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In this manuscript we are discussing our research of the presence of single nucleotide polymorphisms (SNPs) of two proinflammatory cytokines – interleukin 17F (IF-17F) and interleukin 23 (IL-23) in a cohort of Bulgarian patients. The aim of the study was to investigate the presence of SNPs of IL-17F and IL-23 and to explore a relation between IL-23 and IL-17F and severity of periodontitis. In the study 83 individuals were included – 62 patients with severe periodontitis and 21 healthy participants. Detailed periodontal status was taken in order to estimate the diagnosis of each participant. A Real-Time PCR for determination of SNP of IL-17 and IL-23 was performed. The data was summarised and processed by the means of statistical analysis. The results showed that when testing individuals for SNP of IL-17F, three genotypes were detected – TT, CT, CC, with prevalence of the TT genotype. In regards to SNP of IL-23, the widespread distribution of GG genotype represents the major share among all individuals with only three representatives with GA genotype. Important tendencies about the severity of the periodontal disease with regards to the SNPs and their simultaneous presence were found. Conclusion: In the present study two proinflammatory cytokine gene polymorphisms were explored and studied in relation to the severity of the periodontal disease. Their distribution among the tested individuals was established and relation to major parameters of the periodontal disease was evaluated.

INTRODUCTION: Premenstrual symptoms are common and can worsen women's quality of life. This study examines the prevalence of premenstrual symptoms such as weight gain; swelling of ankles, feet, and hands; frequent change of mood; fatigue; difficulty concentrating; depression; nervousness and irritability; and nausea. OBJECTIVES: The objectives of this study are: (1) to reveal the prevalence of premenstrual symptoms among Bulgarian women and (2) to establish how the presence of premenstrual symptoms affects the Emotional well-being of women. METHODS: The applied methodology includes an online-based anonymous study, which focuses on the prevalence of premenstrual symptoms among Bulgarian women and their emotional health. A characteristic of the studied contingent on age, BMI, and physical activity was made. RESULTS: The results of 126 women surveyed were analyzed. Of these, 96.8% have at least one premenstrual symptom. 30.2% have one or two symptoms, 43.7% have 3-4 symptoms and 23% have 5-8 symptoms. 14.8% of women with symptoms reported worsening of their symptoms because of increased stress associated with COVID-19. There is a statistically significant correlation between the number of symptoms and the emotional well-being of women. CONCLUSION: The prevalence of premenstrual symptoms is common among the studied Bulgarian women. A greater number of symptoms has a negative effect on women's emotional well-being. We consider it appropriate to introduce the application of physiotherapeutic methods as well as alternative therapies for the treatment and prevention of premenstrual syndrome.

The aim of the study was to analyze the effectiveness of treatment of patients using the Twin-Forse apparatus in adulthood. A case of a 25-year-old patient was treated with a retroposition of the lower jaw, distal occlusion of the posterior teeth, sagittal incisal disocclusion, deep incisal disocclusion, narrowing of the deformation of the dental alveolar arches, protrusion of the upper and lower incisors, crowded position of the lower teeth. Fixed orthodontic appliances of the Damon Q system (Ormco, USA) were used. Half a year after the fixation of the bracket system, a Twin-Forse apparatus (Ortho Organizers Inc., USA) was installed. After half a year of wearing, the device was removed, the patient was assigned to wear intermaxillary elastics to achieve maximum fissure-tubercular contacts. It has been found that the use of the Twin-Forse device in adult patients helps to achieve optimal functional and aesthetic results.

Purpose No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients. Methods This study is a single-center, randomized, double-masked, vehicle-controlled, parallel group study designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function (Clinicaltrials.gov NCT02855450). Sixty open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/ml rhNGF or vehicle control eye drops in both eyes, three times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed through adverse events, and tolerability, as assessed through patient reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field (HVF), electroretinogram (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12- and 32-weeks total). Results Of the 60 randomized subjects, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with low level of symptom burden mainly eliciting periocular ache (in 52% of treated, 5% of placebo) and only 3 patients (7.5%) discontinuing treatment due to discomfort, out of whom 1 patient (2.5%) prematurely withdrawing from the study. There were no statistically significant differences in global indices of HVF, and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed non-significant trends towards significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies. Conclusions rhNGF is safe and tolerable in a topical 180 μg/ml formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted.

This article presents the clinical observation of a female patient diagnosed with Harding syndrome — a combination of Le­ber’s hereditary optic neuropathy and multiple sclerosis. Distinctive features of pathogenesis are discussed.

The article analyzed the data about the features of leukocyte composition and immunophenotype of peripheral blood (PB) lymphocytes in children and adolescents: 94 DAAb-positive and 272 DAAb-negative in terms of diabetes-associated autoantibodies (DAAbs) content, 49 DAAb-positive patients with newly diagnosed diabetes mellitus type 1 (DM1) and 84 children from the control group, on the preclinical and early clinical stages of DM1. Evaluation of the content and analysis of distribution of lymphocytes with different immunophenotype was performed by flow cytometry method, and determination of DAAbs — using radioimmunoassay technique. It is found that the most significant changes in adaptive and natural immunity occur on the preclinical stage of the disease, which is caused by the most active phase of the autoimmune process. In preclinical period of DM1, in DAAb-positive children we have recorded an increase in the absolute number of monocytes and reduced number of natural killer cells (CD56+- lymphocytes/large granule-containing leukocytes) in the PB, indicating a pathogenetically significant weakening of innate immunity on this stage of the disease. Latent, preclinical period of DM1 in children with elevated titers of DAAb to islet antigens compared to marker-negative patients in terms of DAAb presence and healthy children from the control group has been characterized by impaired adaptive immunity — a reduction in blood flow of total number of CD3+, CD4+, CD8+ T-cells, which are material substrate of determined autoimmune aggression on the preclinical stage of DM1.

This article provides a review of the literature on the symptoms, laboratory blood values of critically ill patients who recovered and those who died of the new coronavirus disease COVID-19. Physicians should consider the following when predicting the course of the disease: in the first 3 days after admission, patients who recovered were slightly more likely to have leukocytosis and leukopenia, normal and increased lymphocyte counts; there were more individuals with increased number of band neutrophils, and patients who subsequently died were more likely to have normocytosis, granulocytosis, lymphopenia, thrombocytopenia, and higher erythrocyte sedimentation rate. The evaluation of laboratory indices in dynamics is of great importance for the prognosis: patients who recovered, on day 4–6 had a less pronounced growth of leukocytes and subsequently, on the contrary, their reduction; on day 4–6 of hospital stay, there was a decrease in the number of lymphocytes with subsequent growth; high creatine phosphokinase values at the beginning of hospitalization decreased significantly from day 7–9 to reference values; from the time of hospitalization, there was a decrease in lactate dehydrogenase content; the average prothrombin index tended to decrease, but within normal limits. Patients who died later, already from day 4–6 had an increase in leukocyte count, a decrease in lymphocyte level; thrombocytopenia was registered more often, which persisted with time and decreased significantly, especially after 9 days; in all periods of observation, erythrocyte sedimentation rate was higher (median of 30–40 mm/h); from day 7, there were significant fluctuations in maximum creatine phosphokinase values with their significant increase; at the beginning of hospitalization, these patients had higher lactate dehydrogenase levels compared to the first group and maintained their advantages during all periods of observation with significant fluctuations of maximal values; when comparing these patients by observation periods, there were slight fluctuations in the prothrombin index, which most often registered in about 80 % of patients with a subsequent increase after day 9, but within normal limits; also, at the beginning of hospitalization, there were significant fluctuations in the minimum prothrombin index towards very low rates.

