Rationale There is a need to minimize oral corticosteroid (OCS) use in patients with asthma to prevent their costly and burdensome adverse effects. Current guidelines do not provide recommendations for OCS tapering in patients with asthma.Objectives To develop expert consensus on OCS tapering among international experts.Methods A modified Delphi method was used to develop expert consensus statements relating to OCS use, tapering, adverse effects, adrenal insufficiency, and patient-physician shared decision-making. Initial statements proposed by experts were categorized, filtered for repetition, and presented back to experts over three ranking rounds to obtain consensus (≥70% agreement).Measurements and Main Results One hundred thirty-one international experts participated in the study, and 296 statements were ranked. Numerous recommendations and guidance regarding appropriate OCS use were established. Experts agreed that OCS tapering should be attempted in all patients with asthma receiving maintenance OCS therapy, with personalization of tapering rhythm and speed. The importance of recognizing individual adverse effects was also established; however, a unified approach to the assessment of adrenal insufficiency was not reached. Shared decision-making was considered an important goal during the tapering process.Conclusions In this Delphi study, expert consensus statements were generated on OCS use, tapering, adverse-effect screening, and shared decision-making, which may be used to inform clinical practice. Areas of nonconsensus were identified, highlighting uncertainty among the experts around some aspects of OCS use in asthma, such as adrenal insufficiency, which underscores the need for further research in these domains.Antarctica is an ideal analogue for studying the limits of life. Despite severe temperature fluctuations and desiccating conditions, life is commonly found colonizing the structural cavities within Antarctic rocks (i.e., endoliths). Previous studies have speculated that the slow cycling of endoliths in the McMurdo Dry Valleys may be the limit of life on Earth. However, very little is known about the in situ activities of these communities-especially in regions outside the McMurdo Dry Valleys where endoliths are thought to be cycling carbon very slowly (e.g., hundreds of years). Here, we show that East Antarctic endoliths found on nunataks are cycling carbon quickly and are therefore quite active. Through radiocarbon (14C) analyses of the viable cell membrane (as phospholipid-derived fatty acids [PLFA]), we found that the Δ14C composition of these microbial communities was on average predominantly modern, with a few samples signaling older carbon in the system. These findings indicate that endoliths inhabiting inland Antarctic nunataks are cycling carbon on decadal timescales, which support the notion that endoliths in Antarctica are cycling carbon quickly. This work provides new insights into the potential variability of Antarctic endolith activities and demonstrates that, despite the climatic extremes that exist farther inland on the most inhospitable continent on Earth, indigenous life can thrive.

Clinicians commonly use short-term physiologic markers to assess the benefit of ventilator adjustments. Improved PaO2/FIO2 after ventilator adjustment in acute respiratory distress syndrome (ARDS) is associated with lower mortality. However, as driving pressure (ΔP) reflects lung stress and strain, changes in ΔP may more accurately reflect benefits or harms of ventilator adjustments compared to changes in oxygenation.

We aimed to compare the association between mortality and the changes in PaO2/FIO2 and ΔP following protocolized ventilator changes.

We assessed associations between mortality and changes in PaO2/FIO2 (ΔPaO2/FIO2) and ΔP (ΔΔP) after post-randomization positive end-expiratory pressure (PEEP) and tidal volume adjustment in re-analyses of the Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury (ALVEOLI) and Expiratory Pressure (ExPress) trials. We included subjects with available pre- and post-intervention PaO2/FIO2 and ΔP (372 in ALVEOLI and 596 in ExPresthe key variable associated with outcome.

Reduced ΔP following protocolized ventilator changes was more strongly and consistently associated with lower mortality than was increased PaO2/FIO2, making ΔΔP more informative about benefit from ventilator adjustments. Our results reinforce the primacy of ΔP, rather than oxygenation, as the key variable associated with outcome.Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular diseases, and kidney disorders are intensively studied to find effective therapeutic targets. Given the serpins’ outstanding functionality, the deficiency or overexpression of certain types of serpin has been associated with diverse pathophysiological events. In particular, we focus here on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.Equid herpesvirus 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. VBIT-4 manufacturer Similarly, to other alphaherpesviruses, EHV-1 is neurotropic and establishes latency in the neurons of its natural host. Despite the fact that many studies have been devoted to the pathogenesis of various clinical forms of EHV-1 infection, mechanisms of the neuronal damage are still not fully understood. The aim of this study was to define the phosphorylation status of tau protein in neuronal cell culture infected with EHV-1. Phosphorylation of tau was tested at tau-ser199/ser202, tau-ser404, tau-ser262, tau-thr181, tau-thr217 and tau-thr205 sites. We described, for the first time, that EHV-1 infection leads to the accumulation of hyperphosphorylated tau in primary murine neurons. We showed that non-neuropathogenic and neuropathogenic EHV-1 strains specifically induce hyperphosphorylation of tau-ser199/ser202, tau-ser404 and tau-thr205 during long-term infection and after a controlled activation of productive infection.