Functional characterization of 8-oxoguanine DNA glycosylase of Trypanosoma cruzi

The oxidative lesion 8-oxoguanine (8-oxoG) is removed during base excision repair by the 8-oxoguanine DNA glycosylase 1 (Ogg1). This lesion can erroneously pair with adenine, and the excision of this damaged base by Ogg1 enables the insertion of a guanine and prevents DNA mutation. In this report, we identified and characterized Ogg1 from the protozoan parasite Trypanosoma cruzi (TcOgg1), the causative agent of Chagas disease. Like most living organisms, T. cruzi is susceptible to oxidative stress, hence DNA repair is essential for its survival and improvement of infection. We verified that the TcOGG1 gene encodes an 8-oxoG DNA glycosylase by complementing an Ogg1-defective Saccharomyces cerevisiae strain. Heterologous expression of TcOGG1 reestablished the mutation frequency of the yeast mutant ogg1-/- (CD138) to wild type levels. We also demonstrate that the overexpression of TcOGG1 increases T. cruzi sensitivity to hydrogen peroxide (H2O2). Analysis of DNA lesions using quantitative PCR suggests that the increased susceptibility to H2O2 of TcOGG1-overexpressor could be a consequence of uncoupled BER in abasic sites and/or strand breaks generated after TcOgg1 removes 8-oxoG, which are not rapidly repaired by the subsequent BER enzymes. This hypothesis is supported by the observation that TcOGG1-overexpressors have reduced levels of 8-oxoG both in the nucleus and in the parasite mitochondrion. The localization of TcOgg1 was examined in parasite transfected with a TcOgg1-GFP fusion, which confirmed that this enzyme is in both organelles. Taken together, our data indicate that T. cruzi has a functional Ogg1 ortholog that participates in nuclear and mitochondrial BER. © 2012 Furtado et al

Upper tropospheric ozone production from lightning NOx-impacted convection: Smoke ingestion case study from the DC3 campaign

©2015. American Geophysical Union. All Rights Reserved. As part of the Deep Convective Cloud and Chemistry (DC3) experiment, the National Science Foundation/National Center for Atmospheric Research (NCAR) Gulfstream-V (GV) and NASA DC-8 research aircraft probed the chemical composition of the inflow and outflow of two convective storms (north storm, NS, south storm, SS) originating in the Colorado region on 22 June 2012, a time when the High Park wildfire was active in the area. A wide range of trace species were measured on board both aircraft including biomass burning (BB) tracers hydrogen cyanide (HCN) and acetonitrile (ACN). Acrolein, a much shorter lived tracer for BB, was also quantified on the GV. The data demonstrated that the NS had ingested fresh smoke from the High Park fire and as a consequence had a higher VOC OH reactivity than the SS. The SS lofted aged fire tracers along with other boundary layer ozone precursors and was more impacted by lightning NOx (LNOx) than the NS. The NCAR master mechanism box model was initialized with measurements made in the outflow of the two storms. The NS and SS were predicted to produce 11 and 14ppbv of O3, respectively, downwind of the storm over 2days. Sensitivity tests revealed that the ozone production potential of the SS was highly dependent on LNOx. Normalized excess mixing ratios, ΔX/ΔCO, for HCN and ACN were determined in both the fire plume and the storm outflow and found to be 7.0±0.5 and 2.3±0.5pptvppbv-1, respectively, and 1.4±0.3pptvppbv-1 for acrolein in the outflow only

Avaliação de desempenho: discutindo a tecnologia para o planejamento e gestão de recursos humanos em saúde

Este ensaio apresenta o produto de reflexões e análises a partir do exame de opções conceituais inerentes às metodologias de avaliação de desempenho (AD) de profissionais e sua possibilidade de aplicação na área da saúde. Estabelece uma discussão conceitual para a área, articulando e integrando conhecimentos de campos distintos - o da saúde e o da administração pública. Promove a intersecção entre a gestão do trabalho em saúde no setor público e as técnicas da administração de pessoal. Pretende gerar novas análises e estudos que possibilitem uma releitura das práticas administrativas para avaliação de desempenho utilizadas nas organizações, adaptá-las para atender às especificidades do setor saúde

