Neuroprotective Effects, Mechanisms of Action and Therapeutic Potential of the Kv7/KCNQ Channel Opener QO-83 in Ischemic Stroke.

Ischemic stroke is a worldwide disease with high mortality and morbidity. Kv7/KCNQ channels are key modulators of neuronal excitability and microglia function, and activation of Kv7/KCNQ channels has emerged as a potential therapeutic avenue for ischemic stroke. In the present study, we focused on a new Kv7/KCNQ channel opener QO-83 on the stroke outcomes and its therapeutic potential.

Prospective Harmonization, Common Data Elements, and Sharing Strategies for Multicenter Pre-Clinical Traumatic Brain Injury Research in the Translational Outcomes Project in Neurotrauma Consortium.

Effective team science requires procedural harmonization for rigor and reproducibility. Multicenter studies across experimental modalities (domains) can help accelerate translation. The Translational Outcomes Project in NeuroTrauma (TOP-NT) is a pre-clinical traumatic brain injury (TBI) consortium charged with establishing and validating noninvasive TBI assessment tools through team science.

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.

Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment.

Soluble guanylate cyclase (sGC) stands as a pivotal regulatory element in intracellular signalling pathways, mediating the formation of cyclic guanosine monophosphate (cGMP) and impacting diverse physiological processes across tissues. Increased formation of reactive oxygen species (ROS) is widely recognized to modulate cGMP signalling. Indeed, oxidatively damaged, and therefore inactive sGC, contributes to poor vascular reactivity and more severe neurological damage upon stroke.

The clinical diagnostic value of right-to-left shunt in cryptogenic stroke under right heart contrast echocardiography: a retrospective case-control study.

Background: About 30% of ischemic strokes do not have a clear cause, which is called cryptogenic stroke (CS). Increasing evidence suggests a potential link between CS and right-to-left shunt (RLS). RLS may lead to CS via paradoxical embolic mechanism.

The Role of Atrial Fibrillation and Oral Anticoagulation Status in Health-Related Quality of Life 12 Months After Ischemic Stroke or TIA.

Aims: Atrial fibrillation (AF) accounts for about 20% of all ischemic strokes worldwide. It is known that AF impairs health-related quality of life (HRQOL) in the general population, but data on HRQOL in stroke patients with newly diagnosed AF are sparse.

Methods: Post hoc analysis of the prospective, investigator-initiated, multicenter MonDAFIS study (NCT02204267) to analyze whether AF-related oral anticoagulation (OAC), and/or AF-symptom severity are associated with HRQOL after ischemic stroke or transient ischemic attack (TIA).

Building a growing genomic repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Of note, prenatal Zika infection can cause a spectrum of neurodevelopmental disorders, including congenital Zika syndrome.

Neuroticism and cerebral small vessel disease: A genetic correlation and Mendelian randomization analysis.

Objectives: The association of neuroticism and cerebral small vessel disease (CSVD) development remains unclear. In this study, we used Mendelian randomization (MR) to explore the potential role of neuroticism in CSVD development.

Methods: We collected data on ischemic stroke (IS); small vessel stroke (SVS); three neuroimaging markers altered in CSVD, including white matter hyperintensity (WMH), fractional anisotropy (FA), and mean diffusivity (MD); and three neuroticism clusters, including depressed affect, worry, sensitivity to environmental stress and adversity (SESA), from large-scale genome-wide association studies (GWAS).

Epstein-Barr virus infection in patients with MOGAD.

Background: Epstein-Barr virus (EBV) infection increases the risk of having multiple sclerosis (MS). Data on adults with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are lacking.

Objective: To compare EBV serological status in MOGAD versus MS.

The effects of Dapagliflozin in a real-world population of HFrEF patients with different hemodynamic profiles: worse is better.

Background: Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) represent a deep revolution of the therapeutic approach to heart failure (HF), preventing its insurgence but also improving the management of the disease and slowing its natural progression. To date, few studies have explored the effectiveness of SGLT2i and, in particular, Dapagliflozin in a real-world population. Therefore, in this observational prospective study, we evaluated Dapagliflozin's effectiveness in a real-world HF population categorized in the different hemodynamic profiles.

