Subcortical Volumes as Early Predictors of Fatigue in Multiple Sclerosis.

Objective: Fatigue is a frequent and severe symptom in multiple sclerosis (MS), but its pathophysiological origin remains incompletely understood. We aimed to examine the predictive value of subcortical gray matter volumes for fatigue severity at disease onset and after 4 years by applying structural equation modeling (SEM).

Methods: This multicenter cohort study included 601 treatment-naive patients with MS after the first demyelinating event.

Time for change in research careers: We as research organizations doing everything we can for postdocs?: Are we as research organizations doing everything we can for postdocs?

Postdocs are at a challenging step in the career ladder and research organisations could do more to help them along the way.

Anatomical and functional visual network patterns in progressive multiple sclerosis.

The gradual accrual of disability over time in progressive multiple sclerosis is believed to be driven by widespread degeneration. Yet another facet of the problem may reside in the loss of the brain's ability to adapt to the damage incurred as the disease progresses. In this study, we attempted to examine whether changes associated with optic neuritis in the structural and functional visual networks can still be discerned in progressive patients even years after the acute insult.

Seasonal variation in attacks of neuromyelitis optica spectrum disorders and multiple sclerosis: Evaluation of 794 attacks from a nationwide registry in Argentina.

Background: Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders.

Methods: A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients.

The SEQC2 epigenomics quality control (EpiQC) study.

Background: Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA's Epigenomics Quality Control Group.

Immune signature of multiple sclerosis-associated depression.

Multiple neurobiological pathways have been implicated in the pathobiology of major depressive disorder (MDD). The identification of reliable biological substrates across the entire MDD spectrum, however, is hampered by a vast heterogeneity in the clinical presentation, presumably as a consequence of heterogeneous pathobiology. One way to overcome this limitation could be to explore disease subtypes based on biological similarity such as "inflammatory depression".

Frailty and Falls in People Living With Multiple Sclerosis.

Objective: To explore the association between frailty and history of falls in people living with multiple sclerosis (MS).

Design: Secondary analysis.

Setting: University research laboratories in the United States and Israel.

Diffusion-weighted magnetic resonance imaging in rat kidney using two-dimensional navigated, interleaved echo-planar imaging at 7.0 T.

The purpose of this study was to investigate the feasibility of two-dimensional (2D) navigated, interleaved multishot echo-planar imaging (EPI) to enhance kidney diffusion-weighted imaging (DWI) in rats at 7.0 T. Fully sampled interleaved four-shot EPI with 2D navigators was tailored for kidney DWI (Sprague-Dawley rats, n = 7) on a 7.

SORLA is required for insulin-induced expansion of the adipocyte precursor pool in visceral fat.

Visceral adipose tissue shows remarkable plasticity, constantly replacing mature adipocytes from an inherent pool of adipocyte precursors. The number of precursors is set in the juvenile organism and remains constant in adult life. Which signals drive precursor pool expansion in juveniles and why they operate in visceral but not in subcutaneous white adipose tissue (WAT) are unclear.

Network Meta-analysis of Food and Drug Administration-approved Treatment Options for Adults with Aquaporin-4 Immunoglobulin G-positive Neuromyelitis Optica Spectrum Disorder.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease defined by attacks on the central nervous system that cause irreversible damage. Recent approval of NMOSD therapies warrants investigations of comparative efficacy to inform treatment decisions.

Methods: A network meta-analysis (NMA) of all U.

Reduced mitochondrial respiration in T cells of patients with major depressive disorder.

Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC).

Impact of Dietary Intervention on Serum Neurofilament Light Chain in Multiple Sclerosis.

Background And Objectives: Adapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for multiple sclerosis (MS), but information on their impact on neuroaxonal damage is lacking. Thus, we explored the impact of diets on serum neurofilament light chain (sNfL) levels in patients with relapsing-remitting MS.

Methods: We retrospectively evaluated a prospective randomized controlled trial of 60 patients with MS who were on a common diet or ketogenic diet or fasting.

Progressive myocardial injury in myotonic dystrophy type II and facioscapulohumeral muscular dystrophy 1: a cardiovascular magnetic resonance follow-up study.

Aim: Muscular dystrophy (MD) is a progressive disease with predominantly muscular symptoms. Myotonic dystrophy type II (MD2) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) are gaining an increasing awareness, but data on cardiac involvement are conflicting. The aim of this study was to determine a progression of cardiac remodeling in both entities by applying cardiovascular magnetic resonance (CMR) and evaluate its potential relation to arrhythmias as well as to conduction abnormalities.

A medullary centre for lapping in mice.

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRt and Peri5, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve.

GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium.

Growth arrest-specific 1 (GAS1) acts as a co-receptor to patched 1, promoting sonic hedgehog (SHH) signaling in the developing nervous system. GAS1 mutations in humans and animal models result in forebrain and craniofacial malformations, defects ascribed to a function for GAS1 in SHH signaling during early neurulation. Here, we confirm loss of SHH activity in the forebrain neuroepithelium in GAS1-deficient mice and in induced pluripotent stem cell-derived cell models of human neuroepithelial differentiation.

Characteristics of secondary progressive multiple sclerosis: Disease activity and provision of care in Germany - A registry-based/multicentric cohort study.

Background: The tailored immunomodulatory treatment strategy for secondary progressive multiple sclerosis (SPMS) depends on disease activity.

Objective: To assess the real-world situation in monitoring disease activity in SPMS patients and to identify associations of resulting subgroups with demographics, symptomatology, and therapy METHODS: This study included 4,263 SPMS patients from the German MS register (GMSR). For the classification into 'active' and 'inactive' according to relapse activity and MRI findings during the year prior to the latest clinical visit, we used the following definitions: active - gadolinium enhancing (Gd+)/new T2 lesions or ≥1 relapse, inactive - neither Gd+/new T2 lesions nor relapses.

ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling.

Sortilin is a neuronal receptor for apolipoprotein E (apoE). Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with the apoE3 variant but is lost with the apoE4 variant, the main risk factor for Alzheimer's disease (AD).

Reduction of cortical parvalbumin-expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition.

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the underlying mechanisms are not known. In a translational hyperoxia model, exposing mice pups at P5 to 80% oxygen for 48 h to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin-expressing interneurons until adulthood.

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing.

Dataset for: Modeling chemotherapy induced neurotoxicity with human induced pluripotent stem cell (iPSC)-derived sensory neurons.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and potentially irreversible adverse event of cytotoxic chemotherapy. We evaluate whether sensory neurons derived from induced pluripotent stem cells (iPSC-DSN) can serve as human disease model system for chemotherapy induced neurotoxicity. Sensory neurons differentiated from two established induced pluripotent stem cell lines were used (s.

Cross-reactive CD4 T cells enhance SARS-CoV-2 immune responses upon infection and vaccination.

The functional relevance of preexisting cross-immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)–reactive and SARS-CoV-2–cross-reactive CD4 T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that preexisting spike- and S816-830–reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti–SARS-CoV-2-S1-IgG antibodies.