Structural and functional characteristics of the T helpers 17 subpopulation in allergic diseases of the respiratory organs in children

Phenotypes of asthma and allergic rhinitis are classified depending on the prevailing direction of the immune response the T lymphocyte profile and spectrum of cytokines that regulate the subpopulations of T lymphocyte helper cells. Therefore, the studies on the pathogenesis in various phenotypes of allergic respiratory diseases, and assessment of structural and functional characteristics of Th17 lymphocytes and interleukin 17 are relevant. The purpose of the present study was to analyze the subpopulations of Th17 lymphocytes and IL-17A, IL-17F interleukins in children with atopic asthma and allergic rhinitis. Materials and methods: a comprehensive assessment of structural and functional characteristics of T helper cells was carried out in 60 children aged 3-11 years with a verified diagnosis of atopic asthma. In 44 children (73.33% of total) bronchial asthma was combined with allergic rhinitis, and 30 healthy peers formed the control group. The population and subpopulation composition of blood lymphocytes was assessed by flow cytofluorimetry using monoclonal antibodies to CD3, CD4, CD8, CD19, CD45RA, CD45RO and CD196. To determine the intracellular content of IL-17, monoclonal antibodies against IL-17A (clone REA1063) labeled with PE-Vio770, isotypic control of antibodies against REA (Miltenyi Biotec GmbH, Germany) were used. The contents of total, specific IgE and interleukins IL-17A and IL-17F were determined by the enzyme-linked immunosorbent assay in the blood serum. Statistical processing of the results was performed using the “Statistica 10” applied software. When studying functional and quantitative characteristics of immunocompetent cells in children with atopic bronchial asthma and allergic rhinitis, a sufficient variability was revealed for relative and absolute numbers of CD3+CD4-CD8+, CD3+CD8+CD45RA+ and CD3+CD4+CD45RA+CD45RO"T lymphocyte subpopulations in peripheral blood, without significant differences with appropriate parameters in healthy controls (p < 0.001). A significant increase in the number of T lymphocytes was found in children with atopic bronchial asthma, with respect to CD3+CD8+CD45RA"CD45RO+ subpopulation (p < 0.001), the differentiated population of CD3CD4 positive T helpers (p < 0.05), and the Th effector subpopulations expressing both isoforms of CD45RA and CD45RO receptor (p < 0.01). The proportion of CD4CD45RO positive memory cells in children with atopic bronchial asthma and allergic rhinitis proved to be lower (p < 0.001), and the number of CD8+CD45RO+T lymphocytes, on the contrary, was higher (p < 0.025) than in the group of healthy controls. A diagnostically significant increase in the absolute and relative amounts of T helper 17 type with detectable changes in their functional characteristics, i.e., by the CCR6 chemokine receptor (CD196) expression levels, and presence of IL17A interleukin in children with atopic asthma and allergic rhinitis. The contents of this T helper 17 type subpopulation, and concentration of interleukins IL-17A, IL-17F in the blood serum of children with atopic asthma and allergic rhinitis showed the variability of functional and quantitative characteristics of cells that depended on the prevalence of allergic inflammation, evident imbalance in the interleukin 17 system, and the influence of Th17 lymphocytes on various aspects of inflammation and bronchial hyperreactivity associated with Th1 and Th2 response

Клинические проявления астенического синдрома после коронавирусной инфекции, вызванной SARS-CoV-2

