New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Terapia cognitiva : aplicações de uma técnica para qualidade de vida e saúde

Esta pesquisa teve por objetivo geral aplicar e avaliar uma técnica específica de terapia cognitiva - organizada em 12 sessões grupais e denominada Tomada de Decisão e Qualidade de Vida -, destinada a promover saúde e incrementar qualidade de vida. No total, participaram 18 servidores de uma instituição pública de ensino superior. Nas etapas de admissão e de encerramento, aplicaram-se : Questionário de Qualidade de Vida, Inventário Beck de Ansiedade e Inventário Beck de Depressão. Foram identificadas melhoras significativas nos domínios físico, psicológico, meio ambiente, geral e saúde, relacionados à qualidade de vida. Não se verificaram alterações significantes nos escores de ansiedade (p=0,26). Em contrapartida, os escores de depressão indicaram melhora (p=0,02). Os resultados sugerem que a técnica pode ser empregada para promover saúde e qualidade de vida.In this study we implemented and assessed a specific cognitive therapy technique - Decision Making and Quality of Life, which is used to promote health and improve quality of life. Eighteen employees from a higher education institution participated in the study, which was organized into 12 group sessions. At the admission and concluding phases, we asked participants to complete the World Health Organization Quality of Life - Bref Questionnaire, the Beck Anxiety Inventory and the Beck Depression Inventory. Results showed significant improvement in five of the domains that measure quality of life: physical, psychological, environmental, general, and health. There were no significant changes (p=0.26) in anxiety scores. In contrast, the depression scores got significantly better (p=0.02). The results suggest that the proposed technique is conducive to health promotion and quality of life

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt