Student Attitude to Internet Search Engines: Navigation and Optimization Problems

The article relevance. Currently, the world is rapidly undergoing the process of Informatization of all aspects of society, the development and introduction of new information technologies. This highlights the need for further reflection and research on the development of the Internet and its opening opportunities for people. The aim of the research is to study the peculiarities of the attitude of students to search and recommendation services on the Internet. Research methods: as a research method, we used a questionnaire survey as a method of collecting primary information, which allows us to identify various aspects related to the attitude of students to search and recommendation systems on the Internet. Research results: the article examines the specifics of Russian search and recommendation systems, students' attitude to these services, and their place in their lives. The novelty and originality of the research lies in the fact that for the first time the search and recommendation services of the Internet space were studied. It is shown that these services were initially developed in the sphere of culture and gradually began to spread to other spheres of people's life, which attracted e-Commerce figures. It is revealed that those students who discovered search and recommendation services a few years ago still use them to choose leisure activities. It is shown that students still identify some disadvantages of these systems: inaccurate recommendations, a large number of questions to determine preferences. There is some distrust to new Internet technologies among those who are used to relying on their intuition when choosing. It is determined that students often use search and recommendation services, since in most cases gadgets help them spend their free time, have fun: read a book, watch a movie, listen to music. It is revealed that the majority of students trust Internet services, although they are not always satisfied with the recommendations. It is shown that the level of student-user confidence in traditional advertising and marketing decreases simultaneously. It is determined that from the point of view of students, today not only printed versions of Newspapers, traditional radio, but even mass broadcast television are losing ground before the Internet as the most promising communication channel. Practical significance: the data Obtained in this work can be used in marketing research, economic Sciences, advertising psychology, as well as for further theoretical development of this issue

OPPORTUNITIES OF LOW-DOSE DIGITAL FLUOROGRAPHY IN DIAGNOSIS OF PHENOTYPIC VARIANTS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objective. To determine the opportunities of low-dose digital fluorography (LDDF) in differential diagnosis of phenotypic variants of chronic obstructive pulmonary disease (COPD).Material and methods. There were 107 patients with clinically diagnosed COPD of varying severity examined. The average age of the patients was 51.8±1.5 years (46–59 years). All patients for LDDF of the chest in the frontal projection in the inspiratory and expiratory phase of respiration were undergone.Results. The electron optical density of the lungs was determined in the upper, middle and lower zones of both lungs. As a result in patients with a predominance of emphysematous variant of COPD (n=15) the most characteristic radiological symptom was lung hyperventilation (14% of 107 patients) and inspiratory electron optical density value was 748.18±4.72 optical density units (ODU). In patients with a predominance of bronchitic variant of COPD (n=43) the most common radiological symptom was the presence of symptom amplification and deformation of lung pattern (40% of 107 patients) and inspiratory electron optical density value was 668.04±12.26 ODU. For patients with mixed phenotypic variant of COPD (n=49) it was characterized by a combination of X-ray symptom amplification and deformation of lung pattern with lung emphysema (46% of 107 patients); the average value of inspiratory electron optical density value was 815.24±17.25 ODU.Conclusion. The technique of LDDF can detect X-ray symptoms and determine inspiratory and expiratory electron optical density of the lungs in patients with COPD that allows optimizing the differential diagnosis of phenotypic variants of chronic obstructive pulmonary disease

Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design

The aim of rational drug design is to develop small molecules using a quantitative approach to optimize affinity. This should enhance the development of chemical compounds that would specifically, selectively, reversibly, and with high affinity interact with a target protein. It is not yet possible to develop such compounds using computational (i.e., in silico) approach and instead the lead molecules are discovered in high-throughput screening searches of large compound libraries. The main reason why in silico methods are not capable to deliver is our poor understanding of the compound structure–thermodynamics and structure–kinetics correlations. There is a need for databases of intrinsic binding parameters (e.g., the change upon binding in standard Gibbs energy (ΔGint), enthalpy (ΔHint), entropy (ΔSint), volume (ΔVintr), heat capacity (ΔCp,int), association rate (ka,int), and dissociation rate (kd,int)) between a series of closely related proteins and a chemically diverse, but pharmacophoric group-guided library of compounds together with the co-crystal structures that could help explain the structure–energetics correlations and rationally design novel compounds. Assembly of these data will facilitate attempts to provide correlations and train data for modeling of compound binding. Here, we report large datasets of the intrinsic thermodynamic and kinetic data including over 400 primary sulfonamide compound binding to a family of 12 catalytically active human carbonic anhydrases (CA). Thermodynamic parameters have been determined by the fluorescent thermal shift assay, isothermal titration calorimetry, and by the stopped-flow assay of the inhibition of enzymatic activity. Kinetic measurements were performed using surface plasmon resonance. Intrinsic thermodynamic and kinetic parameters of binding were determined by dissecting the binding-linked protonation reactions of the protein and sulfonamide. The compound structure–thermodynamics and kinetics correlations reported here helped to discover compounds that exhibited picomolar affinities, hour-long residence times, and million-fold selectivities over non-target CA isoforms. Drug-lead compounds are suggested for anticancer target CA IX and CA XII, antiglaucoma CA IV, antiobesity CA VA and CA VB, and other isoforms. Together with 85 X-ray crystallographic structures of 60 compounds bound to six CA isoforms, the database should be of help to continue developing the principles of rational target-based drug design

