A DNA vaccine against tuberculosis based on the 65 kDa heat-shock protein differentially activates human macrophages and dendritic cells

Abstract Background A number of reports have demonstrated that rodents immunized with DNA vaccines can produce antibodies and cellular immune responses presenting a long-lasting protective immunity. These findings have attracted considerable interest in the field of DNA vaccination. We have previously described the prophylactic and therapeutic effects of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in a murine model of tuberculosis. As DNA vaccines are often less effective in humans, we aimed to find out how the DNA-HSP65 stimulates human immune responses. Methods To address this question, we analysed the activation of both human macrophages and dendritic cells (DCs) cultured with DNA-HSP65. Then, these cells stimulated with the DNA vaccine were evaluated regarding the expression of surface markers, cytokine production and microbicidal activity. Results It was observed that DCs and macrophages presented different ability to uptake DNA vaccine. Under DNA stimulation, macrophages, characterized as CD11b+/CD86+/HLA-DR+, produced high levels of TNF-alpha, IL-6 (pro-inflammatory cytokines), and IL-10 (anti-inflammatory cytokine). Besides, they also presented a microbicidal activity higher than that observed in DCs after infection with M. tuberculosis. On the other hand, DCs, characterized as CD11c+/CD86+/CD123-/BDCA-4+/IFN-alpha-, produced high levels of IL-12 and low levels of TNF-alpha, IL-6 and IL-10. Finally, the DNA-HSP65 vaccine was able to induce proliferation of peripheral blood lymphocytes. Conclusion Our data suggest that the immune response is differently activated by the DNA-HSP65 vaccine in humans. These findings provide important clues to the design of new strategies for using DNA vaccines in human immunotherapy.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study

Abstract Background Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. Methods The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case–control approach. Results The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%–1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. Conclusions The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.

Análise crítica das recomendações do uso das vacinas meningocócicas conjugadas

OBJETIVOS: Analisar a epidemiologia da doença meningocócica no Brasil e o impacto que as recentes evidências acumuladas com a incorporação das vacinas meningocócicas C conjugadas nos programas de imunização podem ter nas diferentes estratégias de uso dessas vacinas. FONTES DOS DADOS: Revisão nas bases de dados MEDLINE, SciELO e LILACS no período de 2000 a 2011. SÍNTESE DOS DADOS: No Brasil, a doença meningocócica é endêmica, com ocorrência periódica de surtos. Os maiores coeficientes de incidência ocorrem em lactentes, sendo o sorogrupo C responsável pela maioria dos casos, motivando a introdução da vacina meningocócica C conjugada no Programa Nacional de Imunizações, em 2010, para crianças menores de 2 anos. A introdução das vacinas meningocócicas C conjugadas nos programas de imunização na Europa, Canadá e Austrália mostrou-se efetiva, com dramática redução na incidência de doença causada pelo sorogrupo C, não apenas nos vacinados, mas também em não vacinados. A efetividade em longo prazo dessas vacinas mostrou-se dependente de uma combinação de persistência de anticorpos, memória imunológica e proteção indireta. Recentes evidências indicando que a persistência de anticorpos não é duradoura em crianças pequenas imunizadas e que a memória imunológica não é rápida o suficiente para protegê-las contra a doença enfatizam a importância da proteção indireta para manutenção da população protegida. CONCLUSÕES: A rápida queda de títulos de anticorpos em crianças vacinadas nos primeiros anos de vida sugere a necessidade de incorporarmos doses de reforço antes da adolescência, especialmente em locais como o Brasil, onde ainda não contamos com o efeito da proteção indireta da população.

