Genetic Susceptibility to Arsenic Exposure and Arsenical Skin Lesion Prevalence in Bangladesh

Elevated concentrations of arsenic in groundwater pose a public health threat to millions of people worldwide. While arsenic is an established human carcinogen, a mode of action has yet to be determined for arsenic carcinogenesis. However, the oxidative stress and DNA repair pathways have been implicated in arsenic toxicity and have been hypothesized to underlie arsenic carcinogenesis. To date, few epidemiologic studies have evaluated genetic susceptibility to arsenical skin lesions based on single nucleotide polymorphisms (SNPs) in antioxidant enzyme or DNA repair genes. Utilizing cross-sectional data from the 2000-2002 survey of the Health Effects of Arsenic Longitudinal Study (HEALS) for 610 prevalent arsenical skin lesion cases and 1,079 randomly selected controls, I evaluated the associations of SNPs in genes encoding antioxidant enzymes and DNA repair enzymes on skin lesion prevalence. I also evaluated potential interactions between the SNPS as well as SNP-environment interactions in determining skin lesion prevalence. In the first study of this dissertation (Chapter 2), I assessed the relationship between SNPs in antioxidant enzyme genes and skin lesion prevalence, as well as possible interactions of these associations on the additive scale by various environmental factors. There were no statistically significant associations between these SNPs (SOD2, rs4880; CAT, rs1001179; GPX1, rs1050450; and MPO, rs2333227) and skin lesion prevalence. Additionally, there was no evidence of additive interaction by arsenic exposure levels, body mass index, smoking status, or fruit and vegetable intake with the SNPs in relation to skin lesion prevalence. However, there was marginal evidence that skin lesion prevalence was increased among individuals who carried 4 or more risk alleles compared to individuals carrying 0-3 risk alleles in these SNPs. Additionally, I observed a significant departure from additivity for the risk allele score and primary methylation index on skin lesion prevalence. In the second study of this dissertation (Chapter 3), I assessed the relationship between SNPs in DNA repair genes (OGG1, rs1052133; XRCC1, rs25487 and rs1799782; XRCC3, rs861539; ERCC2, rs1052559; ERCC5, rs17655; and LIG4, rs1805388) and skin lesion prevalence, as well as possible interactions of these associations on the additive scale by various environmental factors. In logistic regression models controlling for sex, age, and well water arsenic concentration, no associations were observed between measured SNPs and skin lesion prevalence. The results did not vary by arsenic exposure levels, body mass index, or smoking status. However, I did observe a significant inverse association of total fruit and vegetable consumption with skin lesion prevalence, and its additive interaction with the polymorphism in ERCC5. In the third study of this dissertation (Chapter 4), I utilized a multi-analytic approach to explore gene-gene, gene-environment, and higher-order interactions among 10 SNPs related to the oxidative stress and DNA repair pathways by MDR, CART, and logistic regression models. As shown in Chapters 2 and 3, none of these SNPs were associated with skin lesion prevalence, however, were evaluated for potential SNP-SNP interactions. MDR and CART modeling approaches were utilized for the selection of potential gene-gene and gene-environment interactions. Considerable overlap of the interactions detected by both these methods was observed, which were further evaluated by logistic regression. Results from logistic regression modeling, provided some evidence of these statistical interactions; however, their biological interpretation was limited. In summary, there was marginal evidence that skin lesion prevalence was increased among individuals who carried 4 or more risk alleles in genotyped SNPs related to the oxidative stress pathway compared to individuals carrying 0-3 risk alleles in these SNPs and, a significant departure from additivity was observed for the risk allele score and primary methylation index on skin lesion prevalence. Additionally, a significant inverse association of total fruit and vegetable consumption with skin lesion prevalence was observed and, a significant interaction between the polymorphism in ERCC5 and total fruit and vegetable intake was observed in relation to skin lesion prevalence on the additive scale. However, these finding require replication in other studies

Memorial 10 Anos do Programa de Mestrado em Desenvolvimento Regional da Universidade do Contestado

