Associations between Butylparaben and Thyroid Levels in Females Aged 12 and over (NHANES, 2007-2008)

Background: Paraben exposure occurs everyday to most people unknowingly. Parabens are present in most personal care products in varying amounts. Presently, parabens are not listed as endocrine disruptors; however, some research has shown parabens associated with decreases in thyroid hormone levels. The chemical and adsorption mechanism for parabens in association with thyroid hormones is not well understood. Determining whether parabens are associated with a change in thyroid hormone levels can help reduce the incidence of possible adverse health effects with exposure to parabens. Methodology: The selected study variables were analyzed using SAS version 9.2. Data were obtained from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Analyses were performed separately for adolescent females (12-19) and adult females (20+). Weighted means were performed for the main independent and dependent variables of interest stratified by race/ethnicity groups and by smoking status. Independent samples t-test and ANOVA was used to test significance of differences of weighted means. Weighted bivariate linear regression was performed for each dependent variable (Thyroid Stimulating Hormone [TSH], Triiodothyronine [T3], and Thyroxine [T4]) regressed on butylparaben. Weighted multiple linear regressions were performed and parameter estimates with 95% confidence intervals were used to ascertain the measure of effect. Separate regression models stratified by age group (adolescent vs. adult) were ran for each dependent variable (TSH, T3, and T4) regressed on butylparaben level and covariates, race/ethnicity and smoking status (ever smoked). Results: Weighted bivariate linear regression showed that among adult females, for each ng/ml increase in butylparaben, there was a -1.07 decrease in ng/dL T3 (p Weighted multiple linear regression showed higher butylparaben levels among adult females were associated with 0.12 ug/dL lower than average T4 levels (p Conclusion: While parabens are currently not considered endocrine disruptors, the human metabolism of and effects from exposure to parabens are not well understood. Results from this study showing decreased levels of some thyroid hormone levels (TSH, T3, and T4) associated with increased levels of butylparaben was found, as well as differences in thyroid hormone levels among racial/ethnic groups. Although not many human studies have found significant results, 10 some rodent studies have found butylparaben associations with thyroid hormone changes.4, 6, 19, 54 The results of this study indicating no statistically significant association between butylparaben and decreases in thyroid hormone levels are consistent with results of some rodent studies.7, 8, 54, 55 In light of these findings, additional human studies with paraben exposure and thyroid hormone levels are needed to increase knowledge of the mechanism and effect of parabens in the human body

Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

Estimating the abundance of common dolphins on the southern coast of South Africa

Sightings made on an aerial survey in December 1982 and on a ship-based survey in January/February 1983 have been used to assess the size of the population of common dolphins (Delphinus capensis) occurring over the continental shelf south of South Africa. Thirteen sightings (12 primary) were made in 2,445.7 n. miles flown on the aerial survey and 10 sightings (6 primary) in 1,772.2 n. miles steamed on the ship-based survey. Sightings and effort in both surveys have been stratified by water depth (0-100 m, 100- 200 m) and geographical region (west coast, south coast). Because of difficulties in accurately estimating the size of schools in this highly gregarious species, numbers of individuals were counted in composite aerial photographs taken of the school. Radial distance and angle estimates to sightings from the ship were smeared to allow for estimation errors. Assuming g(0) = 1.0, both data sets resulted in roughly similar estimates of the number of schools (52-58 for aerial, 40-59 for ship-based across a range of sensitivity tests), but mean school size estimates differed significantly (454 SE 90 for aerial, 159 SE 27 for ship-based). As the aerial estimates were based on counts of animals in composite vertical photographs, they are considered more reliable than the ship-based estimates that were made from a lower vantage point and at a greater angle. Given the small number of primary sightings on each survey, it was considered preferable to produce a combined estimate using school density estimates from both surveys weighted by their inverse variances but applying the mean school size from the aircraft. The resultant population estimate of 49 schools (CV = 0.29) and 22200 individuals (CV = 0.35) is discussed in relation to known or estimated incidental mortalities in South African waters

Editorial: special issues in Business History

No abstract available

Editorial

With the first issue of the 56th volume of Business History, a new editorial team has taken over responsibility for direction and management of the journal. Led by executive editor Ray Stokes (University of Glasgow), the team includes as co-editors Andrea Colli (Bocconi University), Stephanie Decker (Aston University), Paloma Fernández Pérez (University of Barcelona), Abe de Jong (Erasmus University Rotterdam) and Neil Rollings (University of Glasgow), who will also serve as deputy editor. In addition, the book review editorship has been expanded. Joining Kevin Tennent (York University), who has acted as sole book review editor over the past years, will be Veronica Binda (Bocconi University). Veronica Binda will be primarily responsible for books published in, or reviewed by, authors from Italy, Spain, France, and Portugal

Gene Expression Profiling of Mono- and Co-Culture Models of the Respiratory Tract Exposed to Crystalline Quartz under Submerged and Air-Liquid Interface Conditions

In vitro lung cell models like air-liquid interface (ALI) and 3D cell cultures have advanced greatly in recent years, being especially valuable for testing advanced materials (e.g., nanomaterials, fibrous substances) when considering inhalative exposure. Within this study, we established submerged and ALI cell culture models utilizing A549 cells as mono-cultures and co-cultures with differentiated THP-1 (dTHP-1), as well as mono-cultures of dTHP-1. After ALI and submerged exposures towards α-quartz particles (Min-U-Sil5), with depositions ranging from 15 to 60 µg/cm(2), comparison was made with respect to their transcriptional cellular responses employing high-throughput RT-qPCR. A significant dose- and time-dependent induction of genes coding for inflammatory proteins, e.g., IL-1A, IL-1B, IL-6, IL-8, and CCL22, as well as genes associated with oxidative stress response such as SOD2, was observed, even more pronounced in co-cultures. Changes in the expression of similar genes were more pronounced under submerged conditions when compared to ALI exposure in the case of A549 mono-cultures. Hereby, the activation of the NF-κB signaling pathway and the NLRP3 inflammasome seem to play an important role. Regarding genotoxicity, neither DNA strand breaks in ALI cultivated cells nor a transcriptional response to DNA damage were observed. Altogether, the toxicological responses depended considerably on the cell culture model and exposure scenario, relevant to be considered to improve toxicological risk assessment

Comparing α-Quartz-Induced Cytotoxicity and Interleukin-8 Release in Pulmonary Mono- and Co-Cultures Exposed under Submerged and Air-Liquid Interface Conditions

The occupational exposure to particles such as crystalline quartz and its impact on the respiratory tract have been studied extensively in recent years. For hazard assessment, the development of physiologically more relevant in-vitro models, i.e., air-liquid interface (ALI) cell cultures, has greatly progressed. Within this study, pulmonary culture models employing A549 and differentiated THP-1 cells as mono-and co-cultures were investigated. The different cultures were exposed to α-quartz particles (Min-U-Sil5) with doses ranging from 15 to 66 µg/cm(2) under submerged and ALI conditions and cytotoxicity as well as cytokine release were analyzed. No cytotoxicity was observed after ALI exposure. Contrarily, Min-U-Sil5 was cytotoxic at the highest dose in both submerged mono- and co-cultures. A concentration-dependent release of interleukin-8 was shown for both exposure types, which was overall stronger in co-cultures. Our findings showed considerable differences in the toxicological responses between ALI and submerged exposure and between mono- and co-cultures. A substantial influence of the presence or absence of serum in cell culture media was noted as well. Within this study, the submerged culture was revealed to be more sensitive. This shows the importance of considering different culture and exposure models and highlights the relevance of communication between different cell types for toxicological investigations

Response to interferons and antibacterial innate immunity in the absence of tyrosine-phosphorylated STAT1

