Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

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Not AvailableBacterial blight is a widespread disease in pomegranate that causes great loss to farmers. The causative agent for this disease is Xanthomonas axonopodis pv. punicae. The present study was taken up to standardize protocol for quality total RNA extraction from various tissues of pomegranate, cDNA synthesis and qPCR validation of differentially expressed gene(s) identified from RNA sequencing data of susceptible and moderately resistant pomegranate genotypes upon challenge inoculation using qPCR. In the study, Phenol-Chloroform, Modified CTAB-LiCl and Trizol methods were evaluated for their efficiency to extract quality total RNA from infected and uninfected leaf and fruit tissues of pomegranate genotypes (Bhagwa and IC-1181). The concentration of extracted total RNA were quantified using Qubit Fluorometer and Qiagen QIAxpert and the quality of 18 and 28S bands of ribosomal RNA also assessed on agarose gel electrophoresis. Phenol-Chloroform method gave the highest concentration of total RNA having Qubit Fluorometer and QIAxpert readings ranged from 3.86 to 5.78 ng/μl and 543.5 to 1684.3 ng/μl, respectively. The time consumed and cost incurred on total RNA isolation were also least in Phenol-Chloroform method (50 minutes and Rs. 29.75/sample, respectively) as compared to other methods. From the high quantity total RNA, cDNA were synthesized using cDNA synthesis kit (HiMedia cDNA synthesis kit) and Xyloglucan endotransglucosylase coding gene was validated using qPCR. The qRT-PCR results showed that gene which code for Xyloglucan endo transglycosylase was slightly over expressed in the infected leaf samples of Bhagwa at infection stage 1 and 3 as compared with the control sample whereas the same gene had under expression in infected leaf sample of IC 1181 as compared to control.Not Availabl

INO prototype detector and data acquisition system

India-based Neutrino Observatory (INO) collaboration is proposing to build a 50 kton magnetised iron calorimetric (ICAL) detector in an underground laboratory to be located in South India. Glass resistive plate chambers (RPCs) of about 2 m x 2 m in size will be used as active elements for the ICAL detector. As a first step towards building the ICAL detector, a 35 ton prototype of the same is being set up over ground to track cosmic muons. Design and construction details of the prototype detector and its data acquisition system will be discussed. Some of the preliminary results from the detector stack will also be highlighted. (C) 2009 Elsevier B.V. All rights reserved