Background Pakistan is fifth among high burden countries for tuberculosis. A steady increase is seen in extrapulmonary tuberculosis (EPTB), which now accounts for 20% of all notified TB cases. There is very limited information on the epidemiology of EPTB. This study was performed with the aim to describe the demographic characteristics, clinical manifestations and treatment outcomes of EPTB patients in Pakistan. Method We performed descriptive analysis on routinely collected data for cohorts of TB patients registered nationwide in 2016 at health facilities selected using stratified convenient sampling. Findings Altogether 54092 TB including 15790 (29.2%) EPTB cases were registered in 2016 at 50 study sites. The median age was 24 years for EPTB and 30 years for PTB patients. The crude prevalence of EPTB in females was 30.5% (95%CI; 29.9-31.0) compared to 27.9% (95%CI; 27.3-28.4) in males. The likelihood of having EPTB (OR), was 1.1 times greater for females, 2.0 times for children, and 3.3 times for residents of provinces in the NorthWest .
Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments.
Background: Silver nanoparticles (AgNPs) are toxic to microorganisms and can potentially kill multidrug-resistant bacteria. Nanoparticles can be synthesized in many ways, such as physical or chemical methods. Recently, it has been found that plant molecules can perform the same reduction reactions necessary for the production of nanoparticles but in a much more efficient way. Results: Here, green chemistry was employed to synthesize AgNPs using leaf extracts of Cymbopogon citratus. The effects of different parameters such as temperature, pH, and the volume of plant extract were also tested using their absorbance pattern at different wavelengths. The Surface Plasmon Resonance (SPR) changed with the changes in parameters. Changes in temperature from 20 °C to 60 °C have changed the highest absorbance from 0.972 to 3.893 with an SPR of 470 nm. At higher pH (11.1), the particles become highly unstable and have irregular shapes and sizes. The peak shifts to the right at a lower pH level (3.97), indicating a smaller but unstable compound. We have also investigated the effect of the volume of plant extracts on the reaction time. The sample with the highest amount of plant extract showed the most absorbance with a value of 0.963 at λmax, calculated to be 470 nm. The total formation of the AgNPs was observed visually with a color change from yellow to brownish-black. UV-visible spectroscopy was used to monitor the quantitative formation of AgNPs, showing a signature peak in absorbance between 400 and 500 nm. We have estimated the size of the nanoparticles as 47 nm by comparing the experimental data with the theoretical value using Mieplot. The biosynthesized AgNPs showed enhanced antibacterial activity against several multidrug-resistant bacteria, determined based on the minimal inhibitory concentration and zone of inhibition. Conclusion: The findings of this study indicate that an aqueous extract of C. citratus can synthesize AgNPs when silver nitrate is used as a precursor, and AgNPs act as antimicrobial property enhancers, which can be used to treat antibiotic-resistant bacteria. Hence, mass production and green synthesis of AgNPs from C. citratus will be able to increase the overall health of the general population. Moreover, it will enormously reduce the costs for drug development and provide employment options in the remotely located source areas. Finally, our findings will influence further studies in this field to better understand the properties and applications of AgNPs and ultimately contribute to improving planetary health by increasing immunity with high biocompatibility and less drug toxicity.
Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.
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