Alterations in cardiac contractility can have significant clinical implications, highlighting the need for early detection of potential liabilities. Pre-clinical methods to assess contractility are typically invasive and their translation to human measures of cardiac function are not well defined. Clinically, cardiac function is most often measured non-invasively using echocardiography. The objective of these studies was to introduce echocardiography into standard large animal cardiovascular safety pharmacology studies and determine the feasibility of this combination.
There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, HESI held a workshop, “The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity” to identify data gaps in determining how gut microbiome alterations may affect human health. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.
Physiologically-based pharmacokinetic (PBPK) modeling analysis does not stand on its own for regulatory purposes but is a robust tool to support drug/chemical safety assessment. While the development of PBPK models have grown steadily since their emergence, only a handful of models have been accepted to support regulatory purposes due to obstacles such as the lack of a standardized template for reporting PBPK analysis. Here, we expand the existing guidances designed for pharmaceutical applications by recommending additional elements that are relevant to environmental chemicals.
Current demand for SARS‐CoV‐2 testing is straining material resource and labor capacity around the globe. As a result, the public health and clinical community are hindered in their ability to monitor and contain the spread of COVID‐19. Despite broad consensus that more testing is needed, pragmatic guidance towards realizing this objective has been limited. This paper addresses this limitation by proposing a novel and geographically agnostic framework (the 4Ps Framework) to guide multidisciplinary, scalable, resource‐efficient, and achievable efforts towards enhanced testing capacity. The 4Ps (Prioritize, Propagate, Partition, and Provide) are described in terms of specific opportunities to enhance the volume, diversity, characterization, and implementation of SARS‐CoV‐2 testing to benefit public health. Coordinated deployment of the strategic and tactical recommendations described in this framework have the potential to rapidly expand available testing capacity, improve public health decision‐making in response to the COVID‐19 pandemic, and/or to be applied in future emergent disease outbreaks.
This review provides insight in cross-species developmental differences of absorption, distribution, metabolism, and excretion properties in the kidney, which should be considered in neonate/juvenile study interpretation, hypotheses generation, and experimental design.