Natural variation of HIV-1 group M integrase: Implications for a new class of antiretroviral inhibitors

HIV-1 integrase is the third enzymatic target of antiretroviral (ARV) therapy. However, few data have been published on the distribution of naturally occurring amino acid variation in this enzyme. We therefore characterized the distribution of integrase variants among more than 1,800 published group M HIV-1 isolates from more than 1,500 integrase inhibitor (INI)-naïve individuals. Polymorphism rates equal or above 0.5% were found for 34% of the central core domain positions, 42% of the C-terminal domain positions, and 50% of the N-terminal domain positions. Among 727 ARV-naïve individuals in whom the complete pol gene was sequenced, integrase displayed significantly decreased inter- and intra-subtype diversity and a lower Shannon's entropy than protease or RT. All primary INI-resistance mutations with the exception of E157Q – which was present in 1.1% of sequences – were nonpolymorphic. Several accessory INI-resistance mutations including L74M, T97A, V151I, G163R, and S230N were also polymorphic with polymorphism rates ranging between 0.5% to 2.0%

Participatory democratic practices in the construction of social development agendas in municipalities in the southeast of Brazil

We present the results of a study that focused on local processes of implementation of social agendas - Agenda 21 and Healthy Cities - in the Southeast region of Brazil, relating the effort and its effects on the social determinants of health, especially those who may be understood by considering the relationship between social actors and system. There were 6 case studies to analyze the social experience to implement their agenda. Individual and collective interviews, survey documentation and direct observation of the experiences that produced the data were analyzed according to the previously defined research themes. Results show that values such as participation, collective construction of policies, sustainability and empowerment becomes part of the ideology and experience of those directly involved and is interfering so that positive actions have been adopted in the municipalities where they were developed, promoting health and quality of life of citizens living in these places.Se presentan los resultados de un estudio sobre los procesos locales de desarrollo de agendas sociales - Ciudades Saludables y Agenda 21 - en ciudades de la región sureste de Brasil, relacionando el esfuerzo empleado y sus efectos sobre los determinantes sociales de la salud, especialmente aquellos que se pueden comprender teniendo en cuenta la relación entre actores sociales y sistema. Se realizaron 6 estudios de caso para analizar la experiencia social de implementar las agendas. Entrevistas individuales y colectivas, reunión de documentación y observación directa produjeron los datos que se analizaron en términos de temas de investigación previamente definidos. Los resultados muestran que valores como participación, construcción colectiva de políticas, sostenibilidad y empoderamiento se convierten en parte de la ideología y experiencia de los directamente involucrados y que interfieren para la adopción de acciones positivas, promoviendo la salud y la calidad de vida de los ciudadanos que viven en estos lugares.Este artigo apresenta os resultados e a análise de um estudo que focalizou os processos locais de implantação das agendas sociais - Cidades Saudáveis e Agenda 21 - em municípios da região Sudeste do Brasil, relacionando o esforço realizado e seus efeitos sobre os determinantes sociais de saúde, especialmente os que podem ser apreendidos considerando-se a relação entre atores sociais e sistema. Realizaram-se estudos de caso em seis municípios para análise da experiência social de implementação da respectiva agenda. Entrevistas individuais e coletivas, levantamento de documentação e observação direta produziram os dados que foram analisados em função de temas de pesquisa previamente definidos. Resultados demonstram que valores como participação, construção coletiva de políticas, sustentabilidade e empoderamento, passam a integrar o ideário e a experiência dos atores diretamente envolvidos, além de interferirem ao ponto de ações positivas serem adotadas e implementadas, para promover a saúde e a qualidade de vida dos cidadãos que vivem nestes locais.Universidade de São Paulo Faculdade de Saúde PúblicaUniversidade Estadual de Campinas Faculdade de Ciências Médica Departamento de Saúde ColetivaUSP Faculdade de Saúde PúblicaUSP Faculdade de saúde PúblicaUniversidade de São Paulo e do Centro de Estudos Faculdade de Saúde Pública Departamento de Prática de Saúde PúblicaUniversidade Federal de São Paulo (UNIFESP) CEPEDOCCentro de Estudos, Pesquisa e Documentação em Cidades SaudáveisMinistério da Saúde Fundação Oswaldo Cruz Centro de Pesquisas Aggeu MagalhãesUNIFESP, CEPEDOCSciEL

Participatory democratic practices in the construction of social development agendas in municipalities in the southeast of Brazil

We present the results of a study that focused on local processes of implementation of social agendas - Agenda 21 and Healthy Cities - in the Southeast region of Brazil, relating the effort and its effects on the social determinants of health, especially those who may be understood by considering the relationship between social actors and system. There were 6 case studies to analyze the social experience to implement their agenda. Individual and collective interviews, survey documentation and direct observation of the experiences that produced the data were analyzed according to the previously defined research themes. Results show that values such as participation, collective construction of policies, sustainability and empowerment becomes part of the ideology and experience of those directly involved and is interfering so that positive actions have been adopted in the municipalities where they were developed, promoting health and quality of life of citizens living in these places.Este artigo apresenta os resultados e a análise de um estudo que focalizou os processos locais de implantação das agendas sociais - Cidades Saudáveis e Agenda 21 - em municípios da região Sudeste do Brasil, relacionando o esforço realizado e seus efeitos sobre os determinantes sociais de saúde, especialmente os que podem ser apreendidos considerando-se a relação entre atores sociais e sistema. Realizaram-se estudos de caso em seis municípios para análise da experiência social de implementação da respectiva agenda. Entrevistas individuais e coletivas, levantamento de documentação e observação direta produziram os dados que foram analisados em função de temas de pesquisa previamente definidos. Resultados demonstram que valores como participação, construção coletiva de políticas, sustentabilidade e empoderamento, passam a integrar o ideário e a experiência dos atores diretamente envolvidos, além de interferirem ao ponto de ações positivas serem adotadas e implementadas, para promover a saúde e a qualidade de vida dos cidadãos que vivem nestes locais.Se presentan los resultados de un estudio sobre los procesos locales de desarrollo de agendas sociales - Ciudades Saludables y Agenda 21 - en ciudades de la región sureste de Brasil, relacionando el esfuerzo empleado y sus efectos sobre los determinantes sociales de la salud, especialmente aquellos que se pueden comprender teniendo en cuenta la relación entre actores sociales y sistema. Se realizaron 6 estudios de caso para analizar la experiencia social de implementar las agendas. Entrevistas individuales y colectivas, reunión de documentación y observación directa produjeron los datos que se analizaron en términos de temas de investigación previamente definidos. Los resultados muestran que valores como participación, construcción colectiva de políticas, sostenibilidad y empoderamiento se convierten en parte de la ideología y experiencia de los directamente involucrados y que interfieren para la adopción de acciones positivas, promoviendo la salud y la calidad de vida de los ciudadanos que viven en estos lugares.10312

