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Not AvailableThree open reading frames (ORF0, ORF1 and ORF3) of Sugarcane yellow leaf virus (SCYLV) genome which play an important role in virus replication and accumulation in plants have been characterized. Transcript levels of three genes varied among infected plants but overall expression of ORF1 was higher than ORF0 and ORF3. Cultivar H73-6110 (susceptible) yielded the highest transcript levels of ORF1 whereas cultivar H78-4153 (resistant) exhibited the lowest levels. The sugarcane cultivars exhibited no significant differences between them for the ORF0 transcripts in mature leaves and seedling tissues. The ORF0, ORF1 and ORF3 of the SCYLV isolates varied in amino acid sequence similarity and it was in the ranges of 69-99%, 73-99%, and 93-100%, respectively. Possible recombination events located in the three ORFs were identified using TOPALi (v2.5), RECCO, and RDP software’s. The results showed strong presence of recombination in the aligned sequences of ORF0 and ORF1 when TOPALi and RECCO programs were used. In contrast, no recombination signals were detected in ORF3 with all the analysis tools used in this study. Similarly, the RDP program did not reveal any recombination signals in ORF0 and ORF3 with the exception of ORF1 where numerous accessions were found to be recombinantsNot Availabl

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)