COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, ...antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.
Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the ...discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes.
Children who grow up in developing countries of the world must work to help financially support their families, and they must also attend school. We investigated the impact of work on the sleep of ...working vs. nonworking high school students. Twenty-seven São Paulo, Brazil, public high school students (eight male and eight female working students plus six nonworking female and five nonworking male students) 14-18 yrs of age who attended school Monday-Friday between 19:00 to 22:30 h participated. A comprehensive questionnaire about work and living conditions, health status, and diseases and their symptoms was also answered. The activity level and rest pattern (sleep at night and napping during the day) were continuously assessed by wrist actigraphy (Ambulatory Monitoring, USA). The main variables were analyzed by a two-factor ANOVA with application of the Tukey HSD test for multiple comparisons, and the length of sleep during weekdays vs. weekends was compared by Student t-test. Working students went to sleep earlier weekends F(1,23) = 6.1; p = 0.02 and woke up earlier work days than nonworking students F(1,23) = 17.3; p = 0.001. The length of nighttime sleep during weekdays was shorter among all the working F(1,23) = 16.7; p < 0.001 than all the nonworking students. The sleep duration of boys was shorter than of girls during weekends F(1,23) = 10.8; p < 0.001. During weekdays, the duration of napping by working and nonworking male students was shorter than nonworking female students. During weekdays, working girls took the shortest naps F(1,23) = 5.6; p = 0.03. The most commonly reported sleep complaint during weekdays was difficulty waking up in the morning F(1,23) = 6.5; p = 0.02. During weekdays, the self-perceived sleep quality of working students was worse than nonworking students F(1,23) = 6.2; p = 0.02. The findings of this study show that work has negative effects on the sleep of adolescents, with the possible build-up of a chronic sleep debt with potential consequent impact on quality of life and school learning.
The Health Care Dilemma should be of interest to local and international health care constituencies, including leaders of health care delivery networks, academic professionals, students, and ...government and ministerial authorities globally with interest in health care systems and policy development.The patient case studies collected in this book provide first-hand accounts of health care delivery in multiple settings in a variety of national and local systems. These accounts, focusing on real experiences and real patients, transcend the rhetoric of political debate about health care delivery. The cases offer lessons for how we might draw on the virtues of other health care systems, understand strengths and shortcomings in our current system, and work toward potential improvements.All royalties derived from the sale of this book are contributed to the Harvard Macy Institute in support of the worldwide community of health care professionals innovating through education.
Communication failures are a key cause of medical errors and are particularly prevalent during handovers of patients between services.
To explore current perceptions of effectiveness in communicating ...critical patient information during admission handovers between emergency medicine (EM) residents and internal medicine (IM) residents.
Study design was a survey of IM and EM residents at a large urban hospital. Residents were surveyed about whether critical information was communicated during patient handovers. Measurements included comparisons between IM and EM residents about their perceptions of effective communication of key patient information and the quality of handovers.
Ninety-three percent of EM residents (50 of 54) and 80% of IM residents (74 of 93) responded to the survey. The EM residents judged their handover performance to be better than how their IM colleagues assessed them on most questions. The IM residents reported that one-half of the time, EM residents provided organized and clear information, whereas EM residents self-reported that they did so most of the time (80%-90%). The IM residents reported that 25% of handovers were suboptimal and resulted in admission to an inappropriate level of care, and 10% led to harm or delay in care. The EM residents reported suboptimal communication was less common (5%). On the global assessment of whether the admission handover provided the information needed for good patient care, IM residents rated the quality of the handover data lower than did responding EM residents.
There are gaps in communicating critical patient information during admission handovers as perceived by EM and IM residents. This information can form the basis for efforts to improve these handovers.
BACKGROUND: Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of ...5-lipoxygenase activating protein, BAYx 1005, on the bronchospastic response to cold dry air hyperventilation was investigated in asthmatic patients. METHODS: After a screening cold dry air hyperventilation challenge to document cold air responsiveness, 16 asthmatic subjects (baseline forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a randomised, double blind, crossover design. Leukotriene synthesis inhibition was estimated by measuring the concentration of leukotriene B4 in whole blood stimulated with calcium ionophore A21387. RESULTS: Treatment with BAYx 1005 produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production, while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02). CONCLUSIONS: Treatment with BAYx 1005, a novel inhibitor of leukotriene synthesis, produced a significant blunting of cold dry air responsiveness consistent with the hypothesis that leukotrienes mediate part of the bronchoconstriction induced by hyperventilation of cold dry air.
We measure the color ratio-metric response of alkaline-earth rare-earth upconverting nanoparticles with a diamond anvil cell. We find ensembles of SrLuF particles detect 32.8 MPa in pressure change ...corresponding to 24 nN of force.
Genetic features determine the site of polarized growth in filamentous fungi and lead to hyphal tip extension or subapical branching. We have isolated the samB gene (suppressor of anucleate metulae) ...of Aspergillus nidulans which encodes a 66 kDa protein carrying an atypical Cys4 and an additional Cys2/His/Cys Zn finger motif at the carboxy‐terminus. Such novel Zn finger‐like domains have recently been found in several other developmental regulators in organisms ranging from yeast to man. Deletion of this domain at the carboxy‐terminus of SamB led to premature hyphal ramification, mislocalization of septa and suppression of the asporogenous phenotype of the developmental mutant aps (anucleate primary sterigmata). A ΔsamB deletion strain displayed an identical phenotype. A homologous gene in Saccharomyces cerevisiae was also characterized whose deletion resulted in a multi‐budding phenotype; thus it was named MUB1. An underlying common mechanism for both genes in determination of the onset of polarized growth and its links to other cellular developmental processes is discussed.
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