O texto aborda aspectos relacionados à trajetória da legitimação do Stricto Sensu na Universidade do Contestado (UnC), bem como do Programa de Mestrado em Desenvolvimento Regional (PMDR) na UnC, desde sua autorização em questões de processo, avanços e desafios. A pesquisa de características quali-quantitativa e descritiva revela que mesmo com os enfrentamentos, o PMDR demonstra relevante contribuição ao desenvolvimento, não apenas na abrangência territorial do Planalto Norte Catarinense (PNC). Analisando a sua trajetória de 10 anos, o PMDR contribui com a formação de pesquisadores e intelectuais. Evidencia fundamentos éticos e políticos da multiprofissionalidade e interdisciplinaridade, pelos quais sujeitos e atores devem mover-se no rumo do bem estar da sociedade. Internamente, o PMDR como processo vivo, avança nos seus compromissos e fundamentos, quando cerca as dimensões do desenvolvimento por duas linhas de pesquisa: a) Políticas Públicas e Desenvolvimento Regional; b) Gestão, Território e Desenvolvimento. As dissertações defendidas mesmo abordando a abrangência local e microrregional, promovem análises de temáticas vinculadas às necessidades humanas e socioeconômicas, com destaque para a saúde, educação, agricultura e pecuária, meio ambiente e indústria e comércio. A produção científica do PMDR sustenta também os meios de comunicação e as intervenções sociais dos múltiplos atores, ao mesmo tempo em que se constitui como fonte fidedigna dos anseios, demandas e perspectiva de desenvolvimento não apenas do Planalto Norte Catarinense, mas de qualquer território ousado que deseje modificar e superar os impasses do bem estar da sociedade

Educação ambiental e intervenção na microbacia do Lajeado Sabão, em Concórdia-SC

The purpose of this article is to present the process of an environmental pedagogical experience developed at the Professor Olavo Cecco Rigon Basic Education School, located in the hydrographic watershed of the Rio Lajeado Sabão, in the municipality of Concórdia-SC. In 2016, the project entitled “Knowing and interacting with and in the School's watershed” started, financed by the National Water Agency and the Higher Education Personnel Improvement Coordination. The methodology adopted includes action research, applied exploratory, bibliographic, field and qualitative. Among the results obtained are the development of pedagogical works on the theme of water generation, on the implementation of practices or social technologies for water management, governance and preservation and on the production of educational teaching materials. Based on the theme, the research developed environmental education in an interdisciplinary and continuous way with students, volunteers, the population surrounding the watershed, in addition to implementing intervention projects in the spaces mentioned. Keywords: Waters. Regional Development. Basic Education. Environment.El propósito de este artículo es presentar el proceso de una experiencia pedagógica ambiental desarrollada en la Escuela de Educación Básica del Profesor Olavo Cecco Rigon, ubicada en la cuenca hidrográfica del río Lajeado Sabão, en el municipio de Concórdia-SC. En 2016, comenzó el proyecto denominado "Conocer e interactuar con y en la cuenca de la escuela", financiado por la Agencia Nacional del Agua y la Coordinación de Mejoramiento del Personal de Educación Superior. El estudio se realizó con dos clases de tercer año de secundaria. Entre los resultados obtenidos se encuentran el desarrollo de trabajos pedagógicos sobre el tema de la generación de agua, sobre la implementación de prácticas o tecnologías sociales para la gestión, gobernabilidad y preservación del agua y sobre la producción de materiales didácticos educativos. Con base en el tema, la investigación desarrolló la educación ambiental de manera interdisciplinaria y continua para estudiantes, voluntarios, la población que rodea la cuenca, además de implementar proyectos de intervención en los espacios mencionados. Palavras clave: Aguas. Desarrollo Regional. Educación Básica. Medio Ambiente.O objetivo deste artigo é apresentar o processo de uma experiência pedagógica ambiental desenvolvida na Escola de Educação Básica Professor Olavo Cecco Rigon, localizada na microbacia hidrográfica do Rio Lajeado Sabão, no Município de Concórdia-SC. No ano de 2016 iniciou-se o Projeto denominado “Conhecer e interagir com e na bacia hidrográfica da Escola”, financiado pela Agência Nacional de Águas e Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior. A metodologia adotada engloba a pesquisa-ação, aplicada exploratória, bibliográfica, de campo e qualitativa. O estudo ocorreu com duas turmas de terceiros anos do ensino médio. Dentre os resultados obtidos estão o desenvolvimento de trabalhos pedagógicos sobre o tema gerador água, sobre a implementação de práticas ou tecnologias sociais de gestão, governança e preservação das águas e sobre a produção de materiais didáticos pedagógicos. A partir da temática, a pesquisa desenvolveu a educação ambiental de forma interdisciplinar e continuada com os estudantes, voluntários, população do entorno da microbacia, além de implementar projetos de intervenções nos espaços mencionados. Palavras-chave: Águas. Desenvolvimento Regional. Educação Básica. Meio Ambiente

