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Cutaneous T-cell lymphomas are a heterogeneous group of T-cell lymphoproliferative diseases affecting the skin. Mycosis fungoides and Sezary syndrome are the most studied variants of them. The literature review includes the latest published data on the pathological processes development in mycosis fungoides and Sezary syndrome and the diagnosis of these diseases. The genomic instability features in cutaneous T-cell lymphomas are described, the existing hypotheses of the origin of these diseases are considered based on the results of T-cell receptor repertoire studying.

Introduction. Recent trends in the sphere of internationalisation of higher education expand theoretical insights into the dialectical nature of correlation between pedagogical science and educational practice, as well as the relationship between the general direc tions of the development of higher education, its national and regional specifics. An analysis of the experience of internationalisation of universities is required for the development of various models to modernise higher education, including legal education, and to substantiate practical recommendations for reforming the Russian higher education system. To date, an understanding has been reached of the need to internationalise higher education in the context of globalization to increase the competitiveness of the Russian higher education system, as evidenced by the Federal project to maximise the competitive position of Russian universities among the world’s leading scientific and educational centres (The Russian Academic Excellence Project 5-100). Internationalisation, being the key to optimising the export potential of Russian higher education, is essential for the modernisation of legal education.Aim. The research aimed to evaluate the productivity of actual instruments of international cooperation between universities and to outline optimal approaches to the usage of successful practices of international and Russian educational space to enhance the attractiveness of Russian legal education, and, as a consequence, the creation of a sustainable competitive advantage of a higher education institution.Methodology and research methods. Complex, interdisciplinary goals and tasks of the present research predetermined the application of gnoseological and synergetic approaches to the selection of research tools. The gnoseological approach facilitated a more profound analysis of the nature of internationalisation and integration of education in the current international processes. The synergetic approach resulted in the integration of pedagogical and legal research methods to define an optimal internationalisation strategy for the training of multiskilled legal professionals.Results. The authors assessed the effectiveness of the existing ways of internationalization of Russian legal education according to foreign student demand. A comprehensive analysis of the legal, political and social aspects of the current state of attractiveness of the Russian market of educational services and the need to identify the specifics of the internationalization of higher legal education was carried out. The experience monitoring of inter-university international cooperation allowed the authors to determine the conditions for the effectiveness of joint legal programmes (creation of an innovative educational environment, project activities and a flexible management system); to analyse modern pedagogical technologies applicable to legal disciplines; to determine the best schemes used by Russian and European universities for external mobility of students and teachers; to develop the proposals for the introduction of disciplines (for Russian students) provided in foreign languages by Russian and foreign teachers; to propose measures to improve the state policy in the field of interest, aimed at stimulating Russian universities to develop international joint educational programmes.Scientific novelty. The article presented the analysis of positive and negative experiences of Russian universities in application of internationalisation key tools in legal higher education. The acknowledged internationalisation methods of higher education were systematised in general. The additional ways for the integration of Russian legal education, in particular, to the international educational space, were identified.Practical significance consists in the approbation of new methods based on competency and practice-oriented approaches. The authors developed the guidelines for the implementation of internationalisation to enhance university competitive advantage and to increase the demand for graduates in labour market.

The course and management of coronavirus infection (CI) in patients with severe comorbidity are extremely important scientific and practical issues in the era of COVID-19. Kidney transplant recipients make up one of the most vulnerable groups for CI-associated adverse outcomes. Considering the presence of comorbidities, the optimal pharmacotherapy regimens for CI and its complications have not yet been worked out for these patients. In this article, we present two clinical observations demonstrating typical manifestations of coronavirus pneumonia (CP) in kidney transplant recipients, the COVID-19 diagnostic and verification algorithm, and the therapeutic options used to achieve a favorable outcome of CP and to prevent fatal complications. Our findings confirm that in kidney transplant recipients CP is linked to increased disease severity with rapid progression of lung damage and a high risk of developing systemic complications, including thrombotic microangiopathy. It is shown that compliance with the current recommendations for a rational combination of antiviral, anti-inflammatory, anticoagulant and basic immunosuppressive agents in this group of patients provides good treatment outcomes and prevents kidney transplant failure. Two adverse outcomes in the observed group were due to associated opportunistic infection. Based on our findings and clinical data, we conclude that preemptive therapy with IL-6 inhibitors or colchicine is an effective therapeutic option in kidney transplant recipients.

