Hirschsprung-associated enterocolitis develops independently of NOD2 variants

Backgroud/Purpose

Hirschsprung-associated enterocolitis (HAEC) represents a cause for significant pre- and postoperative morbidity and mortality in Hirschsprung disease (HD). Although multiple studies on HAEC have been performed and several mechanisms have been presumed, the pathogenesis of this condition remains unclear. As changes in colonic mucosal defense are key factors suggested in both Crohn's disease (CD) and HAEC pathogenesis, the aim of the current study was to investigate genetic alterations in the most important susceptibility gene for Crohn's enterocolitis (NOD2) to see whether carriers of polymorphisms within the NOD2 gene are predisposed to the development of HAEC.

Methods

Genotyping for the NOD2 variants in exon 4 (p.Arg702Trp [rs2066844]), exon 8 (p.Gly908Arg [rs2066845]), and exon 11 (p.1007fs [rs2066847]) was performed in 52 white children with HD (41 boys, 11 girls), 152 healthy controls, and 152 children with CD (onset of disease <17 years; mean, 11.8 years). Seventeen patients with HD (32.7%) were carriers of a RET germline mutation, 35 children (67.3%) had short segment disease, and 17 (32.7%) had long segment disease.

Results

Ten children (19.2%) with HD were heterozygous carriers of at least one NOD2 variant vs 17 (11.2%) in the healthy control group and 69 (45.4%) in the CD cohort. Hirschsprung-associated enterocolitis was observed in 7 children (13.5%), with 4 having short segment HD and 3 with long segment HD; but none of them were carriers of NOD2 variants.

Conclusion

Our study shows that NOD2 variants described to be causatively associated with CD do not predispose to the development of HAEC. As data on the molecular basis of HAEC are limited, the distinct mechanisms involved in the pathogenesis of this complication remain unclear.     

Usual Intake of Flavonoids Is Inversely Associated with Metabolic Syndrome in African American and White Males but Not Females in Baltimore City,Maryland, USA

Despite research that suggests flavonoids protect against metabolic syndrome (MetS) and evidence that intake of these compounds differs by race, knowledge about whether flavonoid–MetS associations vary among racial groups is limited. This study sought to estimate usual total flavonoid intake in African American and White adults and assess its sex- and sex/race-specific associations with MetS and its risk factors. Analysis of cross-sectional data from 1837 adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were analyzed. Usual total flavonoid intake was estimated using the NCI Method, and logistic regression measured its linkages with health outcomes. Among males overall and when stratified by race, odds of MetS and its risk factors low high-density lipoprotein cholesterol (HDL-C) and elevated glucose were lower at the 75th percentile of usual total flavonoid intake than at the 25th percentile (OR for MetS = 0.62; 95% CI = 0.53, 0.71). However, low HDL-C and elevated glucose were positively associated with usual flavonoid intake among females. The comparable associations by race within sex imply that the relationships between flavonoid and health outcomes may be evident across an array of intakes.     

Why MSM in Rural South African Communities Should be an HIV Prevention Research Priority

Research into HIV and men who have sex with men’s (MSM) health in South Africa has been largely confined to the metropolitan centres. Only two studies were located making reference to MSM in rural contexts or same-sex behaviors among men in the same. There is growing recognition in South Africa that MSM are not only disproportionately affected by HIV and have been underserved by the country’s national response, but that they contribute significantly to sustaining the high number of new infections recorded each year. We argue that to meet the objectives of the country’s national strategic plan for HIV, STI and TB it is important we know how these behaviours may be contributing to the sustained rural HIV epidemic in the youngest age groups and determine what constitutes appropriate and feasible programmatic response that can be implemented in the country’s public sector health services.     

An analysis of the influence of framework aspects on the study design of health economic modeling evaluations

Research and practical guidelines have many implications for how to structure a health economic study. A major focus in recent decades has been the quality of health economic research. In practice, the factors influencing a study design are not limited to the quest for quality. Moreover, the framework of the study is important. This research addresses three major questions related to these framework aspects. First, we want to know whether the design of health economic studies has changed over time. Second, we want to know how the subject of a study, whether it is a process or product innovation, influences the parameters of the study design. Third, one of the most important questions we will answer is whether and how the study’s source of funding has an impact on the design of the research. To answer these questions, a total of 234 health economic studies were analyzed using a correspondence analysis and a logistic regression analysis. All three categories of framework factors have an influence on the aspects of the study design. Health economic studies have evolved over time, leading to the use of more advanced methods like complex sensitivity analyses. Additionally, the patient’s point of view has increased in importance. The evaluation of product innovations has focused more on utility concepts. On the other hand, the source of funding may influence only a few aspects of the study design, such as the use of evaluation methods, the source of data, and the use of certain utility measures. The most important trends in health care, such as the emphasis on the patients’ point of view, become increasingly established in health economic evaluations with the passage of time. Although methodological challenges remain, modern information and communication technologies provide a basis for increasing the complexity and quality of health economic studies if used frequently.     

MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage

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