Moderate-vigorous physical activity and health-related quality of life among Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BackgroundPhysical activity is a modifiable healthy behavior that has been shown to positively influence health-related quality of life. However, research examining the link between physical activity and health-related quality of life among Hispanic/Latino adults is limited and inconsistent. The purpose of this study is to assess whether accelerometer-measured moderate-vigorous physical activity (MVPA) is associated with self-reported (a) mental health-related quality of life, and (b) physical health-related quality of life among diverse Hispanic/Latino adults in the US.MethodsCross-sectional data from 12,379 adults ages 18-74 years in 2008-2011, who participated in HCHS/SOL and had complete data were analyzed using complex survey design methods. Accelerometer data were categorized into no MVPA, low, moderate, and high MVPA. Health-related quality of life was assessed with the Short-Form 12 and we used the mental and physical component subscales where higher scores indicate better health-related quality of life. Multivariate linear regression models were used to derive adjusted means with 95% confidence intervals and linear trends.ResultsWe observed no significant linear trend between accelerometer-measured MVPA and mental health-related quality of life (ptrend = 0.73). There was a significant positive association between MVPA and physical health-related quality of life (ptrend < 0.001) where higher MVPA corresponded with higher scores in physical health-related quality of life. The adjusted means were 46.67 (44.85-48.48) for no MVPA, 49.33 (49.03-49.63) for low MVPA, 50.61 (50.09-51.13) for moderate MVPA, and 51.36 (50.86-51.86) for high MVPA.ConclusionsAmong diverse Hispanic/Latino adults in the US, accelerometer-measured MVPA was associated with physical health-related quality of life, but not mental health-related quality of life. Future interventions should evaluate if increases in MVPA lead to improvements in health-related quality of life

Relationships Between Urinary Metals and Diabetes Traits among Mexican americans in Starr County, Texas, Usa

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of diabetes and diabetes-associated mortality. We used multivariable linear regression to quantify the differences in homeostatic model assessments for pancreatic β-cell function, insulin resistance, and insulin sensitivity (HOMA-β, HOMA-IR, HOMA-S, respectively), plasma insulin, plasma glucose, and hemoglobin A1c (HbA1c) associated with increasing urinary metal concentrations. Quantile-based g-computation was utilized to assess mixture effects. After multivariable adjustment, urinary arsenic and molybdenum were associated with lower HOMA-β, HOMA-IR, and plasma insulin levels and higher HOMA-S. Additionally, higher urinary copper levels were associated with a reduced HOMA-β. Lastly, a higher concentration of the 8 metal mixtures was associated with lower HOMA-β, HOMA-IR, and plasma insulin levels as well as higher HOMA-S. Our data indicate that arsenic, molybdenum, copper, and this metal mixture are associated with alterations in measures of glucose homeostasis among non-diabetics in Starr County. This study is one of the first to comprehensively evaluate associations of urinary metals with glycemic measures in a high-risk Mexican American population

A Prospective Study of Tobacco Smoking and Mortality in Bangladesh

Background: Limited data are available on smoking-related mortality in low-income countries, where both chronic disease burden and prevalence of smoking are increasing.Methods: Using data on 20, 033 individuals in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, we prospectively evaluated the association between tobacco smoking and all-cause, cancer, and cardiovascular disease mortality during ∼7.6 years of follow-up.Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for deaths from all-cause, cancer, CVD, ischemic heart disease (IHD), and stroke, in relation to status, duration, and intensity of cigarette/bidi and hookah smoking.Results: Among men, cigarette/bidi smoking was positively associated with all-cause (HR 1.40, 95% CI 1.06 1.86) and cancer mortality (HR 2.91, 1.24 6.80), and there was a dose-response relationship between increasing intensity of cigarette/bidi consumption and increasing mortality. An elevated risk of death from ischemic heart disease (HR 1.87, 1.08 3.24) was associated with current cigarette/bidi smoking. Among women, the corresponding HRs were 1.65 (95% CI 1.16 2.36) for all-cause mortality and 2.69 (95% CI 1.20 6.01) for ischemic heart disease mortality. Similar associations were observed for hookah smoking. There was a trend towards reduced risk for the mortality outcomes with older age at onset of cigarette/bidi smoking and increasing years since quitting cigarette/bibi smoking among men. We estimated that cigarette/bidi smoking accounted for about 25.0% of deaths in men and 7.6% in women.Conclusions: Tobacco smoking was responsible for substantial proportion of premature deaths in the Bangladeshi population, especially among men. Stringent measures of tobacco control and cessation are needed to reduce tobacco-related deaths in Bangladesh.</p

