Within-laboratory reproducibility of Ames test results: Are repeat tests necessary?

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross-sector working group examined the within-laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals.

Adaptation behaviors modify the effects of body fat on heat-related symptoms among Taiwanese elderly.

Background: The aging process increases body fat and susceptibility to heat-related illnesses. The relationship between body composition and symptoms associated with exposure to extreme heat among the elderly is unclear. Additionally, the influence of individual adaptive behaviors in mitigating these risks has not been adequately explored.

Air pollution enhance the progression of restrictive lung function impairment and diffusion capacity reduction: an elderly cohort study.

Background: Some evidences have shown the association between air pollution exposure and the development of interstitial lung diseases. However, the effect of air pollution on the progression of restrictive ventilatory impairment and diffusion capacity reduction is unknown. This study aimed to evaluate the effects of long-term exposure to ambient air pollution on the change rates of total lung capacity, residual volume, and diffusion capacity among the elderly.

Acute effects of ambient temperature on lung function of a panel of school children living in Dhaka, Bangladesh.

Introduction: Short-term exposure to ambient temperature plays a significant role in human health. However, studies examining ambient temperature and lung function are scarce in locations with a tropical environment. To address this research gap, the current study investigated the effects of short-term ambient temperature on lung function in children and seasonal variation in this association in Dhaka, Bangladesh.

Nitrogen and Oxygen Isotope Signatures of Nitrogen Compounds during Anammox in the Laboratory and a Wastewater Treatment Plant.

Isotopic fractionation factors against N and O during anammox (anaerobic ammonia oxidization by nitrite) are critical for evaluating the importance of this process in natural environments. We performed batch incubation experiments with an anammox-dominated biomass to investigate nitrogen (N) and oxygen (O) isotopic fractionation factors during anammox and also examined apparent isotope fractionation factors during anammox in an actual wastewater treatment plant. We conducted one incubation experiment with high δO of water to investigate the effects of water δO.

Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus.

Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR.

Association between short-term exposure to fine particulate matter and daily emergency room visits at a cardiovascular hospital in Dhaka, Bangladesh.

Background: It has been suggested that exposure to fine particulate matter (PM) adversely affects cardiovascular health. However, the effect modifications by individual characteristics and season have been less studied in developing countries where PM levels are high.

Objectives: To estimate the risks of cardiovascular emergency room visits in relation to daily concentrations of PM and to assess how these associations can be modified by age, sex, and nutritional status of patients and by season.

Human and animal evidence of potential transgenerational inheritance of health effects: An evidence map and state-of-the-science evaluation.

Background: An increasing number of reports suggest early life exposures result in adverse effects in offspring who were never directly exposed; this phenomenon is termed "transgenerational inheritance." Given concern for public health implications for potential effects of exposures transmitted to subsequent generations, it is critical to determine how widespread and robust this phenomenon is and to identify the range of exposures and possible outcomes.

Objectives: This scoping report examines the evidence for transgenerational inheritance associated with exposure to a wide range of stressors in humans and animals to identify areas of consistency, uncertainty, data gaps, and to evaluate general risk of bias issues for the transgenerational study design.

U-shaped association between fertility and mortality in a community-based sample of Japanese women.

Background: Prospective cohort studies of contemporary populations in both Western and Asian settings have reported a U-shaped association between fertility and mortality. We examined whether an association exists between fertility and all-cause and cause-specific mortality in a sample of Japanese women.

Methods: A prospective cohort study was conducted in one rural and one urban community in Gunma Prefecture, Japan, in 1993.

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 2 of 2).

To test the diagnostic approach described in part 1 of this article, 2 exercises were completed by pathologists from multiple companies/agencies. Pathologist's examination of whole slide image (WSI) heart sections from rats using personal diagnostic approaches (exercise #1) corroborated conclusions from study #1. Using the diagnostic approach described in part 1, these pathologists examined the same WSI heart sections (exercise #2) to determine whether that approach increased consistency of diagnosis of rodent progressive cardiomyopathy (PCM) lesions.

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2).

Spontaneous rodent progressive cardiomyopathy (PCM) in the Sprague Dawley rat may confound identification and/or interpretation of potential test article (TA)-related cardiotoxicity. Pathologists apply diagnostic term(s) and thresholds for diagnosing and assigning severity grades for PCM and/or PCM-like (PCM/like) lesions consistently within a study, which is necessary to identify and interpret TA-related findings. Due to differences in training and/or experiences, diagnostic terms and thresholds may vary between pathologists.

Glucose elicits serine/threonine kinase VRK1 to phosphorylate nuclear pregnane X receptor as a novel hepatic gluconeogenic signal.

Low glucose stimulated phosphorylation of pregnane X receptor (PXR) at Ser in correlation with an increased gluconeogenesis in human hepatoma-derived HepG2 cells. Only glucose, but neither insulin nor glucagon, stimulated this phosphorylation. Here, serine/threonine kinase, vaccinia related kinase 1 (VRK1)-mediated phosphorylation of PXR is now defined as this glucose-elicited novel signal.

Sleep Apnea and Hypoventilation in Patients with Down Syndrome: Analysis of 144 Polysomnogram Studies.

Patients with Down syndrome (DS) are at risk for both obstructive sleep apnea (OSA) and central sleep apnea (CSA); however, it is unclear how these components evolve as patients age and whether patients are also at risk for hypoventilation. A retrospective review of 144 diagnostic polysomnograms (PSG) in a tertiary care facility over 10 years was conducted. Descriptive data and exploratory correlation analyses were performed.

R2d2 Drives Selfish Sweeps in the House Mouse.

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness.

Implementing systematic review techniques in chemical risk assessment: Challenges, opportunities and recommendations.

Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question. Taking as a comparator the use of SR in synthesising research in healthcare, we argue that SR methods could also pave the way for a "step change" in the transparency, objectivity and communication of chemical risk assessments (CRA) in Europe and elsewhere. We suggest that current controversies around the safety of certain chemicals are partly due to limitations in current CRA procedures which have contributed to ambiguity about the health risks posed by these substances.

Endocrine disruptors and obesity.

The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development.

A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2.

Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.

The perfect storm for obesity.

Obesity rates have risen steadily in the United States and around the world over the past century, with a marked escalation within the past two decades. Conventional wisdom within the medical community is that the burgeoning obesity epidemic is the product of poor nutrition and lack of exercise, but increasingly researchers are questioning whether those factors are wholly responsible. Emerging research about alternative factors is setting the stage for today's "Perfect Storm" for obesity.

RAP80 is critical in maintaining genomic stability and suppressing tumor development.

The ubiquitin interaction motif-containing protein RAP80 was recently found to play a key role in DNA damage response (DDR) signaling by facilitating the translocation of several DDR mediators, including BRCA1, to ionizing irradiation (IR)-induced foci. In this study, we examine the effect of the loss of RAP80 on genomic stability and the susceptibility to cancer development in RAP80 null (RAP80(-/-)) mice. RAP80(-/-) mice are viable and did not exhibit any apparent developmental defects.

Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review.

Background: Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda.

Environmental factors preceding illness onset differ in phenotypes of the juvenile idiopathic inflammatory myopathies.

Objective: To assess whether certain environmental factors temporally associated with the onset of juvenile idiopathic inflammatory myopathies (JIIMs) differ between phenotypes.

Methods: Physicians completed questionnaires regarding documented infections, medications, immunizations and an open-ended question about other noted exposures within 6 months before illness onset for 285 patients with probable or definite JIIM. Medical records were reviewed for 81% of the patients.

Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development.

Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands.