Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development

Congenital heart disease (CHD) occurs in similar to 1% of newborns. CHD arises from many distinct etiologies, ranging from genetic or genomic variation to exposure to teratogens, which elicit diverse cell and molecular responses during cardiac development. To systematically explore the relationships between CHD risk factors and responses, we compiled and integrated comprehensive datasets from studies of CHD in humans and model organisms. We examined two alternative models of potential functional relationships between genes in these datasets: direct convergence, in which CHD risk factors significantly and directly impact the same genes and molecules and functional convergence, in which risk factors significantly impact different molecules that participate in a discrete heart development network. We observed no evidence for direct convergence. In contrast, we show that CHD risk factors functionally converge in protein networks driving the development of specific anatomical structures (e.g., outflow tract, ventricular septum, and atrial septum) that are malformed by CHD. This integrative analysis of CHD risk factors and responses suggests a complex pattern of functional interactions between genomic variation and environmental exposures that modulate critical biological systems during heart development.

Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. (C) 2012 Elsevier B.V. All rights reserved.

An Insight into the Sialotranscriptome of Triatoma matogrossensis, a Kissing Bug Associated with Fogo Selvagem in South America

Triatoma matogrossensis is a Hemiptera that belongs to the oliveirai complex, a vector of Chagas' disease that feeds on vertebrate blood in all life stages. Hematophagous insects' salivary glands (SGs) produce potent pharmacologic compounds that counteract host hemostasis, including anticlotting, antiplatelet, and vasodilatory molecules. Exposure to T. matogrossensis was also found to be a risk factor associated with the endemic form of the autoimmune skin disease pemphigus foliaceus, which is described in the same regions where Chagas' disease is observed in Brazil. To obtain a further insight into the salivary biochemical and pharmacologic diversity of this kissing bug and to identify possible allergens that might be associated with this autoimmune disease, a cDNA library from its SGs was randomly sequenced. We present the analysis of a set of 2,230 (SG) cDNA sequences, 1,182 of which coded for proteins of a putative secretory nature.

Parent psychopathology and offspring mental disorders: results from the WHO World Mental Health Surveys

Background Associations between specific parent and offspring mental disorders are likely to have been overestimated in studies that have failed to control for parent comorbidity. Aims To examine the associations of parent with respondent disorders. Method Data come from the World Health Organization (WHO) World Mental Health Surveys (n = 51 507). Respondent disorders were assessed with the Composite International Diagnostic Interview and parent disorders with informant-based Family History Research Diagnostic Criteria interviews. Results Although virtually all parent disorders examined (major depressive, generalised anxiety, panic, substance and antisocial behaviour disorders and suicidality) were significantly associated with offspring disorders in multivariate analyses, little specificity was found. Comorbid parent disorders had significant sub-additive associations with offspring disorders. Population-attributable risk proportions for parent disorders were 12.4% across all offspring disorders, generally higher in high- and upper-middle-than low-/lower-middle-income countries, and consistently higher for behaviour (11.0-19.9%) than other (7.1-14.0%) disorders. Conclusions Parent psychopathology is a robust non-specific predictor associated with a substantial proportion of offspring disorders.

Associação de variáveis ambientais à ocorrência de leptospirose canina e humana na cidade de São Paulo

Foi realizada uma análise espacial da ocorrência de leptospirose humana e canina na Supervisão de Vigilância em Saúde do Butantã, situada no município de São Paulo, no ano de 2007, associada a variáveis ambientais de risco, tais como: focos de enchente e áreas de desratização. Foram encontrados aglomerados espaciais de pontos de alagamentos em 12 setores censitários e de casos de leptospirose humana em quatro setores censitários, sem correlação entre ambos. Não foram encontrados agrupamentos de casos em cães, possivelmente devido à subnotificação. As proporções casos humanos de leptospirose : população humana dentro e fora da área de desratização foram 7:199.600 e 9:257.980, respectivamente. Conclui-se que medidas de controle de roedores como a desratização foram responsáveis pela minimização dos efeitos dos fatores de risco para a transmissão de leptospirose para humanos.

Oral cleft prevention program (OCPP)

Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT00397917

Work Precariousness and Risk of Accidents in Civil Construction: A study based on the Collective Work Analysis

This paper aims to describe the construction workers' activities, as well as their perceptions about risks and workload. The study, based on the Collective Work Analysis, is part of a broader public policies project for the improvement of SIVAT (Surveillance System of Work Accidents) - in the city of Piracicaba (Southeastern Brazil). Civil construction was prioritized given the epidemiological magnitude of the occurrence of work accidents and the limited efficacy of traditional surveillance initiatives in this sector due to informal employment practices, outsourcing, high staff turnover, etc. The workers have a high level of awareness concerning the risk of accidents, but they believe that the main preventive measures hinder or even make it impossible for them to carry out the tasks. Our findings question the efficacy of traditional training for adherence to safety practices, thus highlighting the need for a transformative pedagogy for preventive practices and the health promotion of workers.

