Blood pressure targets, medication considerations and special concerns in elderly hypertension III: Focus on stroke and neurodegenerative disorders.

Controlling hypertension has become an important issue in the elderly population in whom neurological comorbidities are highly prevalent. Most of the large-scale trials focusing on hypertension management in older populations have excluded patients with comorbid neurological disorders. However, this population requires special considerations, as the benefits of antihypertensive agents are mostly uncertain and there is a higher risk of adverse events.

Prognostic Impact of 1-Year Changes in Creatinine- and Cystatin C-Based Estimated Glomerular Filtration Rate After Stroke on 5-Year Outcomes: Insights From the Third China National Stroke Registry.

Background: The impact of long-term renal function change on stroke outcomes remains unclear. This study used the CNSR-III (Third China National Stroke Registry) cohort to determine whether changes in estimated glomerular filtration rate based on creatinine and cystatin C (eGFR) during the first year post stroke were associated with 5-year stroke outcomes.

Methods And Results: We included 4270 patients with centrally tested serum creatinine and cystatin C at admission and 1 year post admission and evaluated 5-year follow-up data.

Elevated Cerebrospinal Fluid α-Synuclein Seeding Activity Predicts Central Lewy Body Diseases.

Background: Cerebrospinal fluid (CSF) α-synuclein seeding activity (SSA) via a seed amplification assay might predict central Lewy body diseases (LBD) in at-risk individuals.

Objective: The aim was to assess CSF SSA in a prospective, longitudinal study.

Methods: Participants self-reported risk factors were genetics, olfactory dysfunction, dream enactment behavior, orthostatic intolerance, or hypotension; individuals who had ≥3 confirmed risk factors underwent CSF sampling and were followed for up to 7.

Diagnosing Epilepsy with Normal Interictal EEG Using Dynamic Network Models.

Objective: Whereas a scalp electroencephalogram (EEG) is important for diagnosing epilepsy, a single routine EEG is limited in its diagnostic value. Only a small percentage of routine EEGs show interictal epileptiform discharges (IEDs) and overall misdiagnosis rates of epilepsy are 20% to 30%. We aim to demonstrate how network properties in EEG recordings can be used to improve the speed and accuracy differentiating epilepsy from mimics, such as functional seizures - even in the absence of IEDs.

Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study.

Introduction: Managing idiopathic intracranial hypertension (IIH) is challenging due to limited treatment options. This study evaluates metformin as a potential therapy for IIH, examining its impact on disease outcomes and safety.

Methods: We performed a retrospective cohort study using the TriNetX database, covering data from 2009 to August 2024.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

High-Field-Blinded Assessment of Portable Ultra-Low-Field Brain MRI for Multiple Sclerosis.

Background And Purpose: MRI is crucial for multiple sclerosis (MS), but the relative value of portable ultra-low field MRI (pULF-MRI), a technology that holds promise for extending access to MRI, is unknown. We assessed white matter lesion (WML) detection on pULF-MRI compared to high-field MRI (HF-MRI), focusing on blinded assessments, assessor self-training, and multiplanar acquisitions.

Methods: Fifty-five adults with MS underwent pULF-MRI following their HF-MRI.

The TRP Channels Serving as Chemical-to-Electrical Signal Converter.

Biology uses many signaling mechanisms. Among them, calcium and membrane potential are two prominent mediators for cellular signaling. TRPM4 and TRPM5, two calcium-activated monovalent cation-conducting ion channels, offer a direct linkage between these two signals.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease.

Introduction: This study aimed to identify cognitive tests that optimally relate to tau positron emission tomography (PET) signal in the inferior temporal cortex (ITC), a neocortical region associated with early tau accumulation in Alzheimer's disease (AD).

Methods: We analyzed cross-sectional data from the harvard aging brain study (HABS) (= 128) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study (= 393). We used elastic net regression to identify the most robust cognitive correlates of tau PET signal in the ITC.

Dense-core vesicles contain exosomes in secretory cells.

Dense-core vesicles (DCVs) are found in various types of cells, such as neurons, pancreatic β-cells, and chromaffin cells. These vesicles release transmitters, peptides, and hormones to regulate diverse functions, such as the stress response, immune response, behavior, and blood glucose levels. In traditional electron microscopy after chemical fixation, it is often reported that the dense cores occupy a portion of the vesicle towards the center and are surrounded by a clear halo.

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.

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.

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.