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Spinal muscular atrophy 5q (SMA) is one of the most common inherited neuromuscular diseases in children with an autosomal recessive type of inheritance. Homozygous deletion of exons 7 or 7–8 of the SMN1 gene encoding the motor neuron survival protein is responsible for 95 % of cases. SMA is characterized by a steadily progressive course with the development of paresis, muscle atrophy, loss of previously acquired motor skills, respiratory failure and skeletal deformities. The introduction of pathogenetic therapy in recent years has significantly changed the trajectory of SMA – patients survive, restore previously lost motor skills and acquire new ones. The clinical classification, which includes 5 types of SMA, is currently not a reliable reflection of the functional state of the child in dynamics. In 2005, a functional classification was recommended based on the patient’s current status: non-sitters (lying), sitters, and walkers. The article provides a summary of historical concepts regarding functional classification in SMA patients, as well as the criteria used in clinical trials and observations. We proposed criteria for categorizing SMA patients into a specific functional class by analyzing the available literature and making recommendations on using the classification in real clinical practice.

Background. One approach to improving overall and relapsefree survival for patients with acute leukemia is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The probability of relapse after allo-HSCT in acute leukemia patients may be influenced by many factors, including the presence of minimal residual disease (MR) before allo-HSCT. Aim. To evaluate the relationship between MR presence in first complete remission and probability of relapse after allo-HSCT in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).Materials and methods. The study included 241 patients: 143 with AML and 98 with ALL (30 patients with Ph-positive leukemia, 22 patients with T-cell ALL and 46 patients with B-cell ALL) who received allo-HSCT at the National Medical Research Center for Hematology from September 2015 to July 2021. The MR analysis was performed using flow cytometry. Statistical analysis was performed using BIM SPSS v. 23 (SA).Results. Univariate event analysis revealed that in AML patients, poor prognosis was most associated with MRD-positive status before allo-HSCT (hazard ratio (HR) 10.249 (95 % confidence interval (CI) 4.137–25.388); p ˂ .0001). Multivariate analysis included MRD-positive status before allo-HSCT (HR 9.161 (95 % CI 3.513–23.652); p < 001), ELN risk (HR 4.423 (95 % CI 1.764–11.092); p ˂ 0.0034), and transplant source (bone marrow/peripheral stem cells) (HR 3.068 (95 % CI 1.188–7.924); p ˂ 0.0156). Three-year overall and relapse-free survival of AML patients in the first complete remission with MRD-positive status were statistically significantly worse than in patients with MRD-negative status (overall survival 43 % versus 78 %; p = 0.0004; relapse-free – 26 % versus 67 %; p ˂ .0001). In the univariate event analysis, it was found that MRD-positive status before allo-HSCT (HR 4.180 (95 % CI 1.333–13.112); p = 0.0142) was most associated with an unfavorable prognosis in ALL patients. In the multivariate analysis, only the MRD status before allo-HSCT was selected (p = 0.0005). The overall survival of MRD-positive ALL patients, although significantly worse, did not differ statistically significantly from that of MRD-negative patients who received allo-HSCT in the first complete remission (28 % versus 68 %; p = 0.09).Conclusion. MRD analysis before allo-HSCT helps to identify a group of patients with an extremely high risk of relapse after transplantation, which dictates the need to correct therapeutic tactics regarding the choice of donor, conditioning regimen, immunosuppressive therapy, or early prophylactic antirelapse therapy.

