T lymphocyte insensitivity to corticosteroids in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>There are increased numbers of activated lymphocytes in the lungs of chronic obstructive pulmonary disease (COPD) patients. The clinical benefits of corticosteroids in COPD patients are limited. Our hypothesis is that lymphocytes play a role in this corticosteroid insensitivity.</p> <p>Objectives</p> <p>To investigate the effects of the corticosteroid dexamethasone on lung lymphocyte cytokine production from patients with COPD compared to controls.</p> <p>Methods</p> <p>Cultured airway lymphocytes obtained by bronchoscopy from healthy non-smokers (HNS), smokers (S) and COPD patients were stimulated with phytohaemagglutinin (PHA) & phorbol myristate acetate (PMA), +/- dexamethasone. Supernatants were assayed for interleukin (IL)-2 and interferon (IFN)γ. Immunofluoresence was used to analyse changes in CD8 glucocorticoid receptor (GRα and GRβ) expression.</p> <p>Results</p> <p>The inhibition of PHA/PMA stimulated IFNγ production by dexamethasone was reduced in COPD patients compared to HNS (<it>p </it>< 0.05 at concentrations from 0.1-1 μM). There was also a significant reduction (<it>p </it>< 0.05) in the mean inhibitory effect at 1 μM in COPD patients (54.1%) compared to smokers (72.1%), and in smokers compared to HNS (85.5%). There was a numerically reduced effect of dexamethasone on IL-2 production that did not reach statistical significance. There was no difference in GRα and GRβ expression in follicular CD8 cells between COPD patients (50.9% and 30.4% respectively) and smokers (52.9% and 29.7% respectively).</p> <p>Conclusions</p> <p>IFNγ production from COPD airway lymphocytes is corticosteroid insensitive. This phenomenon may be important in the poor clinical response often observed with corticosteroids.</p

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

The CardioMetabolic Health Alliance Working Toward a New Care Model for the Metabolic Syndrome

AbstractThe Cardiometabolic Think Tank was convened on June 20, 2014, in Washington, DC, as a “call to action” activity focused on defining new patient care models and approaches to address contemporary issues of cardiometabolic risk and disease. Individual experts representing >20 professional organizations participated in this roundtable discussion. The Think Tank consensus was that the metabolic syndrome (MetS) is a complex pathophysiological state comprised of a cluster of clinically measured and typically unmeasured risk factors, is progressive in its course, and is associated with serious and extensive comorbidity, but tends to be clinically under-recognized. The ideal patient care model for MetS must accurately identify those at risk before MetS develops and must recognize subtypes and stages of MetS to more effectively direct prevention and therapies. This new MetS care model introduces both affirmed and emerging concepts that will require consensus development, validation, and optimization in the future

Precipitation gradients drive high tree species turnover in the woodlands of eastern and southern Africa

Savannas cover one-fifth of the Earth's surface, harbour substantial biodiversity, and provide a broad range of ecosystem services to hundreds of millions of people. The community composition of trees in tropical moist forests varies with climate, but whether the same processes structure communities in disturbance-driven savannas remains relatively unknown. We investigate how biodiversity is structured over large environmental and disturbance gradients in woodlands of eastern and southern Africa. We use tree inventory data from the Socio-Ecological Observatory for Studying African Woodlands (SEOSAW) network, covering 755 ha in a total of 6780 plots across nine countries of eastern and southern Africa, to investigate how alpha, beta, and phylogenetic diversity varies across environmental and disturbance gradients. We find strong climate-richness patterns, with precipitation playing a primary role in determining patterns of tree richness and high turnover across these savannas. Savannas with greater rainfall contain more tree species, suggesting that low water availability places distributional limits on species, creating the observed climate-richness patterns. Both fire and herbivory have minimal effects on tree diversity, despite their role in determining savanna distribution and structure. High turnover of tree species, genera, and families is similar to turnover in seasonally dry tropical forests of the Americas, suggesting this is a feature of semiarid tree floras. The greater richness and phylogenetic diversity of wetter plots shows that broad-scale ecological patterns apply to disturbance-driven savanna systems. High taxonomic turnover suggests that savannas from across the regional rainfall gradient should be protected if we are to maximise the conservation of unique tree communities

Precipitation gradients drive high tree species turnover in the woodlands of eastern and southern Africa

DATA AVAILABILITY STATEMENT : Data are available from the Dryad Digital Repository: https://DOI.org/10.5061/dryad.k98sf7mcb (Davies et al. 2023).Savannas cover one-fifth of the Earth’s surface, harbour substantial biodiversity, and provide a broad range of ecosystem services to hundreds of millions of people. The community composition of trees in tropical moist forests varies with climate, but whether the same processes structure communities in disturbance-driven savannas remains relatively unknown. We investigate how biodiversity is structured over large environmental and disturbance gradients in woodlands of eastern and southern Africa. We use tree inventory data from the Socio-Ecological Observatory for Studying African Woodlands (SEOSAW) network, covering 755 ha in a total of 6780 plots across nine countries of eastern and southern Africa, to investigate how alpha, beta, and phylogenetic diversity varies across environmental and disturbance gradients. We find strong climate-richness patterns, with precipitation playing a primary role in determining patterns of tree richness and high turnover across these savannas. Savannas with greater rainfall contain more tree species, suggesting that low water availability places distributional limits on species, creating the observed climate-richness patterns. Both fire and herbivory have minimal effects on tree diversity, despite their role in determining savanna distribution and structure. High turnover of tree species, genera, and families is similar to turnover in seasonally dry tropical forests of the Americas, suggesting this is a feature of semiarid tree floras. The greater richness and phylogenetic diversity of wetter plots shows that broad-scale ecological patterns apply to disturbance-driven savanna systems. High taxonomic turnover suggests that savannas from across the regional rainfall gradient should be protected if we are to maximise the conservation of unique tree communities.The UK Natural Environment Research Council.http://www.ecography.orgam2024Plant Production and Soil ScienceSDG-15:Life on lan

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome