Maternal Effects and Offspring Behavior: Potential Contributors to the Lack of Recruitment in Mississippi Gopher Tortoises (\u3ci\u3eGopherus polyphemus\u3c/i\u3e)

Federally threatened in Mississippi, gopher tortoise (Gopherus polyphemus) populations within the state have strongly variable recruitment and are generally in decline. Hatching success is significantly lower in Mississippi than in any other part of the species’ range , and most hatchlings die within the first year. There are few refuges where survival and hatching success is high. Here I compare two populations that differ in recruitment and offspring survival for differences in corticosterone. Corticosterone is a hormone that influences both energy availability and is released in elevated levels during stressful events, like living in poor quality habitat. Prolonged corticosterone elevation can impede growth and immune responses and result in early death. To assess adult stress, I utilized leukocyte profiles as they are influenced by prolonged elevation of corticosterone. A viable yolk sampling technique was used to collect yolk samples to determine levels of yolk CORT. Hatchlings were then kept in captivity for two years to observe growth rates and burrowing behavior before being released and monitored via radiotelemetry to monitor dispersal and survival. I found no differences in adult stress or egg yolk CORT between populations. This suggests adults are not excessively stressed. Survival of hatchlings did not differ between sites. Captive-reared hatchlings were larger and may have better survival than similar aged wild hatchlings. Overall, the poor survival of gopher tortoises may be more strongly linked to environmental variables such as soil structure than physiological ones

Demographic, Psychological, and Social Characteristics of Self-Identified Lesbian, Gay, and Bisexual Adults in a US Probability Sample

Using data from a US national probability sample of self-identified lesbian, gay, and bisexual adults (N = 662), this article reports population parameter estimates for a variety of demographic, psychological, and social variables. Special emphasis is given to information with relevance to public policy and law. Compared with the US adult population, respondents were younger, more highly educated, and less likely to be non-Hispanic White, but differences were observed between gender and sexual orientation groups on all of these variables. Overall, respondents tended to be politically liberal, not highly religious, and supportive of marriage equality for same-sex couples. Women were more likely than men to be in a committed relationship. Virtually all coupled gay men and lesbians had a same-sex partner, whereas the vast majority of coupled bisexuals were in a heterosexual relationship. Compared with bisexuals, gay men and lesbians reported stronger commitment to a sexual-minority identity, greater community identification and involvement, and more extensive disclosure of their sexual orientation to others. Most respondents reported experiencing little or no choice about their sexual orientation. The importance of distinguishing among lesbians, gay men, bisexual women, and bisexual men in behavioral and social research is discussed

General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and Drug Administration–sponsored Think Tank Meeting on May 22, 2018. The meeting was convened to evaluate the progress in the development of a new cardiac safety paradigm, the Comprehensive in Vitro Proarrhythmia Assay (CiPA). The opinions regarding these principles reflect the collective views of those who participated in the discussion of this topic both at and after the breakout session. Although primarily discussed in the context of in silico models, these principles describe the interface between experimental input and model‐based interpretation and are intended to be general enough to be applied to other types of nonclinical models for proarrhythmia assessment. This document was developed with the intention of providing a foundation for more consistency and harmonization in developing and validating different models for proarrhythmia risk prediction using the example of the CiPA paradigm

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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

Management of a Long-Standing Organic Intracranial Foreign Body

Organic foreign bodies of the skull base are an uncommon problem with the potential for serious morbidity that present complicated treatment dilemmas best managed by a multidisciplinary approach. A 58-year-old male presented to the emergency department with fevers and mental status changes and was found to have bacterial meningitis. Computed tomography of the sinuses revealed two adjacent defects of the ethmoid roof with associated soft tissue density concerning for an encephalocele. He had a remote history of a penetrating left maxilla injury with a stick 13 years earlier. An attempted endoscopic repair of the defects revealed a pulsating splinter of wood emanating from the ethmoid roof defect. Neurosurgery and infectious disease were consulted and several wood fragments were removed endoscopically from the intracranial space. The skull base defects were closed using a septal cartilage underlay and free mucosal overlay graft. The patient has done well in follow-up with no evidence of cerebrospinal fluid leak. Organic foreign bodies from skull base trauma can have a delayed presentation and require a multidisciplinary team approach. In the appropriate setting endoscopic removal is a minimally morbid option

Non-Breeding Gonadal Testosterone Production of Male and Female Northern Cardinals (\u3ci\u3eCardinalis cardinalis\u3c/i\u3e) Following GnRH Challenge

Yearly, testosterone (T) levels fluctuate as many vertebrates cycle through reproductive and non-reproductive periods. Among many temperate birds, it is well established that levels of T peak as gonads recrudesce for breeding and then fall as gonads regress prior to the non-breeding season. While the tissues producing breeding season T are well studied, the tissues responsible for non-breeding T have received less investigative attention. We examined the ability of male and female Northern Cardinals (Cardinalis cardinalis) to elevate gonadal T following standardized injections of gonadotropin-releasing hormone (GnRH) across three non-breeding seasons. Males and females were capable of significantly elevating gonadal T production following GnRH injections during periods of reproductive quiescence. The magnitude of T elevation varied across the non-breeding season, but not between sexes. To our knowledge, this is the first report of a significant increase in gonadal T production following GnRH injections administered in the non-breeding season