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The search for rational treatment of diseases of the nasal cavity and paranasal sinuses is due to the high incidence among the world's population. Despite the absolutely clear recommendations that would seem to greatly facilitate the choice and scope of therapy, it is extremely important to have a differentiated approach to each patient, depending on age, concomitant pathology, the nature of the course of the disease, the severity of clinical, primarily pain symptoms, and the presence of rhinogenic complications. Differential diagnosis of viral and bacterial acute rhinosinusitis (ARS) allows to avoid unreasonable prescription of antibiotics in the former case and choose therapy in such a way as to help relieve clinical symptoms, timely cure the disease and prevent complications. A systematic review of the literature was conducted with the analysis of scientific research data on the evaluation of the effectiveness of protargol or silver proteinate in the local treatment of upper respiratory tract diseases. A review of studies shows that silver proteinate has astringent, antiseptic and anti-inflammatory effects. The spectrum of antimicrobial action of silver is much wider than many antibiotics and sulfonamides. At the same time, pathogenic microflora is more sensitive to silver ions than non-pathogenic microflora. The analysis of the works also demonstrates the absence of adverse reactions when using this drug. The obtained data allow us to recommend preparations based on silver proteinate as a complex therapy for acute and chronic diseases of the nasal cavity and nasopharynx. The vasoconstrictive effect of protargol allows it to be used as an alternative to decongestants in order to avoid the development of drug-induced rhinitis and tachyphylaxis. Sialor® is a new, convenient, affordable, longer-shelf-life form of silver proteinate.

Otitis media with effusion is difficult to diagnose, since the course of the disease is mostly asymptomatic, while the initial stage of the disease is very similar to Eustachiitis or the pre-perforative stage of acute otitis media. At this stage, dysfunction of the auditory tube and negative pressure in the tympanic cavity creates the conditions for the production of transudate, which clinically, in addition to hearing loss, is accompanied by soreness, a feeling of congestion, pressure, fluid transfusion in the ear. When conducting local medical procedures, they are primarily guided by the condition of the mucous membrane of the eustachian tube, nasopharynx and nasal cavity, but changes in the eardrum are no less important. Thus, the use of topical analgesics with an anti-inflammatory effect becomes no less relevant in the treatment.A literature review was carried out with an analysis of scientific research data on the use of a topical combination drug that has a local anesthetic and anti-inflammatory effect in the treatment of diseases of the external and middle ear.Analysis of the literature showed that the use of lidocaine-phenazone-containing drops promotes rapid regression of the inflammation in the external auditory canal and the tympanic membrane, as well as relieving of pain. It can be used both in children (including newborns) and in adults who are suffering from otitis media but with intact tympanic membrane, including otitis media with effusion.Combined topical drugs containing lidocaine-phenazone demonstrate efficacy and safety in the treatment of catarrhal and otitis media with effusion in all age groups.

Introduction. Preoperative, in particular, antiseptic, preparation of the external auditory canal (EAC) is an important issue for the otosurgeon to take in mind, especially with endaural approach.The aim of the study is to assess the skin microbiota of the EAC and the effectiveness of antiseptic treatment before endaural intervention.Materials and methods. A prospective study including 19 patients who underwent ear surgery by endaural approach: 10 stapedoplasty; 9 tympanoplasty. Ear swabs culture were taken from all the patients preoperatively and after removing the tamponade. Of the 10 patients with otosclerosis, 5 underwent skin preparation with 10% povidone iodine and a swab culture.Results. According to the microbiological examination results, Staphulacoccus Auricularis prevailed in the first smear - 52.6%. In 5 patients with otosclerosis, in comparison to the 1st swab: one case with absence of microorganisms growth, in the other 4 -decrease in the degree of contamination by half. In the 3rd swab, there was no growth in these patients and in the rest, who didn't undergo antiseptic preparation. Patients, without antiseptic preparation of the ear canal, after tympanoplasty (9 patients) in the second smear, had an increase of contamination (from 105 to 106 CFU/ml).Conclusions. Analysis of the microbiome before and after the operation revealed the growth of predominantly (94.7%) opportunistic microorganisms. Preoperative antiseptic preparation reduces the degree of contamination of the skin, which, in our opinion, prevents complications and improves the healing process.

