Virtual Structural Similarity Elucidates Bioactivity of Fenchone: A Phytochemical Enriched in Fennel Essential Oil.

BACKGROUND: Fenchone is a natural monoterpene abundantly present in fennel essential oil. It is known for its wound healing properties but its other biological activities are less explored. METHODS: We used an in silico structural similarity searching approache to identify various biological activities of fenchone. The identified biological activities of fenchone (purchased from Sigma Aldrich) were validated by conducting DPPH free radical scavenging assay, MTT assay, well diffusion assay for antimicrobial activity and enzymatic assays to analyze the activity of different antioxidant enzymes. RESULTS: Camphor was found to possess maximum structural similarity with fenchone (similarityindex 100). Molecular docking demonstrated that the binding modes of fenchone were also similar to camphor against protein Cytochrome CYP101D1 (PDB ID: 4C9K). Fenchone also demonstrated to possess an antioxidant activity (IC50: 3.32±0.008mM), an antimicrobial activity (MIC: 0.49mM) and a very strong antifungal activity. Fenchone protects yeast cells from H2O2 induced cytotoxicity and is cytotoxic to cancerous Hela cells (IC50: 12.63±0.12 µM). Fenchone treatment also showed the reduced activity of antioxidant enzymes i.e glutathione-S-transferase, catalase and lipid peroxidase. CONCLUSION: To the best of our knowledge, this is the first report that used structural similarity searching to explore the biological activities of fenchone.

Transradial vs Transfemoral Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction: A Systemic Review and Meta-analysis.

BACKGROUND: The objective of this meta-analysis to evaluate safety and efficacy of transradial vs the transfemoral approach for primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients. METHODS: Randomized controlled trials that compared the transfemoral vs the transradial approach in STEMI patients who underwent PCI were searched in PubMed, Embase, CENTRAL, Cumulative Index to Nursing and Allied Health Literature, and clinicaltrials.gov. Random effect models were used to pool effect sizes. RESULTS: Sixteen trials, comprising data from 9726 patients, were included in the meta-analysis. All-cause mortality (risk ratio [RR], 0.68; 95% confidence interval [CI], 0.54-0.85; relative risk reduction [RRR], 32.8%; I(2) = 0), major bleeding (RR 0.56; 95% CI, 0.42-0.74; RRR, 48.1%; I(2) = 0), access site bleeding (RR, 0.38; 95% CI, 0.29-0.50; RRR, 63.9%; I(2) = 0), major adverse cardiovascular events (RR, 0.80; 95% CI, 0.68-0.94; RRR, 19.3%; I(2) = 0), and length of hospital stay (standardized mean difference, -0.38 days; 95% CI, -0.46 to -0.31 days) were significantly lower with the transradial compared with the transfemoral approach. The greatest reduction in major bleeding was found in the subgroup with trials recruiting only primary PCI participants compared with varying proportions of rescue PCIs. Glycoprotein IIb/IIIa inhibitor use and cross-over rates did not have a significant association with outcome measures in the subgroup analysis. Incidence of stroke was numerically greater with the transradial approach but did not achieve statistical significance (RR, 1.22; 95% CI, 0.56-2.66; I(2) = 0). Overall statistical heterogeneity (I(2)) was very low except for length of hospital stay. CONCLUSIONS: The transradial approach for PCI in STEMI patients significantly reduced all-cause mortality, major and access site bleeding, major adverse cardiovascular events, and length of hospital stay. Difference in stroke incidence was not statistically significant with the transradial vs the transfemoral approach.

MIRACLE: Mobility Prediction Inside a Coverage Hole Using Stochastic Learning Weak Estimator.

