal surface staining (CSS), and self-recorded forms for safety and adverse effects were measured at baseline, week 4, and week 12. An independent sample t test, paired t test, and repeated measures (ANOVA) were used to compare results between both groups, study visits, and primary and secondary outcome measurements, respectively. The p values <0.05 were considered statistically significant.

RESULTS: The characteristics were not statistically different between both groups at the baseline. The mean OSDI scores were significantly reduced in both groups at week 4 and week 12 compared to baseline (p value <0.05). Additionally, both CEA and STD showed significant improvement in TBUT and SIT (p value <0.05). CSS was significantly improved only in the CEA groups (p value <0.05). No significant differences were observed between the study groups, except for SIT at week 12 (p value <0.05). For the safety, there were no adverse side effects in either group.

CONCLUSION: CEA seemed to be as effective as STD in improving the OSDI, TBUT, and SIT of DED without causing any side effects.

UNLABELLED: Das Trockene Auge (Dry eye disorder, DED) ist weltweit ein zunehmendes Problem, das mit übermässiger Bildschirmarbeit zusammenhängt. Die chinesische Augenübung der Akupunkturpunkte (Chinese eye exercise of acupoint, CEA), eine Reihe von Selbstmassagen an gemeinsamen CA-Akupunkturpunkten, wird zur Linderung visusbezogener Augensymptome und als mögliche alternative Behandlung für DED eingesetzt. Mit dieser Studie sollte die Wirksamkeit und Sicherheit von CEA bewertet werden.Am Thammasat-Universitätsklinikum in Thailand wurde eine einfach verblindete, randomisierte, kontrollierte Studie mit 56 Teilnehmern im Alter von 20 bis 60 Jahren durchgeführt, die zu gleichen Teilen zwei Gruppen zugewiesen wurden: die Behandlungsgruppe mit CEA und die Kontrollgruppe, die die Standard-Lidhygienebehandlung erhielt (STD). Das Interventionsprogramm dauerte 12 Wochen. Die Haupt-Zielkriterien, der Ocular Surface Disease Index (OSDI), die Tränenfilmaufreisszeit (tear break-up time, TBUT), der Schirmer-I-Test (SIT), das Corneal Surface Staining (CSS) und Selbstauskunftsformulare zur Sicherheit und zu unerwünschten Wirkungen wurden zu Beginn der Behandlung, in Woche 4 und in Woche 12 ermittelt. Für den Vergleich der Ergebnisse zwischen den beiden Gruppen, den Studienvisiten bzw. den primären und sekundären Zielkriterien wurden ein t Test für unabhängige Stichproben, ein t Test für paarige Stichproben und eine ANOVA mit Messwiederholungen verwendet. p-Werte <0,05 galten als statistisch signifikant.Hinsichtlich der Merkmale bestand zwischen den beiden Gruppen kein statistischer Unterschied bei Studienbeginn. In beiden Gruppen fielen die mittleren OSDI-Scores in Woche 4 und Woche 12 im Vergleich zum Ausgangswert signifikant geringer aus (p-Wert <0,05). Darüber hinaus zeigten sowohl die CEA- als auch die STD-Gruppe eine signifikante Verbesserung der TBUT- und SIT-Werte (p-Wert <0,05). Das CSS verbesserte sich nur in der CEA-Gruppe signifikant (p-Wert <0,05). Zwischen den Studiengruppen waren keine signifikanten Unterschiede zu beobachten, ausser beim SIT in Woche 12 (p-Wert <0,05). Was die Sicherheit betrifft, so traten in beiden Gruppen keine unerwünschten Nebenwirkungen auf.Die CEA schien die OSDI-, TBUT- und SIT-Werte bei DED ebenso wirksam zu verbessern wie die Standardbehandlung, ohne Nebenwirkungen zu verursachen.},
}

@article {pmid38286113,
year = {2024},
author = {Dutta, A and Manna, A and Ghosh, S and Mundle, M and Saha, M and Gourav, K and Maiti, S and Chattopadhyay, B},
title = {Prespecified Homeopathic Medicines in the Prevention of Confirmed and Suspected Cases of COVID-19: A Community-Based, Double-Blind, Randomized, Placebo-Controlled Prophylaxis Trial.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {140-148},
doi = {10.1159/000536395},
pmid = {38286113},
issn = {2504-2106},
abstract = {INTRODUCTION: Homeopathic medicines have been used for decades in the prevention and treatment of infectious diseases. However, the preventive efficacy of specific homeopathic medicines in COVID-19 is not well characterized. This study aimed to evaluate the comparative efficacy of prespecified homeopathic medicines in preventing COVID-19.

