Integrated analysis of the prevalence and influencing factors of poststroke dysphagia.

Objectives: Poststroke dysphagia (PSD) is a common complication after stroke but there is limited information on its global prevalence and influencing factors, such as spatial, temporal, demographic characteristics, and stroke-related factors. Our study seeks to fill this knowledge gap by exploring the overall prevalence of PSD and its influencing factors.

Methods: A search of English-language literature from database inception from 2005 until May 2022 was performed using PubMed, Embase, Web of Science, Cochrane Library, and Scopus.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

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.

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.

Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma.

The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.

14-3-3θ phosphorylation exacerbates alpha-synuclein aggregation and toxicity.

Aggregation of alpha-synuclein (αsyn) plays an integral role in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). 14-3-3θ is a highly expressed brain protein with chaperone-like activity that regulates αsyn folding. 14-3-3θ overexpression reduces αsyn aggregation, transmission between cells, and neuronal loss, while 14-3-3 inhibition promotes αsyn pathology.

Pathophysiological Significance of α-Synuclein in Sympathetic Nerves: In Vivo Observations.

Background And Objectives: Lewy body diseases (LBDs) such as Parkinson disease (PD) feature increased deposition of α-synuclein (α-syn) in cutaneous sympathetic noradrenergic nerves. The pathophysiologic significance of sympathetic intraneuronal α-syn is unclear. We reviewed data about immunoreactive α-syn, tyrosine hydroxylase (TH, a marker of catecholaminergic fibers), and the sympathetic neurotransmitter norepinephrine (NE) in skin biopsies from control participants and patients with PD, the related LBD pure autonomic failure (PAF), the non-LBD synucleinopathy multiple system atrophy (MSA), or neurologic postacute sequelae of severe acute respiratory syndrome coronavirus 2 (neuro-PASC).

Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.

Background And Objectives: Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.

Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease.

It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian and European ancestries to show that genes causing neurodegeneration are preferentially expressed in innate rather than adaptive immune cells, and that expression of these genes mediates the risk of neurodegenerative disease in monocytes in an ancestry-specific manner.

Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance.

Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice.

Introduction: In USA, six million individuals with Sub-Saharan ancestry carry two high-risk variants, which increase the risk for kidney diseases. Whether APOL1 high-risk variants are independent risk factors for cardiovascular diseases is unclear and requires further investigation.

Methods: We characterized a mouse model to investigate the role of APOL1 in dyslipidemia and cardiovascular diseases.

ENDOTHELIAL PROX1 INDUCES BLOOD-BRAIN BARRIER DISRUPTION IN THE CENTRAL NERVOUS SYSTEM.

The central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific overexpression mutants.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in .

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (). This variant (rs3115534-G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups, but is almost absent in European and Asian ancestry populations.

Structural variation in nebulin and its implications on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.

Introduction: Structural variants (SVs) of the nebulin gene (), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in .

Genetic regulation of splicing contributes to reduced or elevated cancer risk by altering cellular longevity and replicative potential.

The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.

Sleep macro-architecture and dementia risk in adults: Meta-analysis of 5 cohorts from the Sleep and Dementia Consortium.

Study Objectives: Poor sleep may play a role in the risk of dementia. However, few studies have investigated the association between polysomnography (PSG)-derived sleep architecture and dementia incidence. We examined the relationship between sleep macro-architecture and dementia incidence across five US-based cohort studies from the Sleep and Dementia Consortium (SDC).

Impact of the COVID-19 pandemic on cerebral venous sinus thrombosis in China: a comparative study.

Background: Cerebral venous sinus thrombosis (CVST) is a rare yet significant neurological disorder with high mortality. Understanding its evolving characteristics, risk factors, and outcomes, particularly in Chinese patients after the COVID-19 pandemic, is critical for developing effective preventive and therapeutic strategies.

Methods: A retrospective analysis was conducted on 471 CVST cases from Xuanwu Hospital, comparing data before (2013-2017, n = 243) and after (2021-2023, n = 228) the COVID-19 pandemic.

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Synapse-specific catecholaminergic modulation of neuronal glutamate release.

Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, larvae switch activity in type II octopaminergic motor neurons (MNs) to high-frequency bursts, which coincide with locomotion-driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the G-coupled octopamine receptor (OAMB).

"In the spectrum of people who are healthy": Views of individuals at risk of dementia on using neurotechnology for cognitive enhancement.

Neurotechnological cognitive enhancement has become an area of intense scientific, policy, and ethical interest. However, while work has increasingly focused on ethical views of the general public, less studied are those with personal connections to cognitive impairment. Using a mixed-methods design, we surveyed attitudes regarding implantable neurotechnological cognitive enhancement in individuals who self-identified as having increased likelihood of developing dementia (n=25; 'Our Study'), compared to a nationally representative sample of Americans (n=4726; 'Pew Study').

Sarcolemma resilience and skeletal muscle health require O-mannosylation of dystroglycan.

Background: Maintaining the connection between skeletal muscle fibers and the surrounding basement membrane is essential for muscle function. Dystroglycan (DG) serves as a basement membrane extracellular matrix (ECM) receptor in many cells, and is also expressed in the outward-facing membrane, or sarcolemma, of skeletal muscle fibers. DG is a transmembrane protein comprised of two subunits: alpha-DG (α-DG), which resides in the peripheral membrane, and beta-DG (β-DG), which spans the membrane to intracellular regions.

RNA dysregulation in neurodegenerative diseases.

Dysregulation of RNA processing has in recent years emerged as a significant contributor to neurodegeneration. The diverse mechanisms and molecular functions underlying RNA processing underscore the essential role of RNA regulation in maintaining neuronal health and function. RNA molecules are bound by RNA-binding proteins (RBPs), and interactions between RNAs and RBPs are commonly affected in neurodegeneration.

Molecular logic for cellular specializations that initiate the auditory parallel processing pathways.

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity.