Colonization is prerequisite for infection and transmission of Streptococcus pneumoniae, or pneumococcus. Currently available pneumococcal conjugate and pneumococcal polysaccharide vaccines can provide protection against a limited number of capsular serotypes. Implementation of vaccines has decreased the frequency of invasive pneumococcal disease and their colonization rates, but only in a serotype-dependent manner. This has led to serotype replacement in pneumococcal ecology and increased invasive disease caused by non-vaccine serotypes. Development of conserved protein-based vaccine that can provide protection against all pneumococcal serotypes is needed. Numerous surface proteins are conserved in all serotypes, and some are known to be involved in the colonization process. Understanding how pneumococcal surface proteins interact with host cells and determining their roles in colonization will aid in vaccine development. In this dissertation, we characterized host cell receptors of pneumococcal surface proteins, and proteins involved in biofilm formation, and their effect in colonization. We utilized a novel protein expression vector, pOS1, which can express secreted proteins with no LPS, IPTG induction, or cell lysis requirement. These expressed recombinant proteins were used for further investigation. We identified that human Annexin A2 (ANXA2) interacts with pneumococcal surface adhesion A (PsaA) protein. ANXA2 transduced cells showed significant increase in binding with pneumococcus compared to non-transduced cells. We conducted proteomic profiling of planktonic and biofilm membrane proteins and identified that two lipoproteins (AmiA, SP_0148) were overexpressed during biofilm formation. Isogenic mutants lacking these individual proteins showed decreased in biofilm formation compared to their parental strain. Deletion of SP_0148 led to decreased adhesion of pneumococcus to human nasopharyngeal epithelial cells (Detroit 562). These results increased our understanding of pneumococcal surface proteins involved in biofilm-formation and colonization as well as identifying new host receptors ligands for these adhesins.

O monitoramento da qualidade do ar em Ribeirão Preto-SP é realizado pela Cetesb por métodos convencionais e, até o momento, nenhum estudo experimental sobre biomonitoramento da poluição atmosférica foi realizado na região. O município apresenta um crescente número de veículos automotores e está localizado em uma das regiões mais importantes do país para o setor sucroalcooleiro. A frequente queima da biomassa insere a região na lista do campo de atuação do VIGIAR-Programa de Vigilância em Saúde Ambiental do Ministério da Saúde, sendo de interesse, tanto o monitoramento da poluição do ar, como o conhecimento dos indicadores de saúde da população exposta. Nesse contexto, esta pesquisa teve como objetivo avaliar a qualidade do ar em Ribeirão Preto por meio de biomonitoramento vegetal, relacionando ao quadro de morbidade respiratória da população. Os experimentos foram conduzidos em três regiões urbanas do município, durante dois períodos: março a junho e julho a outubro de 2011. Em cada região foram expostas 24 mudas de cada espécie, Tibouchina pulchra e Tradescantia pallida, a 50% de sombreamento e a pleno sol. Foram analisados parâmetros fisiológicos, anatômicos, de crescimento e a composição química foliar. Os resultados foram comparados entre regiões e tratamentos de sol e sombra, relacionado-os com parâmetros ambientais (MP10, NO2, O3, temperatura, umidade relativa do ar, precipitação e radiação solar). O quadro de morbidade respiratória da população foi analisado, buscando-se relacionar dados de internações do Datasus com indicadores ambientais obtidos na Cetesb e no CIIAgro, entre 2009 e 2011. Os resultados indicaram que os níveis de poluentes atmosféricos no município, no período do estudo, comprometeram a capacidade fotossintética das plantas, afetando significativamente o seu crescimento. Em geral, as plantas expostas na região central apresentaram maior fotoinibição, menor teor de clorofila total, menor atividade específica da SOD, menor espessura foliar, menor AFE, menor produção de biomassa e maior acúmulo foliar de elementos químicos relacionados à poluição atmosférica. Ainda, foi possível observar maior efeito genotóxico durante a formação de gametas em T. pallida, em plantas expostas nessa região, caracterizada por intenso fluxo de veículos. Quanto à relação entre a taxa de internações hospitalares por doenças respiratórias e a concentração mensal de MP10 e NO2, destaca- se que, mesmo diante de níveis de poluição abaixo dos limites permitidos pelos padrões nacionais, foi observada uma associação moderada, principalmente entre crianças menores de cinco anos de idade, no período mais seco e frio do ano. Os resultados encontrados com esta pesquisa poderão servir como subsídios para a implementação dos novos padrões de qualidade do ar, atualmente em discussão no estado de São Paulo, ao revelar importantes indicadores de estresse em plantas devido à exposição a poluentes atmosféricos, mostrando ser factível a utilização do biomonitoramento para avaliação da qualidade do ar, como ferramenta complementar, além de um importante elemento para programas de educação ambiental. Esta pesquisa também revela a importância de adoção de evidências científicas, quanto ao impacto da poluição do ar sobre a saúde, pelo sistema de gestão ambiental, estimulando o desenvolvimento de estratégias inovadoras para alcançar melhores indicadores de qualidade do ar. Ainda, esta investigação traz novas ferramentas para a identificação de áreas de atenção ambiental atmosférica de interesse para a saúde, assim como de grupos populacionais expostos à poluição do ar, o que representa um dos grandes desafios do Programa de Ações Prioritárias da Vigilância em Saúde do VIGIAR, não apenas no estado de São Paulo, mas também em realidades similares. / The air quality monitoring in Ribeirão Preto is carried out by Cetesb with conventional methods and, until now, no experimental study on air pollution biomonitoring was conducted in the region. The city has a growing number of motor vehicles and is located in one of the most important regions of the country for the sugarcane sector. The frequent burning of biomass inserts the region in the list of VIGIAR-Surveillance Program on Environmental Health of the Ministry of Health, and is of interest, both the monitoring of air pollution, such as knowledge of the health indicators of the population exposed, being of interest, both the monitoring of air pollution, and the indicators of exposed population\'s health. In this context, this study aimed to assess the air quality in Ribeirão Preto through plant biomonitoring, relating to the framework of respiratory morbidity of the population. The experiments were conducted in three points of the city during two periods: from March to June and from July to October 2011. In each point 24 seedlings of each species, Tibouchina pulchra and Tradescantia pallida, were exposed in 50% shade and full sun. Physiological, anatomical, growth parameters and chemical leaf composition were analyzed in these plants. The results were compared between regions, under treatments of sun and shade, relating them with environmental parameters (PM10, NO2, O3, temperature, air relative humidity, rainfall and solar radiation). Still, the respiratory morbidity of the population was analyzed, relating Datasus data on respiratory hospitalizations with environmental indicators obtained in Cetesb and CIIAgro between 2009 and 2011. The results indicated that the levels of air pollutants in the city undertook the photosynthetic capacity of the plants, significantly affecting their growth. In general, the plants exposed in the central region showed greater photoinhibition, lower total chlorophyll content, lower specific activity of SOD, lower leaf thickness, lower AFE, lower biomass production and higher accumulation of leaf chemical elements related to air pollution. It was also possible to notice greater genotoxic effect during the gametes formation in T. pallida, in plants exposed in this region, characterized by intense traffic flow and consequently higher concentration of air pollutants. Even with pollution levels below the limits allowed by national standards, it was observed a moderate association between the rate of hospitalization for respiratory diseases and the monthly concentration of PM10 and NO2, especially among children under five years old, in the driest and coldest period of the year. The results of this research may serve as subsidies for the implementation of new air quality standards, currently under discussion in the São Paulo state, revealing important indicators of stress in plants due to exposure to air pollutants, showing to be feasible the use of biomonitoring assessment of air quality as a complementary tool, and an important element for environmental education programs. This research also shows the importance of adopting scientific evidence about the impact of air pollution on health, by the environmental management system, stimulating the development of innovative strategies to achieve better indicators of air quality. Still, this research provides new tools for identifying areas of atmospheric environmental attention, of interest to health, and population groups exposed to air pollution, which is one of the great challenges of the Priority Actions Programme of Surveillance health of VIGIAR, not only for the state of São Paulo but also in similar situations.