METHODS: A community-based, double-blind, randomized, placebo-controlled trial was conducted on 4,034 participants residing in Ward No. 27 of the Howrah Municipal Corporation in India. Participants were randomized to receive one of three prespecified homeopathic medicines [Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®)], or placebo. The outcomes were the incidence of laboratory-confirmed and suspected cases of COVID-19 during a follow-up period of 1 month.

RESULTS: During the follow-up period, a total of 13 new laboratory-confirmed COVID-19 cases were reported in the study population. Among these, 5 cases in Influenzinum group, 2 cases in Arsenicum album group, 1 case in Oscillococcinum® group, and 5 cases in Placebo group were reported. On the other hand, number of suspected COVID-19 cases was significantly less in all the three homeopathic medicine groups compared to placebo. The least number of suspected cases reported in the Oscillococcinum® group (aOR: 0.058; 95% confidence interval [CI]: 0.029, 0.114), followed by the Arsenicum album (aOR: 0.337; 95% CI: 0.238, 0.475) and Influenzinum (aOR: 0.539; 95% CI: 0.401, 0.726) groups.

CONCLUSION: Prespecified homeopathic medicines, particularly Oscillococcinum® and Arsenicum album 30C, may have a role in preventing COVID-19, especially in reducing the incidence of suspected or COVID-19-like respiratory illnesses. However, the result failed to demonstrate a statistically significant difference in the occurrence of confirmed cases of COVID-19 between the study groups. Further research is needed to evaluate the efficacy of these medicines in different populations and settings.

UNLABELLED: Homöopathische Arzneimittel werden seit Jahrzehnten zur Prävention und Behandlung von Infektionskrankheiten eingesetzt. Die Wirksamkeit spezifischer homöopathischer Arzneimittel zur Prophylaxe von COVID-19 ist jedoch nicht gut untersucht. Mit dieser Studie sollte die vergleichende Wirksamkeit spezifischer homöopathischer Arzneimittel bei der Prävention von COVID-19 untersucht werden.Es handelte sich um eine gemeindebasierte, doppelblinde, randomisierte, placebokontrollierte Studie mit 4.034 Teilnehmern, die im Bezirk Nr. 27 der Howrah Municipal Corporation in Indien lebten. Die Teilnehmer erhielten randomisiert eines von drei zuvor festgelegten homöopathischen Arzneimitteln [Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®)] oder Placebo. Zielkriterien waren die Inzidenz von laborchemisch bestätigten und vermuteten COVID-19-Fällen während des Follow-up-Zeitraums von einem Monat.Während des Follow-up-Zeitraums wurden insgesamt 13 neue, laborchemisch bestätigte COVID-19-Fälle in der Studienpopulation berichtet, davon 5 Fälle in der Influenzinum-Gruppe, 2 Fälle in der Arsenicum album-Gruppe, 1 Fall in der Oscillococcinum®-Gruppe und 5 Fälle in der Placebo-Gruppe. Demgegenüber fiel Zahl der COVID-19-Verdachtsfälle in allen drei homöopathischen Arzneimittelgruppen signifikant geringer aus als in der Placebogruppe. Die wenigsten Verdachtsfälle wurden in der Oscillococcinum®-Gruppe berichtet (aOR: 0.058; 95%-KI: 0.029, 0.114), gefolgt von der Arsenicum album- (aOR: 0.337; 95%-KI: 0.238, 0.475) und der Influenzinum- (aOR: 0.539; 95%-KI: 0.401, 0.726) Gruppe.Spezifische homöopathische Arzneimittel, insbesondere Oscillococcinum® und Arsenicum album 30C, könnten bei der Prävention von COVID-19 eine Rolle spielen, vor allem bei der Senkung der Inzidenz von COVID-19-Verdachtsfällen oder COVID-19-ähnlichen Atemwegserkrankungen. Allerdings war kein statistisch signifikanter Unterschied im Auftreten von bestätigten COVID-19-Fällen zwischen den Studiengruppen nachweisbar. Weitere Untersuchungen sind erforderlich, um die Wirksamkeit dieser Arzneimittel in verschiedenen Populationen und Umgebungen zu bewerten.},
}