In target tracking applications of wireless sensor networks (WSNs), one of the important but overlooked issues is the estimation of mobility behavior of a target inside a coverage hole. The existing approaches are restricted to networks with effective coverage by wireless sensors. Additionally, those works implicitly considered that a target does not change its mobility pattern inside the entire tracking region. In this paper, we address the above lacunae by designing a stochastic learning weak estimation-based scheme, namely mobility prediction inside a coverage hole (MIRACLE). The objectives of MIRACLE are two fold. First, one should be able to correctly predict the mobility pattern of a target inside a coverage hole with low computational overhead. Second, if a target changes its mobility pattern inside the coverage hole, the proposed estimator should give some estimation about all possible transitions among the mobility models. We use the trajectory extrapolation and fusion techniques for exploring all possible transitions among the mobility models. We validate the results with simulated traces of mobile targets generated using network simulator NS-2. Simulation results show that MIRACLE estimates the mobility patterns inside coverage hole with an accuracy of more than 60% in WSNs.

Comparative Efficacy and Safety of Prasugrel, Ticagrelor, and Standard-Dose and High-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis.

Authors aimed to compare efficacy and safety of prasugrel, ticagrelor, and standard-dose (SD) and high-dose (HD) clopidogrel in patients undergoing percutaneous coronary intervention (PCI). PubMed, EMBASE, CENTRAL, and clinicaltrials.gov were searched for studies comparing prasugrel, ticagrelor, SD and HD clopidogrel in patients undergoing PCI. Frequentist and Bayesian network meta-analyses were performed besides direct pairwise comparisons. Thirty trials, comprising 34,563 person-year data, were included. Prasugrel emerged as a best drug to prevent definite or probable stent thrombosis, followed by HD clopidogrel and ticagrelor, with SD clopidogrel being the worst. Myocardial infarction was least likely to be prevented by SD clopidogrel after PCI, and remaining 3 were superior to it with little difference among them. SD clopidogrel was least effective in preventing cardiovascular deaths after PCI. Prasugrel was most effective in preventing cardiovascular deaths, although having only small advantage over ticagrelor and HD clopidogrel. Ticagrelor reduced all-cause mortality by a small margin compared with rest of treatments. SD clopidogrel, followed by ticagrelor, resulted in significantly lower thrombolysis in myocardial infarction major bleeding complications compared with prasugrel. Analysis of any bleeding revealed similar trend. HD clopidogrel performed better than prasugrel in terms of bleeding complications. In conclusion, Prasugrel is likely most effective drug to prevent post-PCI ischemic events but at the expense of higher bleeding. Ticagrelor followed by HD clopidogrel seems to strike the right balance between efficacy and safety. HD clopidogrel can be considered as an alternative to newer P2Y12 inhibitors.

A rare case of acute pancreatitis and life-threatening hemolytic anemia associated with Epstein-Barr virus infection in a young healthy adult.

Epstein-Barr virus (EBV) is a common infection that affects 95% of adults worldwide at some point during life. It is usually asymptomatic or causes a self-limiting clinical syndrome known as infectious mononucleosis. It rarely causes complications. Here, we present a case of a healthy 21-year-old female college student who suffered from severe pancreatitis and life-threatening autoimmune hemolytic anemia in association with EBV infection, and we also discuss the common presentation of EBV infection and the diagnosis and treatment of simple and complicated EBV infection.

The fluoroscopy time, door to balloon time, contrast volume use and prevalence of vascular access site failure with transradial versus transfemoral approach in ST segment elevation myocardial infarction: A systematic review & meta-analysis.