В статье приводятся данные об иммунологических механизмах развития сахарного диабета 1-го типа (СД-1) на доклинической и ранней клинической стадиях формирования заболевания на основании исследования особенностей патогенеза заболевания, мониторинга процессов аутоиммунной деструкции инсулинпродуцирующих β-клеток по определению содержания диабетассоциированных аутоантител (ДААт) (частота встречаемости и динамика титров), изучения особенностей секреции цитокинов на доклиническом этапе развития СД-1 у детей и подростков. Освещение новых подходов к доклинической диагностике СД-1 позволило определить группу маркерпозитивных детей с отягощенной наследственностью и прогнозируемым риском развития заболевания. Обследовано 450 практически здоровых нормогликемических детей и подростков в возрасте от 7 до 15 лет. Выявлено, что у 94 (26,7 %) из 366 детей с отягощенной наследственностью при не менее чем двукратном определении у них ДААт наблюдался повышенный их титр, преимущественно GADA и IA-2A; у 49 (52,1 %) из них в период от 6 мес. до 12 лет (30,9 ± 3,2 мес.) манифестировал клинический дебют СД-1. Из 272 (73,3%) ДААт-отрицательных детей за этот же период СД-1 развился у одного ребенка, то есть в 0,8 % случаев. Определена формула сочетанной встречаемости и значений одновременно повышенных титров ДААт к островковым аутоантигенам, а именно IA-2A + GADA, что является предиктором как продолжительности доклинической стадии развития СД-1, так и скорости дебюта. Установлено также нарушение продукции цитокинов (повышение уровня провоспалительных цитокинов ИЛ-1α, ИЛ-6 и ФНО-α, ИЛ-8 и ИЛ-16 при одновременном снижении концентрации ИЛ-4 в плазме крови) как ключевых факторов патогенеза СД-1, обусловливающих как скорость дебюта СД-1, так и агрессивность его течения.

Purpose This study aims to blockchain facilitate information sharing among different players in the food industry, such as farmers, food suppliers and investors, enabling an effective decision-making process where the information about goods is traceable without any inherent risk. Although blockchain technology is emerging, its use in the food industry needs to be explored from different angles, such as organizations’ policy, adoption strategies and potential technology innovations which could positively impact business processes. Design/methodology/approach For this purpose, the authors survey 84 organizations in the food industry. Further, the authors conducted in-depth- interviews with three organizations that applied blockchain technology in the production phase to address the pros and cons of this adaption and discuss how the technology could be improved based on the challenges they faced. Moreover, an overview of current and potential digital transformation uses cases of blockchain technology in the food industry has been provided. Findings The results suggested that perceived efficiency, transparency, standardization and platform development and traceability factors positively influenced intention to use (ITU). Practical implications The adoption of the blockchain cloud solution is neither time-consuming nor expensive; organizations may attempt to predict how regulations or standards will be developed to create a blockchain solution compatible with them. Originality/value This study is among the primary studies investigating the role of blockchain technology in the food sector from the organizations’ viewpoint, highlighting the factors influencing the ITU.

The need to review the guidelines for the management of patients with multiple sclerosis using multiple sclerosis disease modifying drugs has become acute enough since the beginning of 2020 following the outbreak of the COVID-19 pandemic caused by a novel coronavirus SARS-CoV-2. Immunosuppressive drugs were also specifically addressed, as it is during administration of these drugs that the more severe course of COVID-19 disease was expected. Both the Russian and foreign teams published results of their research works. This article presents a retrospective analysis of the incidence rates of COVID-19 in patients with multiple sclerosis after selective immunosuppressive therapy with alemtuzumab and a clinical case when a patient was infected with coronavirus in the first days following the last infusion of the therapy course without clinical manifestations of the infectious disease. The author discusses the mechanisms underlying such a favourable outcome due to the CD52 lymphocyte depletion leading to the reduction of risks of developing hyperimmune reactions that underlie severe complications of COVID-19, and analyses previously published works of our foreign colleagues on the same theme. The review of the accumulated works and personal experience suggest that it is the CD52 lymphocyte depletion that makes it possible to avoid the cytokine storm and, as a result, the more severe course of COVID-19. Amidst the COVID-19 pandemic, during the prescription of multiple sclerosis disease modifying drugs, it should be borne in mind that patients should have access to all types of modern therapy and that the benefits should outweigh the sum of possible risks.

The main theoretical aspects of the features of the formation of the logistics activities of organizations in the modern conditions of the transformation of the world market are considered. The conceptual necessity of using an integration approach in organizing logistics activities, taking into account the influence of factors of the macroeconomic environment, has been substantiated. The main aspects and features of intrafirm and interfirm logistic integration of organizations are interpreted and reasoned, which, in contrast to existing approaches, makes it possible to distinguish this process from its influence on the main activity, taking into account the risk factors. The conceptual factors contributing to the formation of integration processes in the organization in modern conditions of the transformation of the world market are highlighted. It is argued that the modern realities of doing business, regardless of the type of economic activity, necessitate the use of an integrated approach in management when organizing logistics activities. With the help of economic and statistical analysis of the logistics services market in the world, the intensity and need for the use of intrafirm logistics integration are substantiated. The developed theoretical and methodological approach of the integration organization of logistics activities can be applied in practice, taking into account the peculiarities of the economic activities of organizations in modern conditions.

Introduction: TNF-α blocker therapy is part of the treatment with biologics used in the management of inflammatory joint diseases. In recent years, drug-induced neutralizing antibodies have been shown to have a negative effect on the course of the disease process. Aim: To investigate drug-induced neutralizing antibodies against TNF-α blocking drugs used in patients with inflammatory joint diseases and their effect on the clinical course of the disease. Materials and methods: The study included 121 (56.8%) patients with rheumatoid arthritis, 50 (23.5%) patients with ankylosing spondylitis, 42 (19.7%) patients with psoriatic arthritis, and 31 sex and age-matched healthy controls. The patients were monitored at 0, 6, 12, and 24 months after initiation of TNF-α blocker treatment. The demographic data, vital signs and the parameters of inflammatory activity (C-reactive protein, erythrocyte sedimentation rate, and disease activity indices) were analyzed in all patients. Drug-induced anti-TNF-α blockers antibodies (adalimumab and etanercept) were analyzed using ELISA. Statistical analysis was performed with SPSS v. 24. Results: Drug-induced neutralizing antibodies against adalimumab were obtained in 11.57% of patients at 6 month, in 17.64% at 12 month, and in 24.8% at 24 month. Drug-induced neutralizing antibodies to etanercept were not demonstrated in patients followed up at 6 months, at 7.77% at 12 months, and at 9.63% at 24 months. Between the presence of neutralizing antibodies to blockers of TNF-α and indices available for disease activity, there is a strong positive correlation and Pearson Correlation = 0.701, p=0.001. Patients with poor clinical response and available antibodies against adalimumab at 12 months were 82.36% and patients treated with etanercept 71.42%. The difference between the two groups was non-significant (U = 0.527, p> 0.05). Patients with poor clinical response and available anti-adalimumab antibodies at 24 month were 75%, and in patients treated with etanercept – 87.50%, the difference between the two groups not being able to reach significance (U = 0.623, p> 0.05). Conclusion: Drug-induced neutralizing antibodies against TNF-α blockers (adalimumab and etanercept) have a negative effect on the course of inflammatory joint disease and can be used as reliable biomarker to assess the effect of the treatment with these drugs.

Objectives Therapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure. Methods This study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET–CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03. Results Median follow-up was 19 (9–47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50–93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12–53%). Any grade AEs were observed in 12 patients (63%), 3–4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5–21) months. Conclusions Combination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach. Supplementary Information The online version contains supplementary material available at 10.1007/s10147-021-02085-6.

