Statins in Acute Ischemic Stroke: Mechanisms, Resistance, and Precision Strategies for Neurovascular and Cognitive Protection.

Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline.

Brexpiprazole for the Treatment of Agitation in Older Adults with Alzheimer's Disease: A Systematic Review, Bayesian Meta-analysis, and Meta-regression.

Background: Agitation is a common and distressing neuropsychiatric symptom in Alzheimer's disease (AD), affecting up to half of patients and contributing to faster cognitive decline and caregiver burden. Brexpiprazole, a serotonin-dopamine modulator, has been evaluated for this indication, but uncertainties remain regarding its efficacy, safety, and appropriate use in older adults.

Objective: We aimed to assess the efficacy and safety of brexpiprazole for the treatment of agitation in older adults with AD through a systematic review and meta-analysis of randomized controlled trials (RCTs).

Signature White Matter Hyperintensity Locations Associated With Vascular Risk Factors Derived From 15 653 Individuals.

Background: White matter hyperintensities (WMHs) of presumed vascular origin are common in the elderly and are associated with vascular risk factors. There is evidence that vascular risk factors, in particular hypertension, are associated with WMH in particular locations of the white matter. However, it remains unclear whether this is true for all risk factors and whether signature WMH locations differ between risk factors.

Brain-computer interfaces as a causal probe for scientific inquiry.

Establishing causal relationships between neural activity and brain function requires experimental perturbations of neural activity. Many existing perturbation methods modify activity by directly applying external signals to the brain. We review an alternative approach where brain-computer interfaces (BCIs) leverage volitional control of neural activity to manipulate and causally perturb it.

Pulmonary Embolism in Acute Ischaemic Stroke: Evolving Evidence, Diagnostic Challenges, and a Novel Thromboinflammatory Axis Hypothesis.

Pulmonary embolism (PE) is an under-recognised yet serious complication in patients with acute ischaemic stroke (AIS), contributing significantly to morbidity and mortality. The interplay of traditional risk factors-such as immobility, endothelial dysfunction, and hypercoagulability-with AIS-specific conditions, including atrial fibrillation, malignancy, and reperfusion therapies, complicates both diagnosis and management. Despite available prophylactic strategies, including low-molecular-weight heparin and intermittent pneumatic compression, their use remains limited by bleeding concerns and a lack of tailored guidelines.

Immunosuppressant Use in Infective Endocarditis-Associated Glomerulonephritis: A Systematic Review.

Background: Patients with infective endocarditis can develop various renal diseases, including infective endocarditis-associated glomerulonephritis. Antibiotics are essential for eradicating the infection. However, the prognosis for renal function remains poor.

Perinatal Arterial Stroke Treated With Stromal Cells Intranasally: 2-Year Safety and Neurodevelopment.

Background: The PASSIoN study (Perinatal Arterial Stroke Treated With Stromal Cells Intranasally) demonstrated the feasibility and short-term safety of single-dose allogeneic mesenchymal stromal cells (MSCs) administered intranasally to neonates with perinatal arterial ischemic stroke between February 2020 and April 2021. In this study, we assessed long-term safety and neurodevelopmental outcomes and explored outcome differences with a non-MSC-treated cohort.

Methods: In this post hoc analysis, we evaluated the safety of MSC administration by assessing brain tissue loss, adverse events, and neurodevelopmental outcomes of PASSIoN participants (N=10).

Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial.

Background And Objectives: Cerebral cavernous malformations (CCMs) are vascular lesions of the brain that can lead to hemorrhage, focal neurologic deficits, and seizures. Rho-associated kinase (ROCK) overactivation plays a critical role in the development of CCMs, and a novel, selective ROCK2 inhibitor, NRL-1049, mitigated lesion burden and bleeding in mouse models of CCM. This study examined the safety, tolerability, and pharmacokinetics of NRL-1049 in healthy volunteers.

Development of a novel physiologically based biopharmaceutics modeling (PBBM) framework using the open systems pharmacology suite, part 2: in vivo pharmacokinetic modeling of vericiguat.

This manuscript introduces a novel, free and open-source physiologically based biopharmaceutics modeling (PBBM) workflow to support decision-making during oral drug product development. Developed within the Open Systems Pharmacology (OSP) framework, this workflow combines three open-source tools to predict in vivo absorption by integrating solubility, dissolution, and systemic pharmacokinetics. The PBBM workflow was successfully applied by 1) deriving solubility and dissolution parameters for vericiguat from in vitro experiments as detailed in the accompanying Part 1 publication (Vrenken et al.

