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To identify drugs that could potentially be used to treat infection with SARS-CoV-2, a high throughput 384-well assay was developed to measure the binding of the receptor binding domain (RBD) of the viral S1 protein to its main receptor, angiotensin converting enzyme 2 (ACE2). The RBD was fused to both a HiBIT tag and an IL6 secretion signal to enable facile collection from the cell culture media. The addition of culture media containing this protein, termed HiBIT-RBD, to cells expressing ACE2 led to binding that was specific to ACE2 and both time and concentration dependant, Binding could be inhibited by both RBD expressed in E. see more coli and by a full length S1 - Fc fusion protein (Fc-fused S1) expressed in eukaryotic cells. The mutation of residues that are known to play a role in the interaction of RBD with ACE2 also reduced binding. This assay may be used to identify drugs which inhibit the viral uptake into cells mediated by binding to ACE2.
The «Single Anastomosis Duodeno-Ileal bypass with Sleeve gastrectomy» (SADI-S) is a bariatric surgery conceived to simplify the duodenal switch in order to reduce its postoperative complications. The objective of this study is to assess the safety and efficacy of SADI-S, comparing its results in both direct and two-step procedure.
Unicentric cohort study that includes patients submitted to SADI-S, both direct or in two-step, between 2014 and 2019.
Two hundred thirty-two patients were included, 192 were submitted to direct SADI-S and 40 had previously undergone a sleeve gastrectomy. The severe complications rate (Clavien-Dindo ≥IIIA) was 7.8%, being hemoperitoneum and duodenal stump leak the most frequent ones. One patient was exitus between the first 90 days after surgery (0.4%). Patients submitted to direct SADI-S had an initial body mass index (BMI) of 49.6kg/m
in comparison of 56.2kg/m
in the two-step SADI-S (p<0.001). The mean excess weight loss (EWL) at two years was higher in direct SADI-S (77.3 vs. 59.3%, p<0.05). Rate of comorbidities resolution was 88.5% for diabetes, 73.0% for hypertension, 77.0% for dyslipidemia and 85.7% for sleep apnea, with no differences between both techniques.
In medium term, SADI-S is a safe and effective technique that offers a satisfactory weight loss and remission of comorbidities. Patients submitted to two-step SADI-S had a higher initial BMI and presented a lower EWL than direct SADI-S.
In medium term, SADI-S is a safe and effective technique that offers a satisfactory weight loss and remission of comorbidities. Patients submitted to two-step SADI-S had a higher initial BMI and presented a lower EWL than direct SADI-S.
The relationship among distribution of pathological values at the Oral Glucose Tolerance Test (OGTT), metabolic risk factors and pregnancy outcomes in women with Gestational Diabetes (GDM), has not been clearly identified. We retrospectively compared metabolic and therapeutic parameters, maternal-fetal outcomes and post-partum OGTTs, with respect to the number and distribution of altered values of diagnostic OGTT in pregnancy. Secondly, we assessed whether insulin therapy predictive factors were identifiable.
This analysis included 602 pregnant women with GDM, followed in Diabetes and Pregnancy Unit of Perugia Hospital from diagnosis to childbirth. All women were diagnosed diabetic upon 75g OGTT, according IADPSG criteria. Women were divided into 3 groups, respect to distribution of diagnostic blood glucose (BG) values at OGTT Group 1 only fasting BG (OGTT0h); Group 2 1 and/or 2h (OGTT1-2h); Group 3 both fasting and 1h and/or 2h (OGTT0+1-2h) BG. Pregnant women with fasting hyperglycemia at OGTT (Groups 1 ional metabolic characteristics.
Dyslipidemia is a common metabolic disease worldwide and also an important predisposing factor for cardiovascular diseases (CVDs). Coffee is loved by people all over the world; however, the association between coffee consumption and blood lipids has yielded inconsistent results. So we carried this meta-analysis to explore the effects of coffee consumption on blood lipids.
Medline, PubMed, Web of science, Embase, and Cochrane Library databases were systematically searched until April 2020. Combined weighted mean differences (WMD) with their 95% confidence interval (CI) were calculated using random-effects models, and between-study heterogeneity was assessed by Cochran's Q test and I
statistics. link2 Subgroup analysis and meta-regression analysis were also conducted to explore the potential heterogeneity. A total of 12 RCT studies involving the association between coffee consumption and blood lipid levels were included in the meta-analysis. The pooled results showed that coffee consumption significantly increased total cholesterol (TC) (WMD 0.21mmol/L, 95% CI 0.04; 0.39, P=0.017), triglyceride (TG) (WMD 0.12mmol/L, 95% CI 0.03; 0.20, P=0.006) and low-density lipoprotein (LDL-C) (WMD 0.14mmol/L, 95% CI 0.05; 0.24, P=0.003) while had no significant effect on high-density lipoprotein (HDL-C) (WMD -0.01mmol/L, 95% CI -0.06; 0.04, P=0.707). Dose-response analysis results revealed significant positive nonlinear associations between coffee consumption and the increase in TC, LDL-C, and TG levels.
