Can Structural Differences between SARS-CoV and SARS-CoV-2 explain Differences in Drug Efficacy?

The severe acute respiratory syndrome corona virus (SARS-CoV)and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), both virus spike proteins are recognized by the cell surface receptors, human angiotensin converting enzyme-2 (ACE-2).These viruses gain access into the host cell through ACE-2receptors.The main aim of the current study was to elaborate on the structural differences in the receptor binding domain (RBD) of spike glycoprotein in SARS-CoV and SARS-CoV-2 that bind at the same active binding site. The crystal structures of receptor bound spikes of SARS-CoV and SARS-CoV-2 were compared using UCSF Chimera and pyMOL software which revealed significant differences in the receptor binding domain of the spikes with variation in the amino acid residues. It was also observed that conformational changes occurred in the amino acid residues at the binding site on ACE-2 receptor. These conformational changes in ACE-2 binding site of SARS-CoV-2 were attributed to a greater number of contacts forming between RBD and active binding site when compared to that of SARS-CoV and could explain any differences in the effectiveness of drugs against SARS-CoV and SARS-CoV-2. In addition, using Autodock vina software, drugs that were found to be effective in SARS-COV treatment were docked at active binding site on ACE-2.Antivirals, ACE-2 inhibitors and corticosteroids were docked at the active binding site domains of ACE-2 receptor in SARS-CoV andSARS-CoV-2.Antivirals such as Oseltamivir, Umifenovir, Favipiravir, Remdesivir and antibiotics such as Moxifloxacin and Azithromycin, Ace-2. Antivirals inhibitors such as Losartan and steroids such as Dexamethasone have shown a greater negative docking score (indicating more binding affinity) in and SARS-CoV-2 when compared to that of SARS-CoV. This kind of preliminary analysis using computational techniques could help in screening and repurposing the existing drugs that are potential in treating new diseases such as CoVID-19

SIGNIFICANCE OF ANALYTICS

Despite the number of times marketers have been using analytics as a tool to predict and drive consumer behavior, it is a relatively new application of the science. Technology continues to evolve and offers even more data choices and metrics for analysis, increasing the abilities of marketers to reach their audience. This article expands on several sectors of use, including real estate, social media, and healthcare, and theorizes the impact that analytics will have in the future as the technological means to interpret data catches up with the sheer amount of real-time information available for potential use, especially with the development of the Internet of Things, and rising concerns around data use, regarding data protection and copyright.  Article visualizations

Design and evaluation of floating drug delivery systems of Metformin with natural gums as release retarding polymers

Metformin hydrochloride floating tablets were prepared by wet granulation method by using optimized concentrations of gas generating agents, binding agents and natural gums as polymers like gum kondagogu and gum karaya. The formulations F1-F4 with concentrations 2-3.5% were prepared to optimize binding agent and formulations F5-F7 with concentrations 15-20% to optimize gas generating agent where optimum percentage of binding agent was found around 2.3% and gas generating agent was found around 17.25% to get quick floating lag time. The prepared granules evaluated for various parameters showed good results in which the Carrs index, hausner ratio and angle of repose, the values were found in between 9.05-16.78, 1.02-1.46 and 23.17-32.64 respectively. All compressed formulations were evaluated for various parameters and results of hardness, friability, drug content, were found around 7.1-8.8kg/cm2, 0.56-1.48% and 499.3-499.8mg respectively. The tablets prepared by these granules of two natural gums as polymers showed desired floating properties. F6 formulation containing gum kondagogu and F11 formulation containing gum karaya showed good release retardation with release 99.42% and 99.75% respectively after 12 hours in in vitro drug release studies. Formulations F6 and F11 after stability studies showed good results proving stable. In vivo studies also showed good correlation with the results of in vitro and X-ray pictograms proved the formulations is stable in vivo. Formulations F6 and F11 contains natural gums Kondagogu and karaya with 17.25% concentration were considered as best formulation as they showed good release retardation and, in release kinetic studies the n-value found appropriate for controlled release formulations

Mucoadhesive microcapsules of glipizide formulated with gum kondagogu: in vitro and in vivo evaluation

Mucoadhesive microcapsules are proposed for the antidiabetic drug glipizide, to obtain controlled release. Glipizide microcapsules with a coat consisting of alginate and gum kondagogu were prepared by employing ionic gelation process and emulsification ionotropic gelation process. The microcapsules were evaluated for flow properties, Carr’s index, Hausner factor, microencapsulation efficiency, drug release characteristics, surface characteristics, compatibility studies, mucoadhesive properties and in-vivo hypoglycemic activity. These two methods showed individual, large sized, free flowing spherical microcapsules without any interactions. Glipizide release from the microcapsules was slow and followed zero order kinetics and followed non–fickian release and depended on the coat: core ratio and the method employed in the preparation of microcapsules. Among the two methods emulsification ionotropic gelation method was found to be more suitable for slow and complete release of glipizide over a long period of time. These microcapsules exhibited good mucoadhesive property in the in vitro wash-off test. In vivo evaluation in rabbits demonstrated significant hypoglycemic effect of glipizide.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Gender Differences in Symptoms and Care Delivery for Chronic Obstructive Pulmonary Disease