Environmental lead poisoning among children in Porto Alegre state, Southern Brazil

OBJECTIVE: To estimate the prevalence of lead poisoning in children and to identify associated factors, as well as possible local sources of contamination. METHODS: A cross-sectional prevalence study conducted in 2006 with a random sample of 97 children age zero to five years from a neighborhood in Porto Alegre, Southern Brazil. Blood lead levels were measured and a questionnaire administered to collect information on sociodemographics, recycling and dwelling. A preliminary environmental evaluation was carried out with direct analysis of soil and indirect analysis of air pollution with bioindicators to identify possible sources of contamination. To analyze lead concentrations from the different collection sites, for each type of material studied, ANOVA was performed with a Brown-Forsythe adjustment for heteroscedasticity and with Dunnett's T3 procedure for multiple comparisons of unequal variances. RESULTS: Blood lead levels >= 10.0 mu g/dL was found in 16.5% of children. Recycling of waste at home, low father's education level, and increased age of children were associated with increase blood lead levels. High lead levels were found in soil, and there was little indication of lead air pollution. CONCLUSIONS: A high prevalence of lead poisoning was identified, and the potential sources of contamination in this community appear related to waste recylcing activities. Studies should be conducted with other populations of Brazilian children and evaluate potential sources of local and general contamination, to accurately characterize this issue in Brazil.

Prevalence of asthma and risk factors associated: population based study in Sao Paulo, Southeastern Brazil, 2008-2009

OBJECTIVE: To assess the prevalence of asthma and risk factors associated in children and adolescents. METHODS: Population-based cross-sectional study with 1,185 female and male children and adolescents carried out in the city of Sao Paulo, Southeastern Brazil, from 2008 to 2009. Data were collected through home interviews. Respondents were selected from two-stage (census tract, household) cluster random sampling stratified by gender and age. Multiple Poisson regression was used in the adjusted analysis between the outcome and socioeconomic, demographic, lifestyle and health condition variables. RESULTS: Of all respondents, 9.1% (95%CI 7.0; 11.7) reported asthma. After adjustment, the following variables were found independently associated with asthma: age (0 to 4 years vs. 15 to 19) (PR 3.18, 95%CI 1.20;8.42); age (5 to 9 years vs. 15 to 19) (PR 6.37, 95%CI 2.64;15.39); age (10 to 14 years vs. 15 to 19) (PR 4.51,95%CI 1.95;10.40); allergy (yes vs. no) (PR 2.22, 95%CI 1.24;4.00); rhinitis (yes vs. no) (PR 2.13, 95%CI 1.22;3.73); health conditions in the 15 days preceding the interview (yes vs. no) (PR 1.96, 95%CI 1.23;3.11); number of rooms in the household (1 to 3 vs. 4 and more) (PR 1.67, 95%CI 1.05;2.66); and skin color (black and mixed vs. white) (PR 2.00, 95%CI 1.14;3.49). CONCLUSIONS: This study showed the importance of factors associated with asthma including rhinitis and allergy; age between 5 to 9 years old; black and mixed skin color; and household with few rooms. Frequent health problems are seen as a common consequence of asthma.

Profile of Trypanosoma cruzi Reactivity in a Population at High Risk for Endemic Pemphigus Foliaceus (Fogo Selvagem)

Fogo Selvagem (FS) is an autoimmune bullous disease with pathogenic IgG autoantibodies recognizing desmoglein 1 (Dsg1), a desmosomal glycoprotein. In certain settlements of Brazil, a high prevalence of FS (3%) is reported, suggesting environmental factors as triggers of the autoimmune response. Healthy individuals from endemic areas recognize nonpathogenic epitopes of Dsg1, and exposure to hematophagous insects is a risk factor for FS. Fogo selvagem and Chagas disease share some geographic sites, and anti-Dsg1 has been detected in Chagas patients. Indeterminate Chagas disease was identified in a Brazilian Amerindian population of high risk for FS. In counterpart, none of the FS patients living in the same geographic region showed reactivity against Trypanosoma cruzi. The profile of anti-Dsg1 antibodies showed positive results in 15 of 40 FS sera and in 33 of 150 sera from healthy individuals from endemic FS sites, and no cross-reactivity between Chagas disease and FS was observed.

Application of discriminant analysis-based model for prediction of risk of low back disorders due to workplace design in industrial jobs

The occupational exposure limits of different risk factors for development of low back disorders (LBDs) have not yet been established. One of the main problems in setting such guidelines is the limited understanding of how different risk factors for LBDs interact in causing injury, since the nature and mechanism of these disorders are relatively unknown phenomena. Industrial ergonomists' role becomes further complicated because the potential risk factors that may contribute towards the onset of LBDs interact in a complex manner, which makes it difficult to discriminate in detail among the jobs that place workers at high or low risk of LBDs. The purpose of this paper was to develop a comparative study between predictions based on the neural network-based model proposed by Zurada, Karwowski & Marras (1997) and a linear discriminant analysis model, for making predictions about industrial jobs according to their potential risk of low back disorders due to workplace design. The results obtained through applying the discriminant analysis-based model proved that it is as effective as the neural network-based model. Moreover, the discriminant analysis-based model proved to be more advantageous regarding cost and time savings for future data gathering.