Levilimab is anti-interleukin-6 receptor (IL6R) monoclonal antibody. The article presents data obtained during 24 weeks of the SOLAR phase III study.Objective: to confirm efficacy and safety of levilimab in combination with methotrexate (MTX) in patients with methotrexate resistant active rheumatoid arthritis (RA).Patients and methods. 154 adult patients, aged ≥18 years with the diagnosis of RA (ACR/EULAR 2010) and confirmed disease activity at screening despite treatment with MTX for at least 12 weeks (in a stable dose 15-25 mg/week). Patients were randomized 2:1 in levilimab (162 mg once a week, subcutaneously) + MTX (n=102) or placebo + MTX (n=52) group.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy endpoints: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved low disease activity (LDA) of RA (DAS28-CRP Results and discussion. Seventy (68.6%) subjects who received levilimab and 20 (38.5%) who received placebo achieved ACR20 response at week 12. Fifty three (52%) subjects who received levilimab and 3 (5,8%) subjects who received placebo achieved LDA at week 24. The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were (by decreasing frequency): blood c holesterol increase (24% vs 12%), alanine aminotransferase elevation (11% vs 8%), lymphocyte count decrease (9% vs 8%), blood total bilirubin increase (11% vs 0%), blood triglycerides increase (10% vs 2%), aspartate aminotransferase elevation (7% vs 4%), positive interferon-gamma release assay (IGRA) with M.tuberculosis antigen blood test (5% vs 6%), absolute neutrophil count decrease (8% vs 0%). No deaths were occurred.Conclusion. The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. Levilimab showed favorable safety profile and low immunogenicity. No new important safety risks were detected.

Aim: To verify reference values of the heart rate variability (HRV) parameters among healthy 18-27-year olds in the Khanty-Mansi autonomous okrug - Ugra, Eastern Siberia. Methods: Data were collected in series of observational analytical cross-sectional studies between 2006 and 2020. The sample consisted of 13269 subjects - 7442 women and 5827 men aged 18 to 27 years permanently living in Khanty-Mansi autonomous okrug. We studied parameters of background HRV on short-term recordings in the time and frequency domains, Poincare graph and cardiointervalography by R. M. Baevsky. For all HRV parameterswe assessed minimal and maximal values as well as the 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile. Gender differences in all studied variables were studied using Mann-Whitney tests after normality testing using Kolmogorov-Smirnov tests with Lilliefors correction. Results: We observed significant differences between central tendencies of all studied HRV parameters between women and men (p < 0.01) with the exception of the relative power of the spectrum in the very low frequency range - an indicator of the adequacy of the regulation processes and the vegetative rhythm indicator. Conclusions: The reference values of the HRV parameters for young adults living in the Khanty-Mansi Autonomous Okrug-Ugrawere verified. Significant gender differences in all the studied HRV parameters were observed except one, which is considered to be an indicator of the adequacy of the regulation processes and the vegetative rhythm indicator. We also discuss applying centile values of the relative spectral power of HRV to identify categories of heart rate modulation.

We consider actual problems of production, transportation, and storage of hydrogen and demonstrate the urgency and prospects of subsequent investigations and introduction of hydrogen-based technologies in powder metallurgy. We present predictions of an international organization according to which commercial mass production of hydrogen is expected in the nearest future. This will make hydrogen less costly and more available for the extensive applications in various branches of science and industry. It is indicated that hydrogen is not only a promising alternative energy carrier but also an efficient reducer for numerous metals and alloys and an element applied in various technologies of powder metallurgy aimed at getting broad ranges of high-quality products. It is assumed that hydrogen can find extensive applications in industry in the future.

Levilimab (LVL) is a monoclonal antibody against the interleukin-6 receptor (IL6R). The article presents data obtained during 56 weeks of the AURORA phase II study.Objective: to evaluate the efficacy safety and immunogenicity of LVL in methotrexate (MTX) resistant patients with active rheumatoid arthritis (RA).Materials and methods. 105 patients with active RA were randomized in a 1:1:1 ratio into two LVL or placebo groups. LVL was administered subcutaneously at a dose of 162 mg every week (QW) or every other week (Q2W). All patients received MTX. After evaluating the primary endpoint of 20% improvement in ACR criteria (ACR20) at week 12, patients in the placebo group were switched to LVL Q2W. The study duration was 56 weeks. The frequency, profile, degree and severity of adverse events were determined in each group for safety assessment. The immunogenicity of LVL was determined by the proportion of patients with identified binding and neutralizing antidrug antibodies. Results. LVL in both regimens was superior to placebo. At week 12, the incidence of ACR20 achievement was 77.1% (LVL QW), 57.1% (LVL Q2W), and 17.1% (placebo) with 95% confidence intervals [37.53; 82.54] (pConclusion. In MTX-resistant patients with active RA, the efficacy of both LVL regimens at a dose of 162 mg in combination with MTX was significantly superior to MT monotherapy. LVL QW lead to highest treatment response. LVL has been shown to be well tolerated and low immunogenicity. LVL safety profile is similar to IL6R inhibitors.

