Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).

Oxidized high-density lipoprotein and low-density lipoprotein in adolescents with obesity and metabolic dysfunction-associated steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly common in the pediatric population and may increase risk for developing cardiovascular disease (CVD) in people with MASLD. Oxidized high-density lipoprotein (oxHDL) and oxidized low-density lipoprotein (oxLDL) are modified, pro-atherosclerotic lipoproteins that are increased in adults with MASLD and CVD but have not been reported in adolescents with MASLD.

Purpose: To determine if oxLDL and oxHDL are increased in adolescents with MASLD.

An analytical, numerical and experimental study of in-vitro SARS-CoV-2 evolution in Vero B4 cells.

We derive a numerical model representing the emergence and evolution of SARS-CoV-2 variants, informed by data from in-vitro passaging experiments in Vero B4 cells. We compare our numerical simulation results against probabilistic derivations of the expected probability of and time until the fittest variant becomes fixed in the population. Contrary to literature surrounding DNA viruses and eukaryotes where probabilities of fitness extremes are often modelled by exponential decaying tail, we show that above wildtype fitness differences for SARS-CoV-2 are actually best modelled by a heavy-tailed Fréchet distribution.