Genetic Evidence Supporting the Association of Protease and Protease Inhibitor Genes with Inflammatory Bowel Disease: A Systematic Review

As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family

Avaliação de exposições médicas em procedimentos pediátricos de radiologia intervencionista

OBJETIVO: Avaliar as exposições pediátricas de radiologia intervencionista em dois hospitais do Estado da Bahia, visando contribuir para a construção de um cenário estadual e nacional, possibilitando o conhecimento das exposições e da necessidade de sua otimização, visto que as peculiaridades que envolvem a radiologia e a pediatria se potencializam quando se trata de procedimentos de radiologia intervencionista, em razão das doses elevadas de radiação. MATERIAIS E MÉTODOS: Foram avaliados 32 procedimentos em quatro salas nos dois principais hospitais que realizam procedimentos de radiologia intervencionista pediátrica na Bahia. Foram avaliados os valores de kerma no ar incidente e o produto kerma-área no ar de 27 procedimentos cardiológicos e 5 procedimentos cerebrais. RESULTADOS: Os valores máximos de produto kerma-área e kerma obtidos para procedimentos cardiológicos foram, respectivamente, 129,9 Gy.cm² e 947,0 mGy, e para procedimentos cerebrais, 83,3 Gy.cm² e 961,0 mGy. CONCLUSÃO: Os resultados deste estudo mostraram valores de exposições superiores em até 14 vezes os obtidos em estudos realizados em outros países, chegando próximos de resultados obtidos para procedimentos em adultos. Isto revela quão elevadas podem ser as exposições pediátricas, indicando a necessidade de constante otimização dos procedimentos e avaliação das exposições

Genetic Epidemiology of Psoriasis

Psoriasis is a chronic, inflammatory, immune-mediated skin condition with a prevalence of 0-11.8% across the world. It is associated with a number of cardiovascular, metabolic, and autoimmune disease co-morbidities. Psoriasis is a multifactorial disorder, influenced by both genetic and environmental factors. Its genetic basis has long been established through twin studies and familial clustering. The association of psoriasis with the HLA-Cw6 allele has been shown in many studies. Recent genome-wide association studies have identified a large number of other genes associated with psoriasis. Many of these genes regulate the innate and adaptive immune system. These findings indicate that a dysregulated immune system may play a major role in the pathogenesis of psoriasis. In this article, we review the clinical and genetic epidemiology of psoriasis with a brief description of the pathogenesis of disease