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Aim of the study was to analyze the frequency and nature of cardiovascular complications in influenza A/H1N1/09 in Zabaykalsky Krai from 2018 to 2019. Material and methods. 86 cases of severe influenza A/H1N1/09 were analyzed. Results. The patients were divided into 2 groups, comparable by gender and age. The first group consisted of patients with cardiovascular complications of influenza A/H1N1 / 09 (41 people). The second group consisted of patients without complicated flu (45 people). The average age of patients in the first group was 60 ± 13.7 years. According to the ECG results, sinus tachycardia with a heart rate of 94 ± 14.2 beats/min was dominant, in combination with various rhythm and conduction disorders: supraventricular extrasystole – in 5 (12 %) patients, acute (paroxysmal) atrial fibrillation – in 19 (46 %), ventricular extrasystole – in 7 (17 %), complete right and left bundle branch block – in 7 (17 %) and 7 (17 %), respectively, atrioventricular block of the 1st degree – in 1 (2 %) patients. Long QT syndrome was revealed in 5 patients (12 %). The severe cardiovascular system complications were: myopericarditis in 2 (5 %) people, decompensation of chronic heart failure in 4 (10 %) people, pulmonary embolism in 1 (2 %), acute myocardial infarction in 11 (27 %). The mortality rate in this group was 12 (29 %) cases from hospitalized patients. The average age of patients in the second group was 58 ± 14.1 years. According to the ECG results, sinus tachycardia with a heart rate of 91 ± 9.4 beats/min was detected in 98 % of cases, 3 (7 %) patients had complete left bundle branch block, 1 (2 %) patient had atrial fibrillation. No other rhythm or conduction disturbances were detected. No organic heart pathology was detected in this group of patients. The mortality rate was 5 (11 %) people. Conclusion. The analysis of 86 cases showed that elderly patients with a heavy premorbid background prevailed. The severe cardiovascular system complications were mainly represented by cardiac arrhythmias and the development of acute myocardial infarction. The fatal outcome occurred on the 8th-22nd day from the onset of the disease. The presence of cardiovascular complications doubles the mortality rate.

Background. The frequency of occurrence of dislocation of the shoulder joint is the highest among that for all other limb joints. Simultaneously, recurrent instability of the shoulder joint develops majorly in children and adolescents, which, in the future, lead to the development of persistent pain syndrome. Past evidence indicate that the features of the spatial positioning of the articular process of the scapula can be considered as a risk factor toward the development of instability in the shoulder joint among adult patients. However, there is no reliable data in the literature regarding the influence of tilt and rotation of the shoulder blade glenoid on the occurrence of instability in the shoulder joint among children and adolescents. Encouraged, we undertook this subject for our study. Aim. To clarify the impact of changes in the version and inclination of the glenoid on the instability of the shoulder joint among children. Materials and methods. We analyzed the survey data of 42 children with a habitual dislocation of the shoulder of traumatic and atraumatic origins. The average ages of the examined children were 15.57 1.75 and 15.07 1.64 years, respectively, for those with shoulder instability of traumatic and atraumatic origins, respectively. Results. Statistical data processing revealed no significant differences in the versioning and inclination of the glenoid process between the groups with traumatic and atraumatic instabilities of the shoulder joint. Notably, the average values of versioning and inclination indicators were in the normal range. Conclusion. Based on our results, we suggest that, in the childhood, the dynamic and static soft tissue stabilizers of the shoulder joint play the leading role in the formation of instability of the shoulder joint.

The article discusses the problems of international fragmentation of production and global value chains and how they relate to modern aspects, trends and challenges of international trade development. Methodologically the research rests upon the key principles of classical and alternative theories of international trade, the theory of value chains and the basic theories of foreign investment. In the course of the study, the authors apply both general theoretical (formalization, synthesis, analysis) and particular (measurement, comparison, observation) research methods. The main results of the research are as follows: a conceptual rethink of the nature of today’s international trade in terms of influencing factors of global production decomposition; theoretical justification and criticism of contemporary approaches to the organization of value chains between developed and developing countries; the formulation of measures to modify trade and economic policy in the current system-related and structural challenges of value chains’ transformation. The authors conclude that instability of modern global value chains in the world production and international trade is due to the unsteady dynamics of the global economy, industrial differentiation of global value chains, changes in international strategies of multinational companies, innovation and digitalization of global production networks.

