The current methods for direct late-stage and residue-selective installation of a versatile boronic acid (BA) repertoire on peptides are inadequate for a wide range of applications. Here, we show the ...suitability and efficiency of thiol–ene radical click chemistry to install functionally versatile BA derivatives on numerous bioactive, native peptides. Our work highlights that the methodology is operationally simple and adaptable for applications with BA-modified peptides, such as cyclization, conjugation, and functional group alteration.
Patients with unprotected left main coronary artery (ULMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES); however, the ...benefits of DES compared with coronary artery bypass grafting (CABG) in ULMCA remain controversial. This meta-analysis evaluated the effects of PCI with DES compared with CABG for the treatment of ULMCA stenosis. Databases were searched through November 30, 2016. Randomized controlled trials (RCTs) comparing DES with PCI versus CABG for ULMCA stenosis were identified. We calculated summary odds ratios (ORs) and 95% CIs with the random-effects model. The primary outcome was major adverse cardiovascular events, defined as a composite of death from any cause, stroke, or myocardial infarction (MI). The analysis included 4,612 patients from 5 RCTs. Compared with CABG, patients assigned to PCI had a similar rate of major adverse cardiovascular events (OR 1.06, 95% CI 0.79 to 1.43), all-cause mortality (OR 1.03, 95% CI 0.79 to 1.35), cardiovascular death (OR 1.03, 95% CI 0.73 to 1.45), stroke (OR 0.81, 95% CI 0.38 to 1.76), and MI (OR 1.47, 95% CI 0.87 to 2.47). The risk of any repeat revascularization was significantly greater in the PCI group than that in the CABG group (OR 1.85, 95% CI 1.53 to 2.24). In conclusion, our meta-analysis of RCTs suggest that PCI with DES results in comparable mortality, stroke, and MI compared with CABG for revascularization of ULMCA stenosis, with PCI associated with higher rates of repeat revascularization.
A systematic review and meta-analysis was performed to evaluate the effects of carvedilol versus metoprolol on the incidence of postoperative atrial fibrillation in patients undergoing coronary ...artery bypass grafting in randomized controlled trials. Ovid MEDLINE, PubMed, CENTRAL, and Excepta Medica (EMBASE) were searched up to March 2013 for suitable randomized controlled trials. Data were pooled using random-effects model for pairwise analyses. A total of 4 trials with 601 patients were included in this analysis. Pairwise analyses showed that compared with metoprolol, carvedilol significantly reduced the incidence of postoperative atrial fibrillation (odds ratio 0.50, 95% confidence interval 0.32 to 0.80). In conclusion, compared with metoprolol, carvedilol significantly reduces the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting.
To determine the prognostic value of cumulative calcification score of coronary artery calcification (CAC), thoracic aortic calcification (TAC) and aortic valve calcification (AVC) in acute ST ...segment elevation myocardial infarction (STEMI) patients.
This was a retrospective, single-center cohort study. A total of 332 STEMI patients who received primary percutaneous coronary intervention (PPCI) were enrolled in this study between January 2010 to October 2018. We assessed the calcification in the left anterior descending branch (LAD), left circumflex branch (LCX), right coronary artery (RCA), thoracic aorta, and aortic valve. Calcification of each part was counted as 1 point, and the cumulative calcification score was calculated as the sum of all points. The primary endpoint was all-cause mortality. Multivariate Cox proportional hazards models were used to determine association of cumulative calcification score with end points. The performance of the score was evaluated by receiver operating characteristic (ROC) curve analysis and absolute net reclassification improvement (NRI), compared with the Global Registry of Acute Coronary Events (GRACE) risk score.
The overall population's calcification score was 2.0 ± 1.6. During a mean follow-up time of 69.8 ± 29.3 months, the all-cause mortality rate was 12.1%. Kaplan-Meier curve showed that the score was significantly associated with mortality (log-rank p < 0.001). The multivariable Cox proportional hazard analyses showed that a calcification score of 4-5 was independently associated with all-cause death in STEMI patients hazard ratio (HR) = 2.32, 95% confidence interval (CI): 1.01-5.31, p = 0.046. The area under the ROC curve (AUC) of the calcification score was 0.67 (95% CI: 0.61-0.72), and the AUC of the GRACE score was 0.80 (95% CI: 0.75-0.84). There was no statistical difference in the predictive value between both scores for 3-year mortality in STEMI patients after PPCI (p = 0.06). Based on the NRI analysis, the calcification score showed better risk classification compared with the GRACE score (absolute NRI = 6.63%, P = 0.027).
