397 research outputs found

    Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

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    The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

    Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors

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    Here we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin's favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities

    Control of amino-acid transport coordinates metabolic reprogramming in T cell malignancy

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    This study explores the regulation and importance of System L amino acid transport in a murine model of T cell acute lymphoblastic leukemia (T-ALL) caused by deletion of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). There has been a strong focus on glucose transport in leukemias but the present data show that primary T-ALL cells have increased transport of multiple nutrients. Specifically, increased leucine transport in T-ALL fuels mammalian target of rapamycin complex 1 (mTORC1) activity which then sustains expression of hypoxia inducible factor-1α (HIF1α) and c-Myc; drivers of glucose metabolism in T cells. A key finding is that PTEN deletion and phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) accumulation is insufficient to initiate leucine uptake, mTORC1 activity, HIF1α or c-Myc expression in T cells and hence cannot drive T-ALL metabolic reprogramming. Instead, a key regulator for leucine transport in T-ALL is identified as NOTCH. Mass spectrometry based proteomics identifies SLC7A5 as the predominant amino acid transporter in primary PTEN(-/-) T-ALL cells. Importantly, expression of SLC7A5 is critical for the malignant transformation induced by PTEN deletion. These data reveal the importance of regulated amino acid transport for T cell malignancies, highlighting how a single amino acid transporter can play a key role.Leukemia accepted article preview online, 26 May 2017. doi:10.1038/leu.2017.160.</p

    Entrepreneurial-intention constraint model: A comparative analysis among post-graduate management students in India, Singapore and Malaysia

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    YesAlthough literature on entrepreneurship has increasingly focused on intention-based models, not much emphasis has been laid on understanding the combined effect of contextual and situational factors along with support of university environment on the formation of entrepreneurial intention among students. In an effort to make up for this shortfall, by taking Theory of Planned Behavior as basic framework, the present study seeks to understand the influence of three of the most important factors, viz. (a) endogenous barriers, (b) exogenous environment, and (c) university environment and support on the entrepreneurial intention among management students. The study sample consisted of 1,097 students, wherein 526 students were from India, 252 from Singapore, and 319 were from Malaysia. The results indicates that along with positive attitude and perceived behavioral control that directly influences entrepreneurial intention, university environment and support and exogenous environment also have an indirect but significant impact on shaping of entrepreneurial intention among students. With this, it was found that exogenous environment was found to have a negative relationship with both attitude towards behavior and perceived behavioral control for all three countries.The full-text of this article will be released for public view at the end of the publisher embargo on 2 Jun 2018

    Ideological Labels in America

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    This paper extends Ellis and Stimson’s (Ideology in America. New York: Cambridge UniversityPress, 2012) study of the operational-symbolic paradox using issue-level measures of ideological incongruence based on respondent positions and symbolic labels for these positions across 14 issues. Like Ellis and Stimson, we find that substantial numbers—over 30 %—of Americans experience conflicted conservatism. Our issue-level data reveal, furthermore, that conflicted conservatism is most common on the issues of education and welfare spending. In addition, we also find that 20 % of Americans exhibit conflicted liberalism. We then replicate Ellis and Stimson’s finding that conflicted conservatism is associated with low sophistication and religiosity, but also find that it is associated with being socialized in a post-1960s generation and using Fox News as a main news source. Finally, we show the important role played by identities, with both conflicted conservatism and conflicted liberalism linked with partisan and ideological identities, and conflicted liberalism additionally associated with ethnic identities

    The impact of positive psychological interventions on well-being in healthy elderly people

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    This systematic review aims to evaluate the impact of Positive Psychological Interventions (PPIs) on well-being in healthy older adults. Systematic review of PPIs obtained from three electronic databases (PsycINFO, Scopus, and Web of Science) was undertaken. Inclusion criteria were: that they were positive psychology intervention, included measurement of well-being, participants were aged over 60 years, and the studies were in English. The Cochrane Collaboration Guidelines dimensions of quality control, randomization, comparability, follow-up rate, dropout, blinding assessors are used to rate the quality of studies by two reviewers independently. The RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) for evaluation of PPIs effectiveness was also applied. The final review included eight articles, each describing a positive psychological intervention study. The reminiscence interventions were the most prevalent type of PPIs to promote and maintain well-being in later life. Only two studies were rated as high quality, four were of moderate-quality and two were of low-quality. Overall results indicated that efficacy criteria (89%), reach criteria (85%), adoption criteria (73%), implementation criteria (67%), and maintenance criteria (4%) across a variety of RE-AIM dimensions. Directions for future positive psychological research related to RE-AIM, and implications for decision-making, are described

    The combined effect of gender and age on post traumatic stress disorder: do men and women show differences in the lifespan distribution of the disorder?

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    <p>Abstract</p> <p>Background</p> <p>The aim of the study was to examine the combined effect of gender and age on post traumatic stress disorder (PTSD) in order to describe a possible gender difference in the lifespan distribution of PTSD.</p> <p>Methods</p> <p>Data were collected from previous Danish and Nordic studies of PTSD or trauma. The final sample was composed of 6,548 participants, 2,768 (42.3%) men and 3,780 (57.7%) women. PTSD was measured based on the Harvard Trauma Questionnaire, part IV (HTQ-IV).</p> <p>Results</p> <p>Men and women differed in lifespan distribution of PTSD. The highest prevalence of PTSD was seen in the early 40s for men and in the early 50s for women, while the lowest prevalence for both genders was in the early 70s. Women had an overall twofold higher PTSD prevalence than men. However, at some ages the female to male ratio was nearly 3:1. The highest female to male ratio was found for the 21 to 25 year-olds.</p> <p>Conclusions</p> <p>The lifespan gender differences indicate the importance of including reproductive factors and social responsibilities in the understanding of the development of PTSD.</p

    Can differences in medical drug compliance between European countries be explained by social factors: analyses based on data from the European Social Survey, round 2

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    <p>Abstract</p> <p>Background</p> <p>Non-compliance with medication is a major health problem. Cultural differences may explain different compliance patterns. The size of the compliance burden and the impact of socio-demographic and socio-economic status within and across countries in Europe have, however, never been analysed in one survey. The aim of this study was to analyse 1) medical drug compliance in different European countries with respect to socio-demographic and socio-economic factors, and to examine 2) whether cross-national differences could be explained by these factors.</p> <p>Methods</p> <p>A multi-country interview survey <it>European Social Survey, Round 2 </it>was conducted in 2004/05 comprising questions about compliance with last prescribed drug. Non-compliance was classified as primary and secondary, depending whether the drug was purchased or not. Statistical weighting allowed for adjustment for national differences in sample mechanisms. A multiple imputation strategy was used to compensate for missing values. The analytical approach included multivariate and multilevel analyses.</p> <p>Results</p> <p>The survey comprised 45,678 participants. Response rate was 62.5% (range 43.6–79.1%). Reported compliance was generally high (82%) but the pattern of non-compliance showed large variation between countries. Some 3.2% did not purchase the most recently prescribed medicine, and 13.6% did not take the medicine as prescribed. Multiple regression analyses showed that each variable had very different and in some cases opposite impact on compliance within countries. The multilevel analysis showed that the variation between countries did not change significantly when adjusted for increasing numbers of covariates.</p> <p>Conclusion</p> <p>Reported compliance was generally high but showed wide variation between countries. Cross-national differences could, however, not be explained by the socio-demographic and socio-economic variables measured.</p
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