371 research outputs found

    Predicting occupational strain and job satisfaction: the role of stress, coping, personality, and affectivity variables

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    Four studies employed path analysis to examine how measures of occupational stressors, coping resources, and negative affectivity (NA) and positive affectivity (PA) interact to predict occupational strain. The Occupational Stress Inventory (Osipow & Spokane, 1987) was used to measure stress, strain, and coping. The Positive and Negative Affectivity Schedule (Watson, Clark, & Tellegen, 1988) was used for the affectivity variables. The hypothesised model showed NA and PA as background dispositional variables that influenced relations among stress, strain, and coping while still allowing stress and coping to have a direct influence on strain. Goodness of fit indices were acceptable with the model predicting 15 per cent of the variance in stress, 24 per cent of coping, and 70 per cent of strain. Study 2 replicated these findings. Study 3 added a positive outcome variable, job satisfaction (JSI: Brayfield & Rothe, 1951) to the model. The expanded model again fit the data well. A fourth study added a global measure of personality (NEO-FFI: Costa & McCrae, 1991) to the model tested in Study 3. Results indicated that personality measures did not add anything to the prediction of job satisfaction and strain in a model that already included measures of stressors, coping resources, NA and PA. The series of four studies yielded a reliable structural model that highlights the influence of organizational and dispositional variables on occupational strain and job satisfaction

    Top-down and bottom-up identification of proteins by liquid extraction surface analysis mass spectrometry of healthy and diseased human liver tissue

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    Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15–25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-014-0967-z) contains supplementary material, which is available to authorized users

    A flow adhesion assay to study leucocyte recruitment to human hepatic sinusoidal endothelium under conditions of shear stress

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    Leucocyte infiltration into human liver tissue is a common process in all adult inflammatory liver diseases. Chronic infiltration can drive the development of fibrosis and progression to cirrhosis. Understanding the molecular mechanisms that mediate leucocyte recruitment to the liver could identify important therapeutic targets for liver disease. The key interaction during leucocyte recruitment is that of inflammatory cells with endothelium under conditions of shear stress. Recruitment to the liver occurs within the low shear channels of the hepatic sinusoids which are lined by hepatic sinusoidal endothelial cells (HSEC). The conditions within the hepatic sinusoids can be recapitulated by perfusing leucocytes through channels lined by human HSEC monolayers at specific flow rates. In these conditions leucocytes undergo a brief tethering step followed by activation and firm adhesion, followed by a crawling step and subsequent transmigration across the endothelial layer. Using phase contrast microscopy, each step of this 'adhesion cascade' can be visualized and recorded followed by offline analysis. Endothelial cells or leucocytes can be pretreated with inhibitors to determine the role of specific molecules during this process

    Hepatic Endothelial CCL25 Mediates the Recruitment of CCR9+ Gut-homing Lymphocytes to the Liver in Primary Sclerosing Cholangitis

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    Primary sclerosing cholangitis (PSC), a chronic inflammatory liver disease characterized by progressive bile duct destruction, develops as an extra-intestinal complication of inflammatory bowel disease (IBD) (Chapman, R.W. 1991. Gut. 32:1433–1435). However, the liver and bowel inflammation are rarely concomitant, and PSC can develop in patients whose colons have been removed previously. We hypothesized that PSC is mediated by long-lived memory T cells originally activated in the gut, but able to mediate extra-intestinal inflammation in the absence of active IBD (Grant, A.J., P.F. Lalor, M. Salmi, S. Jalkanen, and D.H. Adams. 2002. Lancet. 359:150–157). In support of this, we show that liver-infiltrating lymphocytes in PSC include mucosal T cells recruited to the liver by aberrant expression of the gut-specific chemokine CCL25 that activates α4β7 binding to mucosal addressin cell adhesion molecule 1 on the hepatic endothelium. This is the first demonstration in humans that T cells activated in the gut can be recruited to an extra-intestinal site of disease and provides a paradigm to explain the pathogenesis of extra-intestinal complications of IBD

    Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles.