Diversos estudos afirmam que a exposição à poluição atmosférica pode resultar em aumento de casos de doenças cardiovasculares e respiratórias. Esses desfechos estão relacionados, principalmente, a altas taxas de internações e óbitos em países desenvolvidos. O presente trabalho objetivou estimar os efeitos da variação diária na concentração dos poluentes atmosféricos nos atendimentos de emergência por hipertensão arterial ou doenças respiratórias estratificados por sexo e por faixa etária. Trata-se de estudo ecológico de séries temporais realizado a partir dos registros de prontuários de atendimentos de emergência por hipertensão arterial ou doenças respiratórias de adultos e idosos atendidos no Hospital de Emergências Albert Sabin, do município de São Caetano do Sul, entre janeiro de 2010 a dezembro de 2011. Para a análise dos dados foram utilizados o modelo linear generalizado de regressão de Poisson e o modelo de defasagem de distribuição polinomial de terceiro grau, explorando estruturas de defasagens até seis dias após a exposição aos poluentes. As estimativas foram controladas para variáveis meteorológicas, sazonalidade e tendência de curta duração (dias da semana). Os indivíduos mais idosos se mostraram mais sensíveis aos efeitos dos poluentes do ar. Na estratificação por sexo, os homens foram mais susceptíveis quando expostos ao PM10 para os atendimentos por pneumonias e as mulheres para os atendimentos por doenças chiadoras. Para cada aumento de 22,4ug/m3 de PM10, houve um aumento de 16,2% (25,5% - 7,6%) nos atendimentos de hipertensão arterial nos idosos no dia da exposição ao poluente. Para infecções de vias aéreas superiores, o aumento mais robusto foi notado entre os homens no dia da exposição ao PM10, com 8,6% (3,6% - 14%) e entre os idosos, também de forma aguda, com 7,6% (0,7% - 15%). As mulheres expostas ao PM10 tiveram um aumento de 15,7% (5,4% - 26,3%) nos atendimentos por doenças chiadoras. Entre os idosos, esse aumento foi de 25,4% (12,1% - 40,2%) para este mesmo desfecho. Para pneumonias, o efeito mais robusto foi observado entre os idosos no dia da exposição ao PM10, com um aumento de 15,8% (0,9% - 32,8%) nos atendimentos. A cidade de São Caetano do Sul possui um perfil de poluição semelhante às grandes metrópoles, caracterizada por emissão de veículos e indústrias. Os resultados apresentados neste trabalho alertam para a necessidade da elaboração de políticas públicas na região para um melhor monitoramento e controle da poluição atmosférica, com o intuito de prevenir futuros agravos à saúde da população / Several studies claim that exposure to air pollution can result in increased cases of cardiovascular and respiratory diseases. These outcomes are mainly related to high rates of hospital admissions and deaths in developed countries. This study aimed to estimate the effects of daily variation in the concentration of air pollutants in emergency treatment for high blood pressure or respiratory diseases, stratified by sex and age group. It is an ecological time series study, conducted from emergency visits for high blood pressure or respiratory disease of adults and elderly assisted at the Emergency Hospital Albert Sabin in São Caetano do Sul between January 2010 December 2011. For data analysis was used generalized linear model Poisson regression model and polynomial distribution lag third degree, exploring lags structures up to six days after exposure to pollutants. The estimates were controlled to weather variables, seasonal and short-term trend (weekdays). Older individuals were more sensitive to the effects of air pollutants. In stratification by sex, men were more susceptible when exposed to PM10 to care for pneumonia and women to care for diseases wheezing. For each increase of 22.4 ug / m3 of PM10, there was an increase of 16.2% (25.5% - 7.6%) in hypertension in the elderly care on the day of exposure to the pollutant. For upper respiratory tract infections, the strongest increase was noted among men on the day of exposure to PM10, with 8.6% (3.6% - 14%) and among the elderly, too acutely, with 7, 6% (0.7% - 15%). Women exposed to PM10 increased by 15.7% (5.4% - 26.3%) in treated for wheezing. Among the elderly, the increase was 25.4% (12.1% - 40.2%) for the same outcome. Pneumonias for the most robust effect was observed among the elderly on the day of exposure to PM10, with an increase of 15.8% (0.9% - 32.8%) in attendance. The city of São Caetano do Sul has a pollution profile similar to large cities, characterized by emission vehicles and industries. The results presented in this study point to the need of public policy development in the region for better monitoring and control of air pollution, in order to prevent future health problems of the population

INTRODUÇÃO: Mato Grosso é um dos estados que mais queimam no país e há poucos e recentes estudos que discutem os efeitos adversos da poluição do ar na saúde da população do estado. OBJETIVO: Investigar a relação entre poluição atmosférica e internações por doenças respiratórios e cardiovasculares no estado de Mato Grosso. METODOLOGIA: Uma análise de série temporal foi aplicada para verificar a associação entre queimadas e agravos, com dados semanais. O período estudado foi de primeiro de janeiro de 2008 a 31 de agosto de 2014, foi estudado o estado todo e na análise foi usada Regressão Binomial Negativa, com Modelo Aditivo Generalizado. A única variável que não apresentou relação linear com a variável dependente foi Semana e uma função do tipo Spline foi usada, por este motivo somente ela foi alisada para se controlar este padrão de efeito, com estrutura de defasagem de 1 a 4 semanas. Na segunda análise, outra série temporal, cujo objetivo era investigar os efeitos da variação diária do material particulado e o monóxido de carbono com as internações. O período analisado foi de primeiro de janeiro de 2012 a 30 de junho de 2015, foram estudados quinze municípios e para a análise foram utilizadas Regressões de Poisson e Binomial Negativa, com Modelos Aditivos Generalizados, dependências não lineares entre variáveis explicativas e variáveis resposta foram controladas usando um alisador do tipo Spline, a estrutura de defasagem foi de 1 a 7 dias. A terceira abordagem, foi uma Análise de Autocorrelação Espacial do tipo Moran, onde foi estudado o estado todo em dois períodos: Primeiro de janeiro de 2003 a 31 de dezembro de 2010 e de primeiro de janeiro de 2011 a 31 dezembro de 2016. Foram montados bancos de dados usando incidências e número de focos de queimadas por área para verificar o agrupamento dos municípios de acordo com o Moran Local, foram montados mapas temáticos dos índices univariados e bivariados. RESULTADOS: Na primeira análise, foram encontradas associações significativas entre queimadas e internações por problemas respiratórios em menores de 5 anos: lag 0 (RR = 1,001; IC 95% = 1,00016 - 1,00279), lag 1 (RR = 1,001; IC 95% = 1,00005 - 1,00265) e lag 4 (RR = 1,002; IC 95% = 1,00079 - 1,00342) e associação significativa em maiores de 60 anos somente para lag 0 (RR = 1,001; IC 95% = 1,00013 - 1,00256). Na segunda análise, houveram associações significativas entre todos os agravos e poluentes, exceto para problemas cardiovasculares e monóxido de carbono. Foram encontradas associações com diversas defasagens entre todos os agravos e poluentes. Na análise espacial, para o período entre 2003 e 2010, foram encontrados aglomerados significativos com formato de arco para o Moran univariado de queimadas e bivariado. Para o período de 2011 a 2016, os aglomerados univariado de queimadas e bivariado se concentraram no nordeste do estado. CONCLUSÕES: Nas análises de séries temporais foram encontradas associações entre queimadas e agravos e entre poluentes e agravos (semana e dia), inclusive com defasagens (semana e dia) em ambas as análises. Na análise espacial, a mudança do \"cluster\" entre os períodos estudados mostra a mudança da expansão da fronteira agrícola, antes seguindo o arco de desmatamento e agora abrindo áreas remanescentes no estado, onde o desmatamento é realizado com o uso das queimadas que podem causar doenças respiratórias e cardiovasculares / INTRODUCTION: The State of Mato Grosso is is one of the places in the country and there are few and recent studies discussing the adverse health effects of air pollution on the population in this state. OBJECTIVE: To investigate the relationship between atmospheric pollution and hospitalizations for respiratory and cardiovascular diseases in the state of Mato Grosso. METHODOLOGY: A time series analysis was applied in order to verify the association between number of vegetation burns and diseases. Data were recorded weekly. The period studied was from January 1, 2008 to August 31, 2014, the entire state was studied and it was used Negative Binomial Regression with Generalized Additive Model. The only variable that did not present a linear relationship with the dependent variable was Week and a spline-type function was used to address this pattern of effect, a lag structure up to four weeks was applied. In a second approach, other time series analysis, in order to investigate the effects of daily variations of particulate matter and carbon monoxide on hospitalizations pollutant-specific. The period analyzed was from January 1, 2012 to June 30, 2015, fifteen municipalities were studied and Generalized Additive with Poisson or Negative Binomial Regressions models were used, Non-linear dependencies between the outcomes and covariables was controlled using spline-type smoother. A lag structure up to seven days was applied. To explore spatial patterns of occurrence a Moran Spatial Autocorrelation Analysis was carried out, where the whole state was studied in two periods: January 1, 2003 to December 31, 2010, and from January 1, 2011 to December 31, 2016. Databases were assembled using incidences and number of fires per area, to verify the \"cluster\" formation of municipalities according to Local Moran, thematic maps of the univariate and bivariate indices were set up. RESULTS: In the first analysis, there were significant associations between burns and hospitalizations due to respiratory problems in children under 5 years of age: lag 0 (RR = 1.001, 95% CI = 1.00016 - 1.00279), lags 1 (RR = 1.001, 95% CI = 1.00005 - 1.00265) and lag 4 (RR = 1.002, 95% CI = 1.00079 - 1.00342) and significant association in patients over 60 years only for lag 0 (RR = 1.001, 95% CI = 1.000-13 - 1.00256). For the second analysis, there were significant associations between all the diseases and pollutants, except for cardiovascular problems and carbon monoxide. Associations with different lags between all the diseases and pollutants were found. In the spatial analysis, for the period between 2003 and 2010, significant \"clusters\" with arc shape were found for the univariate \"clusters\" of fires and bivariate. For the period of 2011 and 2016, the univariate \"clusters\" of fires and bivariate were concentrated in the northeast of the state. CONCLUSIONS: In time series analyses, associations between burnings and injuries and between pollutants and injuries were found, at the same period of exposure (week or day) and in subsequent periods (weeks or days). Spatially, the \"cluster\" change between the studied periods shows the change in the expansion of the agricultural frontier, before following the arc of deforestation and now opening remaining areas in the state. Deforestation is carried out with the use of forest fires that can promote respiratory and cardiovascular diseases

Asma é uma doença crônica, de alta prevalência, importante causa de morbidade, responsável por gastos diretos e indiretos significativos. Apesar do cuidado padrão para esta doença estar bem consolidado em diretrizes clínicas baseadas em evidências, frequentemente seus portadores não recebem os cuidados indicados. A qualidade da assistência dispensada pelos profissionais da atenção primária é tanto problema quanto solução. Modelos de cuidados adaptados a doenças crônicas e iniciativas de educação em saúde correspondem a estratégias utilizadas para incremento de qualidade assistencial. As novas tecnologias de informação e comunicação têm encurtado progressivamente as distâncias entre as pessoas. Em saúde, têm sido utilizadas como ferramentas valiosas na disseminação de conhecimentos. Apesar da ampla disponibilidade e utilização, os recursos educativos mediados por tecnologias de informação e comunicação – teleducação – ainda carecem de evidências de maior rigor científico. Objetivo: avaliar a efetividade clínica de uma intervenção multifacetada educativa a distância sobre asma para profissionais da atenção