The cumulative calcification score is independently associated with the long-term prognosis of STEMI patients after PPCI.
Abstract Background Recent reports suggest altered antithrombotic efficacy and higher risk of bleeding with new oral anticoagulants (NOACs) in patients with renal insufficiency. A meta-analysis was ...performed to evaluate the efficacy and safety with recommended doses of NOAC compared with conventional treatment in patients with renal insufficiency. Methods PubMed, Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched from January 1, 2001 through March 23, 2014. Randomized controlled trials that compared NOACs (rivaroxaban, apixaban, and dabigatran) with comparators (vitamin K antagonist/warfarin, low molecular weight heparin, aspirin, placebo) were selected. We defined moderate renal insufficiency as creatinine clearance (estimated glomerular filtration rate eGFR) of 30-49 mL/min, and mild renal insufficiency as eGFR 50-79 mL/min. Results There were 40,693 patients with renal insufficiency in 10 trials. Compared with other anticoagulants in patients with mild renal insufficiency there was significantly less major or clinically relevant nonmajor bleeding (odds ratio OR, 0.81; 95% confidence interval CI, 0.72-0.90) and stroke or systemic embolism (OR, 0.70; 95% CI, 0.54-0.92) with NOACs. Using random effects meta-analysis, there was significantly less stroke or systemic embolism (OR, 0.72; 95% CI, 0.57-0.92) and a trend toward less major or clinically relevant nonmajor bleeding (OR, 0.82; 95% CI, 0.59-1.14) with the NOACs among patients with moderate renal insufficiency, and this became statistically significant when evaluated using a fixed effects model. NOACs showed efficiency comparable with conventional anticoagulants for prevention of venous thromboembolism or related mortality. Conclusions In patients with renal insufficiency, recommended doses of novel anticoagulants are noninferior and relatively safe compared with conventional anticoagulants.
Open and closed type triiron chalcogenide stibine cluster molecules have been synthesized and characterized by single crystal X-ray structural studies. A comparison between the phenyl and isopropyl ...analogues of the open cluster compound shows some unique decarbonylation tendency for the phenyl analogue which easily converts an open cluster to a closed cluster molecule by a “butterfly wing-tip” opening mechanism. DFT study also revealed a critical behavior of such molecules in which the opening of a butterfly wing tip is governed by a decarbonylation step to give a closed cluster geometry. Antibacterial property was also studied with one of the closed cluster compound to understand their inhibition activity.
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•Synthesis of new triiron chalcogenide stibine cluster molecules and their structural characterization.•The study reveals an interesting mechanistic aspect for the opening of a butterfly wing tip within the cluster framework.•DFT calculation supports the mechanism governed by a decarbonylation step to give a closed cluster geometry.
The number of cases from the coronavirus disease 2019 (COVID-19) global pandemic has overwhelmed existing medical facilities and forced clinicians, patients, and families to make pivotal decisions ...with limited time and information.
While machine learning (ML) methods have been previously used to augment clinical decisions, there is now a demand for "Emergency ML." Throughout the patient care pathway, there are opportunities for ML-supported decisions based on collected vitals, laboratory results, medication orders, and comorbidities. With rapidly growing datasets, there also remain important considerations when developing and validating ML models.
This perspective highlights the utility of evidence-based prediction tools in a number of clinical settings, and how similar models can be deployed during the COVID-19 pandemic to guide hospital frontlines and healthcare administrators to make informed decisions about patient care and managing hospital volume.
A novel solvent free synthetic method has been designed by using rice husk ash (RHA) as solid support for the selective functionalization of ferrocenyl derivatives and described the synthesis of a ...1,1′‐unsymmetrically bi‐functionalized ferrocenyl compounds for their biological evaluation. Single crystal X‐ray structural evaluation showed some interesting intra‐molecular hydrogen bonding interactions across the chains of the ferrocenyl molecule, while DFT calculation revealed the significance of the orientation between the two cyclopentadienyl rings for the hydrogen bonding interaction. Redox and antibacterial properties have been studied to understand the electronic and biological effect of different hydrazone system and their potential for future application.
Novel solvent free synthetic method using rice husk ash as solid support for selective functionalization of ferrocenyl derivatives and synthesis of 1,1′‐unsymmetrically bi‐functionalized compounds and their antibacterial evaluation.
Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiology of cardiovascular disease in diabetes may be divided into hyperglycemia per se and ...factors operating through components of metabolic syndrome (MetS). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. MetS is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large numberawaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus,more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of MetS.Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.
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