Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling

Background: Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO2 (as compared with ∼410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied.Objectives: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppm CO2 from preconception to adulthood using a mouse model.Methods: We exposed mice to CO2 (∼890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure.Results: CO2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO2 for a similar amount of time (∼8wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO2.Discussion: To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO2 can impact respiratory function in the mouse. https://doi.org/10.1289/EHP7305     

Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans. We found that the risks of CV effects are largely null across human and experimental animal studies. The few positive associations reported in studies of CV morbidity and mortality are very small in magnitude, mainly reported in single-pollutant models, and likely attributable to bias, chance, or confounding. The few positive effects in experimental animal studies were observed mainly in ex vivo studies at high exposures, and even the in vivo findings are not likely relevant to humans. The available data also do not support a biologically plausible mechanism for the effects of ozone on the CV system. Overall, the current WoE provides no convincing case for a causal relationship between long-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation; thus, we categorize the strength of evidence for a causal relationship between long-term exposure to ozone and CV effects as “below equipoise.”     

Gender disparity in the practice of gastroenterology: the first 5 years of a career

BACKGROUND: Despite an unprecedented demand for gastroenterology services, the number of gastroenterology trainees has decreased over 50% since 1993. Women comprise nearly 50% of the U.S. medical school student population; yet only occupy 16% of gastroenterology fellowship positions. In order to recruit the best candidates to gastroenterology we must be able to demonstrate the attractiveness of a career in the field. A prospective study was performed to identify the career choices of graduates from gastroenterology fellowship programs using a prospective study model and to identify whether gender differences exist in the practice of gastroenterologists up to 5 yr after completion of training. METHODS: A survey gathering information on demographics, practice pattern, and income was mailed to two cohorts of gastroenterology fellows 3 and 5 yr after graduation. RESULTS: A total of 247 subjects completed the 3 yr and 220 subjects responded to the 5-yr survey. At 3 yr, men reported higher income (p < 0.001), worked longer hours per week (p < 0.002), and were more likely to be part owner of the practice (p= 0.027). Females reported fewer children (p < 0.007), lower board certification rates (p < 0. 002), worked for larger, multispecialty practices (p < 0.001), and practiced more internal medicine. These differences were still present at 5 yr into gastroenterology practice. CONCLUSIONS: Significant differences in practice type, earnings, board certification, professional standing, and alterations in family planning are noted between male and female gastroenterologists in the initial 5 yr of their practice.     

Antibody vs. HIV in a clash of evolutionary titans

HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of antibodies have been evolved by the human immune system to recognize conserved parts of the glycoproteins, and therefore, have broadly neutralizing cross-strain activities. These antibodies constitute important tools in the quest to design immunogens that can elicit broadly neutralizing antibodies in humans and hence contribute to an effective HIV vaccine. Crystallographic analyses of the antibodies, in many cases in an antigen-complexed form, have revealed novel and, in some instances, remarkable structural adaptations to attain virus recognition. Antibodies, like HIV, can evolve relatively rapidly through mutation and selection. It seems that the structures of these broadly neutralizing antibodies bear witness to a heroic struggle between two titans of rapid evolution.     

Pragmatic Trials in Long-Term Care: Implementation and Dissemination Challenges and Opportunities

Randomized controlled trials are considered the most rigorous research design in efficacy and effectiveness research; however, such trials present numerous challenges that limit their applicability in real-world settings. As a consequence, pragmatic trials are increasingly viewed as a research design that overcomes some of these barriers with the potential to produce findings that are more reproducible. Although pragmatic methodology in long-term care is receiving increasing attention as an approach to improve successful dissemination and implementation, pragmatic trials present complexities of their own. To address these complexities and related issues, experts with experience conducting pragmatic trials, developing nursing home policy, participating in advocacy efforts, and providing clinical care in long-term care settings participated in a virtual consensus conference funded by the National Institute on Aging in Spring 2021. Participants identified 4 cross-cutting principles key to dissemination and implementation of pragmatic trial interventions: (1) stakeholder engagement, (2) diversity and inclusion, (3) organizational strain and readiness, and (4) learn from adaptations. Participants emphasized that implementation processes must be grounded in the perspectives of the people who will ultimately be responsible for implementing the intervention once it is proven to be effective. In addition, messaging must speak to long-term care staff and all others who have a stake in its outcomes. Although our understanding of dissemination and implementation strategies remains underdeveloped, this article is designed to guide long-term care researchers and community providers who are increasingly aware of the need for pragmatism in disseminating and implementing evidence-based care interventions.     

A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults

BackgroundAnticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.ObjectiveCompare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.DesignProspective cohort study.SettingPrimary care (Australia and USA).Participants19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.MeasurementsBaseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.ResultsAt baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1–2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.LimitationsResidual confounding and reverse causality are possible. Assessment of dose or duration was not possible.ConclusionsHigh anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06550-2.KEY WORDS: anticholinergic burden, dementia, stroke, potentially inappropriate medication