Netakimab is a humanized anti-interleukin-17А monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Herein, we report the accumulated efficacy data and safety findings of 54-week netakimab treatment during the PATERA study. The aim of the study was to assess the long-term efficacy and safety of netakimab in patients with active psoriatic arthritis. Materials and methods. 194 patients with active psoriatic arthritis despite the previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs were initially randomized to receive 120 mg netakimab or placebo (1:1) at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 inadequate responders in placebo group were reassigned to netakimab in a blinded manner. From week 24 all patients receive open-label netakimab. The analyzed period includes 54 weeks. Results. Netakimab demonstrated sustained treatment response. 94.9% of patients in the netakimab group achieved ACR20 at week 54; 89.5% achieved PASI75 response. Axial disease, dactylitis, and enthesitis significantly improved with netakimab. A similar pattern was observed for placebo/netakimab treated patients. Netakimab was well tolerated. The majority of adverse events were mild and moderate. The most frequent treatment-related adverse events were lymphopenia, increased alanine aminotransferase, hypercholesterolemia. Adverse events of grade 3–4 were observed in 2%. Conclusion. Netakimab demonstrated sustained efficacy in key psoriatic arthritis domains at week 54 with a favorable longterm safety profile.

Netakimab (NTK) is a humanized anti-interleukin-17A monoclonal antibody. To date, the drug has been approved to treat ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis. The paper gives the data obtained during 52-week follow-up of AS patients in the phase III ASTERA study.Objective: to study the efficacy and safety of NTK when used long in patients with active AS.Patients and methods. The investigation enrolled 228 patients with active AS, in whom nonsteroidal anti-inflammatory drugs or biological agents were ineffective. The patients were randomized in a 1:1 ratio to receive NTK 120 mg or placebo. The drug was administered subcutaneously at weeks 0, 1, 2, and then once every 2 weeks. Patients who received placebo and achieved a 20% improvement according to the ASAS criteria (ASAS20) were excluded from the study at week 16. At this week, patients who took placebo and did not achieve an ASAS20 response were switched to subcutaneous NTK at 120 mg dose once every two weeks. The follow-up period was 52 weeks.Results and discussion. Patients with active AS who received NTK were more likely to respond to treatment than those who took placebo. The proportion of people who achieved 40% improvement (ASAS40) during treatment with NTK increased throughout the follow-up period and amounted to 80.7% at week 52. Positive changes were achieved in all used clinical and laboratory parameters of AS activity. There was also a decrease in inflammatory changes, as shown by magnetic resonance imaging (MRI). The adverse events (AEs) were mainly laboratory abnormalities and upper respiratory tract infections. Treatment-related AEs were recorded in no more than one third of patients and they were mild to moderate. Severe AEs were singular.Conclusion. Response to NTK therapy generates in the first weeks of drug use and increases throughout a year. The safety profile of NTK when used long is generally favorable.

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

Introduction. The purpose of the study was learning diagnostic tools of Eustachian tube pathology and define the highly specific prognostic test. The Eustachian tube is a specific structure that is difficult to visualize and manipulate due to its location and anatomical features. Maintaining adequate aeration and physiological pressure in the tympanic cavity is extremely important for middle ear function. The preoperative assessment of the auditory tube function is still important. A lot of studies demonstrate majority methods of evaluation tube function. However, there is no gold standard for diagnosing tubular dysfunction.Goal of reserch. The purpose of this review is to analyze methods for studying the function of the auditory tube as a preoperative preparation for hearing-enhancing operations, namely tympanoplasty.Materials and methods. We analyzed the database related to modern methods of evaluation Eustachian tube function and tympanoplasty outcomes.Results. Despite a large number of studies, the question of a priority and universal method for the preoperative assessment of the function of the Eustachian tube remains open. Each of the studies presented in this review has its own advantages and disadvantages associated with the complexity of the implementation or limitation of application. Endoscopic examination is the most informative for assessing the anatomical state of the auditory tube and nasopharynx. To assess the physiological function, a group of manometric tests, namely tubomanometry and the ETF-test, turned out to be more accurate, universal, and easily conducted.Conclusion. The work of the auditory tube is of great prognostic value for conducting auditory-improving operations and determining treatment tactics. Identification of the “gold standard” of diagnosis will help improve the quality and increase the effectiveness of surgical treatment, and therefore, further research in this area is necessary.

