Identifying Regulators for EAG1 Channels with a Novel Electrophysiology and Tryptophan Fluorescence Based Screen

Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands.Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region.Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels

Planning oral health care using the sociodental approach and the index of family living conditions: a cross-sectional study in Brazilian adolescents.

BACKGROUND: Oral health care needs assessment is frequently restricted to clinical measures. Combining normative assessment, behavioural propensity, oral health-related quality of life and information of family living conditions may provide a better comprehensive approach of adolescent's oral health needs assessment. The aim of this study was to compare normative methods of dental caries need with the sociodental approach in 12-year-old adolescents according to family's living conditions in a deprived community in Brazil. In addition, dental caries need assessment using the normative method and the sociodental approach was compared between adolescents living in different living conditions. METHODS: A cross-sectional survey was conducted in the Manguinhos community in the city of Rio de Janeiro, Brazil. A weighted sample of 159 participants was randomly selected to represent the population of 2004 12-year-old adolescents. Socioeconomic characteristics and living conditions of the family were assessed using the Family Development Index (FDI). Oral health-related quality of life (OHRQoL) was assessed using the generic and CS-Child-OIDP, and adolescent's propensity to adopt oral health promoting behaviours was verified through interviews. Dental caries and treatment need were assessed normatively by clinical oral examinations (DMFT Index) and adolescents were classified into two groups (non severe or severe caries). The sociodental approach included clinical measures of caries, propensity to adopt oral health promoting behaviors and OHRQoL. Families were classified based on the FDI as 'not severe', 'severe' and 'very severe'. Measures of caries, OHRQoL and propensity outcomes were compared between FDI groups using Chi-square and Kruskal-Wallis tests. In addition, dental treatment needs using normative method and sociodental approach were compared for the whole sample and according to FDI groups. RESULTS: Dental caries, OHRQoL and lower propensity needs were positively associated with FDI severity. The percentages of adolescents with normative dental needs from families with 'very severe', 'severe' and 'not severe' FDI were 59.3, 48.4 and 17.2 % (P < 0.05). Using the sociodental approach, the treatment needs for the three FDI groups decreased to 8.8, 13.6 and 8.6 %, respectively (P < 0.05). CONCLUSIONS: Using a combination of sociodental approach and the index of family living conditions was useful for defining dental care priorities in adolescents living in deprived communities and can optimise the use of resources in dental services

Neutrophil Paralysis in Plasmodium vivax Malaria

Plasmodium vivax is responsible for approximately 60–80% of the malaria cases in the world, and contributes to significant social and economic instability in the developing countries of Latin America and Asia. The pathogenesis of P. vivax malaria is a consequence of host derived inflammatory mediators. Hence, a better understanding of the mechanisms involved in induction of systemic inflammation during P. vivax malaria is critical for the clinical management and prevention of severe disease. The innate immune receptors recognize Plasmodium sp. and initiate a broad spectrum of host defense mechanisms that mediate resistance to infection. However, the innate immune response is the classic “two-edged sword”, and clinical malaria is associated with high levels of circulating pro-inflammatory cytokines. Our findings show that both monocytes and neutrophils are highly activated during malaria. Monocytes produced high levels of IL-1β, IL-6 and TNF-α during acute malaria. On the other hand, neutrophils were a poor source of cytokines, but displayed an enhanced phagocytic activity and superoxide production. Unexpectedly, we noticed an impaired chemotaxis of neutrophils towards an IL-8 (CXCL8) gradient. We proposed that neutrophil paralysis is in part responsible for the enhanced susceptibility to bacterial infection observed in malaria patients

Asma e gravidez: repercussões no recém-nascido

OBJETIVO: Descrever, numa coorte de nascimentos, aspectos socioeconômicos e comportamentais de gestantes com asma e analisar as repercussões desta sobre alguns parâmetros perinatais. MÉTODOS: Estudo observacional, transversal e analítico a partir de informações de parturientes da coorte de nascimentos ocorridos no período entre 8 de março e 15 de julho de 2005 nas maternidades da Grande Aracaju (SE). A identificação de asma nas gestantes foi obtida segundo informação destas a partir do diagnóstico emitido anteriormente por um médico. Foram analisadas variáveis epidemiológicas, obstétricas e perinatais. RESULTADOS: Das 4.757 parturientes incluídas no estudo, 299 (6,3%) eram asmáticas. As mães asmáticas tinham menor renda familiar e mais frequentemente procuraram assistência no pré-natal e no parto em serviços públicos que as mães sem asma. Embora somente 9,4% das gestantes asmáticas fumaram, e 27,6% ingeriram bebidas alcoólicas, as proporções em relação ao grupo controle foram significativamente maiores. Não se detectou associação entre asma e problemas obstétricos ou do recém-nascido. Não foi encontrada associação entre asma e parto cesariano, prematuridade ou recém-nascido sendo pequeno para a idade gestacional. CONCLUSÕES: O nível socioeconômico inferior parece ser um fator de risco para a asma

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research