Use of \u3e100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged \u3e100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) \u3c 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11–34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations

O PATRIMÔNIO TERRITORIAL COMO REFERÊNCIA PARA O DESENVOLVIMENTO DE MUNICÍPIOS, REGIÕES OU TERRITÓRIOS: possibilidades e desafios

Assume-se a concepção de patrimônio territorial como o conjunto de ativos e recursos, materiais e imateriais, genéricos e específicos, públicos e privados, de um determinado território. Decorrente dessa compreensão, entende-se que impulsionar o desenvolvimento de territórios, regiões ou municípios pela ativação de seu patrimônio territorial, implica reconhecê-los como recortes espaciais específicos, incluindo sua gente, suas infraestruturas, suas institucionalidades, suas paisagens naturais, suas tradições históricas, suas formas de sobrevivência e a especificidade dos produtos que oferecem ao mercado. Nesta perspectiva, o presente texto objetiva avaliar a aplicabilidade de aporte metodológico explicitado em Dallabrida (2020a), que propõe considerar o patrimônio territorial e seus componentes, como ponto de partida e diretriz na elaboração de estratégias localizadas de desenvolvimento, tendo como referência os dados disponíveis sobre dois municípios, Mafra e Canoinhas, Santa Catarina, Brasil

Prevalence of Arsenic Exposure from Drinking Water and Awareness of Its Health Risks in a Bangladeshi Population: Results from a Large Population-Based Study

We conducted a population-based prevalence survey in Araihazar, Bangladesh, to describe the distribution of arsenic exposure in a rural Bangladeshi population and to assess the population’s awareness to this problem as well as to possible remediation options. Water samples from 5,967 contiguous tube wells in a defined geographic area were tested using laboratory-based methods. Additionally, for each well, the owner/caretaker (or a close relative) was interviewed regarding his or her awareness of the health consequences of As exposure. Arsenic exposure data and demographic characteristics for the 65,876 users of these wells were also collected from the 5,967 respondents. Among the 65,876 residents, more than half (54%) regularly consumed well water with an As concentration ≥ 50 μg/L—above the acceptable government standard in Bangladesh. Respondents were 15–92 years of age, with an average age of 42 years, and 43% were male. Presence of awareness was significantly related to male sex, nonlabor head of household occupation, better housing, and having had the well tested for As concentration. Most respondents (92%) expressed a willingness to take steps to reduce their exposure, with switching to a safe well the most favored option (46.2%). Willingness to reduce exposure was positively related to awareness of the health risks of As. However, the association between awareness and switching to a safe well [odds ratio (OR) = 1.25; 95% confidence interval (CI), 1.01–1.54] was no stronger than the associations between awareness and using surface water (with or without treatments) (OR = 1.54; 95% CI, 1.22–1.95) or using an existing well after treatment or increasing the depth (OR = 1.34; 95% CI, 1.08–1.67). These findings suggest that health education programs may need to target individuals with lower socioeconomic status and that well switching should be encouraged with more appropriate health education. Increasing knowledge of the health consequences of As may be an important element in facilitating remediation

A RESTful API for Accessing Microbial Community Data for MG-RAST

Many health outcomes are influenced by a person's body mass index, as well as by the trajectory of body mass index through a lifetime. Although previous research has established that body mass index related traits are influenced by genetics, the relationship between these traits and genetics has not been well characterized in people of South Asian ancestry. To begin to characterize this relationship, we analyzed the association between common genetic variation and five phenotypes related to body mass index in a population-based sample of 5,354 Bangladeshi adults. We discovered a significant association between SNV rs347313 (intron of NOS1AP) and change in body mass index in women over two years. In a linear mixed-model, the G allele was associated with an increase of 0.25 kg/m2 in body mass index over two years (p-value of 2.3·10−8). We also estimated the heritability of these phenotypes from our genotype data. We found significant estimates of heritability for all of the body mass index-related phenotypes. Our study evaluated the genetic determinants of body mass index related phenotypes for the first time in South Asians. The results suggest that these phenotypes are heritable and some of this heritability is driven by variation that differs from those previously reported. We also provide evidence that the genetic etiology of body mass index related traits may differ by ancestry, sex, and environment, and consequently that these factors should be considered when assessing the genetic determinants of the risk of body mass index-related disease