@article {pmid38286111,
year = {2024},
author = {Wang, M and Wang, T and Gu, F},
title = {Efficacy of Huanglian Jiedu Decoction for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {187-200},
doi = {10.1159/000536453},
pmid = {38286111},
issn = {2504-2106},
abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder, and there is an increasing interest in the potential benefits of traditional Chinese medicine, such as Huanglian Jiedu decoction (HJD), for its management. This meta-analysis aimed to determine the efficacy and safety of HJD in the treatment of T2DM.

METHODS: A systematic review was conducted across six databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang, from their inception to August 24, 2023. We focused on randomized controlled trials (RCTs) that evaluated HJD as both a monotherapy and in combination treatments for T2DM patients. Data analysis was performed using RevMan 5.3 and Stata 17.0, with evaluations for heterogeneity and publication bias. Additionally, subgroup analyses were stratified based on the duration of treatment.

RESULTS: A total of 40 studies involving 3,934 participants were included in the meta-analysis. Both HJD monotherapy and combined with other therapies significantly reduced hemoglobin A1C (HbA1c) fasting blood glucose (FBG) and 2-h postprandial glucose (2hPG) levels, as well as improved insulin resistance. Furthermore, combination therapy enhanced the efficacy rate and favorably altered lipid profiles, including increasing HDL-C and decreasing LDL-C, TC, and TG levels. It was worth noting that the results of the subgroup analysis indicated that, in terms of reducing HbA1c and 2hPG, the efficacy of HJD alone for a duration of less than 3 months was found to be potentially superior to that observed in treatments exceeding 3 months. Adverse event assessment suggested that HJD did not increase the incidence of side effects, including diarrhea, affirming its safety.

CONCLUSION: HJD appears to be an effective and safe alternative or adjunctive therapy for T2DM, showing significant improvements in glycemic control and lipid profiles without increasing adverse events. Further rigorous, multicenter RCTs outside China are warranted to validate these findings.

UNLABELLED: Diabetes mellitus Typ 2 (DMT2) ist eine weit verbreitete Stoffwechselerkrankung, und es besteht ein steigendes Interesse an den potenziellen Vorteilen der traditionellen chinesischen Medizin, wie beispielsweise Huanglian Jiedu-Dekokt (HJD), zu seiner Behandlung. Mit dieser Metaanalyse sollten die Wirksamkeit und Sicherheit von HJD zur Behandlung von DMT2 ermittelt werden.Es wurde eine systematische Recherche in sechs Datenbanken durchgeführt, darunter PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI) und Wanfang, für die Zeit vom Beginn der Datenbank bis zum 24. August 2023. Dabei lag unser Hauptaugenmerk auf randomisierten kontrollierten Studien (RCTs), die HJD sowohl als Monotherapie als auch in Kombinationstherapien bei Patienten mit DMT2 untersuchten. Die Datenanalyse erfolgte mithilfe von RevMan 5.3 und Stata 17.0 mit Untersuchungen auf Heterogenität und Publikationsverzerrungen. Darüber hinaus wurden Subgruppenanalysen stratifiziert nach Behandlungsdauer durchgeführt.Insgesamt wurden 40 Studien mit 3.934 Teilnehmern in die Metaanalyse eingeschlossen. HJD führte sowohl als Monotherapie als auch in Kombination mit anderen Therapien zu einer signifikanten Senkung des HbA1c-Nüchternblutzuckerspiegels (fasting blood glucose, FBG) und der postprandialen Blutzuckerwerte 2 Stunden nach dem Essen (2-h postprandial glucose, 2hPG) sowie zu einer Verbesserung der Insulinresistenz. Darüber hinaus verbesserte die Kombinationstherapie die Wirksamkeitsrate und führte zu einer positiven Veränderung der Lipidprofile, die eine Erhöhung der HDL-Cholesterinwerte und eine Senkung der LDL-, Gesamtcholesterin- und Trigylceridwerte einschloss. Erwähnenswert ist, dass nach den Ergebnissen der Subgruppenanalyse die Wirksamkeit von HJD als Monotherapie in Hinblick auf die Senkung der HbA1c- und 2hPG-Werte bei einer Behandlungsdauer von weniger als drei Monaten gegenüber derjenigen von Behandlungen, die länger als drei Monate dauerten, potenziell überlegen war. Die Bewertung der unerwünschten Ereignisse zeigte, dass HJD nicht zu einem Anstieg der Nebenwirkungen wie Durchfall führte, was seine Sicherheit bestätigte.HJD scheint eine wirksame und sichere Alternative oder Zusatztherapie bei DMT2 zu sein, die signifikante Verbesserungen der Blutzuckerkontrolle und der Lipidprofile ohne Zunahme der unerwünschten Ereignisse bewirkt. Weitere rigorose, multizentrische RCTs außerhalb Chinas sind erforderlich, um diese Ergebnisse zu validieren.},
}

