Chagas disease, caused by the parasite Trypanosoma cruzi, occurs most commonly in Latin America. As the treatment is highly toxic and ineffective in the chronic phase of the disease, alternative treatments are needed. Through quantitative structure-activity relationship modeling (QSAR) analysis using ligand-based and structure-based virtual screening methods, we predicted the trypanocidal potential of 47 neolignans against three targets, the enzymes cruzain, trypanothione reductase, and sterol 14-alpha demethylase. A combined analysis allowed for the selection of potent inhibitors against Trypanosoma cruzi. Of these compounds, two were isolated and shown to inhibit the growth of epimastigotes at concentrations of 9.64 and 8.72 µM, and trypomastigote forms at 4.88 and 2.73 µM. Therefore, the compounds (2R, 3R)-2,3-dihydro-2 (4 methoxyphenyl)-3-methyl-5-(E)-propenylbenzofuran (46) and ottomentosa (47) may be a good option of growth inhibitors for the parasite stages and warrant additional study.

Abstract Background The autonomic nervous system (ANS) imbalance in heart failure (HF) creates a vicious cycle, excess sympathetic activity, and decreased vagal activity contributing to the worsening of HF. Low-intensity transcutaneous electrical stimulation of the auricular branch of the vagus nerve (taVNS) is well tolerated and opens new therapeutic possibilities. Objectives To hypothesize the applicability and benefit of taVNS in HF through intergroup comparison of echocardiography parameters, 6-minute walk test, Holter heart rate variability (SDNN and rMSSD), Minnesota quality of life questionnaire, and functional class by the New York Heart Association. In comparisons, p values <0.05 were considered significant. Methods Prospective, double-blind, randomized clinical study with sham methodology, unicentric. Forty-three patients were evaluated and divided into 2 groups: Group 1 received taVNS (frequencies 2/15 Hz), and Group 2 received sham. In comparisons, p values <0.05 were considered significant. Results In the post-intervention phase, it was observed that Group 1 had better rMSSD (31 x 21; p = 0.046) and achieved better SDNN (110 vs. 84, p = 0.033). When comparing intragroup parameters before and after the intervention, it was observed that all of them improved significantly in group 1, and there were no differences in group 2. Conclusion taVNS is a safe to perform and easy intervention and suggests a probable benefit in HF by improving heart rate variability, which indicates better autonomic balance. New studies with more patients are needed to answer the questions raised by this study.

Resumo Fundamento O desequilíbrio do sistema nervoso autônomo (SNA) na insuficiência cardíaca (IC) cria um ciclo vicioso, o excesso de atividade simpática e a diminuição da atividade vagal contribuindo para a piora da IC. A estimulação elétrica transcutânea de baixa intensidade do ramo auricular do nervo vago (taVNS) é bem tolerada e abre novas possibilidades terapêuticas. Objetivos Gerar hipótese da aplicabilidade e benefício da taVNS na IC através da comparação intergrupos de parâmetros ecocardiográficos, teste de caminhada de 6 min, variabilidade da frequência cardíaca pelo Holter (SDNN e rMSSD), questionário de qualidade de vida de Minnesota e classe funcional pela New York Heart Association. Métodos Estudo clínico prospectivo, duplo cego, randomizado com metodologia sham, unicêntrico. Avaliados 43 pacientes e alocados em 2 grupos: o Grupo 1 recebeu taVNS (frequências 2/15 Hz) e Grupo 2 recebeu sham. Nas comparações, valores de p<0,05 foram considerados significativos. Resultados Na fase pós-intervenção, observou-se que o Grupo 1 se manteve com melhor rMSSD (31 x 21; p = 0,046) e atingiu melhor SDNN (110 vs. 84, p = 0,033). Ao compararmos os parâmetros intragrupos, antes e após intervenção, observou-se que todos melhoraram significativamente no grupo 1 e não houve diferenças no grupo 2. Conclusão A taVNS é uma intervenção segura, de fácil execução e que sugere provável benefício na IC pela melhora na variabilidade da frequência cardíaca, o que indica melhor equilíbrio autonômico. Novos estudos com maior número de pacientes são necessários para responder às questões levantadas por esse estudo.

Phytochemical study of the roots of Euphorbia phosphorea Mart. (Euphorbiaceae) was carried out through chromatographic techniques, resulting in the isolation of a new ent-abietane diterpene named 11β,12β-dihydroxy-ent-abieta-8(14),13(15)-dien-16,12α-olide (1), and of nine known ent-abietane diterpenes jolkinolide A (2), jolkinolide E (3), euphorin H (4), euphopilolide (5) jolkinolide F (6), ent-12-hydroxy-12[R]-abieta-8(14),13(15)-dien-16,12-olide (7), ent-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide (8), 17-hydroxyjolkinolide B (9) and caudicifolin (10). The structures of all compounds were established using spectroscopic techniques such as 1D and 2D NMR, and the structure of the compound 1 was established also with MS, IR and ECD. All compounds were submitted to an in silico study through of a predictive model and then submitted to in vitro tests against Mycobacterium tuberculosis and M. smegmatis for evaluation of their antimycobacterial activity. Compounds 5 and 9 showed mycobacterial growth inhibition with MIC values of 62.5 μM against M. tuberculosis and M. smegmatis, respectively.

The Annonaceae family of plants is one of the most anatomically and structurally uniform families. Chemotaxonomy is a common practice to determine the chemical patterns within these families at different phylogenetic levels. The aim of this study was to build a dataset of all the secondary metabolites isolated within the Annonaceae family and to perform the respective chemotaxonomic analysis using self-organizing maps (SOMs). This dataset is composed of 5321botanical occurrences and 1860 unique molecules present in all subfamilies of the Annonaceae. Diterpenes account for 366 unique compounds and 533 botanical occurrences seen in both Annonoideae and Malmeoideae subfamilies. The Annoneae, Xylopieae and Miliuseae tribes had the highest number of botanical occurrences and were therefore selected for the analysis. Molecular descriptors of the diterpenes and their respective botanical occurrences were used to generate the SOMs. These SOMs demonstrated clear and indicative tribe separations, with a match rate higher than 70%. Our results corroborate with the morphological and molecular data. These models can be used to predict the phylogenetic location of certain diterpenes and to accelerate the research of Annonaceae secondary metabolites and their biological potentials.

RESUMO Objetivo: Identificar associação entre exposição ao material particulado fino e internações por doenças respiratórias em crianças de até dez anos de idade, no município de Cuiabá, MT, estratificando a análise por sexo e calculando excesso de custos. Métodos: Estudo ecológico de séries temporais, sendo a variável dependente o número diário de internações por doenças respiratórias, segundo a 10a Revisão da Classificação Internacional de Doenças (CID): J04.0, J12.0 a J18.9, J20.0 a J21.9 e J45.0 a J45.0. As variáveis independentes foram a concentração do particulado fino, estimada pelo modelo matemático, além de temperatura e umidade relativa do ar, controladas pelas tendências de curta e longa duração. Foram calculados riscos relativos, risco atribuível proporcional (RAP) e excessos de internações e seus respectivos custos pela fração atribuível populacional (FAP). Resultados: Foram internadas 1.165 crianças (640 meninos e 525 meninas). A concentração média estimada do particulado fino foi 15,1±2,9 mcg/m3 para particulado fino (PM2,5). Para meninos, não houve associação significativa. Para meninas, observou-se risco relativo (RR) de até 1,04 para o número diário de internações por doenças respiratórias em associação à exposição ao PM2,5 nos lags 1, 2 e 6. O aumento de 5 mcg/m3 nessas concentrações associou-se ao aumento do risco em 18% e o RAP atribuído à exposição foi de 20% das internações das meninas, com excesso de 95 internações e de gastos da ordem de R$ 105 mil. Conclusões: Houve associação da exposição ao particulado fino e número de internações por doenças respiratórias de meninas, sugerindo a necessidade de estratificação por sexos em estudos posteriores.