primária à saúde. Método: ensaio clínico randomizado em cluster com 71 equipes de saúde do interior do Rio Grande do Sul. Foram indicados pela totalidade das equipes 443 pessoas com diagnóstico de asma elegíveis para acompanhamento no estudo. As equipes do grupo intervenção (n = 34) participaram de um programa de 3 sessões interativas online e receberam materiais educativos. As equipes do grupo controle (n = 37) não sofreram intervenção. Sobrecarga de sintomas nos últimos 14 dias, controle da asma no último mês, necessidade de consulta não programada nos últimos 6 meses e uso de corticosteroide inalatório preventivo nos últimos 6 meses foram avaliados nas pessoas indicadas pelas equipes na linha de base e 6 meses após a intervenção. Resultados: a assiduidade geral das equipes de saúde às sessões interativas online foi de 50%. Ambos grupos apresentaram melhora dos desfechos clínicos e menor uso de corticosteroide inalatório no seguimento. Exposição a intervenção educacional esteve associada a razões de chances com melhores desfechos clínicos, entretanto com significância estatística limítrofe. Não foram observadas diferenças no uso de corticosteroides inalatórios preventivos entre os grupos. Conclusão: a intervenção em educação a distância demonstrou potencial apesar da baixa assiduidade das equipes sob intervenção. O modelo proposto é factível e reprodutível. Integração com o sistema de registro clínico pode potencializar os resultados. A implementação de estratégias de aperfeiçoamento profissional em caráter institucional deve ser orientada pelas melhores evidências. / Asthma is a high prevalence chronic disease and an important cause of morbidity, responsible for significant direct and indirect health expenses. Although the standard care for this condition is well established in evidence-based clinical guidelines, often patients do not receive the indicated treatment. The quality of care delivered by primary care professionals is both a problem and a solution. Models of care adapted to chronic diseases and health education initiatives are strategies used to increase care quality. New information and communication technologies have progressively shortened distances between people. In healthcare, they have been used as a valuable tool for knowledge dissemination. Despite widespread availability and use, educational resources mediated by information and communication technologies still lack evidence of greater scientific rigor. Objective: to evaluate the clinical effectiveness of a multifaceted distance educational intervention on asthma for primary health care professionals. Methods: cluster randomized clinical trial with 71 health teams from country towns of Rio Grande do Sul. The teams identified a total of 443 persons diagnosed with asthma who were eligible for follow-up in the study The teams in the intervention group (n = 34) participated in a program of 3 interactive online sessions and received educational materials. There was no intervention in the control group teams (n = 37). Symptoms overload in the last 14 days, control of asthma in the last month, need for unplanned consultation in the last 6 months and use of preventive inhaled corticosteroids in the last 6 months were evaluated in the individuals indicated by the teams at the baseline and 6 months after the intervention. Results: The general assiduity of health teams to online interactive sessions was 50%. Both groups showed improved clinical outcomes and used less inhaled corticosteroids at follow-up. Exposure to educational intervention was associated with better clinical outcomes odds ratios, however, with borderline statistical significance. No differences were observed in the use of preventive inhaled corticosteroids between groups. Conclusion: The distance education intervention showed potential despite the low attendance of the intervention teams. The proposed model is feasible and reproducible. Integration with the clinical record system can boost results. The implementation of professional development strategies should be guided by the best evidence in an institutional setting. / Telemedicina

INTRODUÇÃO: Mato Grosso é um dos estados que mais queimam no país e há poucos e recentes estudos que discutem os efeitos adversos da poluição do ar na saúde da população do estado. OBJETIVO: Investigar a relação entre poluição atmosférica e internações por doenças respiratórios e cardiovasculares no estado de Mato Grosso. METODOLOGIA: Uma análise de série temporal foi aplicada para verificar a associação entre queimadas e agravos, com dados semanais. O período estudado foi de primeiro de janeiro de 2008 a 31 de agosto de 2014, foi estudado o estado todo e na análise foi usada Regressão Binomial Negativa, com Modelo Aditivo Generalizado. A única variável que não apresentou relação linear com a variável dependente foi Semana e uma função do tipo Spline foi usada, por este motivo somente ela foi alisada para se controlar este padrão de efeito, com estrutura de defasagem de 1 a 4 semanas. Na segunda análise, outra série temporal, cujo objetivo era investigar os efeitos da variação diária do material particulado e o monóxido de carbono com as internações. O período analisado foi de primeiro de janeiro de 2012 a 30 de junho de 2015, foram estudados quinze municípios e para a análise foram utilizadas Regressões de Poisson e Binomial Negativa, com Modelos Aditivos Generalizados, dependências não lineares entre variáveis explicativas e variáveis resposta foram controladas usando um alisador do tipo Spline, a estrutura de defasagem foi de 1 a 7 dias. A terceira abordagem, foi uma Análise de Autocorrelação Espacial do tipo Moran, onde foi estudado o estado todo em dois períodos: Primeiro de janeiro de 2003 a 31 de dezembro de 2010 e de primeiro de janeiro de 2011 a 31 dezembro de 2016. Foram montados bancos de dados usando incidências e número de focos de queimadas por área para verificar o agrupamento dos municípios de acordo com o Moran Local, foram montados mapas temáticos dos índices univariados e bivariados. RESULTADOS: Na primeira análise, foram encontradas associações significativas entre queimadas e internações por problemas respiratórios em menores de 5 anos: lag 0 (RR = 1,001; IC 95% = 1,00016 - 1,00279), lag 1 (RR = 1,001; IC 95% = 1,00005 - 1,00265) e lag 4 (RR = 1,002; IC 95% = 1,00079 - 1,00342) e associação significativa em maiores de 60 anos somente para lag 0 (RR = 1,001; IC 95% = 1,00013 - 1,00256). Na segunda análise, houveram associações significativas entre todos os agravos e poluentes, exceto para problemas cardiovasculares e monóxido de carbono. Foram encontradas associações com diversas defasagens entre todos os agravos e poluentes. Na análise espacial, para o período entre 2003 e 2010, foram encontrados aglomerados significativos com formato de arco para o Moran univariado de queimadas e bivariado. Para o período de 2011 a 2016, os aglomerados univariado de queimadas e bivariado se concentraram no nordeste do estado. CONCLUSÕES: Nas análises de séries temporais foram encontradas associações entre queimadas e agravos e entre poluentes e agravos (semana e dia), inclusive com defasagens (semana e dia) em ambas as análises. Na análise espacial, a mudança do \"cluster\" entre os períodos estudados mostra a mudança da expansão da fronteira agrícola, antes seguindo o arco de desmatamento e agora abrindo áreas remanescentes no estado, onde o desmatamento é realizado com o uso das queimadas que podem causar doenças respiratórias e cardiovasculares / INTRODUCTION: The State of Mato Grosso is is one of the places in the country and there are few and recent studies discussing the adverse health effects of air pollution on the population in this state. OBJECTIVE: To investigate the relationship between atmospheric pollution and hospitalizations for respiratory and cardiovascular diseases in the state of Mato Grosso. METHODOLOGY: A time series analysis was applied in order to verify the association between number of vegetation burns and diseases. Data were recorded weekly. The period studied was from January 1, 2008 to August 31, 2014, the entire state was studied and it was used Negative Binomial Regression with Generalized Additive Model. The only variable that did not present a linear relationship with the dependent variable was Week and a spline-type function was used to address this pattern of effect, a lag structure up to four weeks was applied. In a second approach, other time series analysis, in order to investigate the effects of daily variations of particulate matter and carbon monoxide on hospitalizations pollutant-specific. The period analyzed was from January 1, 2012 to June 30, 2015, fifteen municipalities were studied and Generalized Additive with Poisson or Negative Binomial Regressions models were used, Non-linear dependencies between the outcomes and covariables was controlled using spline-type smoother. A lag structure up to seven days was applied. To explore spatial patterns of occurrence a Moran Spatial Autocorrelation Analysis was carried out, where the whole state was studied in two periods: January 1, 2003 to December 31, 2010, and from January 1, 2011 to December 31, 2016. Databases were assembled using incidences and number of fires per area, to verify the \"cluster\" formation of municipalities according to Local Moran, thematic maps of the univariate and bivariate indices were set up. RESULTS: In the first analysis, there were significant associations between burns and hospitalizations due to respiratory problems in children under 5 years of age: lag 0 (RR = 1.001, 95% CI = 1.00016 - 1.00279), lags 1 (RR = 1.001, 95% CI = 1.00005 - 1.00265) and lag 4 (RR = 1.002, 95% CI = 1.00079 - 1.00342) and significant association in patients over 60 years only for lag 0 (RR = 1.001, 95% CI = 1.000-13 - 1.00256). For the second analysis, there were significant associations between all the diseases and pollutants, except for cardiovascular problems and carbon monoxide. Associations with different lags between all the diseases and pollutants were found. In the spatial analysis, for the period between 2003 and 2010, significant \"clusters\" with arc shape were found for the univariate \"clusters\" of fires and bivariate. For the period of 2011 and 2016, the univariate \"clusters\" of fires and bivariate were concentrated in the northeast of the state. CONCLUSIONS: In time series analyses, associations between burnings and injuries and between pollutants and injuries were found, at the same period of exposure (week or day) and in subsequent periods (weeks or days). Spatially, the \"cluster\" change between the studied periods shows the change in the expansion of the agricultural frontier, before following the arc of deforestation and now opening remaining areas in the state. Deforestation is carried out with the use of forest fires that can promote respiratory and cardiovascular diseases

Ma, Hok Lun. / Thesis submitted in: December 2008. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 233-273). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese version) --- p.v / Tables of contents --- p.vi / Acknowledgement --- p.xvi / List of figures --- p.xvii / List of tables --- p.xxi / List of abbreviations and symbols --- p.xxviii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Respiratory illnesses in children --- p.1 / Chapter 1.1.1 --- Worldwide burden of childhood pneumonia --- p.1 / Chapter 1.1.2 --- Further mortality related to childhood pneumonia --- p.4 / Chapter 1.2 --- Etiology agent of childhood respiratory illnesses --- p.5 / Chapter 1.2.1 --- Difficulties in determining etiological agent --- p.5 / Chapter 1.2.2 --- Overall situation of etiological agents in childhood pneumonia --- p.6 / Chapter 1.2.3 --- Relationship between age and pathogens --- p.9 / Chapter 1.2.4 --- "Relationship between serotypes, carriage and invasiveness" --- p.11 / Chapter 1.2.4.1 --- Carriage and Invasiveness --- p.12 / Chapter 1.2.4.2.1 --- Carriage of S. pneumoniae and H. influenzae in children in Hong Kong --- p.12 / Chapter 1.2.4.2.2 --- "Serotypes, carriage and invasiveness in S. pneumoniae" --- p.14 / Chapter 1.2.4.2.3 --- "Serotypes, carriage and invasiveness in H. influenzae" --- p.17 / Chapter 1.3 --- Epidemiology of antibiotic-resistant pathogens --- p.18 / Chapter 1.3.1 --- Molecular typing methods --- p.18 / Chapter 1.3.2 --- Spread of antibiotic-resistant pathogens --- p.20 / Chapter 1.3.2.1 --- Spread of antibiotic-resistant S. pneumoniae --- p.26 / Chapter 1.3.2.1.1 --- Spread of penicillin-resistant S. pneumoniae --- p.26 / Chapter 1.3.2.1.1.1 --- Spread of Spanish-23F-1 --- p.27 / Chapter 1.3.2.1.1.2 --- Spread