Aprendizado eletrônico na formação multiprofissional em saúde: avaliação inicial

O objetivo deste relato é apresentar, dentro da proposta do Programa Nacional de Reorientação da Formação Profissional em Saúde (Pró-Saúde), uma parte do projeto da Faculdade de Medicina de Ribeirão Preto (USP). Trata-se da estratégia de inserção das Tecnologias de Informação e Comunicação (TIC) no ensino de graduação extramuros da FMRP, que visa definir e implantar recursos tecnológicos de Aprendizado Eletrônico para apoiar atividades discentes e docentes, gestão da informação, educação continuada e segunda opinião formativa. A trajetória metodológica delineou tanto o processo de atendimento de parte das ações do eixo Cenário de Prática em Atenção Básica de saúde relativa ao processo de ampliação da rede de malha ótica, essencial para suporte às atividades de desenvolvimento do uso das TIC, quanto a abordagem qualitativa de um estudo exploratório sobre a utilização do Teleduc no primeiro ano do eixo de Atenção à Saúde da Comunidade (ASC) do curso de Medicina. Nesta investigação foram realizados dois grupos focais com aplicação de questionário estruturado a discentes e docentes.

O diálogo em processos de políticas públicas de educação ambiental no Brasil

Políticas públicas de educação ambiental no Brasil estimulam o envolvimento de educadores em processos de políticas públicas mediados pelo diálogo. Isso demanda o desvelamento do conceito de diálogo, objetivo deste trabalho. Os resultados do levantamento bibliográfico estabelecem a relação entre o diálogo, as políticas públicas de educação ambiental e seus pressupostos epistemológicos, trazem a fundamentação filosófica e abordam a teoria operacional para o diálogo. Por fim, indicam obstáculos a sua ocorrência e sugerem a formação de espaços de diálogo para contorná-los.

A história da ciência nos livros didáticos de química do PNLEM 2007

Este trabalho analisa os seis livros didáticos de química indicados pelo Programa Nacional do Livro Didático para o Ensino Médio em 2007 (PNLEM 2007), no que se refere a seus conteúdos de história da ciência. Para isso, partiu-se do instrumento de análise desenvolvido por L. Leite (2002), que foi adaptado para a presente investigação. Os resultados obtidos indicam, como tendência geral, que a história da ciência é apresentada nos livros didáticos de maneira linear e superficial, constando, sobretudo, de nomes e datas. Dessa maneira, concluímos que os conteúdos de história da ciência desses livros não contribuem para que os alunos desenvolvam uma imagem do empreendimento científico condizente com os objetivos educacionais da atualidade.

The phylogeography of trypanosomes from South American alligatorids and African crocodilids is consistent with the geological history of South American river basins and the transoceanic dispersal of Crocodylus at the Miocene

Abstract Background Little is known about the diversity, phylogenetic relationships, and biogeography of trypanosomes infecting non-mammalian hosts. In this study, we investigated the influence of host species and biogeography on shaping the genetic diversity, phylogenetic relationship, and distribution of trypanosomes from South American alligatorids and African crocodilids. Methods Small Subunit rRNA (SSU rRNA) and glycosomal Glyceraldehyde Phosphate Dehydrogenase (gGAPDH) genes were employed for phylogenetic inferences. Trypanosomes from crocodilians were obtained by haemoculturing. Growth behaviour, morphology, and ultrastructural features complement the molecular description of two new species strongly supported by phylogenetic analyses. Results The inferred phylogenies disclosed a strongly supported crocodilian-restricted clade comprising three subclades. The subclade T. grayi comprised the African Trypanosoma grayi from Crocodylus niloticus and tsetse flies. The subclade T. ralphi comprised alligatorid trypanosomes represented by Trypanosoma ralphi n. sp. from Melanosuchus niger, Caiman crocodilus and Caiman yacare from Brazilian river basins. T. grayi and T. ralphi were sister subclades. The basal subclade T. terena comprised alligatorid trypanosomes represented by Trypanosoma terena n. sp. from Ca. yacare sharing hosts and basins with the distantly genetic related T. ralphi. This subclade also included the trypanosome from Ca. crocodilus from the Orinoco basin in Venezuela and, unexpectedly, a trypanosome from the African crocodilian Osteolaemus tetraspis. Conclusion The close relationship between South American and African trypanosomes is consistent with paleontological evidence of recent transoceanic dispersal of Crocodylus at the Miocene/Pliocene boundaries (4–5 mya), and host-switching of trypanosomes throughout the geological configuration of South American hydrographical basins shaping the evolutionary histories of the crocodilians and their trypanosomes.

