Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Computational analysis suggest C2I as a promising vaccine candidate for Botulism caused by C2 toxin

C2 exotoxin, majorly produced by C and D serotypes of anaerobic bacterium class, Clostridia, does not function as a neurotoxin; contrary to other botulism toxins. As a binary toxin, C2I protein, the enzymatic portion of the toxin aided by C2IIa, the activated transporter part, assembles as an active C2 toxin. Upon endocytosis of the complex into the target eukaryotic cell, it causes the actin cytoskeleton to depolarize by ADP-ribosylation and induces rounding of the cell followed by apoptosis. C2I as a recombinant mutant has also been recently studied in relation to vaccinogenic characteristics (1). The C2I being the active cause of the damage inflicted in eukaryotic cells made us keen on exploring its potential as a toxoid vaccine. Hence, in this study, we analyzed if this protein could serve as an ideal candidate for vaccine development targeting C2 toxin. We utilized immunoinformatics and computational algorithms based tools to identify the quality of the vaccine candidate from this bacterial toxin of interest. Using a literature-based cut-off, we obtained a Pi value of 58% from the Vax-ELAN pipeline, indicating that it may be examined further as a vaccine candidate. We acquired an 89.35% vaccine probability from the Vaxi-DL pipeline, indicating that it has the probability to be employed as a promising toxoid or recombinant vaccine candidate. All that being said, it needs more research and testing to function as an effective vaccine against Botulism caused by C2 toxin

A Comprehensive Report on Environmental Sustainability: A Global Perspective

In the last three decades, protecting the earth's environment has become a major challenge in international relations. Hundreds of regional and bilateral agreements, as well as at least ten global environmental agreements, were negotiated. Environmentalism can be seen as a social movement that seeks to influence jobs and education to conserve natural resources and ecosystems. Concerns for environmental protection have emerged in various forms in various parts of the world throughout history. The environmental movement is a diverse scientific, social and political movement. The movement is committed to ecology, health and human rights while accepting people as workers in the ecosystem. Today, it is generally accepted that environmental protection is a part of national policies and plans. The accepted standard to achieve this reduction target is "sustainable development". In fact, all existing laws and policies on environmental protection and human development, at the national or international level, aim at achieving "sustainable development". Despite the great environmental protection that humans have used in the past three decades, global warming has not reduced the occurrence of anomalous atmospheric phenomena due to scientific knowledge and available technology. Although many environmental policies and action plans have been negotiated over the past three decades, significant gaps remain in international environmental policy law. The framework has not yet become a method or method. Rather, each is a collection of commitments related to a democratic international or regional environmental issue. Nature has become negative by affecting the climate on the one hand and the health and safety of all living and non-living beings on the other. The ecosystem resonates with abnormal noise, vibration, dust and smoke from human activities. These events remind people that the environment must be protected with all enthusiasm and energy no matter what. Given the progress we have made in destroying the earth's environment, future global environmental efforts will focus more on environmental restoration than conservation. Human rights will also provide important opportunities for better protection of the environment

Safety of Prasugrel in Indian patients – Multicentric registry of 1000 cases

Background: Clopidogrel has been the only available antiplatelet drug used along with aspirin in patients of ACS. In recent years 2 new antiplatelet drugs (Prasugrel and Ticagrelor) have become available. Prasugrel in the dose of 10 mg OD has been found to be more efficacious but with increased risk of major bleeding. For this reason it has not gained widespread usage in ACS patients undergoing PCI. There are no systematic data on the use of Prasugrel in Indian population. Method: This is a prospective, multicentric, hospital registry of 1000 patients with ACS undergoing PCI who were administered Prasugrel. The primary safety endpoint of this study was major and minor bleeding while the efficacy endpoint is the composite of CV death, nonfatal MI, nonfatal stroke up to 30 days after PCI. Patients with high bleeding risk were excluded. Results: Most patients (91%) received loading dose of Prasugrel along with the maintenance dose getting according to the defined protocol. Patients were followed up to 30 days post procedure. Primary efficacy end point was reached in 3 patients only with two of them dying due to possible stent thrombosis and the third requiring revascularization of the target vessel for stent thrombosis. One major and 19 minor bleeding complications were recorded, with access site bleeding in 0.7% & non-access site bleeding in 1.2% of the subjects. Conclusion: Prasugrel was found to be effective & not associated with a high incidence of bleeding in the high risk ACS patients when those at a high bleeding risk were excluded