Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen.
Venous and arterial thrombosis and thromboembolism are a leading cause of suffering in elderly population. The prevalence of venous and arterial thrombosis (formation of blood clot) and thromboembolism (breakage of thrombus to travel somewhere in circulation) is high in elderly population those above 60 years and poses important cause of morbidity and mortality. Annual incidence of venous thrombosis is 1 in 1000 which rises after age of 45 years and arterial thrombosis as high as 20% as per pooled MPN. Spectrum of thromboembolism (TE) is diverse and etiology, and pathogenesis is varied ranging from atrial fibrillation, hypertension, diabetes mellitus (DM), dilated cardiomyopathy and ischemic cardiomyopathy (ICM), congestive heart failure, acute coronary syndrome, and cases of fracture immobilization leading to deep venous thrombosis and pulmonary embolism or else arterial occlusion leading to cardiac or cerebral strokes Aim of the update is to bring a broad overview of the problem to prevent late disastrous outcomes, putting forth two exemplary case studies of imminent TE risk. Case 1 – elderly hypertensive presenting with paroxysmal AF with high CHA2DS visual analog scale score needing anticoagulation and Case 2 – case of DM, post- percutaneous transluminal coronary angioplasty (PTCA), ICM, severe left ventricular (LV) dysfunction with LV thrombus in sinus rhythm needing anticoagulation. Elderly population suffer from diseases of diverse etiology exposing to high risk of TE and at the same time high bleeding risk of the anticoagulants. Elderly population with diverse disease ailments exposed to high risk of TE and bleeding complications and hence should be dealt with utmost care and sympathy to avoid TE and bleeding complications.
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