Motivation With the increasing availability of 3D-data, the focus of comparative bioinformatic analysis is shifting from protein sequence alignments toward more content-rich 3D-alignments. This raises the need for new ways to improve the accuracy of 3D-superimposition. Results We proposed guide tree optimization with genetic algorithm (GA) as a universal tool to improve the alignment quality of multiple protein 3D-structures systematically. As a proof of concept, we implemented the suggested GA-based approach in popular Matt and Caretta multiple protein 3D-structure alignment (M3DSA) algorithms, leading to a statistically significant improvement of the TM-score quality indicator by up to 220–1523% on ‘SABmark Superfamilies’ (in 49–77% of cases) and ‘SABmark Twilight’ (in 59–80% of cases) datasets. The observed improvement in collections of distant homologies highlights the potentials of GA to optimize 3D-alignments of diverse protein superfamilies as one plausible tool to study the structure–function relationship. Availability and implementation The source codes of patched gaCaretta and gaMatt programs are available open-access at https://github.com/n-canter/gamaps. Supplementary information Supplementary data are available at Bioinformatics online.

BACKGROUND: Allogeneic stem cell transplantation (ASCT) is a potentially curative therapeutic approach in patients with intermediate and high-risk myelodysplastic syndrome (MDS). If a family sibling or unrelated donor is not available mismatched donors are viable option for young patients with no comorbidities. The aim of this case presentation was to evaluate our first experience with haploidentical transplantation for this indication. CASE PRESENTATION: We present a case of 50 years male patient with myelodysplastic syndrome (MDS) diagnosed at University Clinic for hematology, Skopje, North Macedonia. Patient was scored in IPSS -R as high risk patient. He was referred for HLA DNA typing of family siblings and since he didn’t have identical sibling and unrelated donor, he was referred to continue treatment with haploidentical stem cell transplantation. He received Flu Bu conditioning and PTCY, cyclosporine and MMF for GVHD prophylaxis. Peripheral blood stem cells (PBSC) from his mismatched brother were infused in the amount of CD34=5.8x106/kg. He experienced prolonged engraftment, severe infective bacterial infections and CMV reactivation with clinical manifestation of CMV colitis. He was successfully treated with antiviral drug and completely resolved. His bone marrow analysis showed complete remission and chimerism evaluation revealed high donor engraftment. Patient is now +34 months post transplant in complete remission. CONCLUSION: The use of a mismatched donor increases the risk of NRM, but there is also evidence to suggest that an haploidentical donor is a valid choice, as general outcome appears to be at least similar to MUD.

A lot of recommendations has been published regarding the treatment of chronic venous disease. At the same time, none of these documents reflects the complete «path» of the patient from the stage of the initial visit (diagnosis) to the choice of the optimal treatment option. Therefore, the creation of a protocol that would take into account on the one hand the most modern and proven effective approaches to diagnosis and treatment, and on the other hand, the individual characteristics of each clinical case is an urgent task.The main task of the publication is to create a practice-oriented instruction for the diagnosis, comprehensive treatment and prevention of chronic venous insufficiency. The management of a patient with chronic venous insufficiency is presented in the form of «AngioLife Venous Protocol®», a set of clear practical recommendations for vascular surgeon and phlebologist. This protocol is based on our own practical experience, existing protocols and guidelines for the treatment of patients with chronic venous insufficiency. The venous protocol includes four stages of a set of medical measures, the purpose of which is to form a clear program of further examination and treatment of the patient. Adherence to all the recommendations specified in the protocol allows to obtain satisfactory functional and cosmetic results of treatment of patients with chronic venous insufficiency with minimal risk of recurrence.

Background. The problem of diagnostics and treatment of malignant neoplasms of the lungs is urgent. Verification of a malignant process in the case of peripheral localization of a neoplasm in the lung using ultrasound bronchoscopy ranges from 30 to 85%. To improve the efficiency of ultrasound bronchoscopy, a modified biopsy technique for ultrasound bronchoscopy was developed and introduced into clinical practice at the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine. The essence of the modified technique is that it becomes possible for ultrasound visual control over the passage and deployment of biopsy forceps in real time. The technique was patented, patent for invention RU №2719666 C1 was issued. Aim. To clarify the information content of ultrasound bronchoscopy using a modified technique. Materials and methods. On the basis of the endoscopic Department of Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine in 2019 and 2020, ultrasound bronchoscopy using this technique was performed on 40 patients with suspected peripheral malignant neoplasm of the lungs. The diagnosis of malignant neoplasm was verified in 67.5% of cases. Using the standard biopsy technique, the probability of verification of lung malignant neoplasms in 2019 and 2020 was 57.7%. Thus, the modified biopsy technique made it possible to increase the verification probability by 9.8%. The modified technique is relatively safe, complications during the procedure were detected in 2 patients (in 3.8% of cases) and were successfully treated conservatively. During and after the procedure, the patients were monitored and monitored. The ultrasound bronchoscopy according to the modified technique was satisfactorily tolerated by the patients. Results. The period of examination of patients when using this technique does not increase. The technique replaces more invasive diagnostic procedures. Conclusion. The use of the modified technique will improve the information content of ultrasound bronchoscopy, shorten the examination time for patients and accelerate the appointment of special treatment methods.

У цій статті наведено клінічний випадок агресивної форми розсіяного склерозу — варіант Марбурга. Обговорюються питання діагностики й можливі варіанти терапії відповідно до міжнародних опублікованих даних.

OBJECTIVE To evaluate role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, TNF-α, interleukin-1β,) and genetic factors (NOS3 (rs1799983), EDNRA (C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), NOS3 (Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), SOD2 (rs4880), GPX1 (rs1050450) in development of anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases. METHODS A total of 176 women with breast cancer and without cardiovascular diseases who received anthracyclines were enrolled in the study. After the 12 months of chemotherapy (CT), all patients were divided into two groups: group 1 (n = 52) comprised patients with AIC, group 2 (n = 124) comprised those without it. RESULTS Based on ROC-analysis, levels of endothelin-1 of ≥9.0 pg/mL (AUC of 0.699), sFas-L of ≥98.3 ng/mL (AUC of 0.990), and NT-proBNP of ≥71.5 pg/mL (AUC of 0.994;) were identified as a cut-off values predicting AIC during 12 months after CT. Whereas, NT-proBNP and sFas-L were more significant predictors than endothelin-1 (p

(1) Background: to reveal the prevalence of non-motor disorders in Parkinson’s disease (PD), we analyzed both Russian and international studies on the issue of PD-associated non-motor disorders in Caucasian patients; (2) Methods: We have carried out a search for full-text Englishand Russian-language articles published during the last ten years (from 2010 to 2020) in PubMed, Scopus, Web of Science, Springer, Clinical case, and E-library databases using multiple versions of keywords and their combinations. (3) Results: General prevalence of PD-associated non-motor disorders proved to be high. At the same time, we did not find significant differences between the prevalence of cognitive, affective, or behavioral disorders in PD patients. However, depression was found to be more common in PD patients in the Russian Federation; (4) Conclusions: According to the results of our review, cognitive and affective disorders in PD represent the issues of major concern.

Anticonvulsant-induced osteoporosis (AIO) and associated pain syndromes and patient disabilities are an important interdisciplinary medical problem generated by various molecular, genetic and pathophysiological mechanisms. AIO are the most important pathological processes associated with chronic pain in adults with epilepsy. Standard approaches to their prevention and treatment do not always solve the problem of the progression of the pathological process and chronicity of AIO. This is the reason for the search for new personalized strategies for the prevention and treatment of AIO. Vitamin D metabolism, expression and specificity of vitamin D receptors (VDRs) may play a key role in the development of AIO and chronic back pain in patients with epilepsy. The aim of the study was to review publications on changes in the vitamin D system in patients with AIO. We searched for articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar. The search was carried out by key-words and their combinations. The role of vitamin D and VDR in the development of AIO and the chronicity of back pain has been demonstrated mainly in animal models and humans. Associative genetic studies have shown that single nucleotide variants (SNVs) of the VDR gene encoding VDR may be associated with the development of osteoporosis of the spine (including those associated with the intake of an anticonvulsants). The prospects for the use of vitamin D preparations for modulating the effect of anticonvulsants used to treat epilepsy are discussed. Genetic association studies of VDR gene SNVs are important for understanding the genetic predictors of AIO and chronic back pain in patients with epilepsy, as well as for developing new personalized pharmacotherapy strategies.

Aim: The aim of the present study is an epidemiological study of risk factors and the prevalence of periodontal disease in children aged 10-14 years. Materials and methods: The subject of the study were 457 children. All were clinically examined, and the data were recorded on a specially designed card. Each child was assessed for risk periodontal profile in 4 levels, which includes: assessment of oral hygiene habits; registration of dental status, reporting of carious lesions and obturations on surfaces dangerous for periodontal health (proximal, cervical); the presence of orthodontic anomalies and other risk factors; assessment of the plaque index of Silness-Loe (PLSL); assessment of gingival index according to Loe and Silness (GILS) Results: Carious lesions at risk for gingival inflammation surfaces are registered in 59% of children, at risk for periodontal health fillings in 32% and orthodontic anomalies in 37%. The studied children showed relatively good oral hygiene (PLSL-0.43 ± 0.28), which improved with age, with the largest amount of plaque observed on the proximal and vestibular surfaces. Over 88% of children have mild gingival inflammation (GILS-0.56 ± 0.42), mainly affecting the front teeth in both jaws. Conclusions: Gingival inflammation in 10-14 year old children covers more than half of the studied children, with mild forms of inflammation predominating with a relatively low oral hygiene index. 2/3 of registered caries and 1/3 of the fillings have a localization which presents a risk for periodontal health. Orthodontic anomalies are the next most serious risk factor for plaque accumulation and gingival inflammation.

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

The paper is devoted to topical problems of legal regulation of public relations in the field of alternative (renewable) energy sources in Russia and abroad. The paper shows the formation and development of the legal framework governing the investigated area of public relations in Russian and foreign law. The necessity of adopting a special legislative act in the Russian Federation dedicated to the civil regulation of public relations arising from the use of alternative (renewable) energy sources is substantiated.

Objective was to investigate the SARS-CoV-2 collective immunity status of the population of Belarus within the context of the COVID-19 pandemic. Materials and methods. The work was carried out according to the methodology for assessing SARS-CoV-2 population immunity, developed by Rospotrebnadzor Russia and the Ministry of Health of Belarus with the participation of the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The Bioethics Committee of Belarus and the local ethics committee of the St. Petersburg Pasteur Institute approved the study. Selection of participants was carried out using a questionnaire method and online technology (internet, cloud server). Volunteers were randomized into seven age groups (years of age): 1–17; 18–29; 30–39; 40–49; 50–59; 60–69; and 70+. Regional randomization ensured proportional representation of volunteers from each region, and no more than 30 people were included from one enterprise. In accordance with manufacturer instructions, blood plasma samples were analyzed for: IgG antibodies (Abs) to the SARS-CoV-2 nucleocapsid (Nc) using a quantitative ELISA test system; and IgG Abs to the receptor binding domain (RBD) of the SARS-CoV-2 S (spike) surface glycoprotein using a qualitative ELISA test system. Statistical processing was carried out using Excel 2010 and other software. Statistical differences were designated as significant when p 0.05, unless otherwise indicated. Results. The level of seroprevalence, in terms of Abs to Nc among the Belarusian population, was 38.4% (95% CI 37.6–45.4). The highest Ab levels were found among individuals in older age groups (50-70+ years old). The lowest were found in children 1–17 years old and in young people 18–39 years old The distribution of seroprevalence across Belarusian regions was relatively homogeneous, with the exception of the Minsk Region, where a statistically significant decrease in the indicator was noted. In terms of profession, the largest share of seropositive individuals was found among transportation workers; the smallest was found in business. The moderate COVID-19 incidence has not led to a dramatic increase in the number of contacts. The base reproduction number (R0) was 1.3. In the Republic of Belarus, there was a moderate level of asymptomatic COVID-19 among seropositive individuals (45.3% [95% CI 44.0–46.7]). This form of infection was observed most often among children aged 1–17 years old (65.0% [95% CI 61.3–68.6]). In parallel with seroprevalence assessment, SARS-CoV-2 vaccination was carried out. We used two vaccines: Gam-COVID-Vac (also known as Sputnik V, developed by Gamaleya National Center for Epidemiology and Microbiology, Russia); and BBIBP-CorV (Sinopharm, PRC). Vaccination against SARS-CoV-2 was accompanied by an increase in the level of anti-RBD Abs (95% [95% CI 94.7–96.7]). Taking into account the vaccination of a subset of the population with BBIBP-CorV, the overall herd immunity, inferred from the analyzed indicators (presence of anti-Nc or anti-RBD Abs), was 47.1% (95% CI 46.3–48.0). Conclusion. COVID-19 in Belarus was characterized by a moderately pronounced course of the epidemic process. The threshold level of herd immunity to SARS-CoV-2 has not yet been reached, as a result of which the conditions for progression of the epidemic remain.

Stephane Borentain,1 David Williamson,2,3 Ibrahim Turkoz,4 Vanina Popova,5 William V McCall,3 Maju Mathews,1 Frank Wiegand1 1Department of Global Medical Affairs, Janssen Research & Development, LLC, Titusville, NJ, USA; 2CNS Scientific Affairs Liaisons, Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 3Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, GA, USA; 4Department of Clinical Statistics, Janssen Research & Development, LLC, Titusville, NJ, USA; 5Department of Neuroscience Clinical Development, Janssen Research & Development, Beerse, BelgiumCorrespondence: Stephane BorentainDepartment of Global Medical Affairs, Janssen Research & Development, LLC, 1125 Trenton-Harbourton Road, Titusville, NJ, 08560, USATel +1 609-7304420Email SBorent1@ITS.JNJ.comPurpose: To evaluate the relationship of sleep disturbance to the antidepressant effects of esketamine.Materials and Methods: Two double-blind, 4-week studies randomized adults with treatment-resistant depression (TRD) to placebo or esketamine nasal spray, each with newly initiated antidepressant. Sleep was assessed using Montgomery–Åsberg Depression Rating Scale (MADRS) item 4. Change in response (≥ 50% decrease in MADRS total score) and remission (total MADRS score ≤ 12) at day 28 was examined by presence/absence of baseline sleep disturbance using logistic regression models. Impact on reported sleep disturbance (MADRS item 4 score) was examined using ANCOVA models.Results: At baseline, most patients reported disturbed sleep – moderate/severe (65.3%, 369/565), mild (25.3%, 143/565), or none/slightly (9.4%, 53/565) – with similar distribution between treatment groups. A higher proportion of esketamine-treated patients achieved response (OR = 2.05; 95% CI: 1.40– 3.02; P < 0.001) and remission (OR = 1.81; 95% CI: 1.23– 2.66; P = 0.003) at day 28 compared to antidepressant plus placebo, regardless of presence/severity of sleep disturbance. Consistent with this, sleep (MADRS item 4 score) improved in both groups after the first dose, more so with esketamine by day 8 (between-group difference: P ≤ 0.02 at all time points). Across both treatment groups, 1-point improvement in sleep at day 8 increased the probability of antidepressant response on day 28 by 26% (OR = 1.26, 95% CI: 1.12– 1.42; P < 0.001), and remission by 28% (OR = 1.28, 95% CI: 1.14– 1.43; P < 0.001).Conclusion: Antidepressant efficacy of esketamine was demonstrated in patients with TRD, regardless of the presence of sleep disturbance. After 8 days of treatment and thereafter, significantly more esketamine-treated patients reported improvement in sleep versus antidepressant plus placebo.Keywords: esketamine, treatment-resistant depression, sleep disturbance, insomnia