@article {pmid38185101,
year = {2024},
author = {Huber, T and Krüerke, D and Simões-Wüst, AP},
title = {How Physicians and Nursing Staff Perceive Effectiveness and Tolerability of Bryophyllum Preparations: An Online Survey in an Anthroposophic Hospital.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {116-123},
doi = {10.1159/000536015},
pmid = {38185101},
issn = {2504-2106},
abstract = {BACKGROUND: Bryophyllum preparations are widely used in anthroposophic medicine, most often for mental and behavioural disorders. Three prospective studies have revealed positive effects of Bryophyllum pinnatum on sleep quality, and various trials have shown very good tolerability. Results from animal models have indicated CNS depressant and anxiolytic effects. This survey was conducted at the hospital "Klinik Arlesheim" in Switzerland to find out how the physicians and the nursing staff perceive the effectiveness and the tolerability of the Bryophyllum preparations they most frequently use.

DESIGN: Internal, anonymous online survey of healthcare professionals (April 8-May 31, 2022). The questionnaire comprised 105 multiple-choice questions. Answering the questions was taken as consent to participate in the survey.

PARTICIPANTS AND METHODS: All physicians and nursing staff with a valid email address at the hospital "Klinik Arlesheim AG" were invited via email to participate in this REDCap survey. The data were analysed descriptively.

RESULTS: Out of 266 invited participants, 48 answered some and 36 answered all questions (response rate between 18.0% and 13.5%). The participants had long experience with Bryophyllum preparations and were comprised approximately equal numbers of physicians and nursing staff. Various Bryophyllum preparations from the hospital's own production and Wala Heilmittel GmbH (in both cases produced from the species B. daigremontianum) and from Weleda AG (species B. pinnatum) were used. The indications for which most participants had prescribed or administered Bryophyllum preparations "very frequently" were anxiety, sleep disorders, crisis situations in oncology, posttraumatic stress disorder, benzodiazepine dependence/withdrawal, and depression. Improvements such as relief from restlessness, decreased anxiety, balance, easier falling asleep, better sleeping through, increased resilience, mood elevation, and less urge to move one's legs were reported "frequently" or "very frequently." Almost all participants agreed that Bryophyllum can be used to reduce the intake of synthetic sedatives or psychotropic drugs, but only approximately half believed that it could replace them. The majority of participants mentioned good tolerability of the various products, but a few reported occasional stomach or intestinal irritation, daytime fatigue, drowsiness, diarrhoea, and nausea.

CONCLUSION: Bryophyllum preparations are perceived as helpful in the treatment of various mental disorders, particularly anxiety, and are generally well tolerated. Most of these preparations are used for indications that have not yet been clinically investigated.