Objective: to conduct comparative analysis of blood biochemical parameters (urea, ALT, AST, creatinkinase, cortisol, testosterone and testosterone / cortisol ratio) in groups of high­class wrestlers with different levels of sports achievements.Materials and methods: male athletes (n = 78), members of the Russian national team in one of the types of wrestling (the average age is 25.2 (21.5–28.9) years, the average weight is 76.9 (68.4–83.4) kg) were recruited to this study. The examined athletes were divided into two groups according to their sporting achievements. The first one — SHA group (super­high achievements) which included athletes (n = 19) who had victories and prizes at the largest international competitions (European, World, Olympic Games), and the second group — MNT group (members of the national team) which included athletes that did not have similar achievements (n = 59). The following biochemical parameters were studied: urea, creatine kinase, ALT, AST, testosterone, cortisol, anabolic index (AI).Results: the absolute values of all metabolites in the examined athletes were within the reference intervals. Statistically significant differences in most of the biochemical parameters were revealed between the compared groups in terms of the level of sports achievements. The SHA group showed a statistically significant shift in relation to MNT group, in direction of increasing the level of metabolites that characterize the predominance of anabolic processes — ALT, testosterone, AI. Metabolite levels, increase which reflects catabolic processes activity and inadequate or insufficient adaptation processes, in the SHA group were significantly lower than in the MNT group. The above changes of the absolute values of biochemical parameters were confirmed by correlation analysis.Conclusions: the obtained results allow us to state the optimal adaptation of this sport, the adequacy of metabolic processes in the group of highly qualified athletes.

Purpose. Experimental and clinical study of hydrophobic intraocular lenses (IOL) enVista and enVista Toric for the correction of aphakia and corneal astigmatism.Material and methods. In the experimental part, enVista and enVista Toric IOLs (manufactured by Baush&Lomb, USA) were studied by electron scanning microscopy. The clinical part of the study included the results of implantation of 100 IOL enVista in patients with cataract and corneal astigmatism up to 1.25 diopters and 20 IOL enVista Toric in patients with cataract and corneal astigmatism 1.25 diopters or higher.Results. According to the results of electron microscopy, no «defects» were found on the surface and optical edge of the lenses. The optical edge of the lens has a rectangular shape throughout 360°. The deviation of the shape of the optical edge of the IOL from the ideal square edge area was 71.53–164.48 um² and 99.05–338.61 um², respectively, at radii of 40 um and 60 um. High uveal biocompatibility was confirmed by the absence of cellular deposits on the surface of all 120 IOLs. The lens material was not biodegraded, and there was no glistening effect in all cases. The percentage of opacity of the posterior lens capsule due to migration of epithelial cells of the lens was 5.0% in the three-six millimeter zone without indications for laser capsulotomy. After implantation of the envista Toric IOL, the average value of astigmatism decreased from 1.77±0.38 to 0.42±0.11 diopters (p

