Variação de peso corporal de pacientes em diálise peritoneal

Este estudo teve como objetivo principal avaliar a variação de peso corporal de pacientes em diálise peritoneal (DP) durante o primeiro ano de tratamento e, como objetivo secundário, identificar pacientes com critério para síndrome metabólica (SM). Estudo observacional, com 35 pacientes, com o mínimo de um ano em DP, de um hospital universitário. Foram coletados dados quanto à situação clínica e demográfica, à variação de peso corporal e aos critérios para SM. Após doze meses do início da diálise, aproximadamente 40% dos pacientes apresentava sobrepeso e/ou obesidade. A média de variação de peso corporal após um ano foi de 3,7 kg, sendo que a maior variação foi encontrada nos primeiros três meses, com valores de 2,2 kg. A prevalência de SM foi de 30%. Conclui-se que a variação de peso corporal mais importante aconteceu no primeiro ano de tratamento e há uma alta prevalência de SM nos pacientes em DP.

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.info:eu-repo/semantics/publishedVersio

Identification of nuclear factor-kappa B sites in the Slc2a4 gene promoter

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis. Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature. Inflammatory NF-kappa B transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site(s) in Slc2a4 promoter and the direct repressor effect have never been reported yet. A motif-based sequence analysis of mouse Slc2a4 promoter revealed two putative kappa B sites located inside -83/-62 and -134/-113 bp. Eletrophoretic mobility assay showed that p50 and p65 NF-kappa B subunits bind to both putative kappa B sites. Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50- and p65-binding to Slc2a4 promoter. Moreover, transfection experiments revealed that NF-kappa B binds to the -134/-113 bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription. The current findings demonstrate the existence of two kappa B sites in Slc2a4 gene promote, and that NF-kappa B has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.370416718795Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [07/50554-1, 08/09194-4, 11/08570-5