31 research outputs found

    The association between environmental exposures during childhood and the subsequent development of Crohn's Disease: A score analysis approach

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    Background Environmental factors during childhood are thought to play a role in the aetiology of Crohn's Disease (CD). In South Africa, recently published work based on an investigation of 14 childhood environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) has provided insight into the role of timing of exposure in the future development of CD. The 'overlapping' contribution of the investigated variables however, remains unclear. The aim of this study was to perform a post hoc analysis using this data and investigate the extent to which each variable contributes to the subsequent development of CD relative to each aforementioned age interval, based on a score analysis approach. Methods Three methods were used for the score analysis. Two methods employed the subgrouping of one or more (similar) variables (methods A and B), with each subgroup assigned a score value weighting equal to one. For comparison, the third approach (method 0) involved no grouping of the 14 variables. Thus, each variable held a score value of one. Results Results of the score analysis (Method 0) for the environmental exposures during 3 age intervals (0-5, 6-10 and 11-18 years) revealed no significant difference between the case and control groups. By contrast, results from Method A and Method B revealed a significant difference during all 3 age intervals between the case and control groups, with cases having significantly lower exposure scores (approximately 30% and 40% lower, respectively). Conclusion Results from the score analysis provide insight into the 'compound' effects from multiple environmental exposures in the aetiology of CD.IS

    Decreased proliferation of human melanoma cell lines caused by antisense RNA against translation factor eIF-4A1

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    Control of translation initiation was recognised as a critical checkpoint for cell proliferation and tumorigenesis. In human melanoma cells, we have previously reported consistent overexpression of translation initiation factor eIF-4A1. Here, we investigated by transfection of antisense constructs its significance for the control of melanoma cell growth. The tetracycline-inducible expression system was established in melanoma cells, and three fragments of the 5′-, central-, and 3′-portion of the eIF-4A1 cDNA were subcloned in antisense and in sense orientation after a tetracycline inducible promoter. Significant proliferation decrease was obtained after transient transfection and induction of antisense RNA directed against the 5′- and the central portion (up to 10%), whereas, no effects were seen after induction of the 3′-fragment and the sense controls. Cell clones stably transfected with the central antisense fragment revealed after doxycycline induction reduced expression of endogeneous eIF-4A1 mRNA correlated with decreased proliferation rates (up to 6%). These data demonstrate the applicability of antisense strategies against translation factors in melanoma cells. Translation initiation factor eIF-4A1 contributes to the control of melanoma cell proliferation and may be taken into consideration when scheduling new therapeutic approaches targeting the translational control

    Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease

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    We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn’s disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols

    Effective colonoscopy training techniques: strategies to improve patient outcomes

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    Ioannis S Papanikolaou,1 Pantelis S Karatzas,2 Lazaros T Varytimiadis,2 Athanasios Tsigaridas,2 Michail Galanopoulos,2 Nikos Viazis,2 Dimitrios G Karamanolis21Hepato-gastroenterology Unit, 2nd Department of Internal Medicine, Attikon University General Hospital, University of Athens, 2Gastroenterology Department, Evangelismos Hospital, Athens, GreeceAbstract: Colonoscopy has substantially evolved during the last 20 years and many different training techniques have been developed in order to improve the performance of endoscopists. The most known are mechanical simulators, virtual reality simulators, computer-simulating endoscopy, magnetic endoscopic imaging, and composite and explanted animal organ simulators. Current literature generally indicates that the use of simulators improves performance of endoscopists and enhances safety of patients, especially during the initial phase of training. Moreover, newer endoscopes and imaging techniques such as high-definition colonoscopes, chromocolonoscopy with dyes spraying, and third-eye retroscope have been incorporated in everyday practice, offering better visualization of the colon and detection of polyps. Despite the abundance of these different technological features, training devices are not widely used and no official guideline or specified training algorithm or technique for lower gastrointestinal endoscopy has been evolved. In this review, we present the most important training methods currently available and evaluate these using existing literature. We also try to propose a training algorithm for novice endoscopists.Keywords: endoscopy, colonoscopy, teaching techniques, simulator, endoscopists, colon, polyp
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