The rapidly enlarging COVID-19 pandemic caused by the novel SARS-corona virus-2 is a global public health emergency of an unprecedented level. Unfortunately no treatment therapy or vaccine is yet ...available to counter the SARS-CoV-2 infection, which substantiates the need to expand research efforts in this direction. The indispensable function of the main protease in virus replication makes this enzyme a promising target for inhibitors screening and drug discovery to treat novel coronavirus infection. The recently concluded α-ketoamide ligand-bound X-ray crystal structure of SARS-CoV-2 Mpro (PDB ID: 6Y2F) from Zhang et al. has revealed the potential inhibitor binding mechanism and the molecular determinants responsible for substrate binding.
For the study, we have targeted the SARS-CoV-2 Mpro for the screening of FDA approved antiviral drugs and carried out molecular docking based virtual screening. Further molecular dynamic simulation studies of the top three selected drugs carried out to investigated for their binding affinity and stability in the SARS-CoV-2 Mpro active site. The phylogenetic analysis was also performed to know the relatedness between the SARS-CoV-2 genomes isolated from different countries.
The phylogenetic analysis of the SARS-CoV-2 genome reveals that the virus is closely related to the Bat-SL-CoV and does not exhibit any divergence at the genomic level. Molecular docking studies revealed that among the 77 drugs, screened top ten drugs shows good binding affinities, whereas the top three drugs: Lopinavir–Ritonavir, Tipranavir, and Raltegravir were undergone for molecular dynamics simulation studies for their conformational stability in the active site of the SARS-CoV-2 Mpro protein.
In the present study among the library of FDA approved antiviral drugs, the top three inhibitors Lopinavir–Ritonavir, Tipranavir, and Raltegravir show the best molecular interaction with the main protease of SARS-CoV-2. However, the in-vitro efficacy of the drug molecules screened in this study further needs to be corroborated by carrying out a biochemical and structural investigation.
•Numerical and experimental investigations are done using reverse NACA profile ribs.•Optimum results are found with airfoil shaped ribs having chord length of 15 mm.•Nusselt number increased by ...98–193% and friction factor increased by 55–65%.•Maximum Nusselt number and THPP were found to be 104.45 and 2.53 respectively.•Empirical correlations have predicted Nu and f within ±3% of experimental values.
The solar air heater is subjected to a low convective heat transfer coefficient on account of the formation of the laminar sub-layer between the absorber plate and flowing air. To increase the heat transfer coefficient, the laminar sub-layer can be interrupted with the use of artificial roughness (turbulator) on the absorber plate. In the present analysis, the effects of novel type of roughness element in the form of NACA 0040 profile ribs in the reverse position are studied on the performance of the solar air heater. The effects of relative roughness pitch (P/e) and relative roughness height (e/D) were studied for the Reynolds number (Re) ranging from 6000 to 18,000. Among the various roughness parameters, NACA 0040 profile ribs provided in the reverse direction with P/e as 5 and e/D as 0.065 was found to be the optimum. The thermo-hydraulic performance parameter for this case was found to be 2.53 at a Reynolds number of 6000. The experimental results validated the numerical results, and the maximum deviation was found to be 4.84%. An empirical correlation was developed for prediction of Nu and f in terms of Re and e/D and found to conform within ±3% of the corresponding experimental values.
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment ...involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small intestinal microbial diversity while increasing small intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment.
A new series of 1-((1-(4-substituted benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol (9a-x) have been synthesized. The newly synthesized ...1,2,3-triazolyl-quinolinyl-propan-2-ol (9a-x) derivatives were screened for in vitro antimicrobial activity against M. tuberculosis H37Rv, E. coli, P. mirabilis, B. subtilis, and S. albus. Most of the compounds showed good to moderate antibacterial activity and all derivatives have shown excellent to good antitubercular activity with MIC 0.8-12.5 μg/mL. To know the plausible mode of action for antibacterial activity the docking study against DNA gyrase from M. tuberculosis and S. aureus was investigated. The compounds have shown significant docking scores in the range of −9.532 to −7.087 and −9.543 to −6.621 Kcal/mol with the DNA gyrase enzyme of S. aureus (PDB ID: 2XCT) and M. tuberculosis (PDB ID: 5BS8), respectively. Against the S. aureus and M. tuberculosis H37Rv strains, the compound 9 l showed good activity with MIC values of 62.5 and 3.33 μM. It also showed significant docking scores in both targets with −8.291 and −8.885 Kcal/mol, respectively. Molecular dynamics was studied to investigate the structural and dynamics transitions at the atomistic level in S. aureus DNA gyrase (2XCT) and M. tuberculosis DNA gyrase (5BS8). The results revealed that the residues in the active binding pockets of the S. aureus and M. tuberculosis DNA gyrase proteins that interacted with compound 9 l remained relatively consistent throughout the MD simulations and thus, reflected the conformation stability of the respective complexes. Thus, the significant antimicrobial activity of derivatives 9a-x recommended that these compounds could assist in the development of lead compounds to treat for bacterial infections.
