Development and evaluation of an anteriorly mounted microprocessor-controlled powered hip joint prosthesis.

Background: Prosthetic solutions for individuals with hip disarticulation and hemipelvectomy amputations currently rely exclusively on passive hip joint mechanisms. Although powered knee and ankle joint prostheses have improved gait in people with amputation, no powered hip joint options are commercially available.

Objective: To develop and validate the mechanism, structural integrity, and design of an anteriorly mounted powered hip joint prosthesis.

Hip disarticulation and hemipelvectomy prostheses: A review of the literature.

Background: Although the global population of people with a hip disarticulation (HD) or hemipelvectomy (HP) amputation is small, the degree of disability is high, affecting function and independence. A comprehensive literature review is needed to examine the evidence for prostheses in these amputation levels.

Method: A scoping literature review was conducted to examine related research documents from 1950 to September 2020, found using Scopus, Web of Science, PubMed, and Google Scholar databases.

Concordance of 3 alternative teratogenicity assays with results from corresponding in vivo embryo-fetal development studies: Final report from the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) DruSafe working group 2.

An IQ DruSafe working group evaluated the concordance of 3 alternative teratogenicity assays (rat whole embryo culture, rWEC; zebrafish embryo culture, ZEC; and murine embryonic stem cells, mESC) with findings from rat or rabbit embryo-fetal development (EFD) studies. Data for 90 individual compounds from 9 companies were entered into a database. In vivo findings were deemed positive if malformations or embryo-fetal lethality were reported in either species.

Alternative Models of Developmental and Reproductive Toxicity in Pharmaceutical Risk Assessment and the 3Rs.

In the pharmaceutical industry, preclinical developmental and reproductive toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs.

Zebrafish teratogenicity testing.

As a model for teratogenicity research, zebrafish are gaining popularity and creditability. Zebrafish embryos have been proven to be a highly valuable tool in genetics and developmental biology research and have advanced our understanding of a number of known developmental toxicants. It has yet to be determined conclusively how reliably a zebrafish embryo screening assay predicts what will happen in mammalian models, but results from initial assessments have been encouraging.

Establishment of a molecular embryonic stem cell developmental toxicity assay.

The mouse embryonic stem cell test (EST) is a 10-day screen for teratogenic potential developed to reduce animal use for embryotoxicity testing of chemicals (Spielmann, 2005; Spielmann et al., 1997). In this study, we used the cytotoxicity IC(50) values and transcriptional expression changes as primary endpoints in a shorter 4-day version of the EST, the molecular embryonic stem cell assay.

Cannabinoid receptor antagonist-induced striated muscle toxicity and ethylmalonic-adipic aciduria in beagle dogs.

Ibipinabant (IBI), a potent cannabinoid-1 receptor (CB1R) antagonist, previously in development for the treatment of obesity, causes skeletal and cardiac myopathy in beagle dogs. This toxicity was characterized by increases in muscle-derived enzyme activity in serum and microscopic striated muscle degeneration and accumulation of lipid droplets in myofibers. Additional changes in serum chemistry included decreases in glucose and increases in non-esterified fatty acids and cholesterol, and metabolic acidosis, consistent with disturbances in lipid and carbohydrate metabolism.

Developmental toxicology: new directions workshop: refining testing strategies and study designs.

In April 2009, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee held a two-day workshop entitled "Developmental Toxicology-New Directions." The third session of the workshop focused on ways to refine animal studies to improve relevance and predictivity for human risk. The session included five presentations on: (1) considerations for refining developmental toxicology testing and data interpretation; (2) comparative embryology and considerations in study design and interpretation; (3) pharmacokinetic considerations in study design; (4) utility of genetically modified models for understanding mode-of-action; and (5) special considerations in reproductive testing for biologics.

Artesunate and artelinic acid: association of embryotoxicity, reticulocytopenia, and delayed stimulation of hematopoiesis in pregnant rats.

The artemisinin antimalarials cause embryo death and malformations in animals by killing embryonic erythroblasts. Groups of pregnant rats (N = 4) were administered 35 and 48 µmol/kg artesunate and 17.2, 28.

Development of a zebrafish embryo teratogenicity assay and quantitative prediction model.

Background: A zebrafish (Danio rerio) teratogenicity assay has been developed and evaluated for its ability to predict the teratogenic potential of chemicals.

Methods: Zebrafish embryos were dechorionated and then exposed to a test solution from 4-6 hours post-fertilization, and embryos or larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. In preliminary experiments, the potential time points for assessment of compound-induced dysmorphology and general toxicity parameters were evaluated, and 5 dpf was found to be the optimum developmental stage for evaluation.

Methanol exposure during gastrulation causes holoprosencephaly, facial dysgenesis, and cervical vertebral malformations in C57BL/6J mice.

Background: Exposure of pregnant outbred CD-1 mice to methanol during the period of gastrulation results in exencephaly, cleft palate, and cervical vertebra malformations [Rogers and Mole, Teratology 55: 364, 1997], while inbred C57BL/6J mice are sensitive to the teratogenicity of ethanol. C57BL/6J fetuses exhibit the holoprosencephaly spectrum of malformations after maternal exposure to ethanol during gastrulation, but the sensitivity of C57BL/6J mice to methanol-induced teratogenesis has not been previously described.

Methods: Pregnant C57BL/6J mice were administered two i.

Measuring cultural climate in a uniformed services medical center.

The purpose of this study was to determine the employee perceptions of the cultural climate at a large uniformed service medical center in the mid-Atlantic region of the United States. The analyses are based on the responses of 1,751 medical center employees, whose demographic characteristics were representative of the medical center population. Analyses indicate the existence of systematic perceptual differences between: (1) the medical center and Department of Defense personnel, and (2) the following cultural groups: (a) male and female personnel, (b) military and civilian personnel, and (c) majority and minority personnel.

Prenatal exposure to the pesticide dieldrin or the GABA(A) receptor antagonist bicuculline differentially alters expression of GABA(A) receptor subunit mRNAs in fetal rat brainstem.

We have previously shown that GABA acts as a trophic signal for monoamine neurons in embryonic day 14 (E14) rat brainstem cultures [Liu et al., J Neurosci 1997a; 17:2420-2428]. The organochlorine pesticide dieldrin and the classical GABA(A) receptor antagonist bicuculline interfere with the trophic actions of GABA and alter expression of several GABA(A) receptor subunit mRNA transcripts in these cultures [Liu et al.

Prenatal exposure to neurotoxicants dieldrin or lindane alters tert-butylbicyclophosphorothionate binding to GABA(A) receptors in fetal rat brainstem.

GABA acts as a trophic signal for cultured embryonic rat monoamine neurons by activating GABA(A) receptors. These effects are blocked by the organochlorine insecticide dieldrin and the classic GABA(A) antagonist bicuculline. Both dieldrin and another organochlorine insecticide, lindane, block the effects of GABA on the GABA(A) receptor by binding directly to the Cl- channel.