UNLABELLED: Bryophyllum-Präparate werden in der Anthroposophischen Medizin sehr häufig zur Behandlung von psychischen und Verhaltensstörungen eingesetzt. Drei prospektive Studien zeigten zudem positive Wirkungen von Bryophyllum pinnatum (BP) auf die Schlafqualität. Auch die Verträglichkeit wurde in allen bisherigen Studien als sehr gut bewertet. In Tiermodellen wurden ZNS-depressive und anxiolytische Effekte von BP festgestellt. Die hier durchgeführte Umfrage fand an der Klinik Arlesheim (Schweiz) statt. Sie diente dazu herauszufinden, wie Ärztinnen und Ärzte sowie das Pflegepersonal die Wirksamkeit und Verträglichkeit der von ihnen am häufigsten verwendeten Bryophyllum-Präparate wahrnehmen.Interne, anonyme, Online-Befragung unter ärztlichen und pflegerischen Fachkräften (8. April–31. Mai 2022). Der Fragebogen umfasste 105 Multiple-Choice-Fragen. Die Beantwortung der Fragen wurde als Zustimmung zur Teilnahme an der Umfrage interpretiert.Alle Ärztinnen, Ärzte und Pflegefachpersonen mit einer gültigen E-Mail-Adresse der “Klinik Arlesheim AG” wurden per E-Mail eingeladen, an dieser REDCap-Umfrage teilzunehmen. Die Daten wurden deskriptiv ausgewertet.Von den 266 eingeladenen Teilnehmenden beantworteten 48 einige und 36 alle Fragen (Antwortquote zwischen 18.0% und 13.5%). Die Teilnehmenden hatten langjährige Erfahrung mit Bryophyllum-Präparaten und setzten sich etwa zu gleichen Teilen aus ärztlichen und pflegerischen Fachkräften zusammen. Die Resultate zeigen, dass verschiedenste Bryophyllum-Präparate aus klinikeigener Herstellung, von der Wala Heilmittel GmbH (Art B. daigremontianum) und von der Weleda AG (Art B. pinnatum) verwendet werden. Zu den Indikationen, bei denen die meisten Teilnehmenden Bryophyllum-Präparate “sehr häufig” verordnet oder angewendet haben, gehören Angstzustände, Schlafstörungen, Krisensituationen in der Onkologie, Posttraumatische Belastungsstörung, Benzodiazepin-Abhängigkeit/Entzug und Depressionen. Gesundheitsverbesserungen wie Linderung von Unruhe, verminderte Angst, Ausgeglichenheit, leichteres Einschlafen, besseres Durchschlafen, erhöhte Belastbarkeit, Stimmungsaufhellung und weniger Drang, die Beine zu bewegen, wurden als “häufig” oder “sehr häufig” angegeben. Fast alle Teilnehmenden waren sich einig, dass Bryophyllum verwendet werden kann, um die Einnahme von synthetischen Beruhigungsmitteln oder Psychopharmaka zu reduzieren, aber nur etwa die Hälfte gab an, dass es diese ersetzen kann. Die Mehrheit der Teilnehmenden spricht von einer guten Verträglichkeit der verschiedenen Produkte. Einige wenige berichteten von gelegentlicher Magen- oder Darmreizung, Tagesmüdigkeit, Schläfrigkeit, Durchfall und Übelkeit.Bryophyllum-Präparate werden als hilfreich bei der Behandlung verschiedener psychischen Störungen, insbesondere bei Angstzuständen, angesehen und im Allgemeinen gut vertragen. Die meisten der angegebenen Präparate werden für Indikationen verwendet, die noch nicht klinisch untersucht worden sind.},
}

@article {pmid38052188,
year = {2024},
author = {Crowe, AL and Kerr, K and McAneney, H and McMullan, J and Duffy, G and McKnight, AJ},
title = {Stakeholder Perceptions of Complementary and Integrative Medicines from People Living with Rare Diseases in Northern Ireland: A Mixed Methods Study.},
journal = {Complementary medicine research},
volume = {31},
number = {2},
pages = {107-115},
doi = {10.1159/000535480},
pmid = {38052188},
issn = {2504-2106},
abstract = {INTRODUCTION: Only 5% of rare diseases have an approved treatment available, therefore patients often utilise complementary and integrative medicines (CIMs) to help manage their condition. Limited high-quality evidence-based studies are available which support the effectiveness of CIM, as it is difficult to show that an outcome is a direct result of the CIM intervention and not due to bias. Patients and healthcare professionals must weigh up the evidence quality, safety, efficacy, practical logistics, and financial implications of utilising CIM for rare diseases. This study aimed to elucidate perspectives of stakeholders (individuals with rare diseases, carers, family members, CIM practitioners and healthcare professionals), on the usage of CIM for rare diseases across Northern Ireland.