Introduction. Asthenic disorders due to COVID-19 infection are generally classified under a recently introduced category in ICD-10: U09.9 Condition after COVID-19, unspecified. In this regard, it is necessary to study the clinical manifestations and systematize the asthenic syndrome after coronavirus infection in order to better understand the tactics of treatment and rehabilitation of this group of patients.Objective. To assess the prevalence of asthenic syndrome in patients who have had a coronavirus infection, to characterize and present its dynamics.Materials and methods. The study involved 200 people with a confirmed diagnosis of COVID-19, aged 51 to 83, who were undergoing inpatient treatment. After discharge from the hospital after 6 months and 12 months, these patients again underwent a physical examination, anamnesis, complaints, and a questionnaire to identify symptoms of asthenia and other psychopathological syndromes.Results. Asthenic symptoms were found in 2/3 of the examined persons. Autonomic disorders were noted with a slight decrease from 81.5% after 6 months to 74.2% after 12. Sleep disorders and increased fatigue progressed during the observed period from 70.4% to 80.6% and 63.0 to 74.2% respectively. Emotional lability of patients as a whole did not change.Conclusion. Polymorphic symptoms of asthenic syndrome were revealed, the most common phenomena were sleep disorders and symptoms of fatigue.Введение. Астенические расстройства, обусловленные инфекцией COVID-19, как правило, относят к группе недавно введенной рубрики в МКБ-10: U09.9 Состояние после COVID-19 неуточненное. В связи с этим требуется изучение и систематизация клинических проявлений астенического синдрома у пациентов после коронавирусной инфекции для лучшего понимания тактики лечения и реабилитации.Цель: оценить распространенность астенического синдрома у пациентов, перенесших коронавирусную инфекцию, охарактеризовать его и представить динамику.Материалы и методы. В исследовании приняли участие 200 человек с подтвержденным диагнозом COVID-19 в возрасте от 51 до 83 лет, все обследуемые лица подписали информированное согласие на участие в исследовании. Проведено 2 визита: при выписке из стационара через 6 и 12 месяцев. Пациентам проводился физикальный осмотр, сбор анамнеза, жалоб и анкетирование с оценкой субъективного ощущения тяжести астении и других психопатологических синдромов.Результаты. Астенические симптомы обнаружены у 2/3 обследуемых лиц (n=133), у которых вегетативные нарушения отмечались с незначительным снижением от 81,5% через 6 и до 74,2% через 12 месяцев, тогда как в течение наблюдаемого периода нарушения сна и повышенная утомляемость прогрессировали от 70,4% до 80,6% и 63,0 до 74,2% соответственно. Эмоциональная лабильность, в целом, у пациентов не изменялась.Выводы. В постковидный период у пациентов наблюдаются полиморфные симптомы и проявления астенического синдрома с наиболее распространенными феноменами расстройства сна и утомляемости

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions

Immunological Mechanisms Mediating Hantavirus Persistence in Rodent Reservoirs

Hantaviruses, similar to several emerging zoonotic viruses, persistently infect their natural reservoir hosts, without causing overt signs of disease. Spillover to incidental human hosts results in morbidity and mortality mediated by excessive proinflammatory and cellular immune responses. The mechanisms mediating the persistence of hantaviruses and the absence of clinical symptoms in rodent reservoirs are only starting to be uncovered. Recent studies indicate that during hantavirus infection, proinflammatory and antiviral responses are reduced and regulatory responses are elevated at sites of increased virus replication in rodents. The recent discovery of structural and non-structural proteins that suppress type I interferon responses in humans suggests that immune responses in rodent hosts could be mediated directly by the virus. Alternatively, several host factors, including sex steroids, glucocorticoids, and genetic factors, are reported to alter host susceptibility and may contribute to persistence of hantaviruses in rodents. Humans and reservoir hosts differ in infection outcomes and in immune responses to hantavirus infection; thus, understanding the mechanisms mediating viral persistence and the absence of disease in rodents may provide insight into the prevention and treatment of disease in humans. Consideration of the coevolutionary mechanisms mediating hantaviral persistence and rodent host survival is providing insight into the mechanisms by which zoonotic viruses have remained in the environment for millions of years and continue to be transmitted to humans

Features of sound generation by the jet-driven helmholtz oscillator

Experimental studies the model of a jet-driven Helmholtz oscillator has been carried out. The oscillator is a cylindrical cham-ber, closed on the sides by two covers with inlet and outlet holes. The oscillator was excited by a stream of airflow. The influence of the geometric dimensions of the chamber and the openings in the covers on the amplitude of pressure fluctuations was studied and the optimal channel configuration was determined. Particular attention is paid to the study of the influence on the amplitude of pressure fluctuations of the shape and size of the nozzle-the hole in the front cover. There were measured the following processes: the pressure drop across the nozzle, to calculate the speed of the jet at the chamber entrance, and the parameters of pressure fluctuations in the chamber, to plot the amplitude-frequency spectra. There were made certain observations of a jet tone appearance and acoustic modes excitation at the natural frequency of the chamber-resonator with a smooth increase in the jet velocity. The relationship be-tween the jet tone and the resonant in the chamber is noted. Recommendations for designing a Helmholtz jet oscillator are presented

Clinical and pathogenetic interrelation between molecular regulation of apoptosis and cell differentiation in osteoarthritis