Introduction. Тhe search for drugs that accelerate the process of resolving post-traumatic reactive changes, which have both sufficient anti-edema and anti-inflammatory effects, and reparative properties, is relevant.Goal of reserch. The purpose of this review is to find a means to speed wound healing after nasal traumas.Materials and methods. The researchers conducted an analysis of scientific research data to evaluate the efficacy of naturopathic mountain arnica-based remedies for the treatment of patients with an external nose trauma accompanied by the formation of edema, hematoma of lateral nasal wall and/or skin abrasions of external nose.Results. This work shows that topical plant remedies based on Аrnicamontana has a pronounced anti-inflammatory and antiedema effect, comparable to the traditionally used for this purpose heparin-containing ointments and gels. However, unlike the latter, products based on Arnica montana have a pronounced wound- healing effect, which allows to significantly reduce the time to resolve traumatic injuries of the skin of the external nose. The analysis of the work also demonstrates the absence of adverse reactions when using this drug.Conclusion. The obtained data allow us to recommend topical naturpathic remedies based on Arnicamontana for use as a firstchoice drug for wound healing after nasal traumas. In addition, the drug is effective in the complex treatment of patients with nasal trauma requiring surgical intervention: at the preoperative stage - to reduce post-traumatic reactions and prepare for surgery, and at the postoperative stage - for the early recovery, reducing edema and inflammation.

Актуальность. В настоящее время пиелонефрит (ПН) остается одной из самых распространенных бактериальных инфекций в детском возрасте. Лечение хронического ПН (ХП) должно основываться на принципах этапности, непрерывности и преемственности. Цель. Оценка целесообразности назначения противорецидивной терапии, ее переносимости и эффективности различных схем для предотвраще-ния рецидивов у детей с острым ПН и ХП. Материалы и методы. В исследовании принимали участие 167 детей от 2 до 12 лет, в том числе 139 (83,2%) девочек и 28 (16,8%) мальчиков. Дети распределены в следующие группы: 1А (n=32) – с дебютом острого ПН, получала цефалоспорины (ЦС) III поколения 10–14 дней; 1Б (n=35) – с дебю-том острого ПН, получала ЦС III поколения 10–14 дней, далее 1 мес комбинацию стандартизованных экстрактов BNO 1040; группа 2А (n=32) с реци-дивом ХП получала ЦС III поколения 10–14 дней, затем фуразидин 14 дней; группа 2Б (n=34) с рецидивом ХП получала ЦС III поколения 10–14 дней, затем фуразидин 14 дней, далее в течение 1 мес комбинацию стандартизованных экстрактов BNO 1040; группа 2В (n=34) с рецидивом ХП получала ЦС III поколения 10–14 дней, затем в течение 3 мес комбинацию стандартизованных экстрактов BNO 1040. Результаты. При проведении противорецидивной терапии у всех пациентов группы 1Б отмечались отсутствие рецидива заболевания в первые 6 мес после окончания антибактериальной терапии, а также тенденция по увеличению продолжительности периода ремиссии при сравнении с группой 1А. Среди пациентов с ХП наименее эффективна оказалась схема терапии, использованная для группы 2А, она статистически значимо (р

We aimed to evaluate a significance of T-bet transcription factor in bronchial asthma (BA). A total of 102 patients with BA were examined. The control group was represented by healthy subjects (21 people). The study model was represented by peripheral blood mononuclear cells isolated in a density gradient with standard method. It was found that some patients were characterized by high levels of transcription factor T-bet expression (T-bet > 1.0). The bronchial asthma patients with increased T-bet expression were moir often characterized by the severe disease, requiring therapy with systemic glucocorticoids and β2-agonists, did not have genetic predisposal for allergic diseases, the majority of them had excess body weight and concomitant morbidity (mainly, cardiovascular, gastrointestinal and endocrine disorders). The study of rs324011 polymorphism of STAT6 protein gene in these patients revealed CC and CT genotypes, mostly observed in severe BA. Moreover, they were observed in 100% patients with severe clinical course of BA. A positive correlation was found between the number of T allele presentation in loci, and BA severity (r = 0.88, p = 0.002), as well as between the distribution by genotype (CC-CT/TT), and absolute (counts per one L), and relative (%) number of eosinophils in the sputum (r = 0.79, p = 0.034). The detected associations may be referred to as “T-bet elevation syndrome”, being based on the phenomenon of “genetically determined heterogeneity of signaling system defects”. In individuals with an increased T-bet expression, a significant elevation of transcription factors STAT6 and STAT4 was also detected. Taken together, the presented data indicate that this phenomenon reflects a disturbance of the Th1 / Th2 balance, due to increase in both Th1 and Th2 transcriptional activity. Thus, the patients with bronchial asthma with increased expression of T-bet transcription factor revealed a symptom complex, which we have called “T-bet elevation syndrome” (T-bet > 1.0), which is characterized mainly by severe disease and a certain phenotype of patients. Most likely, this feature is caused by genetically determined defects of signaling systems. High T-bet expression has been observed in young patients with mild BA and can be a prognostic sign.