METHODS: This was a mixed methods study. An online survey was open from January to February 2019 (n = 29 responses). Themes identified from the survey were then discussed with stakeholders in a semi-structured discussion workshop in March 2019.

RESULTS: A limited number of participants responded to the survey (n = 29). Some individuals with rare diseases reported CIM as effective in the management of their condition, in particular acupuncture, dietary supplements, herbal medicines, homoeopathy, hydrotherapy, kinesiology, mindfulness, pilates, reflexology, tai chi, and yoga. However, a number of respondents (n = 7) experienced a negative side effect from CIM. Workshop participants raised concerns over the lack of information available about CIM and rare disease. Both the survey and workshop identified inequality of access with participants reporting CIM to be expensive.

CONCLUSIONS: More information, high-quality research, and education about CIM are required for patients and healthcare professionals to help make informed decisions about the usage of CIM for rare diseases. Improved communication, information, and health and social care in general would help individuals be more confident and knowledgeable about therapeutic options in relation to their rare disease(s).

UNLABELLED: Nur für fünf Prozent der seltenen Erkrankungen existiert eine zugelassene Behandlung, weshalb Patienten häufig komplementäre und integrative Medizin (CIM) nutzen, um ihre Krankheit zu behandeln. Es liegen nur wenige qualitativ hochwertige evidenzbasierte Studien vor, die die Wirksamkeit von CIM stützen, da sich schwer nachweisen lässt, dass ein Behandlungsergebnis direkt durch die CIM-Intervention bedingt und nicht Folge einer Verzerrung ist. Patienten und Angehörige der Gesundheitsberufe müssen die Qualität der Evidenz, die Sicherheit und Wirksamkeit sowie praktische logistische Aspekte und die finanziellen Folgen der Anwendung von CIM bei seltenen Erkrankungen abwägen. Mit der vorliegenden Studie sollte die Perspektive der Betroffenen (Menschen mit seltenen Erkrankungen, Betreuungspersonen, Familienangehörige, CIM-Praktiker und Angehörige der Gesundheitsberufe) in Bezug auf die Anwendung von CIM bei seltenen Erkrankungen in Nordirland untersucht werden.Es handelte sich um eine Studie mit gemischten Methoden. Eine Online-Umfrage war von Januar bis Februar 2019 geöffnet (n = 29 Antworten). Die in der Umfrage ermittelten Themen wurden anschließend im März 2019 im Rahmen eines halbstrukturierten Diskussionsworkshops mit den Betroffenen erörtert.Eine begrenzte Anzahl von Teilnehmern antwortete auf die Umfrage (n = 29). Einige Personen mit seltenen Erkrankungen gaben an, dass CIM bei der Behandlung ihrer Erkrankung wirksam war, insbesondere Akupunktur, Nahrungsergänzungsmittel, pflanzliche Arzneimittel, Homöopathie, Hydrotherapie, Kinesiologie, Achtsamkeit, Pilates, Reflexologie, Tai Chi und Yoga. Einige Befragte (n = 7) berichteten jedoch über negative Nebenwirkungen der CIM. Die Workshop-Teilnehmer äußerten Bedenken in Bezug auf den Mangel an Informationen über CIM und seltene Erkrankungen. Sowohl in der Umfrage als auch im Workshop zeigte sich eine Ungleichheit beim Zugang zu CIM und die Teilnehmer berichteten, dass CIM teuer sei.Patienten und Angehörige der Gesundheitsberufe benötigen mehr Informationen, qualitativ hochwertige Forschung und Aufklärung über CIM, um fundierte Entscheidungen über die Anwendung von CIM bei seltenen Erkrankungen treffen zu können. Eine bessere Kommunikation, Information sowie gesundheitliche und soziale Versorgung im Allgemeinen würden zu mehr Selbstvertrauen und Wissen der Betroffenen über die therapeutischen Möglichkeiten im Zusammenhang mit ihrer seltenen Erkrankung beitragen.},
}