The phylogeography of trypanosomes from South American alligatorids and African crocodilids is consistent with the geological history of South American river basins and the transoceanic dispersal of Crocodylus at the Miocene

Background: Little is known about the diversity, phylogenetic relationships, and biogeography of trypanosomes infecting non-mammalian hosts. In this study, we investigated the influence of host species and biogeography on shaping the genetic diversity, phylogenetic relationship, and distribution of trypanosomes from South American alligatorids and African crocodilids. Methods: Small Subunit rRNA (SSU rRNA) and glycosomal Glyceraldehyde Phosphate Dehydrogenase (gGAPDH) genes were employed for phylogenetic inferences. Trypanosomes from crocodilians were obtained by haemoculturing. Growth behaviour, morphology, and ultrastructural features complement the molecular description of two new species strongly supported by phylogenetic analyses. Results: The inferred phylogenies disclosed a strongly supported crocodilian-restricted clade comprising three subclades. The subclade T. grayi comprised the African Trypanosoma grayi from Crocodylus niloticus and tsetse flies. The subclade T. ralphi comprised alligatorid trypanosomes represented by Trypanosoma ralphi n. sp. From Melanosuchus niger, Caiman crocodilus and Caiman yacare from Brazilian river basins. T. grayi and T. ralphi were sister subclades. The basal subclade T. terena comprised alligatorid trypanosomes represented by Trypanosoma terena n. sp. from Ca. yacare sharing hosts and basins with the distantly genetic related T. ralphi. This subclade also included the trypanosome from Ca. crocodilus from the Orinoco basin in Venezuela and, unexpectedly, a trypanosome from the African crocodilian Osteolaemus tetraspis. Conclusion: The close relationship between South American and African trypanosomes is consistent with paleontological evidence of recent transoceanic dispersal of Crocodylus at the Miocene/Pliocene boundaries (4–5 mya), and host-switching of trypanosomes throughout the geological configuration of South American hydrographical basins shaping the evolutionary histories of the crocodilians and their trypanosomes.

Stochastic gravito-inertial modes discovered by CoRoT in the hot Be star HD51452

Context. Be stars are rapidly rotating stars with a circumstellar decretion disk. They usually undergo pressure and/or gravity pulsation modes excited by the κ-mechanism, i.e. an effect of the opacity of iron-peak elements in the envelope of the star. In the Milky Way, p-modes are observed in stars that are hotter than or equal to the B3 spectral type, while g-modes are observed at the B2 spectral type and cooler. Aims. We observed a B0IVe star, HD51452, with the high-precision, high-cadence photometric CoRoT satellite and high-resolution, ground-based HARPS and SOPHIE spectrographs to study its pulsations in great detail. We also used the lower resolution spectra available in the BeSS database. Methods. We analyzed the CoRoT and spectroscopic data with several methods: Clean-NG, FreqFind, and a sliding window method. We also analyzed spectral quantities, such as the violet over red (V/R) emission variations, to obtain information about the variation in the circumstellar environment. We calculated a stellar structure model with the ESTER code to test the various interpretation of the results. Results. We detect 189 frequencies of variations in the CoRoT light curve in the range between 0 and 4.5 c d−1. The main frequencies are also recovered in the spectroscopic data. In particular we find that HD51452 undergoes gravito-inertial modes that are not in the domain of those excited by the κ-mechanism. We propose that these are stochastic modes excited in the convective zones and that at least some of them are a multiplet of r-modes (i.e. subinertial modes mainly driven by the Coriolis acceleration). Stochastically excited gravito-inertial modes had never been observed in any star, and theory predicted that their very low amplitudes would be undetectable even with CoRoT. We suggest that the amplitudes are enhanced in HD51452 because of the very rapid stellar rotation. In addition, we find that the amplitude variations of these modes are related to the occurrence of minor outbursts. Conclusions. Thanks to CoRoT data, we have detected a new kind of pulsations in HD51452, which are stochastically excited gravito-inertial modes, probably due to its very rapid rotation. These modes are probably also present in other rapidly rotating hot Be stars.

The growth of glioblastoma orthotopic xenografts in nude mice is directly correlated with impaired object recognition memory

Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors.