Switching the Inhibitor‐Enzyme Recognition Profile via Chimeric Carbonic Anhydrase XII

A key part of the optimization of small molecules in pharmaceutical inhibitor development is to vary the molecular design to enhance complementarity of chemical features of the compound with the positioning of amino acids in the active site of a target enzyme. Typically this involves iterations of synthesis, to modify the compound, and biophysical assay, to assess the outcomes. Selective targeting of the anti-cancer carbonic anhydrase isoform XII (CA XII), this process is challenging because the overall fold is very similar across the twelve CA isoforms. To enhance drug development for CA XII we used a reverse engineering approach where mutation of the key six amino acids in the active site of human CA XII into the CA II isoform was performed to provide a protein chimera (chCA XII) which is amenable to structure-based compound optimization. Through determination of structural detail and affinity measurement of the interaction with over 60 compounds we observed that the compounds that bound CA XII more strongly than CA II, switched their preference and bound more strongly to the engineered chimera, chCA XII, based on CA II, but containing the 6 key amino acids from CA XII, behaved as CA XII in its compound recognition profile. The structures of the compounds in the chimeric active site also resembled those determined for complexes with CA XII, hence validating this protein engineering approach in the development of new inhibitors

CLINICAL AND RADIOLOGICAL CHARACTERISTICS OF ANCA-ASSOCIATED VASCULITIS: 7 YEARS OF EXPERIENCE IN DIAGNOSIS AND TREATMENT

The aim of the research is to study nosological structure, features of kidney, lung damage, deaths in patients with ANCA – associated vasculitis underwent medical treatment in a multidisciplinary hospital. Material and methods. Selection and subsequent retrospective analysis of the medical histories of 38 inpatient patients observed in nephrological, rheumatological, pulmonological and surgical thoracic departments for the period from January 2012 to december 2018 were carried out. The disease main clinical symptoms, variants of the X-ray picture, and causes of death were assessed in the patients according to the clinical and laboratory examination. Results and discussion. The most common diagnosis was eosinophilic granulomatosis with polyangiitis (EGPA) – 16 cases; microscopic polyangiitis was diagnosed in 11 patients, granulomatosis with polyangiitis – in 9 persons. in 2 cases, ANCA-associated vasculitis was diagnosed without specifying the nosological form. The most common symptoms in patients with ANCA-vasculitis were fever, progressive shortness of breath, weakness, artalgia, eosinophilia, which occurred mainly in patients with EGPA. Among analyzed 38 cases, there were 6 men and 32 women. The average age of patients was 50.72 ± 12.6 years. There were 5 deaths and, in 2 cases, the outcome could not be clarified. All deaths occurred during the first year from the disease onset caused by infectious complications or severe manifestations of the main disease

Apoptosis- and necrosis-induced changes in light attenuation measured by optical coherence tomography

Optical coherence tomography (OCT) was used to determine optical properties of pelleted human fibroblasts in which necrosis or apoptosis had been induced. We analysed the OCT data, including both the scattering properties of the medium and the axial point spread function of the OCT system. The optical attenuation coefficient in necrotic cells decreased from 2.2 ± 0.3 mm−1 to 1.3 ± 0.6 mm−1, whereas, in the apoptotic cells, an increase to 6.4 ± 1.7 mm−1 was observed. The results from cultured cells, as presented in this study, indicate the ability of OCT to detect and differentiate between viable, apoptotic, and necrotic cells, based on their attenuation coefficient. This functional supplement to high-resolution OCT imaging can be of great clinical benefit, enabling on-line monitoring of tissues, e.g. for feedback in cancer treatment

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

Complex metabolic geroprophylaxis in older patients with polymorbidity

The purpose of the study is to detect geroprophylactic activity and its possible mechanisms under the conditions of Inosine + Nicotinamide + Riboflavin + Succinic acid (ATC Code: N07XX) use in older patients with polymorbidity.Цель исследования – обнаружить геропрофилактическую активность и возможные ее механизмы в условиях применения Инозина + Никотинамида + Рибофлавина + Янтарной кислоты; (Код АТХ: N07XX) у пациентов старшего поколения с полиморбидностью