Aim. To determine clinical and pathogenetic relationship between the levels of apoptosis and growth and differentiation regulation (growth inhibitor 1 induced by oxidative stress, growth/differentiation factor 5) in osteoarthritis. Methods. In a rheumatology office of Vladivostok polyclinic №3 65 patients with knee osteoarthritis Kellgren grade 1-4 aged 66.5±8.0 years were examined. 25 healthy volunteers matched by sex and age without clinical and radiologic manifestations of osteoarthritis were included into control group. To measure concentration of the studied molecules in study patients’ blood, ELISA method was used. Results. Patients with osteoarthritis compared to control group had statistically significantly increased levels of Fas, growth/differentiation factor 5 and ratio of growth/differentiation factor 5/growth inhibitor 1 induced by oxidative stress. Fas levels were significantly lower in late stages 2-4 of osteoarthritis compared to stages 1 and 2. Growth/differentiation factor 5 level was lower in patients with stage 3-4 of osteoarthritis compared to stages 1 and 2. As radiologic signs of osteoarthritis progressed, decrease of the ratio of growth/differentiation factor 5/growth inhibitor 1 induced by oxidative stress, was registered which was significantly lower in stages 2 and 3 compared to stage 1. Conclusion. Extrinsic pathway of apoptosis plays a big role in forming pain syndrome in osteoarthritis, and its maintenance is provided by other mechanisms which include influence of oxidative stress via inhibition of cell cycle mediated by growth inhibitor 1 induced by oxidative stress, reduced involvement of growth/differentiation factor 5 in differentiation processes and regulation of protein synthesis of extracellular cartilaginous tissue matrix

Populational composition of CD4⁺5RA/ CD4⁺5RO positive t lymphocytes and cytokine profile in children with allergic respiratory diseases

The changing states of T cell populations responsible for the chronic course of allergic inflammation and diseases, including allergic bronchial asthma, are not yet sufficiently characterized. The aim of this study was to detect phenotypic changes in the CD45RA/CD45RO positive T lymphocytes and the level of regulatory cytokines (TNFα, IFNγ, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17А, IL-17F) in allergic respiratory diseases (ARD) in children. In blood of 90 children aged 3-11 (60 children with ARD and 30 healthy peers) were studied of the immune cellular populations and cytokine indices. The levels of IL-4, IL-8, IL-10, IL-13, IL-17A and IL-17F in blood serum of children with bronchial asthma and allergic rhinitis differed from appropriate indices in control group (p = 0.001). The quantity of CD3+CD8+CD45RACD45RO+ cells, T helpers (p < 0.05) and Th effectors simultaneously expressing both isoforms of the CD45RA+ and CD45RO receptor in peripheral blood of children with ARD significantly exceeded those in control group (p < 0.001). In healthy children, Th17 population (CD3+CD4+CD196 lymphocytes) comprised 9.49±1.6% of CD3+CD4+ of cells, the number of such lymphocytes was significantly increased to 14.5±0.77 in children with allergic diseases (p < 0.001). Absolute numbers of Th17+ cells were 93.0±9.30 and 127,0±72.0 cells/µl respectively (p = 0.002). Indicators of CD4CD45RO positive memory cells in children with ARD was determined as significantly lower (p < 0.001), whereas quantity of CD3+CD19+ proved to be higher (p < 0.05) than in healthy peers. Absolute counts of these cells did not differ between the groups. The number of CD8+CD45RO+T lymphocytes was significantly higher in children with allergic diseases (p < 0.025). This research shows that the quantitative ratio of CD3+CD8+CD45RA+ and CD3+CD8+CD45RO+ populations of T cells, and increased levels of cytokines, synthesizable via Th2 and Th17, in peripheral blood may be helpful for understanding genesis of allergic respiratory diseases, and extends our knowledge on immune mechanisms of allergic disorders for individualization of therapeutic programs

Особливості вмісту мікроелементів і вітамінів у дітей і підлітків з дифузним нетоксичним зобом