of Spanish-6B-2 --- p.28 / Chapter 1.3.2.1.1.3 --- Spread of antibiotic-resistant S. pneumoniae clones in Hong Kong --- p.28 / Chapter 1.3.2.1.2 --- Spread of cephalosporin-resistant S. pneumoniae --- p.29 / Chapter 1.3.2.1.3 --- Spread of macrolide-resistant S. pneumoniae --- p.30 / Chapter 1.3.2.1.4 --- Spread of fluoroquinolone-resistant S. pneumoniae --- p.31 / Chapter 1.3.2.2 --- Spread of antibiotic-resistant H. influenzae --- p.32 / Chapter 1.3.2.2.1 --- Spread of β-lactam-resistant H. influenzae --- p.32 / Chapter 1.3.2.2.2 --- Spread of macrolide-resistant H. influenzae --- p.33 / Chapter 1.3.2.2.3 --- Spread of fluoroquinolone-resistant H. influenzae --- p.34 / Chapter 1.4 --- Mechanism of antibiotic-resistance in respiratory pathogens --- p.36 / Chapter 1.4.1 --- Mechanism of antibiotic-resistance in S. pneumoniae --- p.37 / Chapter 1.4.1.1 --- Mechanism of penicillin- and cephalosporin-resistance in S. pneumoniae --- p.37 / Chapter 1.4.1.1.1 --- Penicillin-binding protein (PBP)-mediated mechanism --- p.37 / Chapter 1.4.1.1.2 --- PBP-independent mechanisms --- p.49 / Chapter 1.4.1.1.2.1 --- "Murine peptide branching genes, murMN operon" --- p.49 / Chapter 1.4.1.1.2.2 --- "Two-component system, CiaRH" --- p.50 / Chapter 1.4.1.1.2.3 --- "Putative glycosyltransferase, CpoA" --- p.52 / Chapter 1.4.1.1.3 --- RNA and protein expression studies on S. pneumoniae for β-lactam-resistance --- p.52 / Chapter 1.4.1.1.3.1 --- RNA expression in penicillin-sensitive S. pneumoniae --- p.53 / Chapter 1.4.1.1.3.2 --- Protein expression in penicillin-resistant S. pneumoniae --- p.53 / Chapter 1.4.1.2 --- Mechanism of macrolide- and lincosamide- resistance in S. pneumoniae --- p.54 / Chapter 1.4.1.3 --- Mechanism of tetracycline-resistance in S. pneumoniae --- p.55 / Chapter 1.4.1.4 --- Mechanism of fluoroquinolone-resistance in S. pneumoniae --- p.55 / Chapter 1.4.2 --- Mechanism of antibiotic-resistant in H. influenzae --- p.56 / Chapter 1.4.2.1 --- Mechanism of β-lactam-resistance in H. influenzae --- p.56 / Chapter 1.4.2.1.1 --- β-lactamase-producing H. influenzae --- p.56 / Chapter 1.4.2.1.2 --- β-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae --- p.58 / Chapter 1.4.2.1.2.1 --- Relationship between amino acid substitutions in PBP3 and β-lactam- resistance --- p.58 / Chapter 1.4.2.1.2.2 --- Relationship between amino acid substitutions in AcrR and β-lactam-resistance --- p.60 / Chapter 1.4.2.2 --- Mechanism of macrolide-resistance in H. influenzae --- p.61 / Chapter 1.4.2.3 --- Mechanism of fluoroquinolone-resistance in H. influenzae --- p.64 / Chapter 1.5 --- Impact of vaccination --- p.65 / Chapter 1.5.1 --- H. influenzae type b vaccination --- p.65 / Chapter 1.5.1.1 --- Efficacy of Hib conjugate vaccine --- p.66 / Chapter 1.5.1.2 --- Herd immunity related to Hib conjugate vaccine --- p.66 / Chapter 1.5.2 --- Pneumococcal vaccination --- p.66 / Chapter 1.5.2.1 --- Vaccine efficacy and herd immunity of pneumococcal vaccines --- p.67 / Chapter 1.5.2.2 --- Development of conjugate vaccines with higher valency --- p.67 / Chapter 1.5.2.3 --- Serotype replacement --- p.67 / Chapter 1.5.2.4 --- Development of pneumococcal vaccines with new targets --- p.69 / Chapter 1.6 --- Objectives of this study --- p.70 / Chapter Chapter 2 --- Materials and methods --- p.72 / Chapter 2.1 --- Collection and Identification of microorganisms --- p.72 / Chapter 2.1.1 --- Collection of S. pneumoniae and H. influenzae --- p.72 / Chapter 2.1.2 --- Identification of S. pneumoniae and H. influenzae --- p.73 / Chapter 2.2 --- Serotyping of S. pneumoniae and H. influenzae --- p.74 / Chapter 2.2.1 --- Serotyping by polymerase chain reaction (PCR) --- p.74 / Chapter 2.2.1.1 --- Preparation of crude DNA extract --- p.74 / Chapter 2.2.1.2 --- Screening for common serotypes by multiplex PCR --- p.74 / Chapter 2.2.1.3 --- Composition of PCR Mix --- p.77 / Chapter 2.2.1.4 --- Serotyping PCR conditions --- p.81 / Chapter 2.2.1.5 --- Gel Electrophoresis --- p.81 / Chapter 2.2.2 --- Serotyping by serum agglutination --- p.82 / Chapter 2.3 --- Antimicrobial susceptibility testing --- p.83 / Chapter 2.4 --- Clonal analysis of penicillin- and cephalosporin-resistant S. pneumoniae --- p.87 / Chapter 2.4.1 --- Pulsed-field Gel Electrophoresis (PFGE) --- p.87 / Chapter 2.4.1.1 --- Preparation of agarose plugs for PFGE --- p.87 / Chapter 2.4.1.2 --- Lysis of bacteria in agarose plugs --- p.89 / Chapter 2.4.1.3 --- Digestion of chromosomal DNA by restriction enzyme --- p.89 / Chapter 2.4.2 --- Multi-locus sequence typing (MLST) --- p.90 / Chapter 2.4.2.1 --- PCR amplification of house-keeping genes in MLST --- p.90 / Chapter 2.4.2.1.1 --- Preparation of DNA from agarose plugs --- p.92 / Chapter 2.4.2.1.2 --- Composition of PCR Mix --- p.92 / Chapter 2.4.2.1.3 --- MLST PCR conditions --- p.92 / Chapter 2.4.2.1.4 --- Gel Electrophoresis of MLST PCR products --- p.92 / Chapter 2.4.2.1.5 --- MLST PCR products purification --- p.93 / Chapter 2.4.2.2 --- Sequencing of housekeeping genes in MLST --- p.93 / Chapter 2.4.2.3 --- Sequencing analysis and sequence type (ST) determination in MLST --- p.94 / Chapter 2.4.3 --- Extended panel of antibiotic susceptibility testing on S. pneumoniae with known STs --- p.94 / Chapter 2.5 --- Analysis on potential penicillin- and cephalosporin-resistance mechanisms in S. pneumoniae --- p.96 / Chapter 2.5.1 --- Sequencing of potnetial penicillin- and cephalosporin- resistance determinants in S. pneumoniae --- p.96 / Chapter 2.5.1.1 --- Primer design of penicillin-binding protein (PBP) genes --- p.96 / Chapter 2.5.1.2 --- Primer design of non-PBP resistance determinants --- p.100 / Chapter 2.5.1.3 --- PCR amplification and sequencing of resistant determinants --- p.100 / Chapter 2.5.1.4 --- Sequence analysis --- p.100 / Chapter 2.5.2 --- Study on efflux mechanism of S. pneumoniae --- p.103 / Chapter 2.5.2.1 --- Modification of macrodilution for efflux assay --- p.103 / Chapter 2.5.2.2 --- Cefotaxime MIC determination with efflux inhibitors --- p.104 / Chapter 2.5.2.3 --- Determination of appropriate CCCP concentration --- p.105 / Chapter 2.5.2.4 --- Growth curve with efflux inhibitor --- p.105 / Chapter 2.5.3 --- Heteroresistance assay of S. pneumoniae --- p.106 / Chapter 2.5.4 --- "RNA expression study on penicillin- and cefotaxime-resistance determinants (pbp2x, pbpla and pbp2a) of S. pneumoniae" --- p.107 / Chapter 2.5.4.1 --- Growth of S. pneumoniae for RNA extraction --- p.107 / Chapter 2.5.4.2 --- RNA extraction and DNase digestion --- p.107 / Chapter 2.5.4.3 --- cDNA synthesis and real-time PCR --- p.108 / Chapter 2.6 --- Analysis on cephalosporin- and macrolide-resistance mechanisms in H. influenzae --- p.111 / Chapter 2.6.1 --- β-lactamase production of H. influenzae --- p.111 / Chapter 2.6.1.1 --- Nitrocefin Hydrolysis --- p.111 / Chapter 2.6.1.2 --- Screening for the presence of p-lactamase gene (blaTEM-1 and blaROB-1) by multiplex PCR --- p.111 / Chapter 2.6.2 --- PCR detection and sequencing of β-lactam- and macrolide- resistance determinants in H. influenzae --- p.113 / Chapter Chapter 3 --- Results of S. pneumoniae and H. influenzae children study --- p.116 / Chapter 3.1 --- Patient demographics of children study --- p.116 / Chapter 3.2 --- Serotype distributions --- p.117 / Chapter 3.2.1 --- Serotypes / serogroup distribution in S. pneumoniae --- p.117 / Chapter 3.2.2 --- Serotype distribution in H. influenzae children study --- p.120 / Chapter 3.3 --- Antibiotic susceptibilities and resistance antibiograms --- p.122 / Chapter 3.3.1 --- Antibiotic susceptibilities of S. pneumoniae --- p.122 / Chapter 3.3.2 --- Relationship between antibiotic resistance profiles and serotypes in S.pneumoniae --- p.126 / Chapter 3.3.3 --- Antibiotic susceptibilities of H. influenzae --- p.135 / Chapter 3.3.4 --- Antibiotic resistance profiles of H. influenzae --- p.138 / Chapter 3.4 --- Clonal analysis of penicillin- and cephalosporin-resistant S.pneumoniae --- p.139 / Chapter 3.4.1 --- Pulsed-field gel electrophoresis (PFGE) of S. pneumoniae --- p.139 / Chapter 3.4.2 --- Multi-locus sequence typing of S. pneumoniae --- p.141 / Chapter 3.5 --- Analysis of the penicillin- and cephalosporin-resistance determinants in S. pneumoniae --- p.143 / Chapter 3.5.1 --- "Sequence analysis of major pbp genes (pbp2x, pbpla and pbp2a)" --- p.143 / Chapter 3.5.2 --- "Sequence analysis of other potential penicillin- and cephalosporin- resistance determinants (pbp 1 b, pbp2b, pbp3, cpoA, ciaRH and murMN)" --- p.152 / Chapter 3.5.3 --- Sequence analysis of putative promoter sequences of pbp genes --- p.167 / Chapter 3.5.4 --- Efflux Inhibition Assay --- p.171 / Chapter 3.5.5 --- Heteroresistance Assay --- p.177 / Chapter 3.5.6 --- "RNA expression study on penicillin- and cephalosporin resistance determinants (pbp2x, pbpla and pbp2a)" --- p.179 / Chapter 3.6 --- Analysis of β-lactam-resistance determinants in H. influenzae --- p.185 / Chapter 3.6.1 --- β-lactamase production and blaTEM-1 promoter study --- p.185 / Chapter 3.6.2 --- "Sequence analysis of β-lactam-resistance determinants (ftsl, acrR genes, AcrAB-TolC efflux pump)" --- p.188 / Chapter 3.6.2.1 --- Sequence analysis offtsl --- p.188 / Chapter 3.6.2.2 --- Analysis of acrR and AcrAB-TolC efflux pump --- p.189 / Chapter 3.7 --- "Analysis of macrolide-resistance determinants in H, influenzae (AcrAB-TolC efflux pump, 23SrRNA, Ribosomal proteins L4 and L22)" --- p.199 / Chapter Chapter 4 --- Discussion on S. pneumoniae and H. influenzae children study --- p.204 / Chapter 4.1 --- Carriage rate of S. pneumoniae children collection --- p.204 / Chapter 4.2 --- Serotype distribution --- p.205 / Chapter 4.2.1 --- Serotype distribution and potential vaccine coverage in S. pneumoniae --- p.205 / Chapter 4.2.2 --- Serotype distribution in H. influenzae --- p.209 / Chapter 4.3 --- Antimicrobial resistance --- p.210 / Chapter 4.3.1 --- Antimicrobial resistance in S. pneumoniae --- p.210 / Chapter 4.3.2 --- Antimicrobial resistance in H. influenzae --- p.214 / Chapter 4.4 --- "Clonal analysis of high-level β-lactam-resistant S, pneumoniae" --- p.217 / Chapter 4.5 --- "β-lactam-resistance mechanisms in S, pneunomiae" --- p.220 / Chapter 4.6 --- Antimicrobial resistance mechanisms in H. influenzae --- p.224 / Chapter 4.6.1 --- β-lactam-resistance mechanism in β-lactamase-producing H. influenzae --- p.224 / Chapter 4.6.1.1 --- Variations in blaTEM-1 promoters in β-lactamase-producing H.influenzae --- p.224 / Chapter 4.6.1.2 --- β-lactam-resistance in β-lactamase-nonproducing H. influenzae --- p.225 / Chapter 4.6.2 --- Macrolide-resistance mechanisms in H. influenzae --- p.228 / Chapter Chapter 5 --- Conclusion and future studies --- p.230 / Chapter 5.1 --- "S, pneumoniae children study" --- p.230 / Chapter 5.2 --- H. influenzae children study --- p.231 / Chapter 5.3 --- Future studies --- p.232 / Bibliography --- p.233 / Appendix I 一 Sequence alignments and Tables --- p.274 / Appendix II 一 Materials and Methods --- p.313

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human cathepsin G (hCatG) and human neutrophil elastase (HNE) were expressed in P. pastoris and HNE was also expressed in K. lactis. The recombinant variants rhCatG and rHNE, with intact C-terminal extensions, were expressed as fusion proteins with the soluble heme-binding domain of cytochrome B5 (CytB5) and an N-terminal hexahistidine (6xHis) tag for purification. The CytB5 domain was linked to the native N-termini of active rhCatG and rHNE by the EPLcleavable substrate sequence DDDDK~I, where ~ is the sessile bond. These fusion proteins were directed for secretion. The yeast P. pastoris expressed up to 3.5 mg/L of EPL-activable rHNE in fermentation broth; however, only 200 μg/L of rhCatG could be produced by this method. Recombinant expression in K. lactis never surpassed 100 μg/L of activable rHNE. The CytB5 fusion domain was present in the heme-bound form, conferring a red color and 410 nm absorbance peak to solutions containing the fusion proteins. This absorbance pattern was most readily visible during the purification of CytB5-rHNE from P. pastoris. Human C-reactive protein (hCRP) and the substitution variant CRP E42Q were expressed in recombinant form and secreted by P. pastoris. Both products were found to bind phosphocholine (PCh) in the same manner as native hCRP. Difficulties encountered during purification revealed that wild type recombinant CRP (rCRP) was produced at 2 different molecular masses. The P. pastoris recombinant expression system yielded better results than K. lactis. Bioreactor-scale fermentation in a 5 L vessel facilitated expression and characterization of these recombinant proteins.