Communicated by Ramaswamy H. Sarma
Abstract only
Background
A considerable proportion of GPs’ workload is dermatological. It is important to investigate what common skin conditions encountered in primary care can be self-managed, in ...an effort to alleviate the burden on primary care.
Aim
The purpose of the audit was to identify the proportion of consultations that are dermatological in nature and analyse potential for self-management by patients.
Method
Data was collected using the patient electronic record system (EMIS) in general practice. A search was made for all consultations from the 17 April to 15 May 2019, which included all new presenting complaints that were dermatological in nature. The criteria for self-management included advising over the counter (OTC) medication or reassurance. On the other hand, a case was deemed not self-manageable if prescription only medication (POM) was prescribed or if a referral to dermatology was made.
Results
There were a total of 2175 consultations, where 246 (11.31%) cases were dermatological. Of the 246, 80 cases (32.5%) could be self-managed. There were 46 different dermatological presenting complaints of which the 5 most common included: rash (51 cases), dermatitis (44 cases), acne vulgaris (13 cases), moles (12 cases), dry skin (11 cases). None of the acne or moles cases could be self-managed, whereas 23%, 68.2%, 72.7% of rashes, dermatitis, and dry skin cases, respectively, could be self-managed.
Conclusion
Certain dermatological conditions have more potential for self-management than others. Research into teledermatology as a means of addressing patient concern and providing clinical information is important in order to reduce unnecessary consultations.
One of the most prevalent respiratory disorders in modern society is chronic obstructive pulmonary disease (COPD). Frequent comorbidities in patients with COPD are abnormal nutritional status and ...body composition variations. Malnutrition-sarcopenia syndrome, which occurs when the 2 conditions - malnutrition and sarcopenia - coexist, raises the risk of death more than either condition alone. The current study sought to determine the prevalence of malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in patients with COPD as well as the association between these diseases and the severity of COPD.
The study was an analytical cross-sectional study conducted on hospitalized patients with COPD. The sample size of the study was calculated to be 160. A self-structured questionnaire was used to collect the data, containing sociodemographic characteristics, clinical profiles, anthropometric assessment, and bioimpedance indices. Sarcopenia was diagnosed with low muscle strength and muscle mass by the EWGSOP2 recommendations. Muscle mass is measured by BIA and muscle strength (Handgrip) was measured by a Hand Dynamometer. Assessment of the risk of malnutrition was performed using the Mini Nutritional Assessment-Short Form questionnaire and was confirmed by GLIM criteria. The COPD assessment test (CAT) tool determined the severity of the condition. For the data analysis, comparisons were made using Student's t test and Mann-Whitney test in bivariate analysis. Multivariate logistic regression analyses were performed considering the outcomes of patients with COPD by CAT scores, prolonged length of stay, and hospital readmission 6 months after discharge.
The mean age of the participants was 48 ± 5 years. Approximately 61.9% were found to be sarcopenic. Approximately 45.6% of participants had malnutrition. Malnutrition sarcopenia syndrome was diagnosed in 32.5% of patients. The study analysis revealed that patients with COPD with malnutrition-sarcopenia syndrome had more than twice the odds of prolonged hospital stay, re-admission within 6 months, and higher CAT scores.
The study revealed a high prevalence of sarcopenia, malnutrition, and malnutrition sarcopenia syndrome in patients with COPD. These conditions were found to be statistically significant with prolonged length of stay, re-admission within 6 months, and CAT scores. The findings highlight the importance of addressing these conditions as part of the management of the patients.
Background Sarcopenia and sarcopenic obesity are growing concerns associated with increasing diabetes incidence, but data from Indian diabetic cohorts are limited. This study examined the prevalence ...and clinical factors associated with sarcopenia and sarcopenic obesity. Methods In this cross-sectional study, 750 participants aged 35-70 years were recruited by systematic stratification and a fixed quota sampling technique from medical camps and categorized into diabetic (n = 250), nondiabetic (n = 250), and obese nondiabetic (n = 250) groups. The assessments included questionnaires, muscle mass estimation by bioimpedance analysis, and blood tests. Sarcopenia was defined using the Asian Working Group consensus, and sarcopenic obesity was defined as sarcopenia with a BMI greater than or equal to 25 kg/m2. Logistic regression was used to analyze risk factors. Results Sarcopenia affected 60% of diabetic patients, 28% of nondiabetic patients, and 38% of nonobese nondiabetic patients (p < 0.001). The prevalence of sarcopenic obesity was 40%, 11%, and 30%, respectively (p < 0.001). Diabetes was associated with 2.3-fold greater odds (95% CI 1.1-4.7) of sarcopenia and 2.4-fold greater odds (1.1-5.0) of sarcopenic obesity after adjustment. A duration greater than 10 years, uncontrolled diabetes, age greater than 65 years, low physical activity, hypertension, and dyslipidemia also independently increased the odds. Conclusion Indian adults with type 2 diabetes have a high burden of sarcopenia and sarcopenic obesity. Early optimization of diabetes care and lifestyle changes are vital for preserving muscle health. Keywords: Sarcopenia, Diabetes, India, Prevalence, Complication
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