Dose Ranging in Pediatric Drug Development Trials Submitted to the US FDA 2012-2020.

Dose selection is a critical process within pediatric drug development and dose-ranging studies are integral to establish a reasonable dose. The objective of this analysis was to examine the dose-ranging trials utilized in pediatric drug development and to determine (1) the dose-ranging strategies that were used in all available pediatric dose-ranging studies, (2) the success of achieving pediatric labeling in those submissions to the US Food and Drug Administration, and (3) ethical aspects of providing a prospect of direct benefit to pediatric patients in dose-ranging studies. Of the 275 programs that previously surveyed pediatric drug development programs from 2012 to 2020, it was determined that dose-ranging studies were used for 97 (35.

Broadly neutralizing antibodies targeting pandemic GII.4 variants or seven GII genotypes of human norovirus.

Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.

Does Excessive Tonic Inhibition Cause Unstable Feedback in Parkinson's Disease?

Parkinson's disease is characterized by decreased dopamine in the basal ganglia, which causes excessive tonic inhibition of the thalamus. This excessive inhibition seems to explain decreased motor vigor in Parkinson's disease, but whether it causes tremor remains unclear. This paper explores how inhibition may change closed-loop characteristics to determine how this established pathophysiology could produce tremor.

Divergent Multiomic Acute Exercise Responses Reveal the Impact of Sex as a Biological Variable.

The majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens.

A review of menopause in transgender and gender diverse individuals.

Purpose Of Review: This review aims to provide a comprehensive overview of the specific challenges, health considerations, and healthcare needs of transgender and gender diverse (TGD) people navigating menopause, highlighting the intersection of gender identity, hormone treatment, and age-related changes.

Recent Findings: Research on menopause in TGD individuals is lacking, without guidelines to support clinical management. This is the first review of its type to summarize the described impact of the menopausal transition on TGD individuals, the potential long-term risks associated with both gender-affirming hormone therapy and the intersectionality with aging, and how these risks may impact hormone management and overall comprehensive care.