Net Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.

Importance: The net clinical effect of early vs later direct oral anticoagulant (DOAC) initiation after atrial fibrillation-associated ischemic stroke is unclear.

Objective: To investigate whether early DOAC treatment is associated with a net clinical benefit (NCB).

Design, Setting, And Participants: This was a post hoc analysis of the Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation (ELAN) open-label randomized clinical trial conducted across 103 sites in 15 countries in Europe, the Middle East, and Asia between November 6, 2017, and September 12, 2022, with a 90-day follow-up.

Temperature Exposure and Psychiatric Symptoms in Adolescents From 2 European Birth Cohorts.

Importance: Climate change can adversely affect mental health, but the association of ambient temperature with psychiatric symptoms remains poorly understood.

Objective: To assess the association of ambient temperature exposure with internalizing, externalizing, and attention problems in adolescents from 2 population-based birth cohorts in Europe.

Design, Setting, And Participants: This cohort study analyzed data from the Dutch Generation R Study and the Spanish INMA (Infancia y Medio Ambiente) Project.

Safety and Efficacy of Lotilaner Ophthalmic Solution (0.25%) in Treating Demodex Blepharitis: Pooled Analysis of Two Pivotal Trials.

Introduction: Lotilaner ophthalmic solution (0.25%) is the first United States Food and Drug Administration (US FDA)-approved drug for treating Demodex blepharitis. In pivotal trials, it was found to be well tolerated and demonstrated a significant reduction in collarettes and mite density after a 6-week treatment regimen.

Early transcriptional effects of inflammatory cytokines reveal highly redundant cytokine networks.

Inflammatory cytokines are fundamental mediators of the organismal response to injury, infection, or other harmful stimuli. To elucidate the early and mostly direct transcriptional signatures of inflammatory cytokines, we profiled all immunologic cell types by RNAseq after systemic exposure to IL1β, IL6, and TNFα. Our results revealed a significant overlap in the responses, with broad divergence between myeloid and lymphoid cells, but with very few cell-type-specific responses.

The meninges host a distinct compartment of regulatory T cells that preserves brain homeostasis.

Our understanding of the meningeal immune system has recently burgeoned, particularly regarding how innate and adaptive effector cells are mobilized to meet brain challenges. However, information on how meningeal immunocytes guard brain homeostasis in healthy individuals remains limited. This study highlights the heterogeneous, polyfunctional regulatory T cell (T) compartment in the meninges.

Development of Potent and Selective CK1α Molecular Glue Degraders.

Molecular glue degraders (MGDs) are small molecules that facilitate proximity between a target protein and an E3 ubiquitin ligase, thereby inducing target protein degradation. Glutarimide-containing compounds are MGDs that bind cereblon (CRBN) and recruit neosubstrates. Through explorative synthesis of a glutarimide-based library, we discovered a series of molecules that induce casein kinase 1 alpha (CK1α) degradation.

Policy Recommendations to Support Equitable Access to Long-Acting Injectables for Human Immunodeficiency Virus Prevention and Treatment: A Policy Paper of the Infectious Diseases Society of America and the HIV Medicine Association.

Long-acting injectables (LAIs) for HIV prevention and treatment could dramatically improve health outcomes and health equity for people with HIV and those who could benefit from pre-exposure prophylaxis. Despite widespread acceptability and demand by providers and potential users of LAIs, implementation has been extremely limited since the introduction of cabotegravir/rilpivirine, the first LAI for HIV treatment, in January 2021, and long-acting cabotegravir, the first LAI for HIV prevention, in December 2021. We report results of a provider survey, conducted by the HIV Medicine Association, which identified LAI implementation barriers related to health insurance processes, staffing and administrative support, drug costs and acquisition, and access for individuals who are uninsured.

Frequently arising ESX-1-associated phase variants influence fitness in the presence of host and antibiotic pressures.

Unlabelled: (Mtb) exhibits an impressive ability to adapt to rapidly changing environments, despite its genome's apparent stability. Recently, phase variation through indel formation in homopolymeric tracts (HT) has emerged as a potentially important mechanism promoting adaptation in Mtb. This study examines the impact of common phase variants associated with the ESX-1 type VII secretion system, focusing on a highly variable HT upstream of the ESX-1 regulatory factor, .

Recovery support services as part of the continuum of care for alcohol or drug use disorders.

Background: The definition of 'recovery' has evolved beyond merely control of problem substance use to include other aspects of health and wellbeing (known as 'recovery capital') which are important to prevent relapse to problematic alcohol or other drug (AOD) use. Developing a Recovery Oriented System of Care (ROSC) requires consideration of interventions or services (Recovery Support Services, RSS) designed to build recovery capital which are often delivered alongside established treatment structures. Lived experience and its application to the process of engaging people, changing behaviour and relapse prevention is an essential part of these services.

Pediatric Transplant Surgeons' Perspectives on Palliative Care for Children With Chronic Kidney Disease: A National Cross-Sectional Survey.

Background: Some adult transplant surgeons consider transplant to be contraindicated in patients receiving palliative care (PC). Little is known about pediatric transplant surgeons' attitudes toward PC. We sought to ascertain pediatric kidney transplant surgeons' perspectives regarding the routine integration of PC for children with chronic kidney disease.

Feasibility and acceptability of engaging care partners of persons living with dementia with electronic outreach for deprescribing.

Background And Objectives: Care partners are critical for making treatment decisions in persons living with dementia. However, identifying them is challenging, hindering the broader use of interventions, such as those using digital technologies. We aimed to (i) assess the feasibility of identifying and contacting care partners using electronic health record (EHR) systems, and (ii) elicit their perspectives on electronic interventions for deprescribing.