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year. The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial. Subjects and methods . The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs. Results and discussion . An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded. Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

This article presents a clinical case of a foreign body of the nasal cavity. To describe a foreign body in the nose, the term «rhinolite» is used, which originated from the Greek «rhino» (which means «nose») and «lithos» (which means stone). In this observation the optical endoscopy and cone-beam computed tomography demonstrated as the most informative methods for confirm the diagnosis and for determine medical tactics.

The authors have formulated and consistently proved the hypothesis that well-functioning interaction of tax and customs authorities is required to increase the effciency of the state revenues administration. The mechanism of this interaction should be formed when implementing the standards of the World Customs Organization and the World Trade Organization into the Russian legislation. The research is particularly relevant since Federal Law No. 289 of 03.08.2018 “On Customs Regulation” has entered into force. This law includes article 222 “Interaction and cooperation of customs and tax authorities”. As scientifc and practical results, promising areas for development have been worked out: improving unifed mechanism of customs, tax administration and currency control based on integrated innovative technologies; implementing international standards developed under the auspices of the World Customs Organization; creating prerequisites for the transition to the payment of import customs duties and taxes after the release of goods for law-abiding business; redistributing functions of customs and tax authorities. The authors propose to leave the control of import duties payments for the customs authorities, and to delegate the control of VAT and excise taxes on imported goods payments to the tax authorities. The article includes the results of a comparative legal analysis of the acts of the World Customs Organization, the Financial Action Task Force on Money Laundering (FATF), the Organization for Economic Cooperation and Development (OECD) and the Agreement on Cooperation of the Federal Customs Service and the Federal Tax Service of Russia. It justifes the conclusion that the studied cooperation is the most important tool for the customs payments administration. This is confrmed by the statistics on additional and pre-leased revenues to the state budget based on the results of joint and coordinated verifcation activities. The result of the study is the formulation of promising areas for improving the interaction of customs and tax authorities in the Eurasian Economic union (EAEu) and Russia.

The paper focused on legal issues of using secondary sources in energy sector and implementation methods and challenges. The main idea of the proposed research is to substantiate the proposals and recommendations aimed at solving scientific and methodological problems of forming an effective economic and legal mechanism of secondary resource use based on a comprehensive approach to legal support for it. The paper underlined that secondary sources as an economic phenomenon occurs in conditions of growing demand for limited natural resources, including energy, increasing consumption, increasing the burden on the environment due to the accumulation of waste that cannot be recycled in natural conditions. The research stated that use of secondary resources is the basis of a circular economy, a new model of management based on the idea of green growth. Formulated prerequisites for involvement in economic circulation are the technological feasibility and economic feasibility of energy generation, which determined by the profitability of each type of production using secondary sources. The authors stressed that there is the urgent need to outline appropriate tools for legal regulation of outsourcing relations at the microeconomic level, the definition and essential characteristics of the most appropriate legal means in the mechanism of economic and legal regulation of outsourcing relations in the energy sector; economic and legal means that provide the optimization effect of outsourcing. Summarizing the research, the five steps methodology for assessing the implementation methods and challenges are formulated.

The article dwells on the results of the survey of the asphalt concrete modified with various additives. It contains the results of the impact made by the modifying additives on the physical mechanic and performance properties (rutting resistance, fatigue life and permanent deformation accumulation resistance) of the Type A Grade I asphalt concretes. In the article the regularities of the influence exerted by the formula-related and technological factors on the asphalt concrete properties were established. Consistent with the obtained results forecasting of rutting in accordance with AVTODOR STO 2.28-2016 and forecasting of fatigue damage accumulation on the basis of the Miner’s cumulative model of damage linear addition were executed. On the basis of the forecast results the interrepair life of the road structures with the pavement courses of asphalt concretes containing the surveyed modifiers was evaluated.

