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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
Harvard Medical School and Brigham & Women's Hospital, Boston, MA, USA.
SORL1 (SORLA, LR11) is a large (2214 residue), multi-domain type 1 integral membrane protein that is the product of the SORL1 gene. In neurons, where it is highly expressed, SORL1 functions as both a substrate of and a cargo receptor for the retromer multi protein complex that is a master regulator of protein trafficking out of the early endosome. The SORL1-Vps26b retromer, in particular, is dedicated to the recycling of cell surface proteins, including APP and AMPA receptor subunit GLUA1, back to the plasma membrane.
View Article and Find Full Text PDFClinical Manifestations.
Alzheimers Dement
December 2024
University of California San Francisco, San Francisco, CA, USA.
Those with neurodegenerative conditions have an increased risk of developing delirium and there is some evidence that delirium may be a risk factor for neurodegenerative disorders. Similar to the interactions between sleep and neurodegenerative conditions, there is increasing evidence for bi-directional relationships between delirium and sleep disorders and disturbances. This presentation will provide an overview of the literature on those relationships, including discussion of the well-characterized changes in sleep that occur in individuals experiencing delirium.
View Article and Find Full Text PDFProposed utilization of PlGF-based diagnostic testing for suspected preeclampsia in Québec: insights from an expert panel discussion.
J Obstet Gynaecol Can
December 2024
Department of Medicine, McGill University Health Centre, Montreal, Qc, Canada; Centre for Translational Biology, Research Institute of the McGill University Health Centre, Montreal, Qc, Canada.
Prompt diagnosis of preeclampsia is key to ensure appropriate management and reduce associated adverse outcomes. Placental growth factor (PlGF)-based biomarkers have been shown to be safe and effective diagnostic tools for preterm preeclampsia, and their use is recommended by most recent Canadian guidelines. The present report summarizes an expert panel discussion that led to the development of a proposed utilization algorithm for PlGF-based diagnostic testing for suspected preeclampsia in Québec.
View Article and Find Full Text PDFAnti-TNF Non-Response in Ulcerative Colitis: Correcting for Mucosal Drug Exposure Reveals Distinct Cytokine Profiles.
J Crohns Colitis
January 2025
Amsterdam UMC, Department of Gastroenterology and Hepatology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
Introduction: It remains unclear why up to 30% of ulcerative colitis patients (UC) do not respond to tumor necrosis factor inhibitors (TNFi). Validated biomarkers for (non-)response ((N)R) are lacking. Most studies investigating underlying mechanisms do not differentiate between pharmacokinetic and inflammatory mechanisms.
View Article and Find Full Text PDFInhibition of nitric oxide synthase transforms carotid occlusion-mediated benign oligemia into large cerebral infarction.
Theranostics
January 2025
Department of neurology, Dongguk University Ilsan Hospital, Goyang 10326, Republic of Korea.
It remains unclear why unilateral proximal carotid artery occlusion (UCAO) causes benign oligemia in mice, yet leads to various outcomes (asymptomatic-to-death) in humans. We hypothesized that inhibition of nitric oxide synthase (NOS) both transforms UCAO-mediated oligemia into full infarction and expands pre-existing infarction. Using 900 mice, we i) investigated stroke-related effects of UCAO with/without intraperitoneal administration of the NOS inhibitor (NOSi) N-nitro-L-arginine methyl ester (L-NAME, 400 mg/kg); ii) examined the rescue effect of the NO-donor, molsidomine (200 mg/kg at 30 minutes); and iii) tested the impact of antiplatelet medications.
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