Weight change and ovarian steroid profiles in young women

Objective: To investigate possible short-term effects of voluntary weight loss on ovarian steroid profiles in young women, in light of better established long-term effects in older women. Design: We tested for an association of voluntary weight change over the course of a menstrual cycle with salivary E2 and P profiles in the same menstrual cycle. Setting: Students were recruited in a college residence hall, and they provided daily saliva samples to a researcher living nearby. Patient(s): The 65 women who participated were all college students and ranged in age between 18 and 23 years. Intervention(s): None. Main Outcome Measure(s): Weight was assessed in the first week of the menstrual cycle and first week of the following menstrual cycle. Estradiol and P were measured by radioimmunoassay in daily saliva samples. Result(s): We did not detect a suppressive effect of weight loss on the overall level of either hormone. However, we did find evidence for more distinct follicular and luteal E2 peaks in women who gained weight. Peak luteal P also arrived about 2 days earlier in women who gained weight. Conclusion(s): This finding adds to evidence that short-term response of ovarian function to weight loss in young women is less pronounced than long-term response in older women.AnthropologyHuman Evolutionary Biolog

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

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

Weight Change And Ovarian Steroid Profiles In Young Women

Objective: To investigate possible short-term effects of voluntary weight loss on ovarian steroid profiles in young women, in light of better established long-term effects in older women. Design: We tested for an association of voluntary weight change over the course of a menstrual cycle with salivary E2 and P profiles in the same menstrual cycle. Setting: Students were recruited in a college residence hall, and they provided daily saliva samples to a researcher living nearby. Patient(s): The 65 women who participated were all college students and ranged in age between 18 and 23 years. Intervention(s): None. Main Outcome Measure(s): Weight was assessed in the first week of the menstrual cycle and first week of the following menstrual cycle. Estradiol and P were measured by radioimmunoassay in daily saliva samples. Result(s): We did not detect a suppressive effect of weight loss on the overall level of either hormone. However, we did find evidence for more distinct follicular and luteal E2 peaks in women who gained weight. Peak luteal P also arrived about 2 days earlier in women who gained weight. Conclusion(s): This finding adds to evidence that short-term response of ovarian function to weight loss in young women is less pronounced than long-term response in older women. © 2009 American Society for Reproductive Medicine

Kupffer Cell-Dependent Hepatitis Occurs during Influenza Infection

Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of “collateral damage” of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology

The health case for economic and social rights against the gobal marketplace

“All observations of life are harsh, because life is. I lament that fact, but I cannot change it.” —Margaret Atwood, The Tent (McClelland and Stewart 2006) Over the past few decades, most of the world's economies and societies have been integrated into the global marketplace, revealing and deepening various socioeconomic divisions. In this article, I undertake three major tasks. First, I outline the processes that have led to that deepening, identify the underlying set of values, and indicate the connection with influences on population health. Second, I compare and contrast a policy perspective that takes seriously economic and social rights related to health with the values of the global marketplace. Third, I argue that emerging aspects of globalization underscore the urgency of the human rights challenge to the global marketplace. I also suggest a research agenda focusing on the conditions under which governments are likely to respond in ways that strengthen their commitment to economic and social rights domestically and internationally, while at the same time offering some rather pessimistic observations about the prospects for policy change