The results of three-year research on the use of allogeneic mesenchymal stem cells of adipose tissue (AMSCs) in the treatment of skin burns of II-III degree are presented. in a complex with wounds dressing of nanofibers chitosan and copolyamide, hyaluronic acid. It was found that with surgical necrectomy, introduction of AMSCs and substitution of defects with natural polymer coatings, the healing time is reduced by 89% (p < 0.05). Isolated administration of MSC reduces the healing period by no more than 5% (p > 0.05). The combined use of wounds dressings of nanofibers chitosan and copo lyamide with MSC accelerates the regeneration process by 26% (p < 0.05), with the introduction of AMSCs accelerating the development of granulation tissue by the fifth day of observation by 83% (p < 0.01). Joint use of wound coverings on the basis of hyaluronic acid with AMSCs is accompanied by an increase in the number of vessels of the microcirculatory bed in the defect area by 185% (p < 0.01). Clinical evaluation of the effectiveness of drugs with stem cells – a gel for topical application and a suspension of MSC LC for injection administration demonstrate their ability to optimize regeneration in the burn zone. Application of gel with AMSCs reduces the duration of epithelialization of border (dermal) burns by 2.2-2.4 times, with the final healing period being reduced by 59% (p < 0.01) and the suppuration frequency by 30% (p < 0.05). The introduction of a suspension of AMSCs into the zone of deep burn increases the frequency of engraftment of autografts, stimulates angiogenesis and proliferation of fibroblasts in the superficial and deep layers of the dermis. In the area of MSC administration, the LC perfusion level and the amplitude of blood flow fluctuation are twice as high as the values in the zones without the introduction of cells.

In the last decade there has been a tendency to move away from the symptomatic treatment and embrace targeted therapies. This process is underpinned by the accumulated knowledge of the mechanisms underlying the pathogenesis of diseases and driven by the advances in biotechnologies. T-cell receptors with variable TRBV9 β-chain regions have been recently associated with spondyloarthritis including its subtype, ankylosing spondylitis. The aim of this work was to engineer a chimeric monoclonal antibody targeting the variable region of the T-cell receptor β-chain encoded by the TRBV9 gene segment and assess its specificity and cytotoxicity. Using flow cytometry and next generation sequencing, we demonstrate that the engineered chimeric antibody is highly specific and exhibits cytotoxic activity against its target. Approaches based on the use of therapeutic chimeric antibodies against pathogenic T-clones may hold great promise for the therapy of autoimmune disorders in general and AS in particular.

This article discusses the results of a continuous study of Russian domestic air carriers conducted in 2006-2016 and analyzes the main barriers to entry into the passenger air travel market and their impact on competition in this field. There are significant structural barriers that prevent companies from entering this market. This situation challenges the existing concept and the idea of the domestic air transportation market as a quasi-competitive one. To describe the structure of the Russian passenger air transport market, we introduce the notion of “discrete competition,” reflecting shifted density of market concentration towards small regional airlines. The latter are usually united by ownership mechanisms or affiliation with an airport. They possess considerable market power, but at the same time have an insignificant market share in the overall Russian passenger air market. Administrative barriers also play a crucial role in restraining competition. Furthermore, current institutional conditions are favourable for vertical "airport - airline" integration which results in a fundamental transformation, as described by Williamson, and can be detrimental to competition. As our research findings have shown, there is a trade-off between existing vertically integrated structures in the air passenger market and public welfare.

