8 research outputs found

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

    Restrain of birds with bottles of polyethylene terephthalate, tested in red-browed from the Atlantic Forest

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    In wild animals, containment is the moment of greatest stress caused by the investigator to the animal due to its natural resistance to the moment of capture, handling, containment and transport, attitudes frankly contrary to his nature. In birds, the restraint must meet certain criteria in order to control the animal's movements, avoiding trauma at the same time that you need to keep your breathing amplitude. The high risk of death during the restraint of these animals raised the need to design a device, from bottles of poly ethylene terephthalate (PET), for containing parrots-browed Amazon (Amazona rhodocorytha), a parrot endemic to the Atlantic Forest in southeastern Brazil, and endangered with extinction, which allowed the observation of respiration, the reduction of handling time of birds for collection of biological material, and consequent reduction of stress and risk of death during the evaluation of several biological data and health of the bird. The PET bottle container can be used as a model for any bird, provided it suits the size of the animal

    Haematological reference for red-browed parrot ( Amazona rhodocorytha , Salvadori, 1890) captive in the Atlantic Forest in Eastern Brazil

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    ABSTRACT To conduct the survey were used 35 (thirty-five) red-browned parrots (A. rhodocorytha), adults, captive, of both genders and clinically healthy, belonging to the live collection of the Museum of Biology Teacher Mello Leitao, located in Santa Teresa, EspĂ­rito Santo, Brazil. Harvests were performed in the morning, by puncture of the brachial vein getting 0.5mL of blood stored in EDTA for a period no longer than 6 hours. Blood smears of fresh material were made at collection, stained using the method of May-Grunwald-Giemsa. Analysis of blood elements was done by cell counting in a mirrored Neubauer chamber using Natt and Herrick solution at a ratio of 2:200 as diluent. For the analysis of the methodology, homoglobinometry cyanide hemoglobin using commercial kits by colorimetry on a semi-automatic biochemical analyzer was used. After completion of the statistical data the following parameters were obtained (mean±standard deviation): Erythrocytes (x106/ÎŒl): 2.68±0.56; Hemoglobin (g/dl): 14.27±0.69; Hematocrit (%): 53±3.38; Mean corpuscular volume (fl): 206.7±45.82; Mean corpuscular hemoglobin (pg): 56.4±14.46; Mean corpuscular hemoglobin concentration (%): 27.5±1.19; Thrombocytes (x3/ÎŒl): 25.8 ± 10.5; Total plasma protein (g/dl) 5.4±0.5; Leukocytes (x103/dl): 3.1±2; Heterophile (/uL): 1937±1676; Lymphocytes (/uL): 1144±599; Monocytes (/uL): 24.4 ± 28.2; Basophils (/uL): 42.2±46.2; Eosinophils (/uL): 11.7±19.9. In the relation between males and females, no significant differences were found in any hematological parameter evaluated
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