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Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.
Proc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
View Article and Find Full Text PDFNet Benefit of Early Anticoagulation for Stroke With Atrial Fibrillation: Post Hoc Analysis of the ELAN Randomized Clinical Trial.
JAMA Netw Open
January 2025
Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
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.
Glycocalyx disruption, endothelial dysfunction and vascular remodeling as underlying mechanisms and treatment targets of chronic venous disease.
Int Angiol
December 2024
Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA -
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.
View Article and Find Full Text PDFOverweight yet Undernourished: A Common Juxtaposition in the Specialist Diabetes Foot Service.
Int J Low Extrem Wounds
January 2025
Department of Endocrinology and Diabetes, St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Aims: To describe the nutritional status of people with diabetes-related foot complications and explore the association between nutrition and ulceration healing.
Methods: This retrospective cohort study included attendees of a diabetes foot service who completed a dietary questionnaire. Diet was compared to guideline recommendations and biochemical measures were recorded.
A Comprehensive Review of the Role of GLP-1 Agonists in Weight Management and Their Effect on Metabolic Parameters Such as Blood Glucose, Cholesterol, and Blood Pressure.
Cureus
December 2024
Internal Medicine, Combined Military Hospital, Quetta, PAK.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been developed to manage type 2 diabetes mellitus. Although, in the last 10 years, the use of GLP-1 RAs, especially semaglutide and liraglutide, has increased, its clinical implications and how it affects metabolic parameters have yet to be fully consolidated. This narrative review explores the metabolic effects of GLP-1 RAs in weight management, blood glucose, cardiovascular health, lipid profiles, and blood pressure.
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