Background:Recently a group of T-cell clones with characteristic T-cell receptor (TCR) motif was identified in peripheral blood and synovial fluid of HLA-B*27+ patients with ankylosing spondylitis (AS) [1-2] - a prototypic disease from a wider group of spondyloarthropathies (SpAs). Extraarticular manifestations of AS could involve skin, intestine or eye. Emerging data indicate linkage between intestinal and joint inflammation, including expression of gut-associated integrins on synovial T-cells [3-4]. However, clonal T-cell composition and presence of identical clones in different inflamed sites in SpAs remains poorly studied.Objectives:To investigate clonal T-cell repertoire and presence of AS-related TCR motif in different sites of inflammation of patients with SpA.Methods:Samples of synovial fluid (SF) were obtained from HLA-B*27+ and HLA-B*27- patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), as well as gut biopsy samples from patients with AS and Crohn’s disease (AS/CD) or ulcerative colitis (AS/UC), and conjunctival swabs from patients with uveitis (Uv) and with or without articular manifestations (Table 1). Also SF and gut biopsy samples were obtained from HLA-B*27+ patients with juvenile idiopathic arthritis (JIA). For one patient PsA patient paired samples of SF and gut biopsy were obtained.Table 1.Detection of the AS-related motif TRBV9_CASS[V/A/L/P][G/A] [L/T/V][F/Y]STDTQYF_TRBJ2-3 in bTCR repertoires of samples from different inflamed sites of patients with SpATissueDiagnosisB27+B27-AS-related TCR motif+ among all samples from B27+ donorsSynovial fluidAS2012PsAJIAIntestinal biopsyAS/CD433 / 4AS/UCJLAConjunctival swabUv804 / 8SF and gut samples were processed to isolate mononuclear cells, while conjunctival swabs were directly lysed in the lysis buffer. CD3+ β7-intergin+ cells were isolated from SF by fluorescence-activated cell sorting. Deep TCR repertoire profiling was carried out using UMI-based cDNA library preparation technology [1].Results:Identical T-cell clonotypes were detected between paired SF and gut samples of the same patient with psoriatic arthritis and intestinal inflammation. The subpopulation of β7-intergin+ SF T-cells shared significantly more identical clonotypes with gut biopsy repertoire compared to the bulk SF T-cell repertoire.Clonotypes belonging to the AS-related TCR beta motif TRBV9_CASS[V/A/L/P][G/A][L/T/V][F/Y]STDTQYF_TRBJ2-3 were detected in all inflamed tissues tested: synovial fluid, intestinal biopsies and conjunctival swabs of SpA patients (Table 1). Importantly, we observed these clonotypes exclusively in samples from HLA-B*27+ donors (n=26), but not in HLA-B27- context (n=15) with comparable analysis depth, thus confirming strong HLA-B*27-restriction of the clonotypes. The AS-related clonotypes were detected in the subpopulation of β7-intergin+ SF T-cells from HLA-B*27+ patients with PsA.Conclusion:For the first time we directly report the T-cell clonal sharing between synovial fluid and inflamed gut tissue of SpA patients. In sum our data suggests involvement of identical T-cell clones in inflammation in different anatomical sites in SpA.References:[1]Komech et al. Rheumatology (Oxford). 2018;57(6):1097-1104.[2]Faham et al. Arthritis Rheumatol. 2016;11(10):300-308.[3]Guggino et al.Ann Rheum Dis. Published Online First: 18 October 2019.doi:10.1136/annrheumdis-2019-216456.[4]Qaiyum et al Ann Rheum Dis. 2019;78(11):1566-1575.Acknowledgements:We thanks all the patients and medical personnel involved in the studyDisclosure of Interests:None declared

Objective. The risk of AS is associated with genomic variants related to antigen presentation and specific cytokine signalling pathways, suggesting the involvement of cellular immunity in disease initiation/progression. The aim of the present study was to explore the repertoire of TCR sequences in healthy donors and AS patients to uncover AS-linked TCR variants. Methods. Using quantitative molecular-barcoded 50-RACE, we performed deep TCR beta repertoire profiling of peripheral blood (PB) and SF samples for 25 AS patients and 108 healthy donors. AS-linked TCR variants were identified using a new computational approach that relies on a probabilistic model of the VDJ rearrangement process. Results. Using the donor-agnostic probabilistic model, we reveal a TCR b motif characteristic for PB of AS patients, represented by eight highly homologous amino acid sequence variants. Some of these variants were previously reported in SF and PB of patients with ReA and in PB of AS patients. We demonstrate that identified AS-linked clones have a CD8(+) phenotype, present at relatively low frequencies in PB, and are significantly enriched in matched SF samples of AS patients. Conclusion. Our results suggest the involvement of a particular antigen-specific subset of CD8+ T cells in AS pathogenesis, confirming and expanding earlier findings. The high similarity of the clonotypes with the ones found in ReA implies common mechanisms for the initiation of the diseases.

Single-molecule localization microscopy relies on either controllable photoswitching of fluorescent probes or their robust blinking. We have found that blinking of monomeric red fluorescent proteins TagRFP, TagRFP-T, and FusionRed occurs at moderate illumination power and matches well with camera acquisition speed. It allows for super-resolution image reconstruction of densely labelled structures in live cells using various algorithms.

Unique molecular identifiers (UMIs) show outstanding performance in targeted high-throughput resequencing, being the most promising approach for the accurate identification of rare variants in complex DNA samples. This approach has application in multiple areas, including cancer diagnostics, thus demanding dedicated software and algorithms. Here we introduce MAGERI, a computational pipeline that efficiently handles all caveats of UMI-based analysis to obtain high-fidelity mutation profiles and call ultra-rare variants. Using an extensive set of benchmark datasets including gold-standard biological samples with known variant frequencies, cell-free DNA from tumor patient blood samples and publicly available UMI-encoded datasets we demonstrate that our method is both robust and efficient in calling rare variants. The versatility of our software is supported by accurate results obtained for both tumor DNA and viral RNA samples in datasets prepared using three different UMI-based protocols.

First autologous hematopoietic SCT for ankylosing spondylitis: a case report and clues to understanding the therapy