OBJECTIVE: The authors aimed to conduct first systematic review and meta-analysis in STEMI patients evaluating vascular access site failure rate, fluoroscopy time, door to balloon time and contrast volume used with transradial vs transfemoral approach (TRA vs TFA) for PCI. METHODS: The PubMed, CINAHL, clinicaltrials.gov, Embase and CENTRAL databases were searched for randomized trials comparing TRA versus TFA. Random effect models were used to conduct this meta-analysis. RESULTS: Fourteen randomized trials comprising 3758 patients met inclusion criteria. The access site failure rate was significantly higher TRA compared to TFA (RR 3.30, CI 2.16-5.03; P=0.000). Random effect inverse variance weighted prevalence rate meta-analysis showed that access site failure rate was predicted to be 4% (95% CI 3.0-6.0%) with TRA versus 1% (95% CI 0.0-1.0 %) with TFA. Door to balloon time (Standardized mean difference [SMD] 0.30 min, 95% CI 0.23-0.37 min; P=0.000) and fluoroscopy time (Standardized mean difference 0.14 min, 95% CI 0.06-0.23 min; P=0.001) were also significantly higher in TRA. There was no difference in the amount of contrast volume used with TRA versus TFA (SMD -0.05 ml, 95% CI -0.14 to 0.04 ml; P=0.275). Statistical heterogeneity was low in cross-over rate and contrast volume use, moderate in fluoroscopy time but high in the door to balloon time comparison. CONCLUSION: Operators need to consider higher cross-over rate with TRA compared to TFA in STEMI patients while attempting PCI. Fluoroscopy and door to balloon times are negligibly higher with TRA but there is no difference in terms of contrast volume use.

Efficacy of various percutaneous interventions for in-stent restenosis: comprehensive network meta-analysis of randomized controlled trials.

BACKGROUND: In-stent restenosis (ISR) remains a difficult problem in interventional cardiology. The relative efficacy and safety of available interventions is not clear. We aimed to perform a network meta-analysis using both direct evidence and indirect evidence to compare all available interventions. METHODS AND RESULTS: We systematically searched electronic databases for randomized trials comparing ≥2 treatments for ISR. A network meta-analysis was performed using a Bayesian approach. Eleven treatments were compared in 31 studies with 8157 patient-years follow-up. Compared with balloon angioplasty, everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13 [0.048-0.35]), paclitaxel-eluting balloon (0.32 [0.20-0.49]), paclitaxel-eluting cutting balloon (0.054 [0.0017-0.5]), paclitaxel-eluting stent (0.39 [0.24-0.62]), and sirolimus-eluting stent (0.32 [0.18-0.50]) are associated with lower target vessel revascularization. Balloon angioplasty is not different from cutting balloon (0.73 [0.31-1.5]), excimer laser (0.89 [0.29-2.7]), rotational atherectomy (0.96 [0.53-1.7]), and vascular brachytherapy (0.60 [0.35-1.0]). In drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting stent (0.19 [0.049-0.76]), paclitaxel-eluting balloon (0.43 [0.18-0.80]), paclitaxel-eluting stent (0.35 [0.13-0.76]), and sirolimus-eluting stent (0.36 [0.11-0.86]) for target vessel revascularization. There was no difference between treatments in probable or definitive stent thrombosis. The results of binary restenosis and target lesion revascularization were similar. Paclitaxel-eluting cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have the highest probability of being in the top 3 treatments based on low target lesion revascularization, but there was no statistical significant difference between them. CONCLUSIONS: Balloon angioplasty is inferior to all drug-eluting treatments for ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly everolimus-eluting stent, or paclitaxel-eluting cutting balloon and paclitaxel-eluting balloon should be preferred for treating ISR.

Comparison of Healthcare Quality Outcomes Between Accountable Care Organizations and Physician Group Practices.

Accountable Care Organizations (ACOs) were created under the Affordable Care Act to deliver better quality of care at reduced cost compare with the traditional fee-for-service model. But their effectiveness in achieving healthcare quality metrics is unclear. We analyzed ACO and physician group practice (PGP) performance rates for the single coronary artery disease measure and four diabetes mellitus measures now publicly reported on the Medicare Physician Compare Web site for program year 2012. There was no statistically significant difference in reported quality measures between ACOs and PGPs. Our study shows that PGPs can achieve outcomes at par with ACOs.

Simultaneously measured inter-arm and inter-leg systolic blood pressure differences and cardiovascular risk stratification: a systemic review and meta-analysis.