HIV-1 Envelope Subregion Length Variation during Disease Progression

The V3 loop of the HIV-1 Env protein is the primary determinant of viral coreceptor usage, whereas the V1V2 loop region is thought to influence coreceptor binding and participate in shielding of neutralization-sensitive regions of the Env glycoprotein gp120 from antibody responses. The functional properties and antigenicity of V1V2 are influenced by changes in amino acid sequence, sequence length and patterns of N-linked glycosylation. However, how these polymorphisms relate to HIV pathogenesis is not fully understood. We examined 5185 HIV-1 gp120 nucleotide sequence fragments and clinical data from 154 individuals (152 were infected with HIV-1 Subtype B). Sequences were aligned, translated, manually edited and separated into V1V2, C2, V3, C3, V4, C4 and V5 subregions. V1-V5 and subregion lengths were calculated, and potential N-linked glycosylation sites (PNLGS) counted. Loop lengths and PNLGS were examined as a function of time since infection, CD4 count, viral load, and calendar year in cross-sectional and longitudinal analyses. V1V2 length and PNLGS increased significantly through chronic infection before declining in late-stage infection. In cross-sectional analyses, V1V2 length also increased by calendar year between 1984 and 2004 in subjects with early and mid-stage illness. Our observations suggest that there is little selection for loop length at the time of transmission; following infection, HIV-1 adapts to host immune responses through increased V1V2 length and/or addition of carbohydrate moieties at N-linked glycosylation sites. V1V2 shortening during early and late-stage infection may reflect ineffective host immunity. Transmission from donors with chronic illness may have caused the modest increase in V1V2 length observed during the course of the pandemic

Impact of the Social Agendas - Agenda 21 and Healthy Cities - upon Social Determinants of Health in Brazilian municipalities: measuring the effects of diffuse social policies through the dimensions of the Millennium Development Goals

INTRODUCTION: In order to improve the quality of life and health of the population in recent years there have been several local social agendas, like Agenda 21 and Healthy Cities. OBJECTIVES: To identify how social agendas are impacting on the living conditions and health in municipalities of the five regions of Brazil. METHODS: Through an ecological longitudinal study, the social agendas' effects on the Social Determinants of Health were measured in 105 municipalities, using indicators related to the eight dimensions of the Millennium Development Goals (MDGs). Indicators were also calculated for other 175 non-exposed municipalities. Descriptive statistics were calculated for each group of municipalities at three different moments: in the year of the agenda implementation, then 3 and 6 years later. The models were adjusted by the method of GEE to assess the effects of the agendas, time and their interaction. Nonparametric analysis of variance was used for the ordinal data with repeated measures. RESULTS: Impacts of the agendas were detected for reduction of hunger and increase of universal access to education: 'percentage of children under one year with protein/caloric undernourishment' (interaction effect: p = 0.02) and 'Age-grade distortion in the 8th grade of fundamental education' (interaction effect: p < 0.001). CONCLUSION: The comparative discussion between model results and descriptive statistics recommends, at further research, extending the period of investigation, using compound indexes, improving the methodology for the apprehension of the impacts of the diffuse social policies for development, as well as using 'mixed methodologies', integrating quantitative and qualitative tools

Impacto das agendas sociais - Agenda 21 e Cidades Saudáveis - nos Determinantes Sociais de Saúde em municípios brasileiros: medindo os efeitos de políticas sociais difusas por meio dos Objetivos de Desenvolvimento do Milênio

Submitted by Kamylla Nascimento ([email protected]) on 2017-11-16T12:47:13Z No. of bitstreams: 1 art. Impact of the Social Agendas - nascimento.pdf: 261866 bytes, checksum: 7fa6f4b652715d17f662210af429f2b5 (MD5)Approved for entry into archive by Kamylla Nascimento ([email protected]) on 2017-11-16T12:56:26Z (GMT) No. of bitstreams: 1 art. Impact of the Social Agendas - nascimento.pdf: 261866 bytes, checksum: 7fa6f4b652715d17f662210af429f2b5 (MD5)Made available in DSpace on 2017-11-16T12:56:26Z (GMT). No. of bitstreams: 1 art. Impact of the Social Agendas - nascimento.pdf: 261866 bytes, checksum: 7fa6f4b652715d17f662210af429f2b5 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Para melhorar a qualidade de vida e a saúde populacionais têm ocorrido nos anos recentes várias agendas sociais locais, como Agenda 21 e Cidades Saudáveis.In order to improve the quality of life and health of the population in recent years there have been several local social agendas, like Agenda 21 and Healthy Cities