Participation, knowledge production, and evaluative research: participation by different actors in a mental health study

This article reflects on the interrelations between participation, knowledge production, and public policy evaluation in light of issues from our own experience with evaluative research on a municipal network of Psychosocial Care Centers (CAPS) in Brazil. The article discusses the coordination of the complex process and the potentials and limits of partnerships for conducting qualitative evaluative studies in mental health with participation by different social actors. The authors conclude that qualitative evaluative research aligned with the perspective of including different points of view representing various segments is the best approach for understanding the numerous spin-offs from the implementation of services linked to the Brazilian psychiatric reform movement, given the inherent specificities of the mental health field.No presente texto apresentamos considerações sobre pesquisa avaliativa qualitativa e participativa com base em investigação desta natureza realizada junto a uma rede municipal de Centros de Atenção Psicossocial (CAPS) ligados ao Sistema Único de Saúde (SUS). A coordenação do complexo processo, bem como as potencialidades e limites do estabelecimento de parcerias para a realização de trabalhos de investigação avaliativa qualitativa em saúde mental, com a inclusão de diferentes atores sociais, são aqui discutidas. Concluímos que a pesquisa avaliativa qualitativa aliada à perspectiva de inclusão de distintos pontos de vista dos vários segmentos envolvidos é a que melhor se adequa à compreensão dos muitos desdobramentos oriundos da implementação de serviços ligados ao movimento de reforma psiquiátrica brasileira, dado as especificidades inerentes ao campo da saúde mental.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP)Universidade Estadual de Campinas FCMUNIFESPSciEL

Factors associated with uninvestigated dyspepsia in students at 4 Latin American schools of medicine: A multicenter study

Introduction and aims: Dyspepsia is a multifactorial disease that can involve alcohol, tobacco, or nonsteroidal anti-inflammatory drug use, as well as lifestyle, diet, socioeconomic elements, or psychologic factors. The aim of the present article was to establish the frequency of uninvestigated dyspepsia and determine its associated factors in students at 4 Latin American schools of medicine. Materials and methods: A cross-sectional, analytic study was conducted, in which a survey made up of closed-ended questions was applied at just one point in time. The association between the variables was then analyzed. A new questionnaire for the diagnosis of dyspepsia was one of the tests utilized to diagnose uninvestigated dyspepsia. Generalized linear models were used for the bivariate and multivariate analyses, employing the Poisson model with the log link function, obtaining crude prevalence ratios, adjusted prevalence ratios, and their 95% confidence intervals. Results: Of the 1,241 individuals surveyed, 54% (841) were females and the median age was 21 years (range: 19-23 years). Prevalence of uninvestigated dyspepsia was 46%. The factors that had a direct association with dyspepsia were: depression, difficulty sleeping, and coffee consumption. On the contrary, eating regularly in a boarding house and the mate sex had an inverse association. Conclusions: Uninvestigated dyspepsia frequency was high in students at 4 Latin American schools. Depression, difficulty sleeping, and steady coffee drinking were factors directly associated with dyspepsia, whereas male sex and eating out at regular hours were factors with a reverse association. Therefore, we recommend that universities implement early detection programs for this highly preventable pathology. Published by Masson Doyma Mexico S.A. on behalf of Asociacion Mexicana de Gastroenterologia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introducción y objetivos: La dispepsia es una enfermedad de naturaleza multifactorial, ya que podrían intervenir distintos factores, como el consumo de alcohol, tabaco o antiinflamatorios no esteroideos, el estilo de vida, factores dietéticos, socioeconómicos y psicológicos. El objetivo es establecer la frecuencia y determinar los factores asociados con dispepsia no investigada en estudiantes de 4 facultades de medicina de Latinoamérica. Materiales y métodos: Estudio transversal analítico, aplicando una encuesta cerrada en un solo periodo, analizando posteriormente la asociación entre las variables. Se usó el test A new questionnaire for the diagnosis of dyspepsia para el diagnóstico de dispepsia no investigada, entre otras pruebas. Para el análisis bivariado y multivariado se utilizaron los modelos lineales generalizados, usando la familia Poisson con función de enlace log, obteniendo razones de prevalencia crudas, ajustadas y sus intervalos de confianza al 95%. Resultados: De los 1,241 encuestados, el 54% (841) fueron del sexo femenino y la mediana de edad fue de 21 a˜nos (rango 19-23 a˜nos). La prevalencia de dispepsia no investigada fue del 46%. Los factores que tuvieron una asociación directa a la dispepsia fueron: depresión, problemas para conciliar el sue˜no y el consumo de café. Por el contrario, comer regularmente en una pensión y el sexo masculino tuvieron una asociación inversa. Conclusiones: La frecuencia de dispepsia no investigada fue alta en estudiantes de 4 escuelas latinoamericanas. La depresión, la dificultad para dormir y el consumo constante de café fueron factores que se asociaron directamente con la dispepsia, mientras que el sexo masculino y el comer regularmente en una pensión fueron factores con una asociación inversa. Por lo tanto, recomendamos que las universidades implementen programas de detección temprana para esta patología altamente prevenible

Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

Dermatological remedies in the traditional pharmacopoeia of Vulture-Alto Bradano, inland southern Italy

Dermatological remedies make up at least one-third of the traditional pharmacopoeia in southern Italy. The identification of folk remedies for the skin is important both for the preservation of traditional medical knowledge and in the search for novel antimicrobial agents in the treatment of skin and soft tissue infection (SSTI). Our goal is to document traditional remedies from botanical, animal, mineral and industrial sources for the topical treatment of skin ailments. In addition to SSTI remedies for humans, we also discuss certain ethnoveterinary applications. Field research was conducted in ten communities in the Vulture-Alto Bradano area of the Basilicata province, southern Italy. We randomly sampled 112 interviewees, stratified by age and gender. After obtaining prior informed consent, we collected data through semi-structured interviews, participant-observation, and small focus groups techniques. Voucher specimens of all cited botanic species were deposited at FTG and HLUC herbaria located in the US and Italy. We report the preparation and topical application of 116 remedies derived from 38 plant species. Remedies are used to treat laceration, burn wound, wart, inflammation, rash, dental abscess, furuncle, dermatitis, and other conditions. The pharmacopoeia also includes 49 animal remedies derived from sources such as pigs, slugs, and humans. Ethnoveterinary medicine, which incorporates both animal and plant derived remedies, is addressed. We also examine the recent decline in knowledge regarding the dermatological pharmacopoeia. The traditional dermatological pharmacopoeia of Vulture-Alto Bradano is based on a dynamic folk medical construct of natural and spiritual illness and healing. Remedies are used to treat more than 45 skin and soft tissue conditions of both humans and animals. Of the total 165 remedies reported, 110 have never before been published in the mainland southern Italian ethnomedical literature

Genetic prediction of complex traits: integrating infinitesimal and marked genetic effects

Genetic prediction for complex traits is usually based on models including individual (infinitesimal) or marker effects. Here, we concentrate on models including both the individual and the marker effects. In particular, we develop a ''Mendelian segregation'' model combining infinitesimal effects for base individuals and realized Mendelian sampling in descendants described by the available DNA data. The model is illustrated with an example and the analyses of a public simulated data file. Further, the potential contribution of such models is assessed by simulation. Accuracy, measured as the correlation between true (simulated) and predicted genetic values, was similar for all models compared under different genetic backgrounds. As expected, the segregation model is worthwhile when markers capture a low fraction of total genetic variance. (Résumé d'auteur