15 research outputs found

    Conservation Genetics and Mark-Recapture Monitoring of the Rare Pigeon Mountain Salamander (Plethodon petraeus) within a Highly Restricted Range

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    Globally, amphibian species are experiencing declines at an alarming rate largely due to habitat loss, disease and climate change. Species with limited ranges are at an elevated risk of a significant decline in population numbers and extinction because of the inability to avoid and recover from these impacts. Long-term management plans are critical for conservation of species with small ranges; however, the knowledge required to develop effective plans is absent from the literature for many species. One such species is the Pigeon Mountain Salamander. The distribution of the Pigeon Mountain Salamander, Plethodon petraeus, is restricted to roughly 17 kilometers along the eastern flank of Pigeon Mountain in northwest Georgia. Consequently, P. petraeus is highly vulnerable to the impacts associated with amphibian declines, a fact that placed the salamander on the list of rare and protected species in Georgia. The distribution of P. petraeus is highly correlated with patchily distributed rocky outcrops, which provides an efficient management target. However, the development of an effective, long-term management plan requires an understanding of genetic population structure, gene flow, and habitat use patterns. Robust design mark-recapture methods and population genetics with cross- amplified microsatellites were used to further our knowledge of how this species is distributed. Mark recapture results indicated high site fidelity of recaptured salamanders and abundance estimates (average number of total salamander abundance in a single plot, 57.8) within two 25 x 25 meter study areas. Population genetic results revealed four distinct populations across the known range of P. petraeus and significant isolation by distance genetic structuring

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

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    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

    Isolation by Distance Shapes Population Genetic Structure of a Rare Terrestrial Salamander, Plethodon petraeus, with an Extremely Small Range

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    —Globally, amphibian species are experiencing declines at an alarming rate largely due to habitat loss, disease, and climate change. Species with limited distributions are at an elevated risk of a significant decline and extinction because of the inability to avoid and recover from these impacts. Long-term management plans are critical for conservation of species with small ranges; however, the knowledge required to develop effective plans is absent from the literature for many species. The distribution of the Pigeon Mountain Salamander, Plethodon petraeus, is restricted to roughly 17 km along the eastern flank of Pigeon Mountain in northwest Georgia, USA. Consequently, P. petraeus is highly vulnerable to the impacts associated with amphibian declines, a fact that placed the salamander on the list of rare and protected species in Georgia. The distribution of P. petraeus is highly correlated with patchily distributed rocky outcrops, which provide a tangible management habitat target. The development of an effective, long-term management plan requires an understanding of genetic population structure, gene flow, and habitat use patterns. We identified polymorphic cross-amplified microsatellites to determine how genetic diversity is structured across the distribution. Population genetic analyses revealed four distinct populations across the known range of P. petraeus and significant isolation-by-distance genetic structuring

    Methamphetamine exposure during pregnancy at pharmacological doses produces neurodevelopmental and behavioural effects in rat offspring.

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    In recent years methamphetamine (MA) use has become more prevalent, and of particular concern is its growing popularity of MA among women of childbearing age. However, to date, studies examining MA effects on the developing offspring in laboratory animals are limited. Thus, the aim of this study was to determine if in utero MA exposure in rats at pharmacological doses can have a negative impact on neonatal neurodevelopment and behaviour. Pregnant Sprague-Dawley dams (n=10 dams/group) received MA (0, 0.625, 1.25, 2.5mg/kg) once daily via oral gavage from gestational day 7 to 21. Maternal body weight, food and water consumption were recorded daily. A range of standard neurodevelopment parameters was examined in the offspring during the neonatal period. There were no neurodevelopmental deficits observed with offspring exposed to 0.625mg/kg MA, in fact, there were enhancements of neurodevelopment in some parameters at this low dose. However, exposure to the 1.25mg/kg MA dose resulted in significant impairments in surface righting reflex and forelimb grip in both sexes. Exposure to the 2.5mg/kg MA dose resulted in a significant reduction in ano-genital distance in males, and in both sexes resulted in delayed fur appearance and eye opening, impairments in surface righting reflex and negative geotaxis, and a reduction in body length. In conclusion, this study demonstrates that pharmacologically relevant doses of MA can have profound dose-related effects on neonatal outcome. If extrapolated to the clinical scenario this will give cause for concern regarding the risks associated with this drug of abuse at relatively low doses
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