Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction.

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model.

Assessment of impulsivity using an automated, self-adjusting delay discounting procedure.

Modelling delay discounting behavior in rodents is important for understanding the neurobiological mechanisms underlying cognitive control and associated impulsivity disorders. Conventional rodent delay discounting procedures require extensive training and frequent experimenter interaction, as rodents are tested in separate operant chambers away from their home cage. To address these limitations, we adapted and characterize here a self-adjusting delay discounting procedure to an automated CombiCage setup.

An international and multidisciplinary EORTC survey on resectability of stage III non-small cell lung cancer.

Introduction: The EORTC-Lung Cancer Group initiated a Delphi consensus process to establish a consensual definition of resectable stage III non-small cell lung cancer (NSCLC) for the use in clinical trials, including a systematic review, survey, and review of clinical cases. Here, the survey results are presented, aimed to identify areas of controversy.

Methods: A survey was distributed among the members of six international organizations related to lung cancer.

Tension at the gate: sensing mechanical forces at the blood-brain barrier in health and disease.

Microvascular brain endothelial cells tightly limit the entry of blood components and peripheral cells into the brain by forming the blood-brain barrier (BBB). The BBB is regulated by a cascade of mechanical and chemical signals including shear stress and elasticity of the adjacent endothelial basement membrane (BM). During physiological aging, but especially in neurological diseases including multiple sclerosis (MS), stroke, small vessel disease, and Alzheimer's disease (AD), the BBB is exposed to inflammation, rigidity changes of the BM, and disturbed cerebral blood flow (CBF).

Unraveling Sex Differences in Kidney Health and Chronic Kidney Disease: a Review of the Impact of Sex Hormones.

Sexual dimorphism plays an important role in the pathogenesis and progression of chronic kidney disease (CKD). Men with CKD often exhibit faster kidney function decline, leading to higher rates of kidney failure and mortality compared to women. Studies suggest that sex hormones may influence this apparent dimorphism, although the mechanisms underlying these influences remain poorly understood.

Comprehensive pan-genome analysis of Mycobacterium marinum: insights into genomic diversity, evolution, and pathogenicity.

Mycobacteria is a diverse genus that includes both innocuous environmental species and serious pathogens like Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium ulcerans, the causative agents of tuberculosis, leprosy, and Buruli ulcer, respectively. This study focuses on Mycobacterium marinum, a closely related species known for its larger genome and ability to infect ectothermic species and cooler human extremities. Utilizing whole-genome sequencing, we conducted a comprehensive pan-genome analysis of 100 M.

Spatially resolved gene signatures of white matter lesion progression in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and progressive neurodegeneration. To understand MS lesion initiation and progression, we generate spatial gene expression maps of white matter (WM) and grey matter (GM) MS lesions. In different MS lesion types, we detect domains characterized by a distinct gene signature, including an identifiable rim around active WM lesions.

The provision of bereavement care by general practitioners: data from a sentinel network.

Background: Limited information exists regarding the prevalence of bereavement care provision by general practitioners (GPs) and in what cases they provide this. Insights into the current practice of bereavement care provision by GPs can highlight areas for improvement of the bereavement care practice. Therefore, we examined in how many cases GPs contacted relatives regarding bereavement care, and which case-specific characteristics are associated.

Aging is associated with reduced inflammatory disease activity independent of disease duration in relapsing multiple sclerosis trial populations.

Background: Higher age is associated with less inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS). It is unknown whether age itself or disease duration underlies this association.

Objectives: This study investigated the effects of age, disease duration, and inflammatory disease activity in people with RRMS.

International Cross-Sectional Srvey O Teatment f ccluded emoro-Popliteal Stents (SUNROOF).

Purpose: The aim of this project is to explore practice patterns of experienced vascular specialists involved in the treatment of patients with arterial femoro-popliteal in-stent occlusion (ISO) and to understand key concepts and shared thoughts, throughout an international cross-sectional survey.

Materials And Methods: The web-based survey was in English and included 31 questions. One-hundred experts were invited by email to fill in the survey anonymously on Google Forms using a dedicated link.

Emerging multimodality imaging techniques for the pulmonary circulation.

Pulmonary hypertension (PH) remains a challenging condition to diagnose, classify and treat. Current approaches to the assessment of PH include echocardiography, ventilation/perfusion scintigraphy, cross-sectional imaging using computed tomography and magnetic resonance imaging, and right heart catheterisation. However, these approaches only provide an indirect readout of the primary pathology of the disease: abnormal vascular remodelling in the pulmonary circulation.

Sex Differences in Pain Sensitivity in a Dutch Cohort: Cross-Sectional and Web-Based Multidimensional Study.

Background: Sex is an important factor influencing the development and treatment of chronic pain, but the extent of its influence is still unclear. Other demographic factors as well as nonpharmacological interventions might influence pain sensitivity differently in men and women.

Objective: In this study, we aimed to investigate the influence of sex and other demographic, lifestyle, behavioral, clinical, and environmental factors on pain sensitivity in the Dutch population.

Individual Placement and Support and Participatory Workplace Intervention on the Work Participation of People with Disabilities: A Randomised Controlled Trial.

Purpose: This study assessed the effectiveness of Individual Placement and Support (IPS), Participatory Workplace Intervention (PWI), and IPS + PWI on work participation and health of people with work disabilities.

Methods: A randomised controlled 2 × 2 factorial trial with 120 clients and an 18-month follow-up was performed. Differences between IPS and no-IPS and between PWI and no-PWI were assessed using log-rank tests and Cox proportional hazards models.

Multimodal explainable artificial intelligence identifies patients with non-ischaemic cardiomyopathy at risk of lethal ventricular arrhythmias.

The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals.

Process Evaluation of Individual Placement and Support and Participatory Workplace Intervention to Increase the Sustainable Work Participation of People with Work Disabilities.

Purpose: This study is a process evaluation of the use of Individual Placement and Support (IPS) and Participatory Workplace Intervention (PWI) to increase the work participation of people with work disabilities. We ran the evaluation alongside a randomized controlled trial (RCT), to investigate whether and to what extent IPS and PWI were executed according to protocol.

Methods: The study population consisted of clients with work disabilities, and their job coaches who were employed by the municipality of a large city in the Netherlands.

Enduring Clinical Remission in Refractory Celiac Disease Type II With Tofacitinib: An Open-Label Clinical Study.

Refractory celiac disease type 2 (RCDII) is a rare condition with high mortality because of a lack of effective treatment strategies. RCDII is caused by clonal expansion of intraepithelial lymphocytes (IELs). Gain-of-function JAK1 mutations are frequently found in these cells.

Modulating mycobacterial envelope integrity for antibiotic synergy with benzothiazoles.

Developing effective tuberculosis drugs is hindered by mycobacteria's intrinsic antibiotic resistance because of their impermeable cell envelope. Using benzothiazole compounds, we aimed to increase mycobacterial cell envelope permeability and weaken the defenses of , serving as a model for Initial hit, BT-08, significantly boosted ethidium bromide uptake, indicating enhanced membrane permeability. It also demonstrated efficacy in the -zebrafish embryo infection model and -infected macrophages.

Diving into drug-screening: zebrafish embryos as an in vivo platform for antimicrobial drug discovery and assessment.

The rise of multidrug-resistant bacteria underlines the need for innovative treatments, yet the introduction of new drugs has stagnated despite numerous antimicrobial discoveries. A major hurdle is a poor correlation between promising in vitro data and in vivo efficacy in animal models, which is essential for clinical development. Early in vivo testing is hindered by the expense and complexity of existing animal models.