Genetic Association Analysis of the Functional c.714T>G Polymorphism and Mucosal Expression of Dectin-1 in Inflammatory Bowel Disease

Contains fulltext : 80614.pdf (publisher's version ) (Open Access)BACKGROUND: Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes beta-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T>G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-alpha, interleukin (IL)-1beta and IL-17 upon in vitro stimulation with Candida albicans or beta-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T>G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients. METHODOLOGY: Paraffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn's disease and 759 patients with ulcerative colitis) and healthy controls (n = 772) was genotyped for the c.714T>G polymorphism and genotype-phenotype interactions were investigated. PRINCIPAL FINDINGS: Increased expression of dectin-1 was observed in actively inflamed colon tissue, as compared to non-inflamed tissue of the same patients. Also an increase in dectin-1 expression was apparent in diverticulitis tissue. No statistically significant difference in DECTIN-1 c.714T>G allele frequencies was observed between IBD patients and healthy controls. Furthermore, no differences in clinical characteristics could be observed related to DECTIN-1 genotype, neither alone, nor stratified for NOD2 genotype. CONCLUSIONS: Our data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in IBD. The DECTIN-1 c.714T>G polymorphism however, is not a major susceptibility factor for developing IBD

Developing argumentation skills in mathematics through computer-supported collaborative learning: the role of transactivity

Collaboration scripts and heuristic worked examples are effective means to scaffold university freshmen’s mathematical argumentation skills. Yet, which collaborative learning processes are responsible for these effects has remained unclear. Learners presumably will gain the most out of collaboration if the collaborators refer to each other’s contributions in a dialectic way (dialectic transactivity). Learners also may refer to each other’s contributions in a dialogic way (dialogic transactivity). Alternatively, learners may not refer to each other’s contributions at all, but still construct knowledge (constructive activities). This article investigates the extent to which constructive activities, dialogic transactivity, and dialectic transactivity generated by either the learner or the learning partner can explain the positive effects of collaboration scripts and heuristic worked examples on the learners’ disposition to use argumentation skills. We conducted a 2 × 2 experiment with the factors collaboration script and heuristic worked examples with N = 101 math teacher students. Results showed that the learners’ engagement in self-generated dialectic transactivity (i.e., responding to the learning partner’s contribution in an argumentative way by critiquing and/or integrating their learning partner’s contributions) mediated the effects of both scaffolds on their disposition to use argumentation skills, whereas partner-generated dialectic transactivity or any other measured collaborative learning activity did not. To support the disposition to use argumentation skills in mathematics, learning environments should thus be designed in a way to help learners display dialectic transactivity. Future research should investigate how learners might better benefit from the dialectic transactivity generated by their learning partners

The Functional −765G→C Polymorphism of the COX-2 Gene May Reduce the Risk of Developing Crohn's Disease

Contains fulltext : 87827.pdf (publisher's version ) (Open Access)BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of arachidonic acid into prostaglandins. COX-2 is mainly induced at sites of inflammation in response to proinflammatory cytokines such as interleukin-1alpha/beta, interferon-gamma and tumor necrosis factor-alpha produced by inflammatory cells. AIM: The aim of this study was to investigate the possible modulating effect of the functional COX-2 polymorphisms -1195 A-->G and -765G-->C on the risk for development of inflammatory bowel disease (IBD) in a Dutch population. METHODS: Genomic DNA of 525 patients with Crohn's disease (CD), 211 patients with ulcerative colitis (UC) and 973 healthy controls was genotyped for the -1195 A-->G (rs689466) and -765G-->C (rs20417) polymorphisms. Distribution of genotypes in patients and controls were compared and genotype-phenotype interactions were investigated. RESULTS: The genotype distribution of the -1195A-->G polymorphism was not different between the patients with CD or UC and the control group. The -765GG genotype was more prevalent in CD patients compared to controls with an OR of 1.33 (95%CI 1.04-1.69, pC polymorphism was associated with a reduced risk for developing Crohn's disease in a Dutch population

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

The functional UGT1A1*28 polymorphism is a protective factor for Crohn’s disease; reply to Dr. Vitek's letter

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Cecal volvulus caused by a large uterine leiomyoma

Introduction: Cecal volvulus is a relatively uncommon encountered clinical condition. Presentation of case: A 48-year-old patient known with a large uterine leiomyoma, presented with progressive abdominal pain since one week. An abdominal computed tomography scan revealed a very large leiomyoma of the uterus, severely distended loops of the small bowel with a caliber change and a suggested ‘whirl sign’ of the mesenteric vessels. A laparotomy was performed, showing a very large uterus as well as torsion of the mesentery of the cecum with a sharp demarcated area of necrosis of the right hemicolon. Discussion: Cecal volvulus due to a large uterine mass is a rare encountered clinical entity. The suggested mechanism might be the same mechanism causing cecal volvulus during pregnancy; the enlarged uterus raisingout the mobile cecum out of the pelvis. Obstruction may occur from kinking of the colon at a fixed point. Conclusion: This case demonstrates that uterine leiomyoma can be a cause of a cecal volvulus, leading to severe intestinal strangulation