Background. Data on the overall survival (OS) of patients with metastatic bladder cancer (BCa) is rarely published.The objective of the URRU register study is to assess OS and collect information on the administration of different treatments in patients with metastatic BCa in routine clinical practice in Russia.Materials and methods. Patients were retrospectively identified in 9 oncology centers in different regions of Russia and included in the study if they were diagnosed with metastatic BCa between January 2017 and January 2018. We collected anonymized data online, including demographic characteristics of patients, details of their therapy, and outcomes.Results. This study included 246 patients. Their mean age upon the diagnosis of metastatic BCa was 72 years with 60.6 % of patients over 70 years of age. The proportion of males was 74.8 %. The histological subtype of BCa (urothelial carcinoma, etc.) was identified in 70.3 % of cases. Ninety-two patients (37.4 %) received pharmacotherapy. The most common treatment option was chemotherapy (76 %); the most common drug combination was gemcitabine and cisplatin (41.3 %). Immunotherapy was used in 19.6 % of patients; 13.6 % of participants received more than two lines of therapy. Three-year OS rate was 10.6 %; median OS was 7 months (95 % confidence interval (CI) 5.4-8.6). Patients receiving systemic therapy demonstrated significantly longer survival than those receiving no therapy (21 months; 95 % CI 17.38-24.62 vs 3 months; 95 % CI 1.79-4.22; p Conclusion. The survival rates in the URRU study were relatively low, which can be attributed to the fact that only one-third of patients received pharmacotherapy and very few patients received immunotherapy. Second and subsequent lines of therapy were rarely used in patients with progressive disease. The implementation of novel treatments, including immune checkpoint inhibitors, will increase the survival of BCa patients.

We examined expression pattern of CD80 and HLA-DR pro-inflammatory molecules on the monocytes in patients with pulmonary tuberculosis (TB), depending on the clinical form of the disease and susceptibility of the pathogen to anti-tuberculosis drugs. The study involved forty-five patients with newly diagnosed pulmonary TB (25 men and 20 women aged 18 to 55 years, average age — 44.0±12.4 years). The control group included 15 healthy donors with similar socio-demographic characteristics as in TB patients. Venous blood was used as biomaterial for assays. Studies of the monocyte immunophenotype were carried out by flow cytometry of whole blood cells using Cytoflex flow cytometer (Beckman Coulter, USA) with specific monoclonal antibodies (eBioscience, USA). We determined the content of cells expressing surface markers of monocytes, i.e., CD14, CD45, CD80, and HLA-DR. The results of this study were evaluated using SPSS Statistics 17.0 standard software package and Microsoft Excel. In the course of the study, we have suggested a working hypothesis that the monocytes in TB patients, still being in circulation, can express activation markers during their migration to inflammation focus, especially CD80 and HLA-DR molecules. Analysis of the total CD14+ monocyte number showed its decrease in all forms and variants of clinical course of pulmonary tuberculosis compared with the control group. Assessment of pro-inflammatory markers expressed on CD14 positive monocytes, i.e., HLA-DR activation marker and CD80 co-stimulatory molecule, showed that the number of monocytes with HLA-DR expression in all TB patients was higher than in healthy donors. HLA- DR expression on CD14+ monocytes in the group of patients with infiltrative TB proved to be 15% higher than in patients with disseminated TB. The expression of CD80 on CD14+ monocytes in TB patients showed no differences between the groups and varied within the normal range. Hence, an imbalance within monocyte population in patients with pulmonary tuberculosis, regardless of its clinical form and drug sensitivity of the pathogen is developed, due to decrease in total number of CD14+ cells, along with increased relative number of monocytes expressing HLA-DR activation marker (pro-inflammatory phenotype). Meanwhile, expression of the CD80 co-stimulatory molecule on monocytes was within normal values.

Undoubtedly, one of the most promising approaches to the treatment of cancer is creation of the pathogenetically based therapeutic drugs. Researchers from all over the world are trying to answer the question on how to select a target that would be effective and, in general, they are quite successful at that. The Nobel Prize-winning discovery of mechanisms for regulating activity of the immune system cells through checkpoint molecules, as well as discovery of the ability of tumor cells to use these mechanisms to suppress immune responses was an impetus for the development of modern immunotherapy, and now such inhibitors of the immune checkpoints as PD-1/PD-L1 are included in the routine chemotherapy. Use of such drugs can prolong the patient's life, but, unfortunately, not cure the disease. This is partially due to heterogeneity of tumor cells and microenvironment, but the main reasons may be in the complex relationships between the tumor and microenvironment, which, at times, are so plastic that they can change, adjusting to newly emerging conditions. Main characteristic of the tumor microenvironment is the type of the ongoing immune-inflammatory response (IIR), and since inhibitors of the immune checkpoints act on the cells involved in IIR, it is obvious that the outcomes of cancer therapy, including outcomes of hyperprogressive disease, can be associated with this parameter. The presented review reveals the essence of interactions between the tumor and its microenvironment during therapy with PD-L1 inhibitors.

The article discusses the main aspects of the draft “Concept for the implementation distant control/monitoring forms of sanitary requirements compliance (remote/contactless supervision).” The project document was developed according to the “National Action Plan Ensuring the Recovery of Employment and Incomes of the Population, Economic Growth and Long-Term Structural Changes in the Economic” control in the Russian Federation”. It has been determined that introducing remote forms of supervision is the general improvement of the state control system with a general decrease in the administrative burden on business entities. The task is also to identify the negative trends in the activities of organizations at the earliest possible stages and adopt proactive state response measures to violations of the law. The concept establishes that the critical difference between remote control and contact, face-to-face forms is the most full use and science-intensive processing of data accumulated in the information field about the activity of the economic unit. The information field is formed by departmental databases collected in the Unified Information System of Rospotrebnadzor (EIAS) and external state, municipal and other databases. An analysis is carried out through remote access to information. The remote control also implies a gradual, but significant expansion of the hardware use for fixing objects and processes status (audio-photo-video tools, sensors for measuring object parameters, etc.).An intelligent information system provides information and analytical support for the entire cycle of actions provided for by the regulations for conducting remote control and supervision activities. The system focuses on identifying evidence of violation or compliance with sanitary legislation based on the study of transmitted information. The functioning of an intelligent system involves the modern methods of machine processing of big data (Big Data), including elements of artificial intelligence based on machine learning of artificial neural networks, etc. The data generated in the system is sent to the shared storage of the EIAS for the combined processing data from remote and contact supervision and systemic complex analysis with the involvement of data from social and hygienic monitoring and other departments. The phased introduction of distant control in the activities of the service requires the improvement of the regulatory, methodological, material, and technical base, as well as the human resources development in the direction, increasing the computer literacy of expert specialists, persons responsible for maintaining the information system, its administration, and ensuring uninterrupted operation. It is shown that the effectiveness of the distant control implementation with the use of information and analytical approach can reduce from 15 to 60% time for one scheduled inspection, decrease the labour costs of inspectors and specialists of supervised facilities, expanding the number of inspected objects. Contribution: Popova A.Yu. — the research concept, editing; Zaitseva N.V. — the research design, writing the text; May I.V. — design of the study, processing of the material, writing the text; Kiryanov D.A. — processing of the material, writing the text; Kolesnik P.A. — processing of the material. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version Conflict of interest. The authors declare no conflict of interest. Acknowledgement. The study had no sponsorship. Received: August 17, 2021 / Accepted: September 28, 2021 / Published: October 31, 2021