Abstract Background: Morbidity and mortality for women with chronic obstructive pulmonary disease (COPD) are increasing, and little is known about gender differences in perception of COPD care. Methods: Surveys were administered to a convenience sample of COPD patients to evaluate perceptions about symptoms, barriers to care, and sources of information about COPD. Results: Data on 295 female and 273 male participants were analyzed. With similar frequencies, women and men reported dyspnea and rated their health as poor/very poor. Although more women than men reported annual household income <$30,000, no significant gender differences in frequency of health insurance, physician visits, or ever having had spirometry were detected. In adjusted models (1) women were more likely to report COPD diagnostic delay (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.13-2.45, p=0.01), although anxiety (OR 1.83, 95% CI 1.10-3.06, p=0.02) and history of exacerbations (OR 1.60, 95% CI 1.08-2.37, p=0.01) were also significant predictors, (2) female gender was associated with difficulty reaching one's physician (OR 2.54, 95% CI 1.33-4.86, p=0.004), as was prior history of exacerbations (OR 2.25, 95% CI 1.21-4.20, p=0.01), and (3) female gender (OR 2.15, 95% CI 1.10-4.21, p=0.02) was the only significant predictor for finding time spent with their physician as insufficient. Conclusions: Significant gender-related differences in the perception of COPD healthcare delivery exist, revealing an opportunity to better understand what influences these attitudes and to improve care for both men and women.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98466/1/jwh%2E2012%2E3650.pd

Factors Related to the Differential Development of Inter-Professional Collaboration Abilities in Medicine and Nursing Students

Introduction: For physicians and nurses, teamwork involves a set of communication and social skills, and specific training in interdisciplinary work in order to be able to work together cooperatively, sharing responsibilities, solving problems, and making decisions to carry out actions centered on patients’ care. Recent studies demonstrate that in the absence of targeted interdisciplinary educational programs, the development of teamwork abilities is sensitive to the influence of the dominant work environment. The purpose of this study was to characterize the role that environmental and individual factors play in the development of teamwork in environments with a dominant hierarchical work model. Methods: Questionnaires were distributed to 1,880 undergraduate students (980 medicine students and 900 nursing students) from three universities of Cusco city (Peru). The Jefferson Scale of Attitudes toward Physician–Nurse Collaboration was used as the main variable. The Jefferson Scales of Empathy and Lifelong Learning, the Social and Emotional Loneliness Scale for Adults, the Scale of Life Satisfaction, sex, discipline, age, and academic semester were used as explanatory variables. After calculating internal reliability and normality of the main measures, descriptive, comparative, and correlation analyses were performed to determine variables influencing the teamwork score. Results: A total of 1,518 (81%) surveys were returned fully completed. Adequate reliability was confirmed in all instruments. In the sample, nursing students showed greater inter-professional collaborative abilities than medicine students (p < 0.001). This attitudinal gap was higher in advanced semesters. A three-way ANOVA indicated differences in teamwork were associated with discipline (p < 0.001), sex (p < 0.01), and university (p < 0.001). However, main effects were associated only with discipline (ηp 2 = 0.14). Teamwork showed an inverse correlation with loneliness (ρ = −0.28; p < 0.001) and a positive correlation with empathy (ρ = + 0.49; p < 0.001) and lifelong earning (ρ = + 0.48; p < 0.001). Teamwork positively correlated with life satisfaction only in the medicine student group (ρ = + 0.15; p < 0.001). Conclusion: These findings bring new evidence to support the main effect that social environments, in the absence of targeted interdisciplinary educational programs, play in the development of teamwork.Peru by the National Council of Science, Technology and Technological Innovation (CONCYTEC)Peru by the National University San Antonio Abad del Cusco (UNSAAC) E041-2017-UNSAAC-02Spain by the Institute of Health Carlos III (ISCIII) PI16/01934Spain by the Operational Program of the European Regional Development Fund (FEDER-LARIOJA) 6FRS-ABC-01

Structural and electronic properties of Aluminum Nano Clusters by DFT

The electronic properties of Al clusters containing up to 60 atoms are investigated using an all electron density functional theory using large polarized Gaussian basis sets with 39 Gaussians per atom (NRLMOL basis). We have performed an extensive search for the lowest energy isomers for clusters up to Al 21. We build a database of candidate structures for the ground state using different strategies. First, a few structures are randomly generated and fully relaxed using plane wave pseudo potential method. We also performed simulated annealing runs using ab initio molecular dynamics for clusters up to Al20. In three sets of simulated annealing runs the clusters were heated up to 900 and 1000K and were slowly cooled to 50K at different rates. After every half pico second, the cluster was quenched. Additionally the best basin hopping geometries obtained using empirical embedded atoms potential were also fully optimized. The process generates 40-50 structures for each size. All the structures are relaxed using full potential PAW method using a large energy cutoff. For larger clusters we used best available geometries from literature obtained from basin hopping and simulated annealing techniques. The electronic properties of Al clusters are subsequently determined for this database at the all-electron level using Gaussian basis set