Prospectus, December 17, 1987

https://spark.parkland.edu/prospectus_1987/1029/thumbnail.jp

Effect of oxygen on the expression of renin-angiotensin system components in a human trophoblast cell line

During the first trimester, normal placental development occurs in a low oxygen environment that is known to stimulate angiogenesis via upregulation of vascular endothelial growth factor (VEGF). Expression of the placental renin-angiotensin system (RAS) is highest in early pregnancy. While the RAS and oxygen both stimulate angiogenesis, how they interact within the placenta is unknown. We postulated that low oxygen increases expression of the proangiogenic RAS pathway and that this is associated with increased VEGF in a first trimester human trophoblast cell line (HTR-8/SVneo). HTR-8/SVneo cells were cultured in one of three oxygen tensions (1%, 5% and 20%). RAS and VEGF mRNA expression were determined by qPCR. Prorenin, angiotensin converting enzyme (ACE) and VEGF protein levels in the supernatant, as well as prorenin and ACE in cell lysates, were measured using ELISAs. Low oxygen significantly increased the expression of both angiotensin II type 1 receptor (AGTR1) and VEGF (both P < 0.05). There was a positive correlation between AGTR1 and VEGF expression at low oxygen (r = 0.64, P < 0.005). Corresponding increases in VEGF protein were observed with low oxygen (P < 0.05). Despite no change in ACE1 mRNA expression, ACE levels in the supernatant increased with low oxygen (1% and 5%, P < 0.05). Expression of other RAS components did not change. Low oxygen increased AGTR1 and VEGF expression, as well as ACE and VEGF protein levels, suggesting that the proangiogenic RAS pathway is activated. This highlights a potential role for the placental RAS in mediating the proangiogenic effects of low oxygen in placental development

A national cohort study and confidential enquiry to investigate ethnic disparities in maternal mortality

Background Ethnic disparities in maternal mortality were first documented in the UK in the early 2000s but are known to be widening. This project aimed to describe the women who died in the UK during or up to a year after the end of pregnancy, to compare the quality of care received by women from different aggregated ethnic groups, and to identify any structural or cultural biases or discrimination affecting their care. Methods National surveillance data was used to identify all 1894 women who died during or up to a year after the end of pregnancy between 2009 and 18 in the UK. Their characteristics and causes of death were described. A Confidential Enquiry was undertaken to describe the quality of care women received. The care of a stratified random sample of 54 women who died during or up to a year after the end of pregnancy between 2009 and 18, (18 from the aggregated group of Black women, 19 from the Asian aggregated group and 17 from the White aggregated group) was re-examined specifically to describe any structural or cultural biases or discrimination identified. Findings There were no major differences causes of death between women from different aggregated ethnic groups, with cardiovascular disease the leading cause of death in all groups. Multiple areas of bias were identified in the care women received, including lack of nuanced care (notable amongst women from Black aggregated ethnic groups who died), microaggressions (most prominent in the care of women from Asian aggregated ethnic groups who died) and clinical, social and cultural complexity (evident across all ethnic groups). Interpretation This confidential enquiry suggests that multiple structural and other biases exist in UK maternity care. Further research on the role of microaggressions is warranted. Funding This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217–21,202. MK is an NIHR Senior Investigator. SK is part funded and FCS fully funded by the National Institute for Health Research (NIHR) Applied Research Centre (ARC) West Midlands. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

Moderation of the Association between Media Exposure and Youth Smoking Onset: Race/Ethnicity, and Parent Smoking

This study of youth smoking onset aims to replicate previously published media moderation effects for race/ethnicity in a national longitudinal multiethnic sample of U.S. adolescents. Previous research has demonstrated that associations between media and smoking during adolescence are greater for Whites than Hispanics or Blacks, and for youth living in non-smoking families. In this study, changes in smoking status over 24 months were assessed among 4,511 baseline never-smokers. The incidence of smoking onset was 14.3% by 24 months with no differences by race/ethnicity. Blacks had higher exposure to movie smoking and overall television viewing compared with Whites and Hispanics. Whites responded to movie smoking regardless of parent smoking but more strongly if their parents were non-smokers. In contrast, Black adolescents showed little behavioral response to any media, regardless of parent smoking. Hispanic adolescents responded only to TV viewing and only when their parents did not smoke. In an analysis assessing the influence of the race of smoking characters on smoking behavior of White and Black adolescents, Whites responded to both White and Black movie character smoking, whereas Blacks responded only to smoking by Black movie characters. Taken as a whole, the findings replicate and extend previous findings, suggesting media factors are more influential among adolescents at low to moderate overall risk for smoking. We draw analogies between these low-moderate risk adolescents and “swing voters” in national elections, suggesting that media effects are more apt to influence an adolescent in the middle of the risk spectrum, compared with his peers at either end of it

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Polyamorous intimacies: from one love, to many, and back again.

Polyamory is frequently heralded as moving towards more egalitarian and explicitly negotiated forms of relating. This chapter overviews the kinds of relations, exchanges and affects that open up in polyamorous relationships, but also argues that a form of ‘polynormativity’ has emerged which limits such openings, and echoes mononormativity in the way that it privileges certain forms of (romantic) relating, and emphases ownership over freedom. An alternative understanding of polyamory is presented which which shifts from a concept of ‘multiple lovers’ to ‘multiple loves’, exploring the potentials of breaking down the distinctions between monogamy and non-monogamy, flattening hierarchies between different kinds of relationship, and focusing on freedom, compassion and non-possession

Assessment of the Rio Mavillas for Inclusion in Puerto Rico's Heritage River Program

The Department of Natural and Environmental Resources (DNER) aims to include the Rio Mavillas of Monte Choca State Forest in Puerto Rico’s Heritage River Program. To support designation, the Visual Assessment Protocol for Puerto Rico Streams, Rosgen Stream Classification, Multihabitat Macroinvertebrate Assessment, and the creation of an interpretive map were completed. Results suggest that the Rio Mavillas contains good water quality and high ecological value, and therefore the river and its surrounding areas should be protected in the program from future anthropogenic modifications for future generations to enjoy