Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.FAPESP [2006/50479-7, 2006/60930-8, 2008/58817-4, 2009/54816-6 2010/50157-5]FAPESPCNPqCNPqINCT_if (CNPq)INCT-if CNPqCAPESCAPESPRP-USPPRPUS

International multicenter observational study on assessment of ventilatory management during general anaesthesia for robotic surgery and its effects on postoperative pulmonary complication (AVATaR) : study protocol and statistical analysis plan

Introduction: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. Methods and analysis: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. Ethics and dissemination: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number: NCT02989415; Pre-results

Incidence and risk factors for Preeclampsia in a cohort of healthy nulliparous pregnant women: a nested case-control study

The objective of this study is to determine the incidence, socio-demographic and clinical risk factors for preeclampsia and associated maternal and perinatal adverse outcomes. This is a nested case-control derived from the multicentre cohort study Preterm SAMBA, in five different centres in Brazil, with nulliparous healthy pregnant women. Clinical data were prospectively collected, and risk factors were assessed comparatively between PE cases and controls using risk ratio (RR) (95% CI) plus multivariate analysis. Complete data were available for 1,165 participants. The incidence of preeclampsia was 7.5%. Body mass index determined at the first medical visit and diastolic blood pressure over 75 mmHg at 20 weeks of gestation were independently associated with the occurrence of preeclampsia. Women with preeclampsia sustained a higher incidence of adverse maternal outcomes, including C-section (3.5 fold), preterm birth below 34 weeks of gestation (3.9 fold) and hospital stay longer than 5 days (5.8 fold) than controls. They also had worse perinatal outcomes, including lower birthweight (a mean 379 g lower), small for gestational age babies (RR 2.45 [1.52-3.95]), 5-minute Apgar score less than 7 (RR 2.11 [1.03-4.29]), NICU admission (RR 3.34 [1.61-6.9]) and Neonatal Near Miss (3.65 [1.78-7.49]). Weight gain rate per week, obesity and diastolic blood pressure equal to or higher than 75 mmHg at 20 weeks of gestation were shown to be associated with preeclampsia. Preeclampsia also led to a higher number of C-sections and prolonged hospital admission, in addition to worse neonatal outcomes9CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ401636/2013-5Bill and Melinda Gates FoundationGates Foundation [OPP1107597]; CNPqNational Council for Scientific and Technological Development (CNPq) [401636/2013-5

Cartografia e diplomacia: usos geopolíticos da informação toponímica (1750-1850)

O artigo explora dimensões geopolíticas da toponímia, registradas em documentos cartográficos, desde as reformas empreendidas pelo consulado pombalino em meados do século XVIII, até às primeiras décadas do século XIX, em meio ao processo de afirmação do Estado imperial pós-colonial.This paper explores the geopolitical dimensions of toponymy as registered in cartographic documents dating from the reforms pushed through by the consulate of Marquis of Pombal in the mid 18th century to the early decades of the 19th century, as the post-colonial imperial State established itself

Dengue Virus Type 4 Phylogenetics in Brazil 2011: Looking beyond the Veil

Dengue Fever and Dengue Hemorrhagic Fever are diseases affecting approximately 100 million people/year and are a major concern in developing countries. In the present study, the phylogenetic relationship of six strains of the first autochthonous cases of DENV-4 infection occurred in Sao Paulo State, Parana State and Rio Grande do Sul State, Brazil, 2011 were studied. Nucleotide sequences of the envelope gene were determined and compared with sequences representative of the genotypes I, II, III and Sylvatic for DEN4 retrieved from GenBank. We employed a Bayesian phylogenetic approach to reconstruct the phylogenetic relationships of Brazilian DENV-4 and we estimated evolutionary rates and dates of divergence for DENV-4 found in Brazil in 2011. All samples sequenced in this study were located in Genotype II. The studied strains are monophyletic and our data suggest that they have been evolving separately for at least 4 to 6 years. Our data suggest that the virus might have been present in the region for some time, without being noticed by Health Surveillance Services due to a low level of circulation and a higher prevalence of DENV-1 and DENV- 2

INVENTÁRIO E DIAGNÓSTICO DA ARBORIZAÇÃO URBANA VIÁRIA DE RIO BRANCO, AC

O presente trabalho foi desenvolvido dentro do perímetro urbano da cidade de Rio BrancoAC, localizada entre as coordenadas geográficas de 9°58’29’’ de latitude sul e 67°48’36’’ de longitude oeste. Teve como objetivo geral o levantamento e diagnóstico da arborização viária. A metodologia estatística utilizada foi definida tomando-se como unidade amostral o quarteirão. Encontrou-se pouquíssimos espécimes nas calçadas dos quarteirões amostrados, totalizando 292 indivíduos distribuídos por 39 espécies, sendo 11 nativas e 28 exóticas. A média por quarteirão foi de 1,83 árvores, e por quilômetro de calçada foi de 4,57 árvores. Concluiu-se que o número de árvores existentes nas calçadas foi muito pequeno, tendo-se como referência 100 árvores por quilômetro de calçada como ideal. A maioria das espécies encontrada era exótica (78,57%), a despeito da cidade encontrar-se numa região com uma das maiores diversidades de espécies arbóreas do planeta. Quanto ao estado físico, a copa normal foi predominante, exceto na região central. As recomendações indicadas foram primeiramente de se elaborar um plano de arborização urbana para o município, contendo referências técnicas para escolha das espécies, técnicas de manejo e programa de educação ambiental