Unconventional life history in a migratory shorebird: desegregating reproduction and migration.

Conventional life-history theory predicts that energy-demanding events such as reproduction and migration must be temporally segregated to avoid resource limitation. Here, we provide, to our knowledge, the first direct evidence of 'itinerant breeding' in a migratory bird, an incredibly rare breeding strategy (less than 0.1% of extant bird species) that involves the temporal overlap of migratory and reproductive periods of the annual cycle.

Whole genome assessment of a declining game bird reveals cryptic genetic structure and insights for population management.

Population genomics applied to game species conservation can help delineate management units, ensure appropriate harvest levels and identify populations needing genetic rescue to safeguard their adaptive potential. The ruffed grouse (Bonasa umbellus) is rapidly declining in much of the eastern USA due to a combination of forest maturation and habitat fragmentation. More recently, mortality from West Nile Virus may have affected connectivity of local populations; however, genetic approaches have never explicitly investigated this issue.

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry.

Introduction: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry.

Patients/methods: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed.

Factors influencing productivity of eastern wild turkeys in northeastern South Dakota.

Population growth is highly sensitive to changes in reproductive rates for many avian species. Understanding how reproductive rates are related to environmental conditions can give managers insight into factors contributing to population change. Harvest trends of eastern wild turkey in northeastern South Dakota suggest a decline in abundance.

Effect of pirfenidone on lung function decline and survival: 5-yr experience from a real-life IPF cohort from the Czech EMPIRE registry.

Introduction: Pirfenidone, an antifibrotic drug, slows-down the disease progression in idiopathic pulmonary fibrosis (IPF) over 12 months, however limited data on the decline of lung function and overall survival (OS) in real-world cohorts on longer follow-up exists.

Patients/methods: Of the enrolled Czech IPF patients (n = 841) from an EMPIRE registry, 383 (45.5%) received pirfenidone, 218 (25.

Real-world Management of Women with Postmenopausal Osteoporosis Treated with Denosumab: A Prospective Observational Study in the Czech Republic and Slovakia.

Introduction: Osteoporosis is characterized by low bone mineral density (BMD) and an increased risk of fracture. In randomized controlled trials, denosumab has been shown to significantly reduce the fracture risk in women with osteoporosis. However, little is known about the real-world management of women who are prescribed denosumab.

EMPIRE Registry, Czech Part: Impact of demographics, pulmonary function and HRCT on survival and clinical course in idiopathic pulmonary fibrosis.

Introduction: Prognostic factors of idiopathic pulmonary fibrosis (IPF) currently recognized include changes in vital capacity and radiologic findings. However, most of the prognostic studies in IPF are based on clinical studies with preselected IPF populations. Therefore, we decided to analyze the factors influencing IPF prognosis based on the real-practice data from our IPF registry.

Developmental toxicity evaluation of esterified propoxylated glycerol (EPG) administered in the diet to New Zealand white rabbits.

The safety of a "core" version of esterified propoxylated glycerols (EPGs) was assessed in a developmental toxicity study in New Zealand white rabbits, Hra:(NZW)SPF. Four groups each of 18 inseminated female rabbits received diets ad libitum containing concentrations of 0%, 2.5%, 5%, and 10% EPG (w/w) with 6% corn oil (w/w).

One-generation reproduction study of esterified propoxylated glycerol (EPG) administered in the feed to CD® (Sprague-Dawley) rats.

This one-generation study assessed the potential of esterified propoxylated glycerol (EPG) to affect reproduction and offspring development in rats. Male and female Crl:CD(SD)BR rats (30/sex/group) were exposed to EPG at 0, 0.5, 1, and 2g/kg bw/day or at 5% (w/w) in the diet prior to (13 weeks), during, and after two consecutive matings.

Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats.

Molybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies.

Abbreviated assessment of bisphenol A toxicology literature.

Bisphenol A (BPA), synthesized in 1891, is produced in quantities of >2 million metric tons annually for polycarbonate plastics, epoxy resins and food contact applications. BPA can be a weak estrogen mimic, and is ubiquitous in humans (in 93% US population; in 96% US pregnant women). European/US food/drug agencies conclude that current BPA levels present no risk to the general population (some include infants/children); basic endocrine disruption (ED) researchers state that entire populations are at risk from these levels.