ABSTRACT Objective: Identify the association between exposure to fine particulate matter and hospitalizations due to respiratory diseases in children up to ten years of age in the city of Cuiabá, Mato Grosso, stratifying the analysis by sex and calculating excess costs. Methods: Ecological study of time series. The dependent variable was daily hospitalizations according to the 10th Revision of the International Classification of Diseases (ICD10): J04.0, J12.0 to J18.9, J20.0 to J21.9 and J45.0 to J45.0. The independent variables were the concentration of fine particulate, estimated by a mathematical model, temperature and relative air humidity, controlled by short and long-term trends. Generalized additive model of Poisson regression was used. Relative risks, proportional attributable risk (PAR) and excess hospitalizations and their respective costs by the population attributable fraction (PAF) were calculated. Results: 1,165 children were hospitalized, 640 males and 525 females. The mean concentration, estimated by the mathematical model, was 15.1±2.9 mcg/m3 for PM2.5. For boys, there was no significant association; for girls a relative risk of up to 1.04 of daily hospitalizations due to respiratory diseases was observed for exposure to PM 2.5 in lags 1, 2 and 6. Increase of 5 µg/m3 in these concentrations increased the percentage of the risk in 18%; with an excess 95 hospital admissions and with excess expenses in the order of US$ 35 thousand. Conclusions: Significant effect in daily hospitalizations due to respiratory diseases related to exposure to fine particulate matter was noted for girls, suggesting the need for stratification by sex in further studies.

RESUMO: Objetivo: Identificar padrões espaciais na distribuição das taxas de internação de crianças por pneumonia no estado de São Paulo, no período de 2009 a 2013. Métodos : Estudo ecológico exploratório com dados obtidos do Departamento de Informática do Sistema Único de Saúde (DATASUS) de internações por pneumonia em crianças relativas aos municípios do estado de São Paulo de 2009 a 2013, dados de escolaridade materna e renda familiar; e foram criadas taxas por mil crianças e inseridas numa base digital de municípios obtida do Instituto Brasileiro de Geografia e Estatística. Foram construídos mapas temáticos, de Kernel e de Moran para as taxas de internação e calculados os índices de Moran. Foi utilizado o programa TerraView para a análise espacial. Resultados : Foram internadas 43.809 crianças no período. A taxa média por município foi de 11,51 (DP = 8,62). O índice de Moran foi de 0,21 (p = 0,01). Há aglomerados nas regiões norte, noroeste, centro-oeste e sudoeste; o mapa de Kernel mostra densidade maior de taxas no noroeste e centro-oeste do estado; e o mapa de Moran identificou 39 municípios que merecem atenção por parte dos gestores municipais e regionais. Conclusões : O geoprocessamento permitiu identificar regiões com maiores taxas de internação por pneumonia e também municípios que merecem prioridade de intervenção.

ABSTRACT: Objective: To identify spatial patterns in the distribution of hospitalization rates of children with pneumonia in the state of São Paulo, Brazil from 2009 to 2013. Methods: This was an exploratory ecological study with data obtained from DATASUS of hospitalizations of children with pneumonia in the municipalities in São Paulo from 2009 to 2013/ Data on maternal education and family income were obtained and rates per thousand children were calculated and inserted in a database of municipalities obtained from IBGE. Thematic, kernel and Moran maps were constructed for the hospitalization rates and the Moran indices were calculated. The TerraView program was used for spatial analysis. Results: A total of 43,809 children were hospitalized in the study period, with a minimum of zero and a maximum of 69,072. The mean rate per municipality was 11.51 ± 8.62 (SD). The Moran index was 0.21 (p = 0.01). The thematic map showed clusters in the northern, northwestern, midwestern and southwestern regions of the state; the kernel map showed a higher density of rates in the northwestern and midwestern areas, and the Moran map identified 39 municipalities that deserve the attention of municipal and regional managers. Conclusions: Geoprocessing identifies regions with higher hospitalization rates for pneumonia and also municipalities that deserve a high intervention priority.