The bile acid chenodeoxycholic acid associates with reduced stroke in humans and mice.

Bile acids are liver-derived signaling molecules that can be found in the brain, but their role there remains largely unknown. We found increased brain chenodeoxycholic acid (CDCA) in mice with absent 12α-hydroxylase (Cyp8b1), a bile acid synthesis enzyme. In these Cyp8b1, and in Wt mice administered CDCA, stroke infarct area was reduced.

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

Association of urban environments with Atherosclerotic cardiovascular disease: A prospective cohort study in the UK Biobank.

Urban environments and cardiovascular health are closely linked, yet only a few specific exposures have been explored in isolation and mostly adopting cross-sectional design. The influence of socioeconomic status and genetic predisposition also remains unclear. Hence, leveraging the UK Biobank data (n = 206,681), we conducted a prospective analysis of 213 urban environmental variables and their association with atherosclerotic cardiovascular disease (ASCVD).

Sensitivity evaluation of an optical microfiber featuring interfaces with various gold nanoparticle morphologies: Application to the GFAP detection.

Glial fibrillary acidic protein (GFAP) is a specific blood biomarker for various neurological diseases, including traumatic brain injury (TBI). In this study, we present a cost-effective, portable, and label-free biosensing method for the sensitive and rapid detection of GFAP in body fluids. As the sensitivity of current optical fiber sensors is insufficient to detect the ultralow concentration of GFAP in early body fluids, interfaces of gold nanoparticles with various morphologies were employed to improve the sensitivity of sensor.

Venous aneurysms in unruptured supratentorial brain arteriovenous malformations: a protective factor against hemorrhagic stroke and insights into hemodynamic mechanisms.

Objective: This study endeavors to clarify the impact of venous aneurysms (VA) on hemorrhagic risk in brain arteriovenous malformations (AVMs) and uncover potential hemodynamic mechanisms, utilizing quantitative digital subtraction angiography (QDSA) technology and survival dataset.

Methods: Patients were enrolled in a multicenter prospective collaboration registry between August 2011 and August 2021, and subsequently categorized into the VA and non-VA cohorts. Using propensity score-matched survival analysis, we quantitatively assessed the natural risk of hemorrhagic stroke in these two cohorts.

Positive association between constipation and mild cognitive impairment in elders: A cross-sectional study.

This study aimed to examine the association between constipation and mild cognitive impairment (MCI); and further elucidate the possible mechanisms involved. A cross-sectional study was conducted among community-dwelling elders (N = 789) in Nanning, China. Trained research staffs collected detailed information through questionnaires and physical examinations.

A global effort to benchmark predictive models and reveal mechanistic diversity in long-term stroke outcomes.

Stroke remains a leading cause of mortality and long-term disability worldwide, with variable recovery trajectories posing substantial challenges in anticipating post-event care and rehabilitation planning. In response, we established the NeuralCup consortium to address these challenges by benchmarking predictive models of stroke outcome through a collaborative, data-driven approach. This study presents the findings of 15 participating teams worldwide who used a comprehensive dataset including clinical and imaging data, to identify and compare predictors of motor, cognitive, and emotional outcomes one-year post-stroke.

Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target.

Cardiac fibrosis impairs cardiac function, but no effective clinical therapies exist. To address this unmet need, we employed a high-throughput screening for antifibrotic compounds using human induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts (CFs). Counter-screening of the initial candidates using iPSC-derived cardiomyocytes and iPSC-derived endothelial cells excluded hits with cardiotoxicity.

Alterations of Nutrient Elements in Hepatocellular Carcinoma Patients Treated with Atezolizumab-Bevacizumab.

Currently, the combination of atezolizumab and bevacizumab (Atez/Bev) is recommended as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC). However, there is a lack of research on the levels of nutrient elements in advanced HCC patients receiving Atez/Bev treatment. In this study, data from 35 patients with advanced HCC and 37 healthy individuals of similar age and sex were included.