Federal University of São Paulo

About: Federal University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Transplantation. The organization has 27971 authors who have published 49365 publications receiving 935536 citations. The organization is also known as: Universidade Federal de São Paulo & Universidade Federal de Sao Paulo.

HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

Abstract: Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

The concepts of health access

Abstract: This article describes four dimensions of health access-availability, acceptability, ability to pay and information-correlating these dimensions to indicators and discussing the complexity of the concept of access. For a study of these four dimensions, searches were conducted using the PubMed/MEDLINE, LILACS, SciELO, and World Health Organization Library & Information Networks for Knowledge (WHOLIS) databases. Large-circulation media vehicles, such as The Economist, The Washington Post, and the BBC network were also searched. The concept of health access has become more complex with time. The first analyses, carried out in the 1970s, suggested a strong emphasis on geographical (availability) and financial (ability to pay) aspects. More recently, the literature has focused on less tangible aspects, such as cultural, educational, and socioeconomic issues, incorporating the element of acceptability into the notion of health access. The literature also shows that information provides the starting point for access to health, in association with health empowerment and literacy for health care decision-making. The study concludes that improvements in access to health and the guarantee of equity will not be achieved by initiatives focusing on health care systems alone, but rather will depend on intersectoral actions and social and economic policies aimed at eliminating income and education differences.

A step test to assess exercise-related oxygen desaturation in interstitial lung disease

Abstract: A 6-min step test (6MST) may constitute a practical method for routinely assessing effort tolerance and exercise-related oxyhaemoglobin desaturation (ERD) in the primary care of patients with interstitial lung disease. In total, 31 patients (19 males) with idiopathic pulmonary fibrosis (n = 25) and chronic hypersensitivity pneumonia were submitted, on different days, to two 6MSTs. Physiological responses were compared with those found on maximal and submaximal cycle ergometer tests at the same oxygen uptake ( V ′ O 2 ). Chronic breathlessness was also determined, as measured by the baseline dyspnoea index (BDI). Responses to 6MST were highly reproducible: 1.3±2.0 steps·min -1 , ±5 beats·min -1 (cardiac frequency), ±50 mL·min -1 ( V ′ O 2 ), ±7 L·min -1 (minute ventilation) and ±2% (arterial oxygen saturation measured by pulse oximetry ( S p,O 2 )). The number of steps climbed in 6 min was correlated to peak V ′ O 2 and the BDI. There were significant associations among the tests in relation to presence (change in S p,O 2 between rest and exercise ≥4%) and severity ( S p,O 2 A single-stage, self-paced 6-min step test provided reliable and reproducible estimates of exercise capacity and exercise-related oxyhaemoglobin desaturation in interstitial lung disease patients.

A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.

Abstract: In eukaryotic cells, phosphoinositides are lipid second messengers important for many cellular processes and have been found dysregulated in several human diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P) phosphatase called myotubularin, and mutations in dominant centronuclear myopathy (CNM) cases were identified in the dynamin 2 gene. The genes mutated in autosomal recessive cases of CNMs have not been found. We have identified a novel phosphoinositide phosphatase (hJUMPY) conserved through evolution, which dephosphorylates the same substrates as myotubularin, PtdIns3P and PtdIns(3,5)P(2), in vitro and ex vivo. We found, in sporadic cases of CNMs, two missense variants that affect the enzymatic function. One of these appeared de novo in a patient also carrying a de novo mutation in the dynamin 2 gene. The other missense (R336Q) found in another patient changes the catalytic arginine residue of the core phosphatase signature present in protein tyrosine/dual-specificity phosphatases and in phosphoinositide phosphatases and drastically reduces the enzymatic activity both in vitro and in transfected cells. The inheritance of the phenotype with regard to this variant is still unclear and could be either recessive with an undetected second allele or digenic. We propose that impairment of hJUMPY function is implicated in some cases of autosomal CNM and that hJUMPY cooperates with myotubularin to regulate the level of phosphoinositides in skeletal muscle.