Recommended approaches for integration of population pharmacokinetic modelling with precision dosing in clinical practice.

Current methods of dose determination have contributed to suboptimal and inequitable health outcomes in underrepresented patient populations. The persistent demand to individualise patient treatment, alongside increasing technological feasibility, is leading to a growing adoption of model-informed precision dosing (MIPD) at point of care. Population pharmacokinetic (popPK) modelling is a technique that supports treatment personalisation by characterising drug exposure in diverse patient groups.

Log D and plasma protein binding of synthetic cannabinoid receptor agonists and a comparison of experimental and predicted lipophilicity.

The emergence of new synthetic cannabinoid receptor agonists (SCRAs) onto the illicit drugs market continues to cause harm, and the overall availability of physicochemical and pharmacokinetic data for new psychoactive substances is lacking. The lipophilicity of 23 SCRAs and the plasma protein binding (PPB) of 11 SCRAs was determined. Lipophilicity was determined using a validated chromatographic hydrophobicity index (CHI) log D method; tested SCRAs showed moderate to high lipophilicity, with experimental log D ranging from 2.

Changing trends in novel benzodiazepine use within Scottish prisons: detection, quantitation, prevalence, and modes of use.

Drug use within prisons is increasingly complex and unpredictable. Benzodiazepines are currently one of the most common drugs detected in individuals leaving Scottish prisons; however, understanding illicit benzodiazepine use within prisons and assessing the potential harm to individuals is challenging due to the lack of available analytical data on the substances circulating. Increasingly, materials, such as paper and clothing, infused with novel benzodiazepines have been identified as a smuggling route into Scottish prisons.

Impact of α-crystallin protein loss on zebrafish lens development.

The α-crystallin small heat shock proteins contribute to the transparency and refractive properties of the vertebrate eye lens and prevent the protein aggregation that would otherwise produce lens cataracts, the leading cause of human blindness. There are conflicting data in the literature as to what role the α-crystallins may play in early lens development. In this study, we used CRISPR gene editing to produce zebrafish lines with mutations in each of the three α-crystallin genes (cryaa, cryaba and cryabb) to prevent protein production.

A Systematic Study of the In Vitro Pharmacokinetics and Estimated Human In Vivo Clearance of Indole and Indazole-3-Carboxamide Synthetic Cannabinoid Receptor Agonists Detected on the Illicit Drug Market.

In vitro pharmacokinetic studies were conducted on enantiomer pairs of twelve valinate or -leucinate indole and indazole-3-carboxamide synthetic cannabinoid receptor agonists (SCRAs) detected on the illicit drug market to investigate their physicochemical parameters and structure-metabolism relationships (SMRs). Experimentally derived Log D ranged from 2.81 (AB-FUBINACA) to 4.

Engineering of Bioenergy Crops: Dominant Genetic Approaches to Improve Polysaccharide Properties and Composition in Biomass.

Large-scale, sustainable production of lignocellulosic bioenergy from biomass will depend on a variety of dedicated bioenergy crops. Despite their great genetic diversity, prospective bioenergy crops share many similarities in the polysaccharide composition of their cell walls, and the changes needed to optimize them for conversion are largely universal. Therefore, biomass modification strategies that do not depend on genetic background or require mutant varieties are extremely valuable.

The zebrafish as a model system for analyzing mammalian and native -crystallin promoter function.

Previous studies have used the zebrafish to investigate the biology of lens crystallin proteins and their roles in development and disease. However, little is known about zebrafish α-crystallin promoter function, how it compares to that of mammals, or whether mammalian α-crystallin promoter activity can be assessed using zebrafish embryos. We injected a variety of α-crystallin promoter fragments from each species combined with the coding sequence for green fluorescent protein (GFP) into zebrafish zygotes to determine the resulting spatiotemporal expression patterns in the developing embryo.

Barrett's esophagus before and after Roux-en-Y gastric bypass for severe obesity.

Introduction: Barrett's esophagus (BE) has been associated with obesity and metabolic syndrome. Laparoscopic Roux-en-Y gastric bypass (LRYGB) may represent a surgical approach which addresses both severe obesity and BE. LRYGB diverts bile away from the gastric pouch and esophagus due to the long Roux limb, and very little acid is produced in the cardia-based gastric pouch.

Is Endoluminal Bariatric Therapy a New Paradigm of Treatment for Obesity?

The prevalence of obesity has steadily increased throughout recent decades, and along with it, the costs of caring for the associated comorbid conditions has increased as well. Traditional bariatric surgical procedures generally are safe and effective, but patient acceptance, the risk of minor and sometimes serious complications, costs, and insurance coverage have limited the application of these techniques to the treatment of a minority of patients. Endoluminal techniques represent newer approaches to weight loss that can be used independently or in concert with traditional medical and surgical treatments for obesity, with varying degrees of success.

Development and evaluation of a decision-based simulation for assessment of team skills.

Background: There is a need to train and evaluate a wide variety of nontechnical surgical skills. The goal of this project was to develop and evaluate a decision-based simulation to assess team skills.

Methods: The decision-based exercise used our previously validated Laparoscopic Ventral Hernia simulator and a newly developed team evaluation survey.