Enhancing the practice of medicine with embedded multi-disciplinary researchers in a model of change.

Successfully embedding researchers in a health care setting brings unique challenges and opportunities. Through a joint clinical and academic partnership, we have developed a novel approach to problem-solving in the health care context, by employing a model for leading through change to embed researchers in transformative initiatives. Using the model, we have been able to leverage our local environment and resources to engage multi-disciplinary researchers in solving complex issues.

Job Demands and Resources among Healthcare Professionals during Virus Pandemics: A Review and Examination of Fluctuations in Mental Health Strain during COVID-19.

The present article examines how job demands and resources are related to indices of strain among healthcare professionals during virus pandemics. The article also presents the results of a study examining the relationships between COVID-19 demands (e.g.

Comparison of in vivo derived and scaled in vitro metabolic rate constants for several volatile organic compounds (VOCs).

Metabolic rate parameters estimation using in vitro data is necessary due to numbers of chemicals for which data are needed, trend towards minimizing laboratory animal use, and limited opportunity to collect data in human subjects. We evaluated how well metabolic rate parameters derived from in vitro data predict overall in vivo metabolism for a set of environmental chemicals for which well validated and established methods exist. We compared values of VmaxC derived from in vivo vapor uptake studies with estimates of VmaxC scaled up from in vitro hepatic microsomal metabolism studies for VOCs for which data were available in male F344 rats.

'It's mostly about the job' - putting the lens on specialist rural retention.

Introduction: Rural health services throughout the world face considerable challenges in the recruitment and retention of medical specialists. This research set out to describe the factors that contribute to specialist workforce retention and attrition in a health service in rural Tasmania, Australia.

Methods: This qualitative study utilised in-depth interviews with 22 medical specialists: 12 currently employed by the service and 10 who had left or intended to leave.

The Impact of Scaling Factor Variability on Risk-Relevant Pharmacokinetic Outcomes in Children: A Case Study Using Bromodichloromethane (BDCM).

Biotransformation rates extrapolated from in vitro data are used increasingly in human physiologically based pharmacokinetic (PBPK) models. This practice requires use of scaling factors, including microsomal content (mg of microsomal protein/g liver, MPPGL), enzyme specific content, and liver mass as a fraction of body weight (FVL). Previous analyses indicated that scaling factor variability impacts pharmacokinetic (PK) outcomes used in adult population dose-response studies.

The impact of variation in scaling factors on the estimation of internal dose metrics: a case study using bromodichloromethane (BDCM).

A rate for hepatic metabolism (V) determined in vitro must be scaled for in vivo use in a physiologically based pharmacokinetic (PBPK) model. This requires the use of scaling factors such as mg of microsomal protein per gram of liver (MPPGL) and liver mass (FVL). Variation in MPPGL and FVL impacts variation in V, and hence PBPK model-derived estimates of internal dose used in dose response analysis.

Development of a human physiologically based pharmacokinetic (PBPK) model for dermal permeability for lindane.

Lindane is a neurotoxicant used for the treatment of lice and scabies present on human skin. Due to its pharmaceutical application, an extensive pharmacokinetic database exists in humans. Mathematical diffusion models allow for calculation of lindane skin permeability coefficients using human kinetic data obtained from in vitro and in vivo experimentation as well as a default compound-specific calculation based on physicochemical characteristics used in the absence of kinetic data.

Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi-route exposure.

As a result of its presence in water as a volatile disinfection byproduct, bromodichloromethane (BDCM), which is mutagenic, poses a potential health risk from exposure via oral, dermal and inhalation routes. We developed a refined human physiologically based pharmacokinetic (PBPK) model for BDCM (including new chemical-specific human parameters) to evaluate the impact of BDCM exposure during showering and bathing on important measures of internal dose compared with oral exposure. The refined model adequately predicted data from the published literature for oral, dermal and bathing/showering exposures.

Estimating Potential Increased Bladder Cancer Risk Due to Increased Bromide Concentrations in Sources of Disinfected Drinking Waters.

Public water systems are increasingly facing higher bromide levels in their source waters from anthropogenic contamination through coal-fired power plants, conventional oil and gas extraction, textile mills, and hydraulic fracturing. Climate change is likely to exacerbate this in coming years. We estimate bladder cancer risk from potential increased bromide levels in source waters of disinfecting public drinking water systems in the United States.

A HER2-specific Modified Fc Fragment (Fcab) Induces Antitumor Effects Through Degradation of HER2 and Apoptosis.

FS102 is a HER2-specific Fcab (Fc fragment with antigen binding), which binds HER2 with high affinity and recognizes an epitope that does not overlap with those of trastuzumab or pertuzumab. In tumor cells that express high levels of HER2, FS102 caused profound HER2 internalization and degradation leading to tumor cell apoptosis. The antitumor effect of FS102 in patient-derived xenografts (PDXs) correlated strongly with the HER2 amplification status of the tumors.

Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: a case study of lindane-induced neurotoxicity.

Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans.

Comparison of trihalomethanes in tap water and blood: a case study in the United States.

Background: Epidemiological studies have used various measures to characterize trihalomethane (THM) exposures, but the relationship of these indicators to exposure biomarkers remains unclear.

Objectives: We examined temporal and spatial variability in baseline blood THM concentrations and assessed the relationship between these concentrations and several exposure indicators (tap water concentration, water-use activities, multiroute exposure metrics).

Methods: We measured water-use activity and THM concentrations in blood and residential tap water from 150 postpartum women from three U.

Development of an inhalation physiologically based pharmacokinetic (PBPK) model for 2,2, 4-trimethylpentane (TMP) in male Long-Evans rats using gas uptake experiments.

2,2,4-Trimethylpentane (TMP) is a volatile colorless liquid used primarily to increase the octane rating of combustible fuels. TMP is released in the environment through the manufacture, use, and disposal of products associated with the gasoline and petroleum industry. Short-term inhalation exposure to TMP (< 4 h; > 1000 ppm) caused sensory and motor irritations in rats and mice.

Analysis of Amblyomma surveillance data in the Caribbean: lessons for future control programmes.

Amblyomma variegatum, the Tropical Bont Tick (TBT), is the principal vector of heartwater and is associated with dermatophilosis, major causes of losses in animal production and mortality in Caribbean livestock. From 1995 to 2007, the Caribbean Amblyomma Programme (CAP) supported treatment and surveillance activities in 11 islands of the Eastern Caribbean with an initial objective of eradicating TBT. In addition to control activities, surveillance data were collected between 1997 and 2006 in a unique regional database.

Amblyomma variegatum ticks and heartwater on three Caribbean Islands.

Amblyomma variegatum tick infestation, tick infection by Ehrlichia ruminantium (ER), and ER genetic diversity were studied in the Caribbean Islands of Guadeloupe, Marie-Galante, and Antigua between 2003 and 2005. Nested PCR for pCS20 was used to detect ER, while ER strains were characterized by sequencing or by restriction fragment length polymorphism (RFLP) profiles of map-1 PCR products. In 2003 in Guadeloupe, the prevalence of tick-infested herds was 35.

The Caribbean animal health network: new tools for harmonization and reinforcement of animal disease surveillance.

The Caribbean Animal Health Network (CaribVET) is a collaboration of veterinary services, diagnostic laboratories, research institutes, universities, and regional/international organizations to improve animal health in the Caribbean. New tools were used by the network to develop regional animal health activities: (1) A steering committee, a coordination unit, and working groups on specific diseases or activities were established. The working group on avian influenza used a collaborative Web site to develop a regionally harmonized avian influenza surveillance protocol and performance indicators.

Integrated disinfection by-products research: salmonella mutagenicity of water concentrates disinfected by chlorination and ozonation/postchlorination.

Although chemical disinfection of drinking water is a highly protective public health practice, the disinfection process is known to produce toxic contaminants. Epidemiological studies associate chlorinated drinking water with quantitatively increased risks of rectal, kidney, and bladder cancer. One study found a significant exposure-response association between water mutagenicity and relative risk for bladder and kidney cancer.

Models of chronic disease management in primary care for patients with mild-to-moderate asthma or COPD: a narrative review.

Objective: To review the literature for any promising strategies for the primary care management of mild-to-moderate asthma and chronic obstructive pulmonary disease (COPD) in adults.

Methods: Using "MeSH" terms for COPD, asthma and primary health care, we conducted an extensive literature search for relevant meta-analyses, systematic reviews, narrative reviews, reports and individual studies. Grey literature was also included.

Disposition of bromodichloromethane in humans following oral and dermal exposure.

Exposure to bromodichloromethane (BDCM), one of the most prevalent disinfection byproducts in drinking water, can occur via ingestion of water and by dermal absorption and inhalation during activities such as bathing and showering. The objectives of this research were to assess BDCM pharmacokinetics in human volunteers exposed percutaneously and orally to (13)C-BDCM and to evaluate factors that could affect disposition of BDCM. Among study subjects, CYP2E1 activity varied fourfold; 20% had the glutathione S-transferase theta 1-1 homozygous null genotype; and body fat ranged from 7 to 22%.

Using invaded range data to model the climate suitability for Amblyomma variegatum (Acari: Ixodidae) in the New World.

Climate matching models are in increasing use to predict distributions of living organisms, using records of the known distribution of a species to map its expected range of habitat suitability. Here, we modelled the known distribution of the tick Amblyomma variegatum in Africa as a preliminary step to delineate the most probable range of climatically suitable habitat for the tick in the New World. We used two presence-only methods (one based in the Gower distance, the other based on the Maximum Entropy principle) to model the distribution range in Africa.

Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat.

Bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss, i.e. full-litter resorption, in F344 rats when treated during the luteinizing hormone (LH)-dependent period.