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    Hepatic sinusoidal endothelial cells are unique among endothelial cells in their ability to internalize and process a diverse range of antigens. DC-SIGNR, a type 2 C-type lectin expressed on liver sinusoids, has been shown to bind with high affinity to hepatitis C virus (HCV) E2 glycoprotein. DC-SIGN is a closely related homologue reported to be expressed only on dendritic cells and a subset of macrophages and has similar binding affinity to HCV E2 glycoprotein. These receptors function as adhesion and antigen presentation molecules. We report distinct patterns of DC-SIGNR and DC-SIGN expression in human liver tissue and show for the first time that both C-type lectins are expressed on sinusoidal endothelial cells. We confirmed that these receptors are functional by demonstrating their ability to bind HCV E2 glycoproteins. Although these lectins on primary sinusoidal cells support HCV E2 binding, they are unable to support HCV entry. These data support a model where DC-SIGN and DC-SIGNR on sinusoidal endothelium provide a mechanism for high affinity binding of circulating HCV within the liver sinusoids allowing subsequent transfer of the virus to underlying hepatocytes, in a manner analogous to DC-SIGN presentation of human immunodeficiency virus on dendritic cells

    Management, regulation and environmental impacts of nitrogen fertilization in northwestern Europe under the Nitrates Directive; a benchmark study

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    Implementation of the Nitrates Directive (NiD) and its environmental impacts were compared for member states in the northwest of the European Union (Ireland, United Kingdom, Denmark, the Netherlands, Belgium, Northern France and Germany). The main sources of data were national reports for the third reporting period for the NiD (2004–2007) and results of the MITERRA-EUROPE model. Implementation of the NiD in the considered member states is fairly comparable regarding restrictions for where and when to apply fertilizer and manure, but very different regarding application limits for N fertilization. Issues of concern and improvement of the implementation of the NiD are accounting for the fertilizer value of nitrogen in manure, and relating application limits for total nitrogen (N) to potential crop yield and N removal. The most significant environmental effect of the implementation of the NiD since 1995 is a major contribution to the decrease of the soil N balance (N surplus), particularly in Belgium, Denmark, Ireland, the Netherlands and the United Kingdom. This decrease is accompanied by a modest decrease of nitrate concentrations since 2000 in fresh surface waters in most countries. This decrease is less prominent for groundwater in view of delayed response of nitrate in deep aquifers. In spite of improved fertilization practices, the southeast of the Netherlands, the Flemish Region and Brittany remain to be regions of major concern in view of a combination of a high nitrogen surplus, high leaching fractions to groundwater and tenacious exceedance of the water quality standards. On average the gross N balance in 2008 for the seven member states in EUROSTAT and in national reports was about 20 kg N ha<sup>−1</sup> yr<sup>−1</sup> lower than by MITERRA. The major cause is higher estimates of N removal in national reports which can amount to more than 50 kg N ha<sup>−1</sup> yr<sup>−1</sup>. Differences between procedures in member states to assess nitrogen balances and water quality and a lack of cross-boundary policy evaluations are handicaps when benchmarking the effectiveness of the NiD. This provides a challenge for the European Commission and its member states, as the NiD remains an important piece of legislation for protecting drinking water quality in regions with many private or small public production facilities and controlling aquatic eutrophication from agricultural sources

    Social disorganization and history of child sexual abuse against girls in sub-Saharan Africa : a multilevel analysis

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    Background: Child sexual abuse (CSA) is a considerable public health problem. Less focus has been paid to the role of community level factors associated with CSA. The aim of this study was to examine the association between neighbourhood-level measures of social disorganization and CSA. Methods: We applied multiple multilevel logistic regression analysis on Demographic and Health Survey data for 6,351 adolescents from six countries in sub-Saharan Africa between 2006 and 2008. Results: The percentage of adolescents that had experienced CSA ranged from 1.04% to 5.84%. There was a significant variation in the odds of reporting CSA across the communities, suggesting 18% of the variation in CSA could be attributed to community level factors. Respondents currently employed were more likely to have reported CSA than those who were unemployed (odds ratio [OR] = 2.05, 95% confidence interval [CI] 1.48 to 2.83). Respondents from communities with a high family disruption rate were 57% more likely to have reported CSA (OR=1.57, 95% CI 1.14 to 2.16). Conclusion: We found that exposure to CSA was associated with high community level of family disruption, thus suggesting that neighbourhoods may indeed have significant important effects on exposure to CSA. Further studies are needed to explore pathways that connect the individual and neighbourhood levels, that is, means through which deleterious neighbourhood effects are transmitted to individuals
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