Comparative Outcomes of Babesiosis in Immunocompromised and Non-Immunocompromised Hosts: A Multicenter Cohort Study.

Background: Babesiosis poses significant risks of adverse outcomes in individuals with immunocompromising conditions (IC) and asplenia/hyposplenia (AH). This study compares clinical outcomes between these vulnerable groups and immunocompetent patients.

Methods: A multicenter retrospective cohort study included adult patients with laboratory-confirmed babesiosis from 2009 to 2023.

Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine.

Although the pathophysiology of migraine involves a complex ensemble of peripheral and central nervous system changes that remain incompletely understood, the activation and sensitization of the trigeminovascular system is believed to play a major role. However, non-invasive, in vivo neuroimaging studies investigating the underlying neural mechanisms of trigeminal system abnormalities in human migraine patients are limited. Here, we studied 60 patients with migraine (55 females, mean age ± SD: 36.

Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.

Background And Aims: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.

Methods: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan.

Efficacy and Safety of Mechanical Thrombectomy in Distal Medium Middle Cerebral Artery Occlusion Ischemic Stroke Patients on Low-Dose Aspirin.

Background: Acute ischemic stroke (AIS) from distal medium vessel occlusion (DMVO) presents unique treatment challenges. Mechanical thrombectomy (MT) is emerging as a viable option for these patients, yet the role of pre-stroke aspirin treatment is unclear. This study evaluates the impact of pre-stroke low-dose aspirin on outcomes in DMVO patients undergoing MT.

Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.

The glycocalyx is an essential structural and functional component of endothelial cells. Extensive hemodynamic changes cause endothelial glycocalyx disruption and vascular dysfunction, leading to multiple arterial and venous disorders. Chronic venous disease (CVD) is a common disorder of the lower extremities with major health and socio-economic implications, but complex pathophysiology.

Family Connections: The Impact of an Education Program for Carers of Individuals With Borderline Personality Disorder in Italian Mental Health Services.

Borderline personality disorder (BPD) has a strong impact not only on patients' lives but also on their families. The presence of an invalidating environment is one of the key factors in the etiology of BPD. This study evaluated the impact of the Family connections (FC) program on burden, grief, and other clinical variables in 202 caregivers and identified the profiles of participants who improved/deteriorated their levels of burden and grief.

Novel early vertical ridge augmentation technique.

Background/purpose: Multiple augmentation protocols are documented in the literature to rebuild the deficient alveolar ridge after tooth extraction; however, achieving adequate vertical augmentation remains the most challenging goal. This study demonstrated a novel surgical technique of early vertical ridge augmentation for post-dental extraction. This technique offers several biological and technical advantages regarding the timing of the procedure and its relative simplicity compared to other complex techniques.

Improving osteogenic properties of zirconia ceramic via glow discharge plasma-enhanced deposition of amine organic compound.

Background/purpose: Osseointegration potential is greatly depended on the interaction between bone cells and dental implant surface. Since zirconia ceramic has a bioinert surface, functionalization of the surface with an organic compound allylamine was conducted to overcome its drawback of minimal interaction with the surrounding bone.

Materials And Methods: The zirconia surface was initially treated with argon glow discharge plasma (GDP), then combined with amine plasma at three different conditions of 50-W, 75-W and 85-W, to prepare the final samples.

Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases.

Cardiovascular diseases cause significant morbidity and mortality worldwide. Engineered cardiac organoids are being developed and used to replicate cardiac tissues supporting cardiac morphogenesis and development. These organoids have applications in drug screening, cardiac disease models and regenerative medicine.

Assessing the cortical microstructure in contralesional sensorimotor areas after stroke.

Cortical thickness analyses have provided valuable insights into changes in cortical brain structure after stroke and their association with recovery. Across studies though, relationships between cortical structure and function show inconsistent results. Recent developments in diffusion-weighted imaging of the cortex have paved the way to uncover hidden aspects of stroke-related alterations in cortical microstructure, going beyond cortical thickness as a surrogate for cortical macrostructure.

An Optimized Protocol for Simultaneous Propagation of Patient-derived Organoids and Matching CAFs.

Recurrent hormone receptor-positive (HR+) breast cancer is a leading cause of cancer mortality in women. Recurrence and resistance to targeted therapies have been difficult to study due to the long clinical course of the disease, the complex nature of resistance, and the lack of clinically relevant model systems. Existing models are limited to a few HR+ cell lines, organoid models, and patient-derived xenograft models, all lacking components of the human tumor microenvironment.

Probing and imaging phospholipid dynamics in live cells.

Distinct phospholipid species display specific distribution patterns across cellular membranes, which are important for their structural and signaling roles and for preserving the integrity and functionality of the plasma membrane and organelles. Recent advancements in lipid biosensor technology and imaging modalities now allow for direct observation of phospholipid distribution, trafficking, and dynamics in living cells. These innovations have markedly advanced our understanding of phospholipid function and regulation at both cellular and subcellular levels.

The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.

An overview is provided of the evolution of strategies towards xenotransplantation during the past almost 40 years, focusing on advances in gene-editing of the organ-source pigs, pre-transplant treatment of the recipient, immunosuppressive protocols, and adjunctive therapy. Despite initial challenges, including hyperacute rejection resulting from natural (preformed) antibody binding and complement activation, significant progress has been made through gene editing of the organ-source pigs and refinement of immunosuppressive regimens. Major steps were the identification and deletion of expression of the three known glycan xenoantigens on pig vascular endothelial cells, the transgenic expression of human "protective" proteins, e.