46 research outputs found

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

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    https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

    Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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    Contains fulltext : 172380.pdf (publisher's version ) (Open Access

    The lower and upper solution method for three-point boundary value problems with integral boundary conditions on a half-line

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    This paper deal with the following second-order three-point boundary value problem with integral boundary condition on a half-line (Formula presented) where ? > 0, 0 < ?? < 1 and f: [0, +?) × R2 › R satisfies a Nagumo’s condition which plays an important role in the nonlinear term depend on the first-order derivative explicitly. By using Schauder’s fixed point theorem, the upper and lower solution method and topological degree theory, first we give sufficient conditions for the existence of at least one solution and next at least three solutions of the above problem. Moreover, an example is included to demonstrate the efficiency of the main results. © 2018, University of Nis. All rights reserved

    Carotid intima‑media thickness and insulin resistance changes in patients who underwent sleeve gastrectomy: A prospective study

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    Objectives: Our aim was to examine changes in insulin resistance, Carotid Intima-Media Thickness (CIMT), in morbid obese patients without any known associated chronic diseases who underwent sleeve gastrectomy.Materials and Methods: The subjects of this study were patients with minimum BMI of 40, who did not have any known chronic diseases. Sleeve gastrectomy was performed and perioperative control endoscopy was performed. The following values were measured before the operation and after follow-up period after the operation: Fasting blood glucose and insulin, lipid profile, BMI, liver function tests, right and left CIMT. Furthermore, the patients’ insulin resistance was calculated by HOMA method, and the values of 2.7. Participants: Six-teen patients (14 women and 2 men, average age: 39.12 ± 10.63 years), who did not have a known additional chronic disease, took part in the study.Results: There was a significant difference between baseline and follow-up values of the patients, and the mean weight loss was 20.5%. Given the statistical evaluation of baseline and follow-up values, there was a significant difference in BMI, insulin resistance rates and right and left CIMT values.Conclusions: Bariatric surgery may provide some additional advantages for the management of cardiovascular risks in obese patients. However, it should be kept in mind that the most important components of fight against obesity are appropriate diet and exercise programs.Keywords: Bariatric surgery, carotid intima‑media thickness, morbid obes
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