Introduction: The T315I mutation in patients with chronic myeloid leukemia (CML) has been associated with therapeutic resistance and an unfavourable prognosis. Aim: To study the frequency of T315I mutation in patients with CML, BCR-ABL(+), their clinical characteristics, disease evolution, and median survival. Patients and methods: We studied 75 patients with CML and BCR-ABL1(+). T315I mutation was detected by digital droplet PCR and BCR-ABL1 was analyzed by RT-PCR. A comparative analysis was performed by sex, age, disease phase, risk group, treatment, molecular response (MR), and median survival in T315I(+) and T315I(−) patients. Results: T315I mutation was detected in 11 patients (14.7%). No significant difference was found in the phase, risk group, and first-line therapy. A significantly higher proportion of T315I(+) did not achieve MR>3.5 log: 8 (72.7%) vs. 22 (34.4%) (p=0.023). The lowest mean BCR-ABL1 levels were significantly higher in the CML T315I(+) group compared to the CML T315I(−) group: 12.1±6.0 vs. 3.77±1.28 (p=0.009). The median survival of T315I(+) patients was significantly shorter: 73 months vs. 175 months (p Conclusions: Our data confirm the world experience on the frequency of T315I mutation, including the unfavourable evolution, resistance to TKI treatment and short survival. ddPCR is a highly sensitive method for early detection of genetic mutations which gives the chance for effective treatment.

The results of research are presented when replacing finely crushed mineral part of asphalt concrete with waste from the production of porcelain stoneware, which is a product of high-temperature firing of a mixture of refractory clay raw materials and feldspar rocks, which provides high physical and mechanical properties of waste and further road surface.

INTRODUCTION: Worldwide, in different ways, ethical dilemmas arise in medicine and life sciences. It is critical for medical professionals to respond with confidence when ethical challenges are addressed in their clinical practice. Medical ethics and bioethics education is recognized as an essential course of the medical curriculum. The course aims to provide students with knowledge and competencies on dealing with moral problems. OBJECTIVES: In this article, we aim to explore students’ views about the importance and role of medical ethics education for their future practice. Their suggestions on specific medical ethics and bioethics topics were also considered, as well as previous knowledge on ethics before they enrolled in university. METHODS: A paper questionnaire was developed and distributed among first-year foreign medical students from the Faculty of Medicine in the Medical University-Sofia in Bulgaria. All students participated in the study anonymously and voluntarily. The study was conducted during January and February 2020. RESULTS: Completed questionnaires were received from 366 medical students. Data collected demonstrates that only 19% of the students were taught ethics before enrolling in university and covered topics on philosophy and ethics, civil and human rights. The majority (92%) of the responders believe that the study of medical ethics and bioethics helps medical professionals to improve their skills in identifying ethical problems in their everyday practice. Interesting were the suggestions for topics in medical ethics and bioethics that needed further study during lectures and seminars and included principles of medical ethics and bioethics, ethical behavior in medicine and health care, ethical dimensions of new technologies in health care, ethical dimensions of clinical decisions and patients’ quality of life, ethics and health management. CONCLUSIONS: Medical ethics education is significant for future physicians, helping them to improve their skills in identifying ethical issues, and base their decisions on fundamental ethical principals in their everyday practice. Attention should be given to topics related to principles of medical ethics, models of patient-physician relationships, new technologies in health care, ethics and health policy.

Objective – integral analysis of effectiveness of anti-epidemic measures applied towards employees of the Amur gas processing plant assigned for rotational work under conditions of COVID-19 pandemic.Materials and methods. Sero-epidemiological study included a questionnaire survey of 1461 workers who arrived through the “clean corridor” in the Amur Region, followed by sampling of biological material (blood and respiratory smears). Testing of blood sera for the presence of antibodies to SARS-CoV-2 of two classes (IgM and IgG) was carried out applying enzyme immunoassay. Using PCR, respiratory smears were examined for the presence of the agent RNA in them. Statistical processing of the results obtained was carried out using conventional methodsResults and discussion. The presence of antibodies of the IgG class was revealed in (4.7±0.55) % of cases. In a small cohort (1.7±0.34 %) of practically healthy individuals, asymptomatic infection was detected, confrmed either by a positive PCR result (0.76±0.23 %), or by the detection of IgM antibodies (1.0±0.08 %). On the basis of the study carried out by the Federal Service for Surveillance in the Sphere of Consumer Rights Protection and Human Welfare on August 01, 2020, “Temporary recommendations on the procedure for admitting to work on a rotational basis under the risk of COVID-19 spread in the Amur Region” were approved. These recommendations set out the algorithm for observation of incoming workers and the order for triage of shift workers after testing by ELISA and PCR. The results of the study demonstrate the effectiveness of anti-epidemic measures related to ensuring the procedure for admission to work on a rotational basis under the risks of the spread of COVID-19.

PURPOSE Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 ( NCT02935257 ) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL. METHODS Patients age ≥ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years. RESULTS Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease–negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4%-84.4%) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up. CONCLUSION AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL.

Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune inflammatory disorders accompanied by central nervous system damage, widespread immunemediated demyelination, and axonal damage, involving mainly the optic nerves, spinal cord, and area postrema. The diagnostic capabilities, administration and routing of patients, and therapeutic approaches to this disease need to be improved. During several expert councils held in 2019–2021 in different regions of the Russian Federation, we discussed multiple issues related to various aspects of medical care for patients with NMOSDs. As a result, the experts developed further steps necessary to improve the medical care to these patients: to write and publish clinical guidelines for the diagnosis and treatment of NMOSDs; to consider the possibility of optimizing the NMOSDs diagnostic program including the aquaporin-4 antibodies (AQP4-IgG) testing; to evaluate the implementation of a set of measures aimed at including the corresponding laboratory investigations into the system of state guarantees (together with the institutions of the Ministry of Health of Russia), if there is clinical and economic feasibility; to include the issues of timely NMOSDs evaluation in educational programs initiated by the scientific medical community, in order to raise awareness of primary care neurologists in relation to the clinical and neuroimaging signs of probable NMOSDs; to assess the possibility of introducing routing schemes for patients with NMOSDs at the regional level; to work out a decision on the collection of NMOSDs epidemiological and clinical data in the Russian Federation.

Varicocele is a common disease that occurs in 35–40% of men with primary infertility and in 80% of men with secondary infertility Disturbance of microcirculation in the testicles, which occurs during varicocele, lead to ischemia and hypoxia of the testicles, which provoke degenerative changes in all testicular cell populations. Retrograde blood flow from the testicular vein and the external spermatic vein into pampiniform venous plexus leads to an increase of hydrostatic pressure in the testicular vascular system and rise of temperature, and it also contributes to the development of sterile inflammation. Oxidative stress, nitrosative stress, and hypoxia are generally recognized elements of the pathogenesis of infertility associated with varicocele. It is known that when the supraphysiological level of reactive oxygen species in the ejaculate is reached, their concentration disrupts the structure and function of spermatozoa. Nitric oxide (NO) is involved in the regulation of body temperature, NO-dependent mechanisms may contribute to the increased scrotal temperature during varicocele. The physiological concentration of NO pro duced by testicular macrophages stimulates steroidogenesis in Leydig cells. However, in the presence of certain reactive oxygen species, NO can transform into peroxynitrite and other strong cytotoxic metabolites, which lead to dysregulation of testosterone synthesis involved in spermatogenesis. Also, manifestations of varicocele among infertile men have decreased expression levels of the testis-specific heat-shock protein, HSPA2, and abnormal methylation of sperm DNA. Therefore, the use of combined anti oxidant supplements as part of adjuvant therapy after surgical treatment or as an independent application in some clinical cases appears to be an adequate strategy to optimize fertility in patients with varicocele. In this review, we evaluated the importance of various antioxidants, such as vitamin E, folic acid, carnitine, inositol, arginine, acetylcysteine, zinc, selenium in spermatogenesis and their effect on reproductive function during varicocele.