RESUMO: Objetivo: Identificar padrões espaciais na distribuição das taxas de internação de crianças por pneumonia no estado de São Paulo, no período de 2009 a 2013. Métodos : Estudo ecológico exploratório com dados obtidos do Departamento de Informática do Sistema Único de Saúde (DATASUS) de internações por pneumonia em crianças relativas aos municípios do estado de São Paulo de 2009 a 2013, dados de escolaridade materna e renda familiar; e foram criadas taxas por mil crianças e inseridas numa base digital de municípios obtida do Instituto Brasileiro de Geografia e Estatística. Foram construídos mapas temáticos, de Kernel e de Moran para as taxas de internação e calculados os índices de Moran. Foi utilizado o programa TerraView para a análise espacial. Resultados : Foram internadas 43.809 crianças no período. A taxa média por município foi de 11,51 (DP = 8,62). O índice de Moran foi de 0,21 (p = 0,01). Há aglomerados nas regiões norte, noroeste, centro-oeste e sudoeste; o mapa de Kernel mostra densidade maior de taxas no noroeste e centro-oeste do estado; e o mapa de Moran identificou 39 municípios que merecem atenção por parte dos gestores municipais e regionais. Conclusões : O geoprocessamento permitiu identificar regiões com maiores taxas de internação por pneumonia e também municípios que merecem prioridade de intervenção.

ABSTRACT: Objective: To identify spatial patterns in the distribution of hospitalization rates of children with pneumonia in the state of São Paulo, Brazil from 2009 to 2013. Methods: This was an exploratory ecological study with data obtained from DATASUS of hospitalizations of children with pneumonia in the municipalities in São Paulo from 2009 to 2013/ Data on maternal education and family income were obtained and rates per thousand children were calculated and inserted in a database of municipalities obtained from IBGE. Thematic, kernel and Moran maps were constructed for the hospitalization rates and the Moran indices were calculated. The TerraView program was used for spatial analysis. Results: A total of 43,809 children were hospitalized in the study period, with a minimum of zero and a maximum of 69,072. The mean rate per municipality was 11.51 ± 8.62 (SD). The Moran index was 0.21 (p = 0.01). The thematic map showed clusters in the northern, northwestern, midwestern and southwestern regions of the state; the kernel map showed a higher density of rates in the northwestern and midwestern areas, and the Moran map identified 39 municipalities that deserve the attention of municipal and regional managers. Conclusions: Geoprocessing identifies regions with higher hospitalization rates for pneumonia and also municipalities that deserve a high intervention priority.

ABSTRACT CONTEXT AND OBJECTIVE: Traffic accidents have gained prominence as one of the modern epidemics that plague the world. The objective of this study was to identify the spatial distribution of potential years of life lost (PYLL) due to accidents involving motorcycles in the state of São Paulo, Brazil. DESIGN AND SETTING: Ecological and exploratory study conducted in São Paulo. METHODS: Data on deaths among individuals aged 20-39 years due to motorcycle accidents (V20-V29 in the International Classification of Diseases, 10th revision) in the state of São Paulo in the years 2007-2011 were obtained from DATASUS. These data were stratified into a database for the 63 microregions of this state, according to where the motorcyclist lived. PYLL rates per 100,000 inhabitants were calculated. Spatial autocorrelations were estimated using the Global Moran index (IM). Thematic, Moran and Kernel maps were constructed using PYLL rates for the age groups of 20-29 and 30-39 years. The Terraview 4.2.2 software was used for the analysis. RESULTS: The PYLL rates were 486.9 for the ages of 20-29 years and 199.5 for 30-39 years. Seventeen microregions with high PYLL rates for the age group of 20-29 years were identified. There was higher density of these rates on the Kernel map of the southeastern region (covering the metropolitan region of São Paulo). There were no spatial autocorrelations between rates. CONCLUSIONS: The data presented in this study identified microregions with high accident rates involving motorcycles and microregions that deserve special attention from regional managers and traffic experts.

