New Synthetic Thrombin Inhibitors: Molecular Design and Experimental Verification

BACKGROUND: The development of new anticoagulants is an important goal for the improvement of thromboses treatments. OBJECTIVES: The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. METHODS: Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. RESULTS: New compounds that are both effective direct thrombin inhibitors (the best K(I) was <1 nM) and strong anticoagulants in plasma (an IC(50) in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD(50) values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. CONCLUSIONS: The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications

Quality management system of professional training of students on the digital technology basis

The role of digital technologies in education is increasing. Digital technologies are characterized by both positive and negative effects. But everyone sees that digital technologies lead to a radical change in socio-economic reality and open up new opportunities. It is necessary to have knowledge and skills of working with modern digital technologies and use them in the professional training of students. The methods of our research are content analysis of scientific literature on the problems of quality management of professional training and modern digital technologies in the education system, observation, training in a remote mode, and a survey of students on the use of digital technologies in the process of distance learning. The development and use of distance learning technologies in the system of professional training of students involves: determining the sequence of operations; development and selection of appropriate methods and tools for each operation; creation of optimal conditions for the learning process. It is difficult to describe the algorithms of the quality management system of professional training and determine the set of methods of realization that make up the management process, but it is possible with proper training of teachers. Digital technologies make it possible to increase the computer literacy of the teaching staff, to update its creative potential, to include teachers in innovative activities related to the search for technologies for managing the quality of professional training of students in a blended educational environment

The Influence of Hop Phenolic Compounds on Dry Hopping Beer Quality

Background: The article considers the phenolic hop compounds&rsquo; effect on the quality indicators of finished beer. The topic under consideration is relevant since it touches on the beer matrix colloidal stability when compounds with potential destabilizing activity are introduced into it from the outside. Methods: The industrial beer samples&rsquo; quality was assessed by industry-accepted methods and using instrumental analysis methods (high-performance liquid chromatography methods&mdash;HPLC). The obtained statistical data were processed by the Statistics program (Microsoft Corporation, Redmond, WA, USA, 2006). Results: The study made it possible to make assumptions about the functional dependence of the iso-&alpha;-bitter resins and isoxanthohumol content in beer samples. Mathematical analysis indicate interactions between protein molecules and different malted grain and hop compounds are involved in beer structure, in contrast to dry hopped beer, where iso-a-bitter resins, protein, and coloring compounds were significant, with a lower coefficient of determination. The main role of rutin in the descriptor hop bitterness has been established in kettle beer hopping technology, and catechin in dry beer hopping technology, respectively. The important role of soluble nitrogen and &beta;-glucan dextrins in the perception of sensory descriptors of various technologies&rsquo; beers, as well as phenolic compounds in relation to the formation of bitterness and astringency of beer of classical technology and cold hopping, has been shown. Conclusions: The obtained mathematical relationships allow predicting the resulting beer quality and also make it possible to create the desired flavor profiles

Elderly consumers’ satisfaction with the quality of community pharmacy services in Ho Chi Minh City, Vietnam: a Q-methodology study

Introduction: The purpose of this study was to understand elderly consumers’ satisfaction on the community pharmacy services in Ho Chi Minh City, Vietnam. Materials and methods: A sample of 32 consumers, aged over 60, was recruited in four pharmacies in Ho Chi Minh City, Vietnam, from December, 2017 to January, 2018. Q-methodology was used to identify the patterns of consumers’ satisfaction. Results: Two distinct patterns of elderly consumers’ viewpoints toward the community pharmacy services were identified. Elderly consumers in viewpoint 1 were satisfied with the geographic accessibility of community pharmacies. Elderly consumers in viewpoint 2 were satisfied with the affordability of medicines. However, consumers of both viewpoints expressed dissatisfaction with the pharmacy staff counseling on missed doses, storage, side effects, and interactions of medicines. Conclusion: The results from this study suggest that pharmacy staff need to spend more time for consultations on proper medication use with elderly consumers

Laboratory capability and surveillance testing for middle east respiratory syndrome coronavirus infection in the who European region, June 2013

Since September 2012, over 90 cases of respiratory disease caused by a novel coronavirus, now named Middle East respiratory syndrome coronavirus (MERS-CoV), have been reported in the Middle East and Europe. To ascertain the capabilities and testing experience of national reference laboratories across the World Health Organization (WHO) European Region to detect this virus, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe conducted a joint survey in November 2012 and a follow-up survey in June 2013. In 2013, 29 of 52 responding WHO European Region countries and 24 of 31 countries of the European Union/European Economic Area (EU/EEA) had laboratory capabilities to detect and confirm MERS-CoV cases, compared with 22 of 46 and 18 of 30 countries, respectively, in 2012. By June 2013, more than 2,300 patients had been tested in 23 countries in the WHO European Region with nine laboratory-confirmed MERS-CoV cases. These data indicate that the Region has developed significant capability to detect this emerging virus in accordance with WHO and ECDC guidance. However, not all countries had developed capabilities, and the needs to do so should be addressed. This includes enhancing collaborations between countries to ensure diagnostic capabilities for surveillance of MERS-CoV infections across the European Region