Isoxazole Nucleosides as Building Blocks for a Plausible Proto-RNA.

The question of how RNA, as the principal carrier of genetic information evolved is fundamentally important for our understanding of the origin of life. The RNA molecule is far too complex to have formed in one evolutionary step, suggesting that ancestral proto-RNAs (first ancestor of RNA) may have existed, which evolved over time into the RNA of today. Here we show that isoxazole nucleosides, which are quickly formed from hydroxylamine, cyanoacetylene, urea and ribose, are plausible precursors for RNA. The isoxazole nucleoside can rearrange within an RNA-strand to give cytidine, which leads to an increase of pairing stability. If the proto-RNA contains a canonical seed-nucleoside with defined stereochemistry, the seed-nucleoside can control the configuration of the anomeric center that forms during the in-RNA transformation. The results demonstrate that RNA could have emerged from evolutionarily primitive precursor isoxazole ribosides after strand formation.

End-of-Life Planning: Normalizing the Process.

End-of-life (EOL) planning occurs across the United States at a frequency of below 50%, suggesting a new approach to encourage action is in order, especially as COVID-19 and other potentially lethal conditions emerge. Utilizing data from a multi-year survey of 2,614 adults in Nebraska, this study examined demographic factors related to completion of EOL planning documents, and identified people with whom EOL wishes could, and had been discussed. Logistic regression estimates indicated more reliance on non-health care providers for EOL discussions. This shift with whom people would discuss EOL wishes may afford others an opportunity to encourage EOL discussions.

The Effects of Exercise on Appetite in Older Adults: A Systematic Review and Meta-Analysis.

Background: The effect of physical activity and exercise on hunger and satiety has been well-studied in younger adults, but the influence of aging is less understood. While some evidence suggests that acute bouts of exercise induce a compensatory eating drive, long-term activity may improve satiety sensitivity. The objective of this study was to investigate the effects of exercise on appetite in older adults. Methods: We systematically reviewed available literature investigating the effect of exercise on appetite in older adults adults (CRD42020208953). PubMed, PsycINFO, Academic Search Complete, the Sports Medicine & Education Index, and Web of Science, were searched for peer-reviewed articles published in English with no date restriction. Included studies implemented a primary exercise or physical activity intervention with a control group, on a generally healthy population ≥60 years of age. Selected studies included at least one appetite outcome. Risk of bias was assessed using the 11-point Physiotherapy Evidence Database (PEDro) tool. Standardized mean difference summary statistics (Hedge's g effect sizes) and 95% confidence intervals were reported. Results: We identified 15 reports (13 studies) which met all inclusion criteria (5 resistance training, 3 aerobic, 6 mixed modalities). Studies included 443 participants (Age = 68.9 ± 5.2, 82.3% female) and had generally "good" bias scores (PEDro = 6.4 ± 0.88). Random effects meta-analyses revealed that the exercising group showed statistically significant reductions in glucose [SMD = -0.34 (95% CI: -0.67, -0.02), p < 0.05, PEDro =6.4 ± 0.45] and leptin [SMD = -0.92 (95% CI: -1.28, -0.57), p < 0.00001, PEDro = 6.2 ± 0.75]. Discussion: This systematic review revealed that exercise and physical activity may modulate resting hunger and satiety in older adults. Decreases in fasting leptin and glucose hormones suggest that exercise promotes satiety sensitivity in adults aged 60+. This review highlights that engaging in exercise and activity programs may provide a meaningful avenue for improving chronic and functional disease burden in later life by promoting appetite control and balanced energy intake. Recommendations for future research include investigations of appetite in response to varied exercise modalities within more diverse and representative samples of older adults.

The Evolving Landscape of Medical Device Regulation in East, Central, and Southern Africa.

Effective regulatory frameworks, harmonized to international standards, are critical to expanding access to quality medical devices in low- and middle-income countries. This review provides a summary of the state of medical device regulation in the 14 member countries of the College of Surgeons of East, Central, and Southern Africa (COSECSA) and South Africa. Countries were categorized according to level of regulatory establishment, which was found to be positively correlated to gross domestic product (GDP; rs=0.90) and years of freedom from colonization (rs=0.60), and less positively correlated to GDP per capita (rs=0.40). Although most countries mandate medical device regulation in national legislation, few employ all the guidelines set forth by the World Health Organization. A streamlined regulatory process across African nations would simplify this process for innovators seeking to bring medical devices to the African market, thereby increasing patient access to safe medical devices.

Proto-Urea-RNA (Wöhler RNA) Containing Unusually Stable Urea Nucleosides.

The RNA world hypothesis assumes that life on Earth began with nucleotides that formed information-carrying RNA oligomers able to self-replicate. Prebiotic reactions leading to the contemporary nucleosides are now known, but their execution often requires specific starting materials and lengthy reaction sequences. It was therefore proposed that the RNA world was likely proceeded by a proto-RNA world constructed from molecules that were likely present on the early Earth in greater abundance. Herein, we show that the prebiotic starting molecules bis-urea (biuret) and tris-urea (triuret) are able to directly react with ribose. The urea-ribosides are remarkably stable because they are held together by a network of intramolecular, bifurcated hydrogen bonds. This even allowed the synthesis of phosphoramidite building blocks and incorporation of the units into RNA. Investigations of the nucleotides' base-pairing potential showed that triuret:G RNA base pairs closely resemble U:G wobble base pairs. Based on the probable abundance of urea on the early Earth, we postulate that urea-containing RNA bases are good candidates for a proto-RNA world.