The article provides an overview of global trends in various treatment approaches for COVID-19 in terms of pharmacoeconomic effectiveness. Different strategies for managing patients with the new coronavirus infection, separate groups of drugs are considered. The current clinical trials for COVID-19, the main directions, problems and challenges facing the healthcare system are discussed in detail. The aspects of the economic efficiency of various measures to prevent the spread of COVID-19 are presented. A thorough study of the pharmacoeconomic features of the new coronavirus infection will allow to develop effective standards for planning the process of supply for medical organizations in the pandemic.

In the late 1940s and early 1950s, the place of physiology in the structure of the Soviet scientific knowledge as well as in the system of its popularization changed. The process of raising the role of the natural sciences in the USSR using them for central ideological aims related to the triumph of materialism was marked by loudly propagated scientific events of greater political significance. Such an event was the so-called Pavlov’s Session in Moscow in 1950, whose decisions influenced the scientific institutions in Soviet Union as well as in the Eastern Bloc countries. The school of the Soviet physiologist of Armenian origin Levon Orbeli was criticised and rejected. A Pavlov’s Committee was set up to control the implementation of the Pavlov’s teaching. The aim of the article is to present the influence of the Pavlov’s session of the development of the Institute of Physiology of the Academy of Sciences in Yerevan in the early 1950-es when its experimental and research work became subordinated to the " Pavlovization " of physiology and political and propaganda tasks were added. The institute staff and activities grew, but institutional life was traumatized by the persecution of Levon Orbeli 's school, which reflected on his adherents like the Institute director Ararat Alexanyan who was pressed to leave the position in 1953 during the power struggles were disguised by the session's rhetoric.

Retinopathy of prematurity (RP) is a complex pathology among prematurely born children, which requires a comprehensive approach, including both prevention of the development of more severe stages of the disease, leading to poor vision and irreversible loss of visual functions, and the organization of dispensary observation and rehabilitation. Modern organization of dispensary observation, which is based on a detailed study of the etiology, pathogenesis, as well as the interaction of local and systemic factors on visual functions, can significantly reduce the visual disability of children as a result of this disease.

The aim of the study was to determine kidney survival and validate the novel international immunoglobulin A nephropathy (IgAN) prediction tool (PT) in the Latvian population. Adults with morphologically confirmed IgAN were included. Kidney survival was analysed with the Kaplan–Meier method. PT-assigned risk was compared with calculated risk by the Cox regression model. The Kaplan–Meier analysis included 95 patients. The five-year kidney survival Q3 was 24 months. Women had longer median kidney-survival time (> 60 months) than men (58 months). Median kidney survival in participants with MEST T0 was longer than 60 months; T1 and T2 were 40 and 18 months, respectively. Median kidney survival in participants with diastolic blood pressure (DBP) < 99 mmHg was longer than 60 months, whereas in patients with DBP 100–109 and 110 mmHg, it was 40 and 24 months, respectively. Cox regression analysis included 68 patients. A moderate degree of correlation was found between predicted and observed five-year risk (p = 0.001). Gender, tubular atrophy/interstitial fibrosis, DBP are significant factors affecting kidney survival. Since there was statistically significant correlation and reliability between PT and follow-up analysis data, we conclude that PT could be applied for use in the Latvian population.

The European Union (EU) is trying to increase its influence on the international regulation of the digital economy through domestic and foreign policy initiatives. The EU’s digital strategy, adopted in 2020, envisages measures to further consolidate the single digital market and promote EU standards and regulation internationally. The main goal of the strategy is to ensure the EU’s digital sovereignty. This objective is at the core of policy measures in three priority areas: the elimination of remaining barriers in the internal market, the development of advanced technologies, and the safeguarding of the rights, freedoms and development of democracy in Europe. These three strategic priorities determine sectoral policies: 5/6G development, high performing computers, regulation of digital markets and platforms, cybersecurity, and data governance. The EU uses regulatory, economic, institutional, networking, and foreign policy instruments and mechanisms to achieve its objectives in specific policy areas. Regulation includes further raising standards for personal data protection and consumer rights, control over digital platforms, laying down a legal framework for the development of cutting-edge technologies, attracting investments, and allocating the EU’s own resources to potentially occupy niches in international markets in the future, all of which will strengthen the EU’s claim to leadership in regulating the digital economy and ensure its digital sovereignty. Foreign policy mechanisms are an important part of the toolkit and include a developed European diplomacy, established ties through the Neighbourhood Policy, and the conditionality of development aid.

The results of the joint work of a panel of experts from Rospotrebnadzor and healthcare professionals of the Republic of Uzbekistan on organizing activities to counter the spread of the SARS-CoV-2 virus are described in the paper.The goal of the study was to determine the main driving forces of COVID-19 spread in the Republic of Uzbekistan and develop an action plan to reduce the incidence of coronavirus infection caused by the SARS-CoV-2 virus.Materials and methods. The organization of work in 14 health care institutions in Tashkent and Samarkand, as well as in Tashkent and Samarkand Regions, was analyzed: in 7 laboratories, 6 hospitals and 1 polyclinic. The routes for the movement of personnel, the demarcation of green and red zones, the features of disinfection and the use of personal protective equipment were studied. Attention is drawn to the diagnosis of COVID-19, the use of therapy aimed at reducing the period of virus shedding, the criteria for lifting quarantine restrictions for patients.Results and discussion. The main factors in the organization of work of institutions that contribute to the spread of COVID-19 among medical personnel and the population have been identifed: the lack of equipped gateways between the red and green zones with the accessibility of adequate disinfection, the wrong choice of personal protective equipment, monitoring of contact persons for 10 days, discharge from hospitals based on clinical improvement. The incorrect use of antiviral therapy, the lack of differentiated approaches to the selection of optimal regimens have been noted. Proposals are formulated for organizing the work of healthcare institutions, taking into account the requirements of biological safety. The introduction of targeted measures in addition to those previously adopted has led to a signifcant improvement in the epidemic situation: the total number of active cases in the Republic of Uzbekistan, despite the increase in testing volumes, decreased from 3,686 people on August 23 to 2335 on October 27. Towards December 20, 2020, 97 % of patients recovered completely. All diagnostic triage centers in the Republic of Uzbekistan are closed due to the absence of patients with COVID-19, most of the country’s medical institutions previously re-profled for patients with coronavirus infection have returned to the routine operations.

This paper discusses a new automated training system called CATS. The proposed system covers all the main components of the educational process, including the simple and convenient formation of educational material, tasks for laboratory works, tests to check knowledge, allows you to monitor the progress of students, the process of studying educational content, check completed work for plagiarism, send incorrectly completed tasks to correction, keep an electronic journal and much more. The automated CATS system has been introduced into the educational process at the Belarusian National Technical University and is actively used, especially in the context of the COVID-19 pandemic. In the spring of 2020 alone, more than a thousand users have registered in the CATS system. The intellectual component in the CATS system allows you to implement a unique training program, which is based on the existing knowledge and the level of perception of the educational material by the students. As mathematical methods, it is proposed to use the analysis of expert systems, as well as artificial neural networks. These mathematical methods made it possible to develop adaptability algorithms, their software implementation and testing in the educational process. Users are provided with a web application and its mobile clients for iOS and Android operating systems. Mobile applications are localized in Russian, Belarusian, English and German. By formalizing the intellectual processes that are carried out by both the teacher and the student, it is possible to automate a certain part of their functions, reduce the cost of manual labor, which will make it easier to control the educational process, and make the training itself more effective.