Background: Chronic obstructive pulmonary disease (COPD) has been a major public health problem due to its high prevalence, morbidity, and mortality. Smoking is a major risk factor for COPD, while serious psychological distress (SPD) is prevalent among COPD patients. However, no study focusing on the effect of SPD on COPD has been so far conducted, while few studies have focused on the associations of SPD and behavioral factors with COPD by smoking status. Objectives: This study aimed to examine the associations of SPD and behavioral factors (such as smoking and physical activity) with COPD. Materials and Methods: Weighted logistic regression models were used for the analysis of 1,248 cases and 39,995 controls from the 2005 California Health Interview Survey (CHIS). Results: The prevalence of SPD was 10% in cases and 4% in controls, respectively. The percentages of past and current smoking were higher in cases than controls (50% vs. 24% and 27% vs. 15%, respectively). After adjusting for other factors, smoking (OR = 4.56, 95% CI = 3.41-6.11 and OR = 3.24, 95% CI = 2.57-4.08 for current and past smoking, respectively), physical activity (OR = 0.69, 95% CI = 0.55-0.87), obesity (OR = 1.25, 95% CI = 1.03-1.52), older age (OR = 2.86, 95% CI = 2.15-3.82, and OR = 5.97, 95% CI = 4.42-8.08 for middle-aged and elder groups, respectively), SPD (OR = 2.11, 95% CI = 1.47-3.04), employment (OR = 0.62, 95% CI = 0.51-0.76), race (OR = 0.35, 95% CI = 0.23-0.54, OR = 0.59, 95% CI = 0.36-0.97, and OR = 0.47, 95% CI=0.29-0.75 for Latino, Asian, and African American, respectively) and lower federal poverty level (OR=1.89, 95% CI = 1.35-2.63, OR = 1.65, 95% CI = 1.27-2.14, and OR = 1.39, 95% CI = 1.12-1.72 for 0-99% FPL, 100-199% FPL and 200-299% FPL, respectively) were all associated with COPD (P < 0.05). Age group, SPD, race, and employment showed significant interactions with smoking status. Stratified by smoking status, aging was the only risk factor for COPD in the never smoking group; whereas, lack of physical activity, older age, SPD, race, unemployment, and lower federal poverty level were associated with COPD in the smoking groups. Conclusions: Smoking and aging were major risk factors for COPD, while lack of physical activity and SPD were strongly associated with COPD in the smoking groups.

Uncontrolled growth of vascular stem cells as a result of endothelial-mesenchymal transition is considered to cause hyper-proliferative vascular remodeling in severe pulmonary arterial hypertension (PAH) patients. Hyperplastic intimal growth is one of the causes of closure of the lumen of pulmonary arterioles. This abnormal vessel remodeling leads to the progressive increase in pressure of the pulmonary arterioles causing severe PAH; and debilitating harm to patients resulting in mortality from right heart failure. Environmental factors, including polychlorinated biphenyls (PCBs), are considered to be involved in hyper-proliferative vascular remodeling because genetic makeup can only explain about 10% of severe PAH cases. PCB involvement in lung toxicity has received attention because (i) they have been reported to accumulate in the lung; (ii) PCBs produce pathological vascular remodeling in the experimental model; high levels of PCBs are found in human lung tissue; and (iii) epidemiological studies show the association between lung toxicity and PCBs; and prevalence of hypertension and elevated concentrations of particularly PCB153. Recent studies identify PCB153 as one of the largest contributors for total PCB body burden in humans. Our previous studies demonstrated PCB153 mediated vascular endothelial dysfunction and activated the inhibitor of differentiation protein 3 (ID3). ID3 is an important determinant of mitogen and reactive oxygen species-induced G1→S phase cell cycle progression. Although phosphorylation of ID3 increases cell growth by antagonizing the transcription of cell cycle inhibitors, still there is a critical gap in understanding the molecular mechanism(s) of pulmonary proliferative vascular remodeling associated with PCB exposure in humans and the role of the transcription regulator ID3. Our overall objective was to investigate ID3 mediated transcriptional reprogramming as a driver of PCB153-induced pathological proliferative vascular remodeling. Stable ectopic expression of ID3 in lung endothelial cells contributed to endothelial-mesenchymal transition (EndMT), cell proliferation, and cell migration. Using an endothelial spheroid assay, an established method to measure aberrant hyper-proliferation of endothelial cells in PAH patients, we show that stable ectopic expression of ID3 increased the number and size of vascular spheres. ID3 overexpressing cells exposed to environmentally relevant concentrations of PCB153 showed a two-fold increase in cell proliferation as determined by MTT, SRB, and BrdU assays. ID3 overexpressing cells showed the loss of VE-cadherin and gain of MMP9 and vimentin, which are markers of EndMT. PCB153 also increased phosphorylation of ID3 in lung endothelial cells. To determine the molecular mechanism by which ID3 contributes to hyper-proliferative endothelial cells, we investigated ID3 transcriptional reprogramming using ChIP-Seq and RNA-Seq technology. We show here for the first time that ID3 is part of a more general mechanism of transcriptional regulation. Our ChIP-Seq data show that ID3 binds to a subset of approximately 1200 target genes. Comprehensive motif analysis of ChIP-Seq data using the MEME Suite software toolkit revealed that ID3 bound to the GAGAGAGAGA motif sequence on genomic DNA. We also show a significant preference of ID3 binding to motifs associated with transcription factors IRF1, BC11A, IRF4, PRDM1, FOXJ3, SMAD4, ZBTB6, GATA1, and STAT2. Using an integrative approach of ChIP-Seq and RNA-Seq data, we identified 19 genes whose promoter region was bound by ID3 and RNA was differentially expressed in ID3 overexpressing cells. In summary, our data demonstrated that PCB153 and/or ID3 induces proliferation of lung endothelial cells via transcriptional reprogramming. Discoveries from these findings will lay the necessary groundbreaking work for testing the efficacy of ID3 antagonists for the prevention and treatment of pathological vascular remodeling as well as provide a new paradigm by which PCBs may contribute to lung vascular toxicity.