Association of inter-arm systolic blood pressure difference (IASBPD) with cardiovascular (CV) morbidity and mortality remains controversial. We aimed to thoroughly examine all available evidence on inter-limb blood pressure (BP) difference and its association with CV risk and outcomes. We searched PubMed, EMBASE, CINAHL, Cochrane library, and Ovid for studies reporting bilateral simultaneous BP measurements in arms or legs and risk of peripheral arterial disease (PAD), coronary artery disease, cerebrovascular disease, subclavian stenosis, or mortality. Random-effect meta-analysis was performed to compare effect estimates. Twenty-seven studies met inclusion criteria, but only 17 studies (18 cohorts) were suitable for analysis. IASBPD of 10 mmHg or more was associated with PAD (risk ratios, 2.22; 1.41-3.5; P = .0006; sensitivity 16.6%; 6.7-35.4; specificity 91.9%; 83.1-96.3; 8 cohorts; 4774 subjects), left ventricular mass index (standardized mean difference 0.21; 0.03-0.39; P = .02; 2 cohort; 1604 subjects), and brachial-ankle pulse wave velocity (PWV) (one cohort). Association of PAD remained significant at cutoff of 15 mmHg (risk ratios, 1.91; 1.28-2.84; P = .001; 5 cohorts; 1914 subjects). We could not find statistically significant direct association of coronary artery disease, cerebrovascular disease, CV, and all-cause mortality in subjects with IASBPD of 10 mmHg or more, 15 mmHg or more, and inter-leg systolic BP difference of 15 mmHg or more. Inter-leg BP difference of 15 mmHg or more was strong predictor of PAD (P = .0001) and brachial-ankle PWV (P = .0001). Two invasive studies showed association of IASBPD and subclavian stenosis (estimates could not be combined). In conclusion, inter-arm and leg BP differences are strong predictors of PAD. IASBPD may be associated with subclavian stenosis, high left ventricular mass effect, and higher brachial-ankle PWVs. Inter-leg BP difference may also be associated with high left ventricular mass effect and higher brachial-ankle PWVs. Presence of inter-limb BP difference may indicate higher global CV risk.

Prevalence of simultaneously measured interarm systolic blood pressure difference and its clinical and demographic predictors: a systemic review and meta-analysis.

Prevalence of interarm systolic blood pressure difference and clinical and demographic characteristics associated with interarm systolic blood pressure difference (IASBPD) have been a matter of debate. We aimed to ascertain the prevalence of IASBPD and clinical and demographic characteristics associated with it. We searched PubMed, EMBASE, and CINAHL, Ovid and Cochrane Library, and Google Scholar. Twenty-seven studies meeting all inclusion criteria were included in the analysis. Weighted average cumulative prevalence of simultaneous IASBPD of 10, 15, and 20 mmHg or greater was 9.49% [95% confidence interval (CI) 7.9-11.1%], 5.3% (95% CI 3.1-7.5%), and 4.4% (95% CI 1.5-7.4%), respectively. The prevalence of IASBPD of 10 mmHg was 9% (95% CI 7-11%), 7.5% (95% CI 5.6-9.4%), and 12.1% (95% CI 8.2-16.1%) in outpatient, community, and hospital-based setting, respectively. The prevalence of IASBPD of 15 mmHg was 4.9% (95% CI 2.7-7.2%) in outpatient and 8% in hospital setting. The prevalence of IASBPD of 20 mmHg was 4.4% (95% CI 2.8-11.6%) in outpatient and 4.4% (95% CI 2.1-6.8%) for the hospital setting. Pairwise meta-analysis of five studies showed that the presence or absence of IASBP was not associated with age, sex, diabetes, hypertension, dyslipidemia, and smoking history. However, participants with IASBPD of 10 mmHg or greater had a higher BMI compared with those with IASBPD of less than 10 mmHg. After BMI, hypertension and dyslipidemia had strongest association with IASBPD, but results were not statistically significant. IASBPD is relatively prevalent, but prevalence is lower than that previously reported. Prevalence is higher when blood pressure is measured in hospital setting compared with outpatient and community setting.