Signal transducer and activator of transcription 1 (STAT1) plays a pivotal role in the innate immune system by directing the transcriptional response to interferons (IFNs). STAT1 is activated by Janus kinase (JAK)‐mediated phosphorylation of Y701. To determine whether STAT1 contributes to cellular responses without this phosphorylation event, we generated mice with Y701 mutated to a phenylalanine (Stat1(Y701F)). We show that heterozygous mice do not exhibit a dominant‐negative phenotype. Homozygous Stat1(Y701F) mice show a profound reduction in Stat1 expression, highlighting an important role for basal IFN‐dependent signaling. The rapid transcriptional response to type I IFN (IFN‐I) and type II IFN (IFNγ) was absent in Stat1(Y701F) cells. Intriguingly, STAT1Y701F suppresses the delayed expression of IFN‐I‐stimulated genes (ISG) observed in Stat1(−/−) cells, mediated by the STAT2/IRF9 complex. Thus, Stat1(Y701F) macrophages are more susceptible to Legionella pneumophila infection than Stat1(−/−) macrophages. Listeria monocytogenes grew less robustly in Stat1(Y701F) macrophages and mice compared to Stat1(−/−) counterparts, but STAT1Y701F is not sufficient to rescue the animals. Our studies are consistent with a potential contribution of Y701‐unphosphorylated STAT1 to innate antibacterial immunity

Transforming the Healthcare Response to Intimate Partner Violence and Taking Best Practices to Scale

BACKGROUND: Intimate partner violence (IPV) is prevalent among adolescent and adult women, with significant physical, sexual, and mental health consequences. In 2011, the Institute of Medicine\u27s Clinical Preventive Services for Women consensus report recommended universal screening for violence as a component of women\u27s preventive services; this policy has been adopted by the Health Resources and Services Administration (HRSA). These policy developments require that effective clinic-based interventions be identified, easily implemented, and taken to scale. METHODS: To foster dialogue about implementing effective interventions, we convened a symposium entitled Responding to Violence Against Women: Emerging Evidence, Implementation Science, and Innovative Interventions, on May 21, 2012. Drawing on multidisciplinary expertise, the agenda integrated data on the prevalence and health impact of IPV violence, with an overview of the implementation science framework, and a panel of innovative IPV screening interventions. Recommendations were generated for developing, testing, and implementing clinic-based interventions to reduce violence and mitigate its health impact. RESULTS: The strength of evidence supporting specific IPV screening interventions has improved, but the optimal implementation and dissemination strategies are not clear. Implementation science, which seeks to close the evidence to program gap, is a useful framework for improving screening and intervention uptake and ensuring the translation of research findings into routine practice. CONCLUSIONS: Findings have substantial relevance to the broader research, clinical, and practitioner community. Our conference proceedings fill a timely gap in knowledge by informing practitioners as they strive to implement universal IPV screening and guiding researchers as they evaluate the success of implementing IPV interventions to improve women\u27s health and well-being

Comparing the Toxicological Responses of Pulmonary Air–Liquid Interface Models upon Exposure to Differentially Treated Carbon Fibers

In recent years, the use of carbon fibers (CFs) in various sectors of industry has been increasing. Despite the similarity of CF degradation products to other toxicologically relevant materials such as asbestos fibers and carbon nanotubes, a detailed toxicological evaluation of this class of material has yet to be performed. In this work, we exposed advanced air–liquid interface cell culture models of the human lung to CF. To simulate different stresses applied to CF throughout their life cycle, they were either mechanically (mCF) or thermo-mechanically pre-treated (tmCF). Different aspects of inhalation toxicity as well as their possible time-dependency were monitored. mCFs were found to induce a moderate inflammatory response, whereas tmCF elicited stronger inflammatory as well as apoptotic effects. Furthermore, thermal treatment changed the surface properties of the CF resulting in a presumed adhesion of the cells to the fiber fragments and subsequent cell loss. Triple-cultures encompassing epithelial, macrophage, and fibroblast cells stood out with an exceptionally high inflammatory response. Only a weak genotoxic effect was detected in the form of DNA strand breaks in mono- and co-cultures, with triple-cultures presenting a possible secondary genotoxicity. This work establishes CF fragments as a potentially harmful material and emphasizes the necessity of further toxicological assessment of existing and upcoming advanced CF-containing materials