79 research outputs found

    MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

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    Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation

    The sequences of 150,119 genomes in the UK Biobank

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    Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data(1,2). Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank(3). This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation

    Functional study of the dermal microcirculation in systemic sclerosis

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTo measure the effect of cooling on digital blood pressure we used a strain-gauge and photoplethysmograph, with an automatic cooling device. Eighteen patients were compared with 18 matched controls. Laser-doppler technique was used to measure the perfusion changes after heating a small area of the skin in 5 locations on the body, readings were given in perfusion units. Eighteen patients with systemic sclerosis were compared with 25 individuals with primary Raynaud's phenomenon and 30 healthy controls. Cooling to 10 degrees C caused a significant digital blood pressure drop of 58 mmHg in patients with systemic sclerosis and 61 mmHg in Raynaud's phenomenon, as compared with controls. The microcirculation in patients with systemic sclerosis responded in the same way to local heating as in the normal population, increasing the perfusion to the same extent. In conclusion, an unselected group of patients with systemic sclerosis have normal dermal microcirculatory response to heating in spite of severe cold intolerance

    Gender Differences in Lying: the Role of Stakes

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    Using an amended Gneezy’s cheap-talk game with multiple decisions, we test whether gender differences in lying depend on the magnitude of gains, as hypothesized in the literature. We find that women may have a greater aversion to lying for small monetary gains; this effect disappears with increased gains

    Fast and simple screening for nutritional status in hospitalized, elderly people

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Undernutrition has been frequently reported among hospitalized elderly patients. The aim of this study was to evaluate the mini nutrition assessment (MNA) and a screening sheet for malnutrition (SSM) by full nutritional assessment (FNA) in elderly people, and to construct a shorter screening method by combining important questions from MNA and SSM. Having a screening tool as fast and simple as possible could increase its use in clinical routines. METHODS: FNA, MNA and SSM were carried out on 60 hospitalized patients (>65 years). Sensitivity and specificity for MNA and SSM were calculated in comparison with FNA. In order to construct a short and simple screening tool, questions from the two screening tools, which differed significantly between mal- and well-nourished patients, were used in a multivariate, stepwise linear regression. The regression model was simplified to be suitable in clinical routines. RESULTS: Malnourishment was diagnosed by FNA in 58.3% of the elderly patients, with no gender difference. Body mass index, unintended weight loss, recent surgery and loss of appetite were predictors of malnutrition in the regression model (R(2) = 60.1%). The sensitivity and specificity of the simplified regression model were 89 and 88%, respectively, which was more precise than MNA (77 and 36%) and SSM (89 and 60%). CONCLUSION: According to FNA, malnutrition is frequent in elderly hospitalized patients. Four questions are sufficient to conduct precise nutritional screening for malnutrition in elderly hospitalized patients. This new screening tool should be verified in other samples

    Use of a bereavement risk assessment checklist in an Icelandic hospital

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    To access publisher's site click on the hyperlink at the bottom of the pageThere are many factors influencing people’s response to the loss of a loved one, including previous experience of death and bereavement, social circumstances, age, relationship to the deceased and personality. Each death – and each bereaved person – is unique and the need for support therefore varies
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