Differential leukocyte expression of IFITM1 and IFITM3 in patients with severe pandemic influenza A(H1N1) and COVID-19

Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.Introduction Methods - Human samples - IFITM expression in humans - Influenza infection in mice - IFITM expression in mice - Cytokine levels in mouse lungs - Study approval - Statistical analysis Results - Participant characteristics - IFITM1 and IFITM3 in patients with severe pandemic influenza A(H1N1) - High-dose influenza A (H1N1) virus infection downregulates IFITM expression in mice - IFITM1 and IFITM3 in severe COVID-19 Discussio

Incidence, clinical characteristics and management of inflammatory bowel disease in Spain: large-scale epidemiological study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD—Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)—during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100, 000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31–56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Increase in size and nitrogen concentration enhances seedling survival in Mediterranean plantations:insights from an ecophysiological conceptual model of plant survival

Reduction in size and tissue nutrient concentration is widely considered to increase seedling drought resistance in dry and oligotrophic plantation sites. However, much evidence indicates that increase in size and tissue nutrient concentration improves seedling survival in Mediterranean forest plantations. This suggests that the ecophysiological processes and functional attributes relevant for early seedling survival in Mediterranean climate must be reconsidered. We propose a ecophysiological conceptual model for seedling survival in Mediterranean-climate plantations to provide a physiological explanation of the frequent positive relationship between outplanting performance and seedling size and nutrient concentration. The model considers the physiological processes outlined in the plantation establishment model of Burdett (Can J For Res 20:415-427, 1990), but incorporates other physiological processes that drive seedling survival, such as N remobilization, carbohydrate storage and plant hydraulics. The model considers that seedling survival in Mediterranean climates is linked to high growth capacity during the wet season. The model is for container plants and is based on three main principles, (1) Mediterranean climates are not dry the entire year but usually have two seasons of contrasting water availability; (2) summer drought is the main cause of seedling mortality; in this context, deep and large roots is a key trait for avoiding lethal water stress; (3) attainment of large root systems in the dry season is promoted when seedlings have high growth during the wet season. High growth is achieved when seedlings can divert large amount of resources to support new root and shoot growth. Functional traits that confer high photosynthesis, nutrient remobilization capacity, and non-structural carbohydrate storage promote high growth. Increases in seedling size and nutrient concentration strongly affect these physiological processes. Traits that confer high drought resistance are of low value during the wet season because hinder growth capacity. We provide specific evidence to support the model and finally we discuss its implications and the factors that may alter the frequent increase in performance with increase in seedling size and tissue nutrient concentration

Management and 1-year outcomes of patients with newly diagnosed atrial fibrillation and chronic kidney disease: Results from the prospective garfield-af registry

Background-—Using data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD–Atrial Fibrillation), we evaluated the impact of chronic kidney disease (CKD) stage on clinical outcomes in patients with newly diagnosed atrial fibrillation (AF). Methods and Results-—GARFIELD-AF is a prospective registry of patients from 35 countries, including patients from Asia (China, India, Japan, Singapore, South Korea, and Thailand). Consecutive patients enrolled (2013–2016) were classified with no, mild, or moderate-to-severe CKD, based on the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative guidelines. Data on CKD status and outcomes were available for 33 024 of 34 854 patients (including 9491 patients from Asia); 10.9% (n=3613) had moderate-to-severe CKD, 16.9% (n=5595) mild CKD, and 72.1% (n=23 816) no CKD. The use of oral anticoagulants was influenced by stroke risk (ie, post hoc assessment of CHA2DS2-VASc score), but not by CKD stage. The quality of anticoagulant control with vitamin K antagonists did not differ with CKD stage. After adjusting for baseline characteristics and antithrombotic use, both mild and moderate-to-severe CKD were independent risk factors for all-cause mortality. Moderate-to-severe CKD was independently associated with a higher risk of stroke/systemic embolism, major bleeding, new-onset acute coronary syndrome, and new or worsening heart failure. The impact of moderate-to-severe CKD on mortality was significantly greater in patients from Asia than the rest of the world (P=0.001). Conclusions-—In GARFIELD-AF, moderate-to-severe CKD was independently associated with stroke/systemic embolism, major bleeding, and mortality. The effect of moderate-to-severe CKD on mortality was even greater in patients from Asia than the rest of the world

Glutathione

Glutathione is a simple sulfur compound composed of three amino acids and the major non-protein thiol in many organisms, including plants. The functions of glutathione are manifold but notably include redox-homeostatic buffering. Glutathione status is modulated by oxidants as well as by nutritional and other factors, and can influence protein structure and activity through changes in thiol-disulfide balance. For these reasons, glutathione is a transducer that integrates environmental information into the cellular network. While the mechanistic details of this function remain to be fully elucidated, accumulating evidence points to important roles for glutathione and glutathione-dependent proteins in phytohormone signaling and in defense against biotic stress. Work in Arabidopsis is beginning to identify the processes that govern glutathione status and that link it to signaling pathways. As well as providing an overview of the components that regulate glutathione homeostasis (synthesis, degradation, transport, and redox turnover), the present discussion considers the roles of this metabolite in physiological processes such as light signaling, cell death, and defense against microbial pathogen and herbivores