GLP-compliant evaluation and standardization of the peripubertal castrate male rat Hershberger assay for oral exposure of test agents.

Since oral exposure is more relevant than the sc route for human exposure to environmental substances, studies to evaluate and standardize this route in the Hershberger assay were conducted in 2001-2003. Interest in environmental androgen agonists is increasing, so the oral route of the Hershberger assay may be useful to quantify agonist activity of these substances. Castrated Sprague-Dawley rats were dosed (PND 60-69) with androgen receptor agonists and/or antagonists, terminated on PND 70, and body, liver, and accessory sex organs (ASOs) weighed.

Commentary on the role of maternal toxicity on developmental toxicity.

Maternal mammalian toxicity impacts prenatal development, with general systemic maternal toxicity, from reduced weight gain to morbidity, causative for reduced fetal weights/litter and increased fetal variations (especially skeletal)/litter, but not, in the author's opinion, for increased fetal malformations, reduced litter sizes or full litter losses. Increased fetal malformations are likely due to exposure to specific chemicals which alter specific maternal functions at critical point(s) in pregnancy, typically exaggerated effects from higher doses by drugs under development with known, desired pharmacological effects. Malformations can also be from genetic/epigenetic alterations, specific altered proteins, molecular pathways, etc.

Interlaboratory study comparison of the 15-day intact adult male rat screening assay: evaluation of an antithyroid chemical and a negative control chemical.

Validation of the 15-day intact adult male rat screening assay (IAMRSA), an endocrine activity screen, was extended beyond the 28 substances evaluated to date. Two independent laboratories evaluated specificity using allyl alcohol (AA), a putative negative control, and DE-71 (technical grade pentabromodiphenyl ether) for comparison with previous pubertal assays that demonstrated thyroid effects. Male rats (15/group) were gavaged daily with AA (0, 10, 30, or 40 mg/kg/day) or DE-71 (0, 3, 30, or 60 mg/kg/day) for 15 days.

Current and future needs for developmental toxicity testing.

A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well.

Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater.

This review is the second in a series of four papers emanating from a workshop entitled "Developmental Toxicology-New Directions," which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data.

Validation of the intact rat weanling uterotrophic assay with notes on the formulation and analysis of the positive control chemical in vehicle.

The intact female weanling version in the Organization for Economic Cooperation and Development (OECD) uterotrophic assay Test Guideline (TG) 440 is proposed as an alternative to the adult ovariectomized female version, because it does not involve surgical intervention (vs the ovariectomized version) and detects direct/indirect-acting estrogenic/anti-estrogenic substances (vs the ovariectomized version which detects only direct-acting estrogenic/anti-estrogenic substances binding to the estrogen receptor). This validation study followed OECD TG 440, with six female weanling rats (postnatal day 21) per dose group and six treatment groups. Females were weighed and dosed once daily by oral gavage for three consecutive days, with one of six doses of 17α-ethinyl estradiol in corn oil at 5 ml kg⁻¹ at 0 and 0.

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.

Basic exploratory research versus guideline-compliant studies used for hazard evaluation and risk assessment: bisphenol A as a case study.

Background: Myers et al. [Environ Health Perspect 117:309-315 (2009)] argued that Good Laboratory Practices (GLPs) cannot be used as a criterion for selecting data for risk assessment, using bisphenol A (BPA) as a case study. They did not discuss the role(s) of guideline-compliant studies versus basic/exploratory research studies, and they criticized both GLPs and guideline-compliant studies and their roles in formal hazard evaluation and risk assessment.

Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test.

Background: The U.S. EPA revised the Reproduction and Fertility Effects Test Guideline (OPPTS 870.

Metabolomics in the assessment of chemical-induced reproductive and developmental outcomes using non-invasive biological fluids: application to the study of butylbenzyl phthalate.

This study was conducted to evaluate the use of metabolomics for improving our ability to draw correlations between early life exposures and reproductive and/or developmental outcomes. Pregnant CD rats were exposed by gavage daily during gestation to vehicle or to butylbenzyl phthalate (BBP) in vehicle at a level known to induce effects in the offspring and at a level previously not shown to induce effects. Urine was collected for 24 h (on dry ice using all glass metabolism chambers) from dams on gestational day 18 (during exposure) and on post natal day (pnd) 21, and from pnd 25 pups.