The paper gives data on the clinical efficiency and safety profile of long-term use of the infliximab (INF) biosimilar BCD-055 versus the reference drug Remicade® (REM) in a population of patients with active ankylosing spondylitis (AS).Subjects and methods. An international multicenter randomized double-blind Phase III clinical trial was conducted in 199 patients who were randomized into two groups in a 2:1 ratio and who received BCD-055 or REM at a dose of 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks. Efficiency assessment was made at 14, 30 and 54 weeks in patients who received at least one dose of INF [intent-to-treat (ITT)], as well as at 54 weeks in those who completed the study according to the Protocol (PP) (per protocol). The efficiency endpoints were the proportion of patients who had achieved ASAS20/ASAS40 responses; changes in BASDAI, BASMI, BASFI, MASES, and SF-36 scores. Immunogenicity was assessed by the proportion of patients in each group with identified binding and neutralizing antibodies (BAbs and NAbs) against INF. The safety analysis included the overall rate of adverse events (AEs), including those that met the respective criteria for serous AEs (SAEs), and grade 3–4 toxicity, as well as the number of cases of early termination of the study because of AEs and SAEs.Results and discussion. The ITT population included 199 patients and the PP one consisted of 161 people. The groups were not statistically different in the rate of and reasons for patient withdrawal from the study. A comparable number of patients achieved ASAS20/ASAS40 responses at 14, 30, 54 weeks (р ≥ 0.05). At 54 week, the proportion of patients who received BCD-055 and REM therapy and achieved an ASAS20 response was 67.42 and 52.24% in the ITT population (p = 0.053) and 80.91 and 68.63% in the PP population (p = 0.128). The BCD-055 and drug comparison groups achieved an ASAS40 response in 53.03 and 38.81% in the ITT population (p = 0.081) and in 63.64 and 50.98% in the PP one (p = 0.177). The proportion of persons with identified BAbs and NAbs was comparable: 21.26 and 3.15% in the BCD-055 group (p = 0.920) and 20.63 and 6.35% in the group REM (p = 0.443), respectively. It was found that the presence of NAbs did not affect the therapeutic response. Both groups did not differ in the detection rate and profile of AEs and SAEs or in the rate of patient withdrawal due to AEs. Most identified AEs were mild to moderate.Conclusion. The efficacy of the INF biosimilar BCD-055 used long in patients with AS did not significantly differ from that of the original drug REM; the safety profile of both drugs was comparable.

This article presents results from two clinical trials of infliximab biosimilar, BCD-055, including comparative data on the pharmacokinetics (PK), efficacy and safety of BCD-055 and innovator infliximab (IFX) in patients with ankylosing spondylitis (AS). Objective : The purpose of phase I clinical study ASART-1 was to evaluate the pharmacokinetic and safety profile of BCD-055 and to prove its equivalence with Remicade®, phase III study ASART-2 was conducted to evaluate the efficacy and tolerability of BCD-055 in comparison with Remicade® in patients with active AS. Patients and methods : Both studies were conducted as international multi-center randomized double-blind studies in direct comparison with innovator IFX. Inclusion and exclusion criteria, main examination methods, and drug regimens were the same in both trials. A total of 199 patients were enrolled in the studies. After the screening, the patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV at 0, 2, 6 and then every 8 weeks (up to week 54). The primary endpoint for PK profile evaluation was the area under the concentration-time curve (AUC(0-tau)), maximum serum concentration of infliximab at steady state Cmax,ss. Efficacy was assessed by achieving ASAS20 at week 30, the endpoints for safety profile were the incidence of adverse events and serious adverse events during the maintenance-dosing phase and withdrawals from the study due to the safety reasons. Results : A total of 81 patients (ASART-1 study) were included in PK analysis, 199 patients were in efficacy and safety analysis. AUC(0-tau) value were 25,420,996.25±11,635,015.74 (ng/ml) Cmax,ss for BCD-055 and 26,114,705.71±12,102,376.9 (ng/ml)⋅h for INF innovator (p>0.05). Cmax,ss for BCD-055/Remicade® was 122,752 [99,401–151,553] ng/ml and 119,844 [98,120–132,772] ng/ml, respectively (p>0.05). ASAS20 was achieved at week 30 by 81.30% of the patients in the BCD-055 group, and 67.74% in the INF innovator group (p=0.061). The analysis of secondary endpoints (BASDAI, BASMI, BASFI, MASES, quality of life, chest excursion, and number of pathologically changed joints) showed no difference between the biosimilar and innovator groups. BCD-055 and innovator IFX showed highly similar safety profiles in both studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and were 48.48% and 58.21% of patients in the BCD-055 and Remicade®, respectively. Conclusion : BCD-055 is found to be equivalent in terms of PK, and showed the similarity in efficacy and safety profile compared with innovator IFX in patients with active AS.

The production method of efficient composite uranium–gadolinium fuel, the application of which will make it possible to improve the technical and economic performance of nuclear power plants, is developed in a laboratory. Based on the analysis of results, the substantiation of implementing the proposed method in industrial conditions is performed. Methods for the preparation and production of the initial materials to prepare gadolinium oxide are described. Necessary characteristics of the pellets of the promising composite uranium–gadolinium fuel are established in the course of experiments, and final requirements for these pellets are formulated allowing for them.

This publication was designed to report the experience gained by the Department of ear, nose and throat diseases at I.M. Sechenov First Moscow State Medical University in the matters concerning professional medical education in the framework of the clinical residency. The main factors that contribute to the adequate shaping of the future ENT-doctor are considered. These include the continuity of generations and conservation of the traditions in the combination with the development of the leading areas of scientific, clinical and educational work.В данной статье представлен опыт коллектива кафедры болезней уха, горла и носа Первого МГМУ им. И.М. Сеченова по обучению в клинической ординатуре. Выделены факторы, влияющие на формирование 'облика' будущего врача-оториноларинголога на кафедре болезней уха, горла и носа. К ним относятся: преемственность поколений, сохранение традиций в сочетании с развитием ведущих направлений научной, клинической и педагогической работы.

The rheumatic manifestations of endocrine diseases are well-known. The endocrine system has a complex effect on the structure and function of musculoskeletal tissues. The symptoms of locomotor apparatus injuries often come to the forefront in the clinical picture of an endocrine disease. It is therefore important to put endocrine diseases, including hypothyroidism, arthropathy, myopathy, etc., in a range of differential diagnoses of musculoskeletal system lesions. It should be remembered that changes in the locomotor system are able to partially or completely regress when endocrine disorders are adequately and long compensated for. The paper describes a clinical case in which, despite an obvious diversity of the typical clinical presentations of hypothyroidism, the main complaint was pain in the joints and muscles. In this connection, the female patient was initially misdiagnosed. This could be avoided if there was alertness to endocrine arthropathies and myopathies.

The myocardium of the right and left atrial appendages (auricles) in patients with paroxysmal, persistent, and permanent forms of atrial fibrillation was examined by histological methods and electron microscopy. Isolated atrial amyloidosis was detected in the left (50.0-56.3% patients) and in the right (45.0-55.6% patients) atrial appendages. In all cases, immunohistochemistry revealed atrial natriuretic peptide in fibrillary amyloid deposits. Ultrastructurally, amyloid masses formed clusters of myofibrils 8-10 nm in diameter. They were chaotically located in the extracellular space along the sarcolemma as well as in membrane invaginations, dilated tubules of cardiomyocyte T-tubular system, and vascular walls. Amyloidosis was predominantly observed in women; its degree positively correlated with age of patients and duration of atrial fibrillation but negatively correlated with atrial fibrosis. The study revealed positive (in permanent atrial fibrillation) and negative (in paroxysmal atrial fibrillation) correlation of amyloidosis with myofibril content in atrial cardiomyocytes.

Forty-two patients with allergic bronchial asthma (ABA) forty persons with non-allergic bronchial asthma (NABA), and 47 healthy controls were involved into the study. Expression of FoxP3 mRNA was analyzed by RT-PCR. In patients with bronchial asthma (ABA and NABA) we have revealed a significant decrease in FoxP3 mRNA expression levels, in comparison with control group. The patients with severe BA exhibited lowest levels of the FoxP3 mRNA expression as compared with other groups. We revealed a decreased FoxP3 mRNA expression in mononuclear cells from peripheral blood, and an increased IL-17 level in blood serum of patients with bronchial asthma. These results may be considered a manifestation of serious inflammatory process. Probably, the data may reflect a disregulated expression of FoxP3 transcription factor. Therefore, we may assume a key role of FoxP3 for regulation of inflammatory activity in bronchial asthma.