Objective: to evaluatethe preventive immunotherapy's (PIT) influence on indicators of cellular immunity of highly qualified combat athletes, depending on the level of sporting achievements. Materials and methods: research included 79 sportsmen with average age of 25,2 years, average weight 76,9 kg, sports experience no less than 10 years and sports rank no less than master of sports. Participants were stratified by the level of achievements in sports. The group 1 with highest level of achievements consisted of 31 sportsmen, each of who earned victory or a prize place on biggest international competitions (such as championships of Europe, World and Olympic Games). Remaining 48 participants didn't have such achievements, but theywere a part of national team (Group 2). PIT included probiotic - Fervital, a complex preparation of omega 3-6-9 fatty acids, vitamin-mineral complex - the Alphabet-biorhythm; antioxidant complex - Ubigold Q10 (coenzyme Q + vitamin E); antihypoxant - Hypoxen; sedative - Novo-Passit; adaptogenic drug - Gerimax Ginseng; polyenzyme complex - Wobenzym. Results: there was a great balance of cellular immunity in the group 1 before the PIT due to the higher content of CD4+ and CD19+ cells. A statistically significant increase in the relative content of CD3+ and CD8+ cells and a decrease in the relative and absolute content of CD16+ cells was detected against the background of PIT in the group l. But the group 2, on the contrary, showed an increase in the relative and absolute content of CD16+ cells. Conclusions: the obtained results showed a different reaction in the both groups to the conducted preventive immunotherapy, which, apparently, was due to the initial difference in the biochemical, genetic, psychological potential of athletes of these two groups.

Janus kinase (JK) inhibitors block the intracellular signaling pathways that are responsible for the synthesis of proinflammatory cytokines and mediators, which in turn cause the activation of pain receptors and central sensitization (CS). It is suggested that JK inhibitors can rapidly eliminate pain and reduce the severity of CS.Objective: to evaluate the effect of the JK inhibitor tofacitinib (TOFA) on the intensity of pain and the signs of CS in patients with active rheumatoid arthritis (RA) at 7 and 28 days after therapy initiation.Patients and methods. A study group consisted of 39 patients (79.5% female) (mean age 50.9±11.1 years) with RA (DAS28 5.8±0.6). Of these, 89.7% were seropositive for rheumatoid factor; 82.0% took methotrexate and 18.0% received leflunomide. All the patients were prescribed TOFA 5 mg twice daily due to the inefficacy or intolerance of biological agents. The investigators estimated pain intensity using a Brief Pain Inventory (BPI), rated the presence of a neuropathic pain component (NPC) with the PainDETECT questionnaire, and assessed the signs of CS with the Central Sensitization Inventory (CSI) during the first 4 weeks after TOFA administration.Results and discussion. The patients initially experienced moderate or severe pain (the mean scores of 5.33±2.51 on the numerical rating scale (NRS) included in BPI); 53.8% had signs of CS (CSI scores of ≥40); 17.9% had signs of a NPC (PainDETECT scores of >18). Already on day 7 after the start of TOFA administration, there was a statistically significant decrease in the mean NRS pain intensity scores to 4.06±2.2 (p=0.01) and by 29.4±17.9%, as shown by the patient's assessment of the analgesic effect of therapy (BPI), as well as the severity of CS, namely a decrease in the mean NRS pain score to 35.9±11.2 (p=0.01). On 28 days, the effect became better: there was a reduction in the level of NRS pain to 2.32±1.57 (p

The JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the study was to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods. The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results. The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI>40), 15.9% had NCP (PainDETECT>18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p

The review article presents a summary of adverse drug reactions (ADR) in children, information about which was received in 1968–2018 in the International database VigiBase (Uppsala monitoring center, UMC). Of the 18.4 million Individual Safety Case Reports (ICSR) received over 50 years by VigiBase, 1.47 million ICSR contain information on the safety of pharmacotherapy in patients under the age of 18, including: 34 510 reports contain information on ADR in children under the age of 27 days, 415 678 — in children aged 28 days to 23 months, 613 676 — aged 2 to 11 years and 405 202 ICSR — in patients aged 12 to 17 years inclusive. During 2018 141 655 ICSR ADR of children in VigiBase was received. The most common reason for submitting reports on adverse effects in children was vaccines, antibiotics, non-steroidal antiinflammatory drugs, analgesics-antipyretics, anti-acne and valproic acid. The most common side effects of drugs in children were the following ADR: hyperthermia, rash, vomiting, nausea, urticaria, diarrhea, itching, headache, erythema at injection site, convulsion. Separate data on 6 age groups about 10 most frequent ADR in children and about 10 medicines which ICSR most often arrived in VigiBase for 50 years and for 2018 are given.

