A PRELIMINARY INVESTIGATION INTO THE EXTENDED LIFESPAN OF BAT SPECIES: THE RELATIONSHIP BETWEEN THE EXTRACELLULAR MATRIX PROTEIN HAS2 AND LONGEVITY

Investigation into physiological and molecular factors influencing the extended lifespan of long-lived species significantly contributes to clinical research aimed at improving the lives of humans. Bats have a significantly longer lifespan than other mammals of similar size and have not been recorded to develop cancer. The longevity and anti-cancer properties displayed by bats are features shared by another well-studied mammal, the naked mole rat. The naked mole rat is currently the longest living rodent with a maximum lifespan of over 30 years, and the species exhibits a novel anti-cancer mechanism involving the rapid production of hyaluronan. The naked mole rat has a unique sequence of hyaluronan synthase 2 (HAS2) which rapidly produces high molecular mass hyaluronan and contributes to reduced activity of hyaluronan degrading enzymes. Known genomic sequences of several species of bats were analyzed to determine differences in amino acid sequence for the HAS2 gene. Furthermore, RNA extracted from captured bats was subjected to real-time polymerase chain reaction to measure the expression level of HAS2 in various tissues. Genomic sequence analysis revealed that the bat species examined did not have the same amino acid substitutions in HAS2 as the naked mole rat. Real-time PCR trials using multiple primers designed to be specific for the HAS2 region resulted in inconclusive data. Therefore, gene expression analysis conclusions cannot be made until successful HAS2 primers are generated to amplify the HAS2 region. Further research needs to be directed towards determining alternative methods to study the longevity and anti-cancer mechanisms bats possess

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

CRIUS:Undergraduate Research Journal 2014

Volume 2 Number 1 Fall 2014Volume 2 Number 1 of the CRIUS. This journal includes the research of undergraduate students as part of Research & Creative Endeavor SymposiumASU Undergraduate Research Initiativ