The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera), a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia®) (the BIORA study) in patients with rheumatoid arthritis (RA) refractory to therapy with tumor necrosis factor- а inhibitors. Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability. Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1): 1) the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2) those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1) with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia®) or Group AM (that was MabThera®), the similar methodology was followed in Group 2 (Groups MM and MA). Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks. Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50) and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773), which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment outcomes.

The article provides data on diagnostics and tactics of patient management with external otitis especially of mycetogenic etiology (otomycosis). Possibiities of combined topical four-component drug Candibiotiс and its universal effect combining antibac-t erial, antifungal, anti-inflammatory and analgesic actions. An experience of application of Candibiotic has been shown in Russia in the recent 10 years, by results of studies its effectiveness in therapy of acute and chronic inflammatory diseases of the middle and external ear is provided, including otomycosis.

Endomyocardial biopsy samples of the interventricular septum from patients with hypertrophic cardiomyopathy isolated during myectomy were examined. We revealed significant variability of cardiomyocyte ploidy (from 2.9c to 13.5c) that directly correlated with myocyte size; the maximum ploidy was found in young patients. Ultrastructural signs of increased contractile and synthetic activity of cells were observed in patients with high DNA content in cardiomyocytes.

The article considers the management of patients with acute otitis media. Special attention is given to an integrated approach of the treatment (etiologic, pathogenic and symptomatic). The article focus on timely and reliable antibiotic therapy, the role of local medicines, depending on the stage of the disease. The paper consists a review of clinical studies on the effectiveness of a complex drug (containing lidocaine hydrochloride and phenazone) in acute otitis media without perforation.

This article was designed to present a concise overview of the literature concerning cholesteatoma of the external auditory meatus and to report the original clinical observation of this condition with special reference to the necessity of its early diagnostics and surgical treatment with the use of the combination of simultaneous sanation and reconstruction.Представлен краткий обзор литературы, а также собственное клиническое наблюдение холестеатомы наружного слухового прохода. На примере клинического наблюдения обоснована необходимость своевременной диагностики и хирургического лечения, сочетающего одномоментную санацию и реконструкцию в необходимом объеме.Представлен краткий обзор литературы, а также собственное клиническое наблюдение холестеатомы наружного слухового прохода. На примере клинического наблюдения обоснована необходимость своевременной диагностики и хирургического лечения, сочетающего одномоментную санацию и реконструкцию в необходимом объеме.

The article describes the clinical case of the cholesteatoma of the temporal bone pyramid, leading to a massive destruction of the surrounding structures. Attention is drawn to the importance of timely diagnosis of this pathology with the use of objective visualization methods to select the optimal surgical approach, which allows to completely remove this formation.В статье описан клинический случай холестеатомы пирамиды височной кости, приводящей к массивной деструкции окружающих структур. Обращается внимание на важность своевременной диагностики данной патологии с применением объективных методов визуализации для выбора оптимального хирургического доступа, позволяющего полностью удалить данное образование.

Aim: to assess clinical efficacy of polietilenglicol (macrogol) with molecular weight 4000 kDa in children with chronic constipation. Patients and methods: clinical efficacy was assessed in 30 children aged 2–12 years with chronic constipation. The follow-up was performed on an out-patient basis, patients and their parents kept diaries, noting stool characteristics according to the Bristol stool scale. Coprological analysis and abdominal ultrasound were carried out. The duration of the follow-up after the withdrawal of the studied drug was 6 months. Results: during the 1st week of treatment the frequency of stool increased in 23 (76,6%) children, normalization of stool frequency to the 4th week of treatment was achieved in 93,3% of patients. Stool consistency in 1 month of treatment met criteria of the 3d and 4th types according to the Bristol stool scale in 27 (90%) children. Painful defecations have been arrested by the 3d week of treatment. Conclusions: the drug was shown to be highly effective in treatment of chronic constipation in children, arresting such symptoms as «fear of the potty» and painful defecations and having a strong positive dynamics after its withdrawal.

We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter

We present the results of treatment of chronic ischemia of the lower extremities (distal form) with angiogenesis stimulators, autologous endothelioblast precursors (CD133+) and gene preparation of vascular endothelial growth factor VEGF165 (angiostimulin). Good clinical effect was attained in all patients, which was confirmed instrumentally 1, 3, and 6 months after administration of the stimulant: transcutaneous oxygen tension on the foot, index of malleolar pressure, and walking duration increased, parameters of microcirculation improved, the number of newly formed collateral arteries increased (angiography findings), quality of life improved (SF 36 questionnaire), and parameters of coagulogram also improved. The maximum positive dynamics was observed by month 3 of the study.

Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofi brillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.