Physical and psychosocial risk factors for musculoskeletal disorders in Brazilian and Italian nurses

As part of the international CUPID investigation, we compared physical and psychosocial risk factors for musculoskeletal disorders among nurses in Brazil and Italy. Using questionnaires, we collected information on musculoskeletal disorders and potential risk factors from 751 nurses employed in public hospitals. By fitting country-specific multiple logistic regression models, we investigated the association of stressful physical activities and psychosocial characteristics with site-specific and multisite pain, and associated sickness absence. We found no clear relationship between low back pain and occupational lifting, but neck and shoulder pain were more common among nurses who reported prolonged work with the arms in an elevated position. After adjustment for potential confounding variables, pain in the low back, neck and shoulder, multisite pain, and sickness absence were all associated with somatizing tendency in both countries. Our findings support a role of somatizing tendency in predisposition to musculoskeletal disorders, acting as an important mediator of the individual response to triggering exposures, such as work-load.

Risk assessment of PM2.5 to child residents in Brazilian Amazon region with biofuel production

Background: Exposure to fine fractions of particulate matter (PM2.5) is associated with increased hospital admissions and mortality for respiratory and cardiovascular disease in children and the elderly. This study aims to estimate the toxicological risk of PM2.5 from biomass burning in children and adolescents between the age of 6 and 14 in Tangara da Serra, a municipality of Subequatorial Brazilian Amazon. Methods: Risk assessment methodology was applied to estimate the risk quotient in two scenarios of exposure according to local seasonality. The potential dose of PM2.5 was estimated using the Monte Carlo simulation, stratifying the population by age, gender, asthma and Body Mass Index (BMI). Results: Male asthmatic children under the age of 8 at normal body rate had the highest risk quotient among the subgroups. The general potential average dose of PM2.5 was 1.95 mu g/kg.day (95% CI: 1.62 - 2.27) during the dry scenario and 0.32 mu g/kg. day (95% CI: 0.29 - 0.34) in the rainy scenario. During the dry season, children and adolescents showed a toxicological risk to PM2.5 of 2.07 mu g/kg. day (95% CI: 1.85 - 2.30). Conclusions: Children and adolescents living in the Subequatorial Brazilian Amazon region were exposed to high levels of PM2.5 resulting in toxicological risk for this multi-pollutant. The toxicological risk quotients of children in this region were comparable or higher to children living in metropolitan regions with PM2.5 air pollution above the recommended limits to human health.

Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium

To investigate the potential role of vitamin or mineral supplementation on the risk of head and neck cancer (HNC), we analyzed individual-level pooled data from 12 casecontrol studies (7,002 HNC cases and 8,383 controls) participating in the International Head and Neck Cancer Epidemiology consortium. There were a total of 2,028 oral cavity cancer, 2,465 pharyngeal cancer, 874 unspecified oral/pharynx cancer, 1,329 laryngeal cancer and 306 overlapping HNC cases. Odds ratios (OR) and 95% confidence intervals (CIs) for self reported ever use of any vitamins, multivitamins, vitamin A, vitamin C, vitamin E, and calcium, beta-carotene, iron, selenium and zinc supplements were assessed. We further examined frequency, duration and cumulative exposure of each vitamin or mineral when possible and stratified by smoking and drinking status. All ORs were adjusted for age, sex, race/ethnicity, study center, education level, pack-years of smoking, frequency of alcohol drinking and fruit/vegetable intake. A decreased risk of HNC was observed with ever use of vitamin C (OR = 0.76, 95% CI = 0.590.96) and with ever use of calcium supplement (OR = 0.64, 95% CI = 0.420.97). The inverse association with HNC risk was also observed for 10 or more years of vitamin C use (OR = 0.72, 95% CI = 0.540.97) and more than 365 tablets of cumulative calcium intake (OR = 0.36, 95% CI = 0.160.83), but linear trends were not observed for the frequency or duration of any supplement intake. We did not observe any strong associations between vitamin or mineral supplement intake and the risk of HNC.

The Environmental Theme in Representations and Practices of Family Health Professionals in the Municipality of Manaus - State of Amazonas/Brazil

There are abundant scientific evidences showing that the increased risk of exposure to diseases is a consequence of anthropogenic environmental changes. In the Family Health Strategy, tasks with a clear environmental focus are prescribed, indicating to the professional teams that they should consider these aspects in their health practices. The objective of this research was to study representations and practices of Family Health Professionals of Manaus - State of Amazonas, Northern Brazil - about environmental issues and their interface with public health. Data were collected by means of participant observation and semi-structured interviews, and the qualitative analysis was carried out through Content Analysis and Methodological Triangulation. The results showed that most professionals do not understand the environment in a systemic way, even though they recognize the great impact that environmental factors have on human health; as interventions, the educational practices follow traditional methodologies and focus on blaming the individual and on the simple transmission of knowledge; the professionals' relationship with the community is limited to personal and/or collective care. It is concluded that in order to the Family Health Strategy to contribute to restructure the system, it is essential to redirect this new health policy model so that it becomes effective as a social and environmental practice.