Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias

Background: In population research, exposure to environmental contaminants is often indirectly assessed by linking residence to geocoded databases of environmental exposures. We explored the potential for misclassification of residence-based environmental exposure as a result of not accounting for the workplace environments of employed pregnant women using data from a National Birth Defects Prevention Study (NBDPS) analysis of drinking water haloacetic acids and hypospadias. Methods: The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). Results: In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Conclusions: Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water

Paternal and joint parental occupational pesticide exposure and spina bifida in the National Birth Defects Prevention Study, 1997 to 2002

Background: Because of persistent concerns over the association between pesticides and spina bifida, we examined the role of paternal and combined parental occupational pesticide exposures in spina bifida in offspring using data from a large population-based study of birth defects. Methods: Occupational information from fathers of 291 spina bifida cases and 2745 unaffected live born control infants with estimated dates of delivery from 1997 to 2002 were collected by means of maternal report. Two expert industrial hygienists estimated exposure intensity and frequency to insecticides, herbicides, and fungicides. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for exposure to any pesticide and to any class of pesticide (yes/no; and by median), and exposure to combinations of pesticides (yes/no) and risk of spina bifida. Adjusted odds ratios were also estimated by parent exposed to pesticides (neither, mother only, father only, both parents). RESULTS: Joint parental occupational pesticide exposure was positively associated with spina bifida (aOR, 1.5; 95% CI, 0.9–2.4) when compared with infants with neither maternal nor paternal exposures; a similar association was not observed when only one parent was exposed. There was a suggested positive association between combined paternal insecticide and fungicide exposures and spina bifida (aOR, 1.5; 95% CI, 0.8–2.8), however, nearly all other aORs were close to unity. Conclusion: Overall, there was little evidence paternal occupational pesticide exposure was associated with spina bifida. However, the small numbers make it difficult to precisely evaluate the role of pesticide classes, individually and in combination. Birth Defects Research (Part A) 106:963–971, 2016

Maternal exposure to disinfection by-products and risk of hypospadias in the national birth defects prevention study (2000–2005)

The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias

The chemical compound 'Heatin' stimulates hypocotyl elongation and interferes with the Arabidopsis NIT1-subfamily of nitrilases

Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis. The small aromatic compound 'Heatin', containing 1-iminomethyl-2-naphthol as a pharmacophore, was selected as an enhancer of elongation growth. We show that ARABIDOPSIS ALDEHYDE OXIDASES redundantly contribute to Heatin-mediated hypocotyl elongation. Following a chemical proteomics approach, the members of the NITRILASE1-subfamily of auxin biosynthesis enzymes were identified among the molecular targets of Heatin. Our data reveal that nitrilases are involved in promotion of hypocotyl elongation in response to high temperature and Heatin-mediated hypocotyl elongation requires the NITRILASE1-subfamily members, NIT1 and NIT2. Heatin inhibits NIT1-subfamily enzymatic activity in vitro and the application of Heatin accordingly results in the accumulation of NIT1-subfamily substrate indole-3-acetonitrile in vivo. However, levels of the NIT1-subfamily product, bioactive auxin (indole-3-acetic acid), were also significantly increased. It is likely that the stimulation of hypocotyl elongation by Heatin might be independent of its observed interaction with NITRILASE1-subfamily members. However, nitrilases may contribute to the Heatin response by stimulating indole-3-acetic acid biosynthesis in an indirect way. Heatin and its functional analogues present novel chemical entities for studying auxin biology

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

A Survey of mid and large bodied mammals in Núcleo Caraguatatuba, Serra do Mar State Park, Brazil

Nós aplicamos técnicas de amostragem complementares para obter uma lista de espécies de mamíferos de médio e grande porte no Núcleo Caraguatatuba, Parque Estadual da Serra do Mar, Brasil. As amostragens de campo realizaram-se nos meses de Maio e Setembro de 2011. Utilizou-se, censo ao longo de transectos (212,4 km), armadilhas fotográficas (223,2 armadilhas-dias) e armadilhas de pegadas (478 armadilhas-dias). Foram obtidos registros de 18 espécies, pertencentes a 14 famílias e oito ordens. Nós registramos a presença de sete espécies consideradas ameaçadas no Estado de São Paulo, incluindo primatas (Brachyteles arachnoides), Artiodactyla (Mazama americana e Tayassu pecari), Carnivora (Leopardus pardalis, Leopardus tigrinus e Puma concolor) e Perissodactyla (Tapirus terrestris). Com base em numa extrapolação da riqueza de espécies (First order jackknife) nós prevemos que existem entre 19 e 32 espécies de mamíferos de médio e grande porte no Núcleo. Nosso Mammal Priority Index classificou o Núcleo Caraguatatuba como uma área de importância média para a conservação de mamíferos de médio e grande porte na Mata Atlântica. Combinado com o número e a diversidade de espécies registradas, nossos resultados demonstram que este Núcleo é uma área importante para a conservação de mamíferos no Estado.We applied complementary survey techniques to obtain a baseline species list of mid and large bodied mammals in Núcleo Caraguatatuba, Serra do Mar State park, Brazil. Between May and September 2011 we surveyed the community of mid and large bodied mammals using diurnal line transect census (212.4 km), camera-traps (223.2 camera-trap days) and track-stations (478 track-station days). A total of 18 species were recorded from 14 families in eight orders. We recorded the presence of seven species considered threatened in the State of São Paulo, including Primates (Brachyteles arachnoides), Artiodactyla (Mazama cf. americana and Tayassu pecari), Carnivora (Leopardus pardalis, Leopardus tigrinus and Puma concolor) and Perissodactyla (Tapirus terrestris). Based on extrapolated (First order jackknife) species richness estimates we predict that there are between 19 and 32 species of mid and large bodied mammals in the Núcleo. Our revised Mammal Priority Index ranked Núcleo Caraguatatuba as being of medium overall importance for the conservation of mid and large bodied mammals in the Atlantic Forest. Combined with the number and diversity of species recorded, our results demonstrate that this Núcleo is an important area for mammal conservation