RESUMO O Amaranthus cruentus L. é uma espécie forrageira, com grãos que possuem ótimas características nutricionais, sendo a cultivar 'BRS Alegria' a primeira recomendada para cultivo no Brasil. Objetivou-se avaliar o efeito do estresse salino no crescimento e concentrações de solutos orgânicos e inorgânicos em Amaranthus cruentus L. cv. 'BRS Alegria'. Foram avaliados a altura, diâmetro do caule, número de folhas, massa seca das folhas, caule e raízes, área foliar, teor relativo de água, porcentagem de integridade das membranas e teores de carboidratos solúveis, aminoácidos livres, proteínas solúveis, prolina livre, Na+, Cl- e K+, nos diferentes órgãos da planta. A salinidade reduziu fortemente a produção de biomassa e a área foliar a partir do tratamento com 25 mM de NaCl, indicando que a cultivar 'BRS Alegria' é sensível ao estresse salino. Os carboidratos solúveis nas folhas diminuíram 59 %, enquanto os demais solutos orgânicos não apresentaram aumentos substanciais. Esses resultados, associados à diminuição do teor relativo de água e da integridade das membranas, sugerem uma baixa capacidade dessa cultivar para o ajustamento osmótico sob estresse salino. A razão K+/Na+ reduziu-se abruptamente em 25 mM de NaCl, sugerindo desequilíbrio iônico, o que pode, ao menos em parte, explicar a redução de crescimento induzida pelo sal.

ABSTRACT Amaranthus cruentus L. is a forage species, with grains that exhibit excellent nutritional characteristics, being the 'BRS Alegria' the first cultivar recommended for cultivation in Brazil. This study aimed at evaluating the effect of salt stress on the growth and concentrations of organic and inorganic solutes in Amaranthus cruentus L. ('BRS Alegria' cultivar). Height, stem diameter, number of leaves, leaf, stem and root dry mass, leaf area, relative water content and membrane integrity percentage, as well as soluble carbohydrate, free amino acid, soluble protein, free proline, Na+, Cl- and K+ contents, were evaluated in different plant organs. Salinity significantly reduced the biomass yield and leaf area from the treatment with 25 mM of NaCl, indicating that the 'BRS Alegria' cultivar is sensitive to salt stress. Soluble carbohydrates in the leaves decreased by 59 %, while the other organic solutes showed no substantial increases. These results, coupled with the reduction in the relative water content and membrane integrity, suggest a low ability of this cultivar to adjust osmotically under salt stress. The K+/Na+ ratio abruptly decreased in 25 mM of NaCl, suggesting an ionic imbalance, which may partially explain the salt-induced growth reduction.

RESUMO Inseridas nas discussões desenvolvidas no contexto do projeto Ateliê de Textos Acadêmicos (ATA) no qual analisamos aspectos linguístico-discursivos de textos acadêmicos em diversos campos de produção do conhecimento, confrontamo-nos com a necessidade de refletir sobre epistemologia e metodologia científica. Objetivamos, portanto, discutir sobre a constituição do conceito de ciência instituído no cerne do Interacionismo Sociodiscursivo (ISD) a partir do aparato conceitual e metodológico empregado por (Bronckart 1999, 2006, 2008) para a abordagem e descrição dos fatos de linguagem, de natureza eminentemente sócio-histórico-cultural. Para tanto, assentaremos nossas discussões nos estudos referentes ao saber/fazer científico, em especial nas obras de (Popper 2007 [1934]) e (Bourdieu, 1983, 2002, 2004). As reflexões apontam que, no processo de construção do conhecimento, o pesquisador deve evitar a submissão a um padrão metodológico dominante, dogmático e autoritário, e estar aberto às várias abordagens disponíveis.

ABSTRACT Due to the discussions and research carried out in the context of the project called Ateliê de Textos Acadêmicos - ATA (Academic Texts Workshop - ATW), within which we analyze academic texts produced in different branches of knowledge, concerning their linguistic-discursive aspects, we have been faced with the need to reflect on epistemology and scientific methodology. Therefore, our main aim is to discuss the construction of the concept of science within the Sociodiscursive Interactionism (SDI) perspective, considering the conceptual and methodological framework used by (Bronckart 1999, 2006, 2008) to approach and describe language facts, considered as being of a socio-historical-cultural nature. In order to do so, we will refer to studies on scientific know-how, especially the work by (Popper 2007 [1934]) and (Bourdieu, 1983, 2002, 2004). The results indicate that the researcher, in the process of knowledge construction, should be open to the many approaches available and not just follow a dominant, dogmatic and authoritarian methodological standard.