The article tells about the results of an open 6-month clinical trial of the innovative drug tofacitinib (trade name Jakvinus), the first oral janus kinase inhibitor, in the treatment of 15 patients with rheumatoid arthritis who failed previous therapy. The study found that a daily dose of 10 mg of tofacitinib (TOFA) has high therapeutic efficacy and good tolerability. TOFA monotherapy (7 patients) and combination treatment with standard baseline medicines such as methotrexate or leflunomide (8 patients) was associated with a significant decrease in mean values of all the analyzed indices of RA activity (DAS28, CDAI, SDAI, RAPID), and a significant clinical improvement of ACR 20/50/70 criteria. The positive dynamics of the basic clinical parameters defining the severity of articular syndrome was combined with decreased levels of immune-inflammatory markers: C-reactive protein and rheumatoid factor in blood, and even resulted in seroconversion in two patients. No critical side effects requiring withdrawal or administration of complementary therapy for managing adverse events were observed in the studied group. The findings allowed to conclude that tofacitinib monotherapy and its combination with traditional disease-modifying drugs enhances RA therapy and thus can be recommended for the treatment of RA after failure of standard baseline therapies or contraindications to their use.

Questions of metabolite therapy with drugs based on glutamic acid in patients with chronic heart failure are considered. Possible modes of action of these drugs are presented. Results of the proper study of glutamic acid based drug in chronic heart failure are presented as examples.

The Russian Federation has not got sufficient experience with tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) so far; in this connection, all follow-ups using this drug in real clinical practice are of particular interest.Objective: to evaluate the efficancy and safety of TOFA in an open-label noncomparative trial of RA patients who have failed to achieve low disease activity or remission in compliance with the EULAR criteria after standard disease-modifying therapy and who have been previously untreated with drugs from a group of biological agents.Subjects and methods. Five patients (4 women and 1 men, whose age was 45 to 58 years (mean age 53 years)) with a valid diagnosis of RA were followed up. All the patients had an advanced clinical stage of RA with erosive arthritis (X-ray Stage III), predominantly involving the minor hand joints. Seropositive and seronegative (for rheumatoid factor (RF)) RA was diagnosed in 4 and 1 patients, respectively. At the inclusion into the study, the patients received disease-modifying antirheumatic drugs. Due to the remaining disease activity, all the patients were given TOFA in a dose of 5 mg twice daily (10 mg/day); moreover, 4 patients received its monotherapy (1 because of intolerability and 3 because of noncompliance); 1 female patient took a combination of TOFA and methotrexate (MT) in a dose of 10 mg/week. Two patients continued to use methylprednisolone 4 mg/day (that had been long taken) in combination with TOFA. The duration of TOFA therapy was 3 months.Results. TOFA 10 mg/day showed high therapeutic efficacy and good tolerability. Three-month disease-modifying therapy with TOFA(4 patients) and its combination with MT (1 patient) resulted in a considerable reduction in DAS28 scores and a significant clinical improvement in ACR 20/50/70 responses. Positive clinical changes were associated with a reduction in the blood level of immune markers (C-reactive protein and RF) up to the seroconversion phenomenon in one female patient.Conclusion. The findings allow TOFA to be recommended for the treatment of RA in case of the inefficiency of standard disease-modifying agents or contraindications to their use.

Abstract. The goal of our research was comparative study of the most important parameters of subset cytoarchitectonics in the patients with the different courses of myocarditis and evaluation of their pathogenetic and clinical value in the practice of the physician. We have investigated 99 patients with myocarditis and 40 healthy donors. In patients with malignant course of disease we revealed increased activation index of T/B-cells; increased expression of the activation markers on the both lines of differentiation; disproportion in the immunoregulatory subsets with increased role of dendric cells; decreased intensity of the autoreactive T-cells apoptosis. in the patient with the In patients with nonmalignant course of disease expressed signs of immunopathology were not found. Thus, study of activation markers on the cells of the peripheral blood is more informative and noninvasive method of diagnostics of myocarditis.