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.

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).

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.

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.

Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.

Background: Blood-brain barrier (BBB) dysfunction and immune cell migration into the central nervous system (CNS) are pathogenic drivers of multiple sclerosis (MS). Ways to reinstate BBB function and subsequently limit neuroinflammation present promising strategies to restrict disease progression. However, to date, the molecular players directing BBB impairment in MS remain poorly understood.

Endothelial cells and macrophages as allies in the healthy and diseased brain.

Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels.

Microbial Volatiles as Diagnostic Biomarkers of Bacterial Lung Infection in Mechanically Ventilated Patients.

Background: Early and accurate recognition of respiratory pathogens is crucial to prevent increased risk of mortality in critically ill patients. Microbial-derived volatile organic compounds (mVOCs) in exhaled breath could be used as noninvasive biomarkers of infection to support clinical diagnosis.

Methods: In this study, we investigated the diagnostic potential of in vitro-confirmed mVOCs in the exhaled breath of patients under mechanical ventilation from the BreathDx study.

Weight Based Heparin Dosage with Activated Clotting Time Monitoring Leads to Adequate and Safe Anticoagulation in Non-Cardiac Arterial Procedures.

Background: Unfractionated heparin has an unpredictable effect in an individual patient. The activated clotting time (ACT) can be used to measure the effect of heparin in the individual patient and guide additional heparin dosages. Previous cohort studies showed that a standardized bolus of 5,000 IU during noncardiac arterial procedures (NCAP) does not lead to an adequate ACT in the vast majority of patients.

18F-FDG PET-CT in rheumatoid arthritis patients tapering TNFi: reliability, validity and predictive value.

Objectives: To investigate the reliability and validity of fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT scanning (FDG-PET) in RA patients with low disease activity tapering TNF inhibitors (TNFis) and its predictive value for successful tapering or discontinuation.

Methods: Patients in the tapering arm of the Dose REduction Strategies of Subcutaneous TNFi study, a randomized controlled trial of TNFi tapering in RA, underwent FDG-PET before tapering (baseline) and after maximal tapering. A total of 48 joints per scan were scored both visually [FDG-avid joint (FAJ), yes/no] and quantitatively [maximal and mean standardized uptake values (SUVmax and SUVmean)].

More Effective Anticoagulation During Non-Cardiac Arterial Procedures Using Activated Clotting Time Guided Heparin Administration.

Objectives: Arterial thrombo-embolic complications (ATEC) are still common during and after non-cardiac arterial procedures (NCAP) despite the administration of (a fixed bolus of) heparin. These ATEC could be due to existing individual differences in heparin sensitivity. The purpose of this study was to evaluate the feasibility and safety of an ACT guided heparin dose protocol and to evaluate if a more effective target ACT can be achieved during NCAP.

Elective Neck Dissection or Sentinel Lymph Node Biopsy in Early Stage Oral Cavity Cancer Patients: The Dutch Experience.

Background: Sentinel lymph node biopsy (SLNB) has been introduced as a diagnostic staging modality for detection of occult metastases in patients with early stage oral cancer. Comparisons regarding accuracy to the routinely used elective neck dissection (END) are lacking in literature.

Methods: A retrospective, multicenter cohort study included 390 patients staged by END and 488 by SLNB.

Propofol for endotracheal intubation in neonates: a dose-finding trial.

Objective: To find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA).

Design And Setting: Prospective multicentere dose-finding study in 3 neonatal intensive care units.

Patients: Neonates with a PNA <28 days requiring non-emergency endotracheal intubation.

Distinct Profiles on Subjective and Objective Adherence Measures in Patients Prescribed Antidepressants.

Objective: A recurrent observation is that associations between self-reported and objective medication adherence measures are often weak to moderate. Our aim was therefore to identify patients with different profiles on self-reported and objective adherence measures.

Study Design And Setting: This was an observational study of 221 community pharmacy patients who were dispensed antidepressants.