Combined Hip Arthroscopy and Periacetabular Osteotomy Performed Under the Same Anesthesia Event Results in Significant Improvement in Outcomes at Short- and Medium-Term Follow-Up With Low Rates of Complications and Conversion to Total Hip Arthroplasty.

Purpose: To summarize and evaluate the surgical technique, patient-reported outcomes (PROs), and complications of combined periacetabular osteotomy (PAO) and hip arthroscopy for the treatment of hip dysplasia and intra- and extra-articular hip pathology, respectively.

Methods: Clinical studies evaluating outcomes of simultaneous combined hip arthroscopy and PAO procedures performed under the same anesthesia event were identified in PubMed, Embase, and The Cochrane Library per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to October 10, 2024. PROs, complications, intraoperative procedures, radiographic parameters, and demographic factors were assessed.

Development and evaluation of an automated classification and counting system for rice planthoppers captured on survey boards.

Rice planthoppers are the most economically important insect pests of rice in Asia. Traditional surveys to examine their abundance and composition in paddy fields involve human visual inspection, which requires considerable time and effort by expert entomologists. We previously developed a deep learning-based object detection system which can detect rice planthopper individuals from scanned images of survey boards, categorize, and count planthopper individuals by 18 categories, based on species, developmental stages, adult sexes, and adult wing-forms, with a mean average precision (mAP) of 79%.

Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants.

CD38, an ecto-enzyme involved in NAD catabolism, is highly expressed in exhausted CD8 T cells and has emerged as an attractive target to improve response to immune checkpoint blockade (ICB) by blunting T cell exhaustion. However, the precise role(s) and regulation of CD38 in exhausted T cells and the efficacy of CD38-directed therapeutic strategies in human cancer remain incompletely defined. Here, we show that CD38CD8 T cells are induced by chronic TCR activation and type I interferon stimulation and confirm their association with ICB resistance in human melanoma.

COSMOS: Interrater and Intrarater Reliability Study of a Novel Outcome Measure.

The vast majority of patients with minor stroke achieve what are considered good or excellent outcomes on the modified Rankin Scale (0-1/0-2), yet many are dissatisfied with their outcomes. There is a need for a functional outcome measure tailored for minor stroke that better reflects the spectrum of clinical outcomes within this population. We developed the Canadian Outcome Scale for Minor Stroke (COSMOS) and performed an interrater and intrarater reliability study.

Antithrombotic approach in percutaneous pulmonary valve implantation (PPVI): What is our standard of care? A study endorsed by the Association for European Paediatric and Congenital Cardiology.

Background: Despite the widespread adoption of percutaneous pulmonary valve implantation, there remains a lack of consensus on the optimal management of peri-interventional and long-term antithrombotic therapies because of a lack of evidence.

Aim: To clarify current practices in peri/postprocedural antithrombotic strategies for percutaneous pulmonary valve implantation.

Methods: An online survey was submitted to the Interventional Working Group of the Association for European Paediatric and Congenital Cardiology, and was completed by 76 congenital interventional cardiologists in 2023-2024.

Structure-based design of a novel series of cholesterol 24-hydroxylase (CH24H) inhibitors bearing 1,3-oxazole as a heme-iron binding group.

Herein, we describe the design, synthesis, and pharmacological evaluation of novel 1,3-oxazole-based inhibitors of cholesterol 24-hydroxylase (CH24H; CYP46A1), a brain-specific cytochrome P450 (CYP) enzyme that metabolizes cholesterol to 24Shydroxycholesterol (24HC). Starting with compound 1a, a scaffold-hopping approach using structure-based drug design identified a series of imidazo[1,2-a]pyridine-3- carboxamide derivatives as novel CH24H inhibitors. Subsequent optimization guided by ligand-lipophilicity efficiency metrics resulted in the discovery of 3k (IC = 4.

Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis.

Objectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS).

Methods: A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date.

Development of a novel physiologically based biopharmaceutics modeling (PBBM) framework using the open systems pharmacology suite, part 1: in vitro modeling of vericiguat.

Physiologically Based Biopharmaceutics Modeling (PBBM) links in vitro solubility and dissolution kinetics of oral drugs to Physiologically Based Pharmacokinetic (PBPK) models, enabling the prediction of drug bioavailability. This approach reduces reliance on animal experimentation during drug development. Part 1 of this series introduces a novel, open-source PBBM workflow using the Open Systems Pharmacology (OSP) Software Suite.

