Mechanosensation by endothelial PIEZO1 is required for leukocyte diapedesis.

The extravasation of leukocytes is a critical step during inflammation that requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as ICAM-1 on the surface of endothelial cells. Here we reveal that mechanical forces generated by leukocyte-induced clustering of ICAM-1 synergize with fluid shear stress exerted by the flowing blood to increase endothelial plasma membrane tension and to activate the mechanosensitive cation channel PIEZO1. This leads to increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of tyrosine kinases sarcoma (SRC) and protein tyrosine kinase 2 (PYK2), as well as of myosin light chain, resulting in opening of the endothelial barrier. Mice with endothelium-specific Piezo1 deficiency show decreased leukocyte extravasation in different inflammation models. Thus, leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis.

[Prevalence of dementia or other form of organic brain disorder on a geriatric psychiatry ward]. / Forekomst af demens eller anden form for erhvervet hjernesygdom på en gerontopsykiatrisk afdeling.

INTRODUCTION: The prevalence of dementia in various geriatric psychiatry settings has previously been investigated and been found to lie between 15.2% and 61%. The present study investigated the percentage of patients with "organic brain disorder" [OBD] (dementia, acquired brain injury or other brain disease) in one geriatric psychiatric department in Copenhagen, Denmark. MATERIALS AND METHODS: The journals of all patients admitted to the geriatric psychiatric department (locked ward, open ward, and day hospital) in 2002 were studied in order to find evidence of (a) psychiatric discharge diagnosis of OBD in 2002 (b) previous diagnosis of OBD (c) the basis of these diagnoses. RESULTS: 130 patients were admitted at least once in 2002. 33.1% had an OBD diagnosis at discharge, whilst a further 18.4% had documented evidence of previously diagnosed OBD and/or assessments supporting the presence of OBD. Effects of gender and age at first admission were found on discharge diagnosis. CONCLUSION: There is evidence that over half of the patients admitted to the geriatric psychiatry department in this study had an OBD, which is higher than the percentage of patients who were discharged with this diagnosis. The possible consequences of findings and the drawbacks of the study are discussed.