The paper presents the results of amber extraction, which was subjected to high-voltage electric pulse treatment in order to intensify the extraction of target components. This method of processing made possible to achieve a high degree of grinding of the material and the appearance of additional micro- and macropores, which increased a total contact area of the phases required for an effective process of extracting raw materials. The processing was carried out in chambers of a high-voltage pulse-periodic generator with the storage capacities of 0.25 and 1.0 μF, an output voltage of 50 kV, and different number of pulses for the corresponding capacitor capacitance. For research, amber stones with an average size of 8.2 mm were selected. The process was carried out in an alcoholic medium with different electrical characteristics. As a result, the dependences of changes in the dry matter content, total mineralization, content of organic acids, active acidity pH, and optical density in the extract on a number of discharges at different pulse energies were obtained. The density of amber before and after processing was determined, which shows the ability of electric spark discharges to create additional porosity of the material necessary to ensure effective internal mass transfer. The results of the work can be used for the industrial implementation of electrospark processing of amber in order to obtain extracts with a complex of useful substances applicable in food, pharmaceutical, and cosmetic industries.

The pathogenesis of pulmonary fibrosis (PF) is accompanied by extracellular matrix (ECM) deposition, oxidative stress, and inflammation progression, as well as hyperactivation of amine oxidases (AOs), which contribute to disease manifestation. The present study aims to elucidate the effect of semicarbazide (SC), an inhibitor of Cu-containing AOs: lysyl oxidase (LOX), semicarbazide sensitive amine oxidase (SSAO), diamine oxidase (DAO), on PF induced in rats by bleomycin (BLM). Eighteen male Wistar rats were randomly divided into four groups: Control, rats of BLM group received BLM (5 mg/kg, intratracheally once), BLM+SC group obtained 0.005% solution of SC (about 50 µg per capita per day) for three weeks starting immediately after BLM injection, and the Control+SC group drank the same solution as BLM+SC group. The content of cross-linked collagen in total bronchi and free radicals in lung, activities of LOX, SSAO, DAO, polyamine oxidase (PAO), Cu, Zn-superoxide dismutase (SOD1), catalase (CAT) and glutathione peroxidase (GPx) in lung and blood were measured. BLM injection induced PF that was confirmed histologically and morphometrically as well as by the elevation of the content of cross-linked collagen and free radicals. The activities of LOX and SSAO involved in post-translational modification of ECM and inflammation were significantly increased (P < 0.05). The activities of DAO, and PAO that control polyamine metabolism were also essentially raised. Among antioxidant enzymes, only GPx was activated in the BLM group as compared to control. These changes were absent in the BLM+SC group. SC intake promoted the fact that the histology and morphometric parameters of lung tissue, the content of cross-linked collagen in the bronchi and free radicals in the lung, as well as the activity of the studied enzymes remained at the control level. Our data suggest that SC suppresses the development of BLM-induced PF by inhibiting AOs activities.

The article emphasizes that Ukraine, as an active exporter of agri-food products and agricultural raw materials to the European market, needs to take into account the new EU approach to categorization of products based on their sustainability indicators. The European Commission will formulate a legislative proposal on the framework of a sustainable food system, and general requirements for sustainable foods, and their certification and labeling according to sustainability indicators by the end of 2023. Based on the presently available EU documents (first of all, the Farm to Fork Strategy) the author generalizes the main principles and requirements for sustainable foods that will become standard for all foods placed on the EU market in accordance with public interests. It is substantiated that the quite new for Ukraine concept of "sustainable agri-food product" has a broader content than the concept of "eco-friendly product" or "organic product", as environmental friendliness is just one of the characteristics of sustainability, along with the climatic and social ones. The main differences between sustainable and eco-friendly/organic products are systematized. A prominent place in the article is given to the climate criterion of sustainability, in particular, the reduction of greenhouse gas emissions in the production and supply of agricultural food (carbon footprint), which meets the target of decarbonization and achieving climate neutrality in Europe. In the context of creating a harmonized EU methodology for food sustainability, the author considers the content and components of the ecological footprint (land area used for production and utilization, water resources, carbon dioxide emissions, and food miles). The article provides global experience of voluntary certification of food sustainability, and national programs for certification of food sustainability, in particular soybeans in the USA and Canada, which testifies to the growing differentiation of the food market and a tendency towards official certification and labeling of sustainable foods. The author highlights the challenges for Ukrainian exports to the EU under the increasing requirements for the sustainability of agri-food products. In particular, high levels of greenhouse gas emissions from crops (corn and oilseeds) may lead to restrictions on their exports as raw materials for biofuel production. Tracking of chemical pesticide and antimicrobial residues in exported products is expected to be tightened, as the use of these hazardous substances in the EU should be reduced by 50% by 2030. The revealed asymmetry of the spread of the concept of "sustainable foods" between foreign (quite common) and domestic (almost absent) scientific and journalistic sources may indicate that domestic farmers might not be prepared for a timely reorientation to production and export to the EU of sustainable agri-food products. It is obvious that the better off countries will be those who manage to modernize their national agri-food systems in advance in the context of ensuring product sustainability.

To assess endothelial function in the newborns born to mothers with preeclampsia and without preeclampsia the scientists assessed the content of nitricoxide and hydrogen sulfide in the umbilical and venous blood of these children. The main group consisted of 80 women with moderate preeclampsia and their80 newborns; the control group included 50 children born to women without preeclampsia. The authors studied the content of nitric oxide by determining the totalnitrates and nitrites (NOx), hydrogen sulfide in mixed cord blood collected within 30 minutes after delivery, and venous blood taken from newborns on the 1-3rd day of life. Umbilical cord blood demonstrated no significant differences in the content of NO xand hydrogen sulfide in newborns of the main and control groups. However, in general, the study of umbilical cord blood revealed a relationship between the concentration of hydrogen sulfide and the possibility of developing intraventricular hemorrhagein a newborn of the main and control groups. In the venous blood there was a significant increase in the content of NOx and hydrogen sulfide in newborns born to mothers with preeclampsia. It may cause vasodilation asa compensatory reaction of the body during the period of postnatal adaptation of the child’s body, aimed at life support.

The article presents literature data on changes in labo­ratory parameters in new coronavirus infection COVID-19 and the results of our own researches. It was found that in the first three days after hospitalization, most patients had normocytosis, a normal number of lymphocytes. In the mild form, there were slightly more people with normal or with an increased number of leukocytes, granulocytes, but in moderate course, leukopenia, lymphopenia, granulocytosis and granulocytopenia, thrombocytosis, thrombocytopenia were registered more often. At the same time, in the mild form, there were more patients with an increased number of band neutrophils. In mild course, there were no individuals with an increased number of band neutrophils after 3 days in the hospital. Leukocytosis, lymphopenia, granulocytosis were no longer detected after 6 days in the hospital; during this period, the number of patients with leukopenia, thrombocytopenia also decreased significantly, most people had normocytosis. In patients with moderate-to-severe course, leukocytosis and leukopenia were observed for a longer period than with the mild course, even after 10 days in hospital. Most patients had normocytosis. By the sixth day of hospital stay, there were more individuals with granulocytosis (no such patients were registered at a later date), with an increased number of band neutrophils. After 6 days, there was greater number of patients with lymphocytosis, thrombocytosis and lymphocytopenia.