Los equipos interdisciplinarios en el abordaje de la salud mental comunitaria. La experiencia en la Provincia de Misiones durante el período 2013-201.16H372

A partir de la Ley Nacional de Salud Mental N° 26657/10, los profesionales del ámbito de la salud enfrentan nuevos desafíos orientados a provocar rupturas con el modelo tradicional. Por un lado, como modelo en construcción, el abordaje de la salud mental debiera ser a nivelcomunitario, con centralidad en los principios de libertad, igualdad, dignidad, autonomía y derechos humanos. Por otro lado, prevé la conformación de equipos interdisciplinarios con el propósito de favorecer la integración y producción de conocimientos, de modo que todos los actores intervinientes puedan participar del proceso. En la Provincia de Misiones, desde el año 2011 se conforman equipos de salud integrados por profesionales y técnicos de distintas disciplinas a través del Programa Nacional de Salud Mental Comunitaria, y la acción ya no se limita a la intervención médica sino que el tratamiento, rehabilitación y reinserción del sujeto se piensa a partir del intercambio disciplinario. Si bien un equipo interdisciplinario es un grupo, la conformación del grupo no garantiza el trabajo interdisciplinario. Por ello, la investigación se propone conocer, describir y analizar cómo se construye la dinámica de los equipos para la elaboración colectiva de diagnósticos y planes de intervención en salud mental comunitaria.

Identidad sociocultural

Fil: Triviño, Luis. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales

Los cambios socioculturales y la participación comunitaria a partir de la experiencia del PROMEBA

Al oeste de capital, en la Primera Décima Sección, se localiza un conglomerado de asentamientos y barrios popularmente conocido como La Favorita, cuyos orígenes se remontan a comienzo de los años 80 del siglo pasado. Es el hogar de muchas familias con necesidades básicas insatisfechas, y en forma consecuente, de una multiplicidad de problemáticas sociales propias de las zonas urbano marginales, como la precariedad de viviendas, déficit de obras de infraestructura básica, irregularidad dominial de la tierra, etc.; a los cuales el Programa nacional de Mejoramiento Barrial en sus dos etapas, (de aquí en adelante PROMEBA I y II) ha intentado dar respuesta desde el inicio de su gestión en el año 2004. Además de las organizaciones gubernamentales como comisarías, escuelas, registro civil, centros de salud; existen en la comunidad diversidad de Organizaciones de la Sociedad Civil (de aquí en adelante OSC) de distinta naturaleza: Uniones vecinales, comedores comunitarios, bibliotecas populares, parroquias, etc.; cada una desde su especificidad presta un servicio de cooperación y solidaridad defendiendo los intereses de los vecinos, sea proveyendo un desayuno integral a los más pequeños, asesorando a mujeres víctimas del delito, ofreciendo un lugar para compartir la lectura de bibliografía escolar, tramitando reclamos vecinales ante las autoridades municipales, etc. Toda esta riqueza de esfuerzo y trabajo colectivo expresa una permanente preocupación y voluntad de los sujetos por responder a las diferentes demandas sociales de la zona; pero en definitiva, todas participan de la dinámica barrial. La actuación del PROMEBA I y II ha producido cambios sociales y culturales en las condiciones de vida familiar y comunitaria de la Favorita, tanto positivos como negativos, en ese sentido, algunos han mejorado la calidad de vida de las familias como la provisión de red cloacal y núcleo húmedo, pero otros no, quedándose en la promesa idealizada de estimular la integración social.

Guía para la atención integral de la hemorragia del primer y segundo trimestre y del post-aborto y sus complicaciones

La presente Guía es una herramienta para los equipos de atención en salud de los tres niveles de atención que provee los lineamientos de atención diagnóstica y terapéutica. Para abordar esta problemática la guía incluye los cinco pilares de atención post-aborto

Guía para la implementación de la atención integrada materna y neonatal calificada con enfoque de género y con pertinencia cultural, en los servicios institucionales de atención del parto

El Ministerio de Salud Pública y Asistencia Social de Guatemala presenta esta guía, la cual ha sido revisada y actualizada utilizando la evidencia científica actual y disponible, y que responde a la necesidad de fortalecimiento de las competencias del recurso humano en los servicios institucionales de atención del parto