Gut microbial-derived short chain fatty acids enhance kidney proximal tubule cell secretory function.

The organic anion transporter-1 (OAT1), located at the basal side of kidney proximal tubule cells, plays a crucial role in metabolic waste excretion. In chronic kidney disease (CKD), the progressive decline in renal function leads to the accumulation of endogenous metabolites in the bloodstream, exacerbating comorbidities. CKD also leads to gut dysbiosis, increasing the production of uremic metabolites and reducing the production of nephroprotective short chain fatty acids (SCFAs), such as acetate, propionate and butyrate, thereby contributing to disease progression.

405 nm light microbicidal efficacy on Treponema pallidum spiked in ex vivo human platelets.

Pathogen reduction technologies using chemicals and or UV light have been demonstrated to improve the safety of ex vivo platelets from infectious diseases. However, UV light exposure also may affect the treated products, depending on wavelength and exposure. Alternatively, visible spectra 405 nm violet-blue light has broad-spectrum microbicidal activity.

Long-Term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder: A 5-Year Observational Study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a severely disabling autoimmune disease that predominantly impacts the optic nerves and spinal cord. It is often linked to immunoglobulin G (IgG) antibodies targeting the aquaporin-4 water channel (AQP4-IgG). Rituximab, which depletes CD20-positive B cells, is effective in reducing the frequency of NMOSD relapses.

RPGR-Related Retinal Dystrophy in Latin America-A Collaborative Study.

Purpose: To provide the first genetic and clinical characterization of RPGR-associated inherited retinal diseases (IRDs) in Latin America and assess their genetic, clinical, and socioeconomic landscape.

Design: Multicenter, international, retrospective, observational cohort study.

Methods: Patients with genetically confirmed RPGR-IRD from Brazil, Argentina, Chile, Mexico, Colombia, and Panama were included in this study.

Increased Meniscal Extrusion at 1 Year After Surgery Is Associated With a Lower Likelihood of Substantial Mid-Term Patient-Perceived Improvement After Medial Meniscal Root Tear Repair.

Purpose: To analyze factors influencing achievement of mid-term substantial clinical improvement after surgical repair of medial meniscal root tears (MMRTs).

Methods: Patients who underwent arthroscopic pullout repair of MMRTs between 2010 and 2018 with minimum 5-year follow-up were reviewed. Patients were classified into 2 groups based on achieving substantial clinical improvement at 5 years using published substantial clinical benefit (SCB) values: Group 1 showed improvement beyond the SCB thresholds in both the International Knee Documentation Committee subjective score and Lysholm score, whereas group 2 did not reach the SCB threshold for one or both scores.

Effects of Blueberry Consumption on Preference, Digestibility, and Oxidative Balance in Dogs.

The growing awareness of the diet-health connection drives interest in natural dog diets, which replace synthetic additives like antioxidants with natural ingredients. In Trial 1 of this study, preference for diets containing powdered algae (1.5%), powdered clove (0.

A wireless device for continuous measurement of brain parenchymal resistance tracks glymphatic function in humans.

Glymphatic function in animal models supports the clearance of brain proteins whose mis-aggregation is implicated in neurodegenerative conditions including Alzheimer's and Parkinson's disease. The measurement of glymphatic function in the human brain has been elusive due to invasive, bespoke and poorly time-resolved existing technologies. Here we describe a non-invasive multimodal device for the continuous measurement of sleep-active changes in parenchymal resistance in humans using repeated electrical impedance spectroscopy measurements in two separate clinical validation studies.

Unveiling the Modes of Action of a Recombinant Antimicrobial Peptide, Hepcidin (rGf-Hep), from Gerres filamentosus Against Pathogenic Vibrios: Membrane Disintegration and Reactive Oxygen Species Generation Leading to Cell Death.

Antimicrobial peptides (AMPs) are essential components of the innate immune response, which play a significant role in combating pathogenic infections. Hepcidin, a peptide hormone predominantly synthesized in the liver, has been identified to exhibit dual functions in iron metabolism and antimicrobial activity across various organisms. In this study, we describe the molecular characteristics, anti-vibrio activity, and mechanisms of action of a novel hepcidin isoform from the commercially important estuarine fish, Whipfin silver-biddy (Gerres filamentosus).