Purpose — to determine the relationship between the microelements and vitamins content and morphofunctional state of the thyroid system in children and adolescents with diffuse nontoxic goiter. Patients and methods. The study involved 85 adolescents with diffuse nontoxic goiter, aged 10–17 y.o. We studied the serum levels of thyrotropin, free thyroxine, zinc, iron, vitamins A and E; the daily urinary levels of vitamins B1 and B2; and the content of selenium, cadmium, cobalt and lead in the hair. Results. The patients with diffuse nontoxic goiter had a decreased selenium level and an increased level of cadmium, cobalt and lead. These changes were accompanied by diffuse nontoxic goiter of II–III degree and depended on gender. The level of vitamin A was associated with morphological and functional state of the thyroid gland. It was reduced in the patients with subclinical hypothyroidism. Conclusion. The findings suggest that a significant dysregulation of vitamin and microelement metabolism in children and adolescents with diffuse nontoxic goiter is associated with the functional state of the thyroid gland. Key words: diffuse nontoxic goiter, adolescents, microelements, vitamins.Цель — определить взаимосвязь между содержанием отдельных микроэлементов, витаминов и морфофункциональным состоянием тиреоидной системы у подростков с диффузным нетоксическим зобом. Пациенты и методы. Обследовано 85 подростков в возрасте 10–17 лет с диффузным нетоксическим зобом. У сыворотке крови изучен уровень тиреотропина, свободного тироксина, цинка, железа, витаминов А и Е, в суточной моче — витаминов В1 и В2, в волосах — содержание селена, кадмия, кобальта и свинца. Результаты. У больных с диффузным нетоксическим зобом установлено снижение уровня селена, увеличения кадмия, кобальта и свинца, изменения которых более выражены при диффузном нетоксическом зобе II–III степени и зависят от пола. Уровень витамина А связан с морфофункциональным состоянием щитовидной железы и снижался при субклиническом гипотиреозе. Выводы. Полученные данные свидетельствуют о существенной дизрегуляции витаминно-минерального обмена у подростков с ДНЗ, связанной с функциональным состоянием щитовидной железы. Ключевые слова: диффузный нетоксический зоб, подростки, микроэлементы, витамины.Мета — визначити взаємозв'язок між вмістом окремих мікроелементів і вітамінів та морфофункціональним станом тиреоїдної системи в підлітків із дифузним нетоксичним зобом. Пацієнти та методи. Обстежено 85 підлітків віком 10–17 років із дифузним нетоксичним зобом. У сироватці крові вивчено рівень тиреотропіну, вільного тироксину, цинку, заліза, вітамінів А і Е, у добовій сечі — вітамінів В1 і В2, у волоссі — вміст селену, кадмію, кобальту та свинцю. Результати. У хворих із дифузним нетоксичним зобом встановлено зниження рівня селену і збільшення кадмію, кобальту і свинцю, зміни яких більш виражені при зазначеній патології II–III ступеня і залежали від статі. Рівень вітаміну А був пов'язаний з морфофункціональним станом щитовидної залози і знижувався при субклінічному гіпотиреозі. Висновки. Отримані дані свідчать про істотну дизрегуляцію вітамінно*мінерального обміну в підлітків із дифузним нетоксичним зобом, яка пов'язана з функціональним станом щитовидної залози. Ключові слова: дифузний нетоксичний зоб, підлітки, мікроелементи, вітаміни

Machine learning for predicting the outcomes and risks of cardiovascular diseases in patients with hypertension: results of ESSE-RF in the Primorsky Krai

Aim. To assess the prospects of using artificial intelligence technologies in predicting the outcomes and risks of cardiovascular diseases (CVD) in patients with hypertension (HTN).Material and methods. A software application was created for data mining from respondent profiles in a semi-automatic mode; libraries with data preprocessing were analyzed. We analyzed the main and additional parameters (35) of CVD risk factors in 2131 people as a part of ESSE-RF study (2014-2019). To create a forecasting model, a high-level language Python 2.7 was used using object-oriented programming and exception handling with multithreading support. Using randomization, learning (n=488) and test (n=245) samples were formed, which included data from patients with an established diagnosis of HTN.Results. The prevalence of HTN among subjects was 34,39%. There were following significant factors for predicting CVD: anthropometric parameters, smoking, biochemical profile (total cholesterol, ApoA, ApoB, glucose, D-dimer, C-reactive protein). As a result of a 5-year follow-up, CVD was found in 235 people (32,06%) with HTN and 187 people (13,38%) without HTN; mortality rates were 1,27% in subjects with HTN and 1,12% — without HTN. The absolute mortality risk among participants with HTN (0,037) was significantly higher (p<0,05) than in patients without HTN (0,017). To create a neural network (NN), the basic Sequential model from the Keras library was used. During machine learning, 26 variables important for the CVD development were used as input and 9 neurons — as output, which corresponded to the number of established cardiovascular events. The created NN had a predictive value of up to 97,9%, which exceeded the SCORE value (34,9%).Conclusion. The data obtained indicate the importance of risk factor phenotyping using anthropometric markers and biochemical profile for determining their significance in the top 20 predictors of CVD. The Python-based machine learning provides CVD prediction according to standard risk assessments

Role and structure of innovation entrepreneurship education in research university

Рассматривается практический опыт создания системы непрерывного многоуровневого пред-принимательского образования в Нижегородском государственном университете (ННГУ). Обосновывается тезис о том, что главным ресурсом развития инновационной экономики считаются высококвалифицированные специалисты, способные к инновационной предпринимательской деятель-ности, и главной задачей ведущих университетов страны является подготовка таких специалистов.The practical experience of creation of a system of continuous multi-tier entrepreneurship education at Lobachevsky State University of Nizhni Novgorod is presented. The idea of qualified specialists capable of innovation entrepreneurship as a key resource for development of innovation economy is elaborated. Training of such specialists is considered to be the main task of modern leading universities