Evidence from this meta-analysis suggested that coffee consumption may be associated with an elevated risk for dyslipidemia and CVDs. So a reasonable habit of coffee consumption (<3cups/d) is essential for the prevention of dyslipidemia.
Evidence from this meta-analysis suggested that coffee consumption may be associated with an elevated risk for dyslipidemia and CVDs. So a reasonable habit of coffee consumption ( less then 3 cups/d) is essential for the prevention of dyslipidemia.
This joint document of the Italian Society of Nephrology and the Italian Diabetes Society reviews the main indications to perform a renal biopsy in diabetic patients, according to the recommendations of a panel of experts based on all available scientific evidence.
Renal biopsy has a pivotal role in assessing the nature and severity of renal injury in patients with diabetic kidney disease (DKD). The procedure is mandatory in the presence of one of more of the following features rapid onset or progression of albuminuria or sudden onset of nephrotic syndrome, rapid GFR decline with or without albuminuria, hematuria, active urine sediment, clinical and/or laboratory suspicion of other systemic diseases, and, in patients with type 1 diabetes, short diabetes duration and absence of retinopathy. Indeed, ~40% of diabetic individuals with kidney injury undergoing renal biopsy are affected by a non-diabetic renal disease (NDRD). Furthermore, the histological evaluation of patients with suspected classical diabetic and therapeutic implications.Biomarkers have a variety of clinical applications in multiple stages of diagnosis and therapy. Troponin T and brain natriuretic peptide are the best-known in the cardiovascular field, but experimental studies have identified new biomarkers with potential clinical value. In this article, novel biomarkers of kidney injury are investigated in the context of their relationship with atherosclerotic coronary disease. This review was carried out through a search in the PubMed database using as keywords each biomarker to be studied with the descriptor (DECS/MeSH) "Myocardial Infarction", and the keywords "coronary" and "cardiovascular", using the Boolean operator "AND". After the selection, 24 articles published between 2003 and 2017 were identified for the review. Eight biomarkers were investigated neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF23), tissue inhibitor of metalloproteinase-2 (TIMP-2), syndecan-1, interleukin-6 (IL-6), galectin-3, and the vascular cell adhesion molecules ICAM-1 and VCAM-1. Most identified articles were experimental studies, studies on human subjects having few participants. There are several promising biomarkers in the setting of coronary disease. The main evidence available in the literature suggests that elevated NGAL levels are associated with better prognosis after cardiac arrest and with comorbid kidney injury; elevated FGF23 is associated with coronary artery disease severity; TIMP-2 protects against coronary artery disease; increased expression of syndecan-1 is observed in myocardial infarction (MI) and protects against an exacerbated inflammatory response; IL-6 is associated with atherosclerotic disease and major cardiovascular outcomes; galectin-3 correlates with adverse clinical events post-MI; and elevated ICAM-1/VCAM-1 levels are associated with risk of coronary disease. Further studies are required to better investigate the role of each of these biomarkers in both stable coronary disease and acute coronary syndrome.
Chest wall (CW) toxicity is a potentially debilitating complication of stereotactic body radiation therapy for non-small cell lung cancer, occurring in 10% to 40% of patients. Smaller tumor-to-CW distance has been identified as a risk factor for CW toxicity. We report our experience with individualizing the planning target volume (PTV) along the CW in an effort to reduce the volume of this organ at risk receiving 30 Gy to 50 Gy.
We performed an institutional review board-approved retrospective analysis of patients with stage I (T1-2aN0M0) non-small cell lung cancer who received stereotactic body radiation therapy between June 2009 and July 2016. Four-dimensional computed tomography was used for treatment planning. A uniform 5-mm expansion of the internal target volume was generated for the PTV. Areas of overlap with the CW were removed from the PTV. Treatment was delivered with cone beam computed tomography guidance. CW toxicity was assessed per the Common Terminology Criteria for Adverse Events, version ce.
Truncation of the PTV margin along the CW resulted in a marked reduction of CW toxicity for tumors in close proximity to the CW, with only a 2.8% rate of grade 1 to 2 CW toxicity. Despite PTV reduction, there was no appreciable increase in local failures. A multi-institutional validation of this technique is needed before general incorporation into clinical practice.
The authors describe 3 cases of retrograde peri-implantitis associated with residual cysts and their successful surgical and regenerative management. Implants were originally placed with both immediate and delayed protocols.
Three patients sought treatment at the authors' specialist private practices with the chief symptoms of pain and swelling in association with implant-retained restorations. link3 Clinical, radiographic, and histopathologic findings supported the diagnoses of infected residual cysts. The lesions were enucleated in toto, the implant surfaces were decontaminated, and bone regeneration procedures were carried out. Long-term recall visits, ranging from 3 through 10 years, confirmed successful retention of all implants treated accordingly.
The authors describe an unusual clinical manifestation and emphasize the role of local procedures during implant placement in areas compromised with infection, cysts, or both and the importance of long-term recall visits.
The authors describe an unusual clinical manifestation and emphasize the role of local procedures during implant placement in areas compromised with infection, cysts, or both and the importance of long-term recall visits.