Maternal Gut Inflammation Aggravates Acute Liver Failure Through Facilitating Ferroptosis via Altering Gut Microbial Metabolism in Offspring.

Microbial transmission from mother to infant is important for offspring microbiome formation and health. However, it is unclear whether maternal gut inflammation (MGI) during lactation influences mother-to-infant microbial transmission and offspring microbiota and disease susceptibility. In this study, it is found that MGI during lactation altered the gut microbiota of suckling pups by shaping the maternal microbiota in the gut and mammary glands.

Machine learning validation of a simple prediction model for the correlation between advanced age and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage.

Adverse effects of advanced age and poor initial neurological status on outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH) have been documented. While a predictive model of the non-linear correlation between advanced age and clinical outcome has been reported, no previous model has been validated. Therefore, we created a prediction model of the non-linear correlation between advanced age and clinical outcome by machine learning and validated it using a separate cohort.

"The M-APNE score: an objective screening tool for OSA highlighting the area under the inspiratory flow-volume curve".

Background: Polysomnography (PSG) is resource-intensive but remains the gold standard for diagnosing Obstructive Sleep Apnea (OSA). We aimed to develop a screening tool to better allocate resources by identifying individuals at higher risk for OSA, overcoming limitations of current tools that may under-diagnose based on self-reported symptoms.

Methods: A total of 884 patients (490 diagnosed with OSA) were included, which was divided into the training, validation, and test sets.

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010-2021.

Background And Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2.

Myotonic Dystrophy type 2 (DM2) is a multisystem disease affecting many tissues, including skeletal muscle, heart, and brain. DM2 is caused by unstable expansion of CCTG repeats in an intron 1 of a gene coding for cellular nuclear binding protein (CNBP). The expanded CCTG repeats cause DM2 pathology due to the accumulation of RNA CCUG repeats, which affect RNA processing in patients' cells.

Inhibition of IFITM3 in cerebrovascular endothelium alleviates Alzheimer's-related phenotypes.

Introduction: Interferon-induced transmembrane protein 3 (IFITM3) modulates γ-secretase in Alzheimer's Disease (AD). Although IFITM3 knockout reduces amyloid β protein (Aβ) production, its cell-specific effect on AD remains unclear.

Methods: Single nucleus RNA sequencing (snRNA-seq) was used to assess IFITM3 expression.

Early Versus Delayed Antihypertensive Treatment After Acute Ischemic Stroke by Hypertension History.

Background: We performed a prespecified subgroup analysis of the CATIS-2 trial (China Antihypertensive Trial in Acute Ischemic Stroke II) to compare the effect of early versus delayed antihypertensive treatment on death and disability in patients with and without medical history of hypertension.

Methods: CATIS-2 is a multicenter randomized clinical trial conducted in 106 hospitals in China. The trial randomized 4810 patients with acute ischemic stroke within 24 to 48 hours of symptom onset and elevated systolic blood pressure between 140 and <220 mm Hg to receive antihypertensive treatment immediately after randomization or to discontinue antihypertensive medications for 7 days and then receive treatment on day 8.

Usefulness of Myelin Quantification Using Synthetic Magnetic Resonance Imaging for Predicting Outcomes in Patients With Acute Ischemic Stroke.

Background: Synthetic magnetic resonance imaging (MRI) is an innovative MRI technology that enables the acquisition of multiple quantitative values, including T1 and T2 values, proton density, and myelin volume, in a single scan. Although the usefulness of myelin measurement with synthetic MRI has been reported for assessing several diseases, investigations in patients with stroke have not been reported. We aimed to explore the utility of myelin quantification using synthetic MRI in predicting outcomes in patients with acute ischemic stroke.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Effects of Genetic Risk and Lifestyle Habits on Gout: A Korean Cohort Study.

Background: Gout is a type of inflammatory arthritis caused by monosodium urate crystal deposits, and the prevalence of this condition has been increasing. This study aimed to determine the combined effects of genetic risk factors and lifestyle habits on gout, using data from a Korean cohort study. Identifying high-risk individuals in advance can help prevent gout and its associated disorders.

Intracerebral hemorrhage in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. This review highlights the increasing recognition of intracerebral hemorrhage (ICH) as a significant manifestation of CADASIL, often predominantly characterized by ischemic strokes and vascular dementia. Recent studies indicate that the prevalence of ICH in CADASIL patients ranges from 0.

Relationship between LE8 score and peripheral arterial disease from NHANES perspective.

This study examined the link between the Life's Essential 8 (LE8) metric and peripheral artery disease (PAD) prevalence in the U.S. This population-based prospective cohort study analyzed data from 6,076 participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004.

Association between forced expiratory volume in 1 s and relapse-free survival in operable non-small cell lung cancer: a prospective cohort study with propensity score overlap weighting.

Objectives: Investigate the correlation between the percentage of predicted forced expiratory volume in 1 s (FEV1%pred) and survival outcomes, namely relapse-free survival (RFS) and overall survival (OS), in patients diagnosed with operable early-stage non-small cell lung cancer (NSCLC).

Design: Prospective observational study.

Setting: Clinical settings in Xiangya Hospital, Central South University, Hunan, China.

Temporal Lobe Epilepsy Perturbs the Brain-Wide Excitation-Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction.

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models.

PAK3 pathogenic variant associated with sleep-related hypermotor epilepsy in a family with parental mosaicism.

Protein-activated kinases mediate spine morphogenesis and synaptic plasticity. PAK3 is part of the p21-activated kinases (PAKs) family of Ras-signaling serine/threonine kinases. Pathogenic variants in the X-linked gene PAK3 have been described in patients with neurodevelopmental syndromes.

Combined 25-hydroxyvitamin D concentrations and physical activity on mortality in US stroke survivors: findings from the NHANES.

Background: 25-hydroxyvitamin D [25(OH)D] concentrations and physical activity (PA) are linked and both are associated with changes in mortality. We examined the association of 25(OH)D and PA with all-cause or cause-specific mortality risk in stroke survivors.

Methods: The analysis included 677 stroke survivors from National Health and Nutrition Examination Survey (NHANES) 2007-2008 to 2017-2018.

Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm.

Remote, digital cognitive testing on an individual's own device provides the opportunity to deploy previously understudied but promising cognitive paradigms in preclinical Alzheimer's disease (AD). The Boston Remote Assessment for NeuroCognitive Health (BRANCH) captures a personalized learning curve for the same information presented over seven consecutive days. Here, we examined BRANCH multi-day learning curves (MDLCs) in 167 cognitively unimpaired older adults (age = 74.

Glycogen synthase GYS1 overactivation contributes to glycogen insolubility and malto-oligoglucan-associated neurodegenerative disease.

Polyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD.

E3 ubiquitin ligase CHIP facilitates cAMP and cGMP signalling cross-talk by polyubiquitinating PDE9A.

The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a valid, highly utilized measure for assessing ADL impacts in patients with Friedreich ataxia. We provide evidence of the psychometric validity of the FARS-ADL in two cohorts of patients with spinocerebellar ataxia (SCA).

Methods: Using data from a cohort of real-world subjects with SCA (recruited at Massachusetts General Hospital [MGH]; n = 33) and a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), comprising a subset of patients with the SCA3 genotype (n = 89), the psychometric measurement properties and minimal change thresholds of the FARS-ADL were examined.

Lifetime risk and projected burden of dementia.

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.