Background. Autologous hematopoietic stem cell transplantation remains in demand for patients with hematological malignancies. The pool of hematopoietic stem cells is known to be heterogeneous. e studied various factors associated with previous treatment, patient and disease characteristics, as well as the composition of the C34+ pool in peripheral blood (), associated with the number of C34+ cells in the first leukocyte concentrate (LC).Aim. To determine the factors associated with C34+ , C34+ C143+ , C34+ C38– HLA-DR+/– and C34+ C38+/– HLA-DR– cells count in the first LC of patients with hematological malignancies.Materials and methods. Subpopulations of hematopoietic stem cells in the and first LC were studied in 80 patients with hematological malignancies (male to female ratio 1:1, median age 51 years). The control group included 24 healthy donors. Flow cytometry was used to determine the number of C34+, C34+ C38– HLA-DR+/–, C34+ C38+/– HLA-DR– and C34+ C143+ cells. Immunophenotyping was performed on samples of patients before mobilization and on the 1st day of leukapheresis, as well as on first LC samples on the 1st day of hematopoietic stem cells collection.Results. It was shown that the presence of early progenitor cells with C34+ C38– HLA-DR+/– immunophenotype in the before mobilization is associated with a higher first LC C34+ cells number (p = 0.003). In the presence of C34+ C38– HLA-DR+/– cells in the before mobilization, the median number of C34+ cells in the first LC was 2.6 %, and in their absence – 0.71 %. hen using granulocyte colonystimulating factor as monotherapy, the C34+ C143+ cells number in the first LC was significantly lower than when using chemotherapy and granulocyte colonystimulating factor (p = 0.03). However, the majority (9 of 16) of patients in the granulocyte colonystimulating factor monotherapy group had renal failure before mobilization. No factors associated with the number of C34+ C38– HLA-DR+/– cells in the first LC were found. In patients >60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients ˂ 60 years old (p = 0.043). In patients with infectious complications during hematopoietic stem cell mobilization, the number of C34+ C38+/– HLA-DR– cells in the first LC was lower than in patients without them (p = 0.019).Conclusion. The first LC number of C34+ cells is associated with number of C34+ C38– HLA-DR+/– cells, i. e. cells of the early differentiation stage with a high proliferation potential. A relationship was established between C34+ C143+ cells number before mobilization and first LC C34+ cells count: in the paired model – within the borderline values (p = 0.05), and in the multifactorial covariance model – with high significance (p = 0.0033). It has been proven that with increasing patient age and in the presence of infectious complications, the number of longterm repopulating C34+ C38+/– HLA-DR– cells decreases.

Background. Benign recurrent intrahepatic cholestasis is a rare inherited disorder characterized by recurrent episodes of severe hyperbilirubinemia and pruritus that resolve spontaneously. However, attacks of cholestasis may persist for several months and in some cases be associated with frequent recurrences, which may be grounds for liver transplantation.Objective. To present a clinical case of debut benign recurrent intrahepatic cholestasis following acute hepatitis A.Results. A 30-year-old patient was admitted at the Liver Transplantation Center of Moscow Regional Research and Clinical Institute n.a. M.F. Vladimirskiy for a prolonged episode of intrahepatic cholestasis with severe coagulopathy after acute hepatitis A. Total bilirubin was elevated up to 835 µmol/L and INR was 3.6. The manifestations of vitamin K-associated coagulopathy were controlled after the first dose of parenteral menadione sodium bisulfite. Glucocorticosteroids, ursodeoxycholic acid and plasmapheresis turned ineffective in the treatment of hyperbilirubinemia. Due to long-persisting cholestasis resistant to conservative therapy, the patient was considered for inclusion to the liver transplant waiting list. However, spontaneous resolution of the cholestatic episode was achieved at 5 months after the onset of manifestations. Benign recurrent intrahepatic cholestasis type 2 was diagnosed on the basis of the specific clinical signs, laboratory blood tests and genetic testing.Conclusion. The present Case Report shows a long-lasting episode of cholestasis with severe coagulopathy in acute hepatitis A in a patient with benign recurrent intrahepatic cholestasis with subsequent spontaneous resolution of the clinical symptoms at 5 months after their manifestation onset. Therefore, the differential diagnosis of benign recurrent intrahepatic cholestasis should be considered prior to liver transplantation in patients with intrahepatic cholestasis.

This paper is devoted to the memory of Volodymyr Methodyevich Yakovenko, an outstanding scientist in the field of solid-state radio physics, Honored Worker of Science and Technology of Ukraine, Full Member of the National Academy of Sciences (NAS) of Ukraine, Honorary Director of the O.Ya. Usykov Institute for Radiophysics and Electronics (IRE) within the NAS. At the IRE, Dr. Yakovenko founded a scientific school that is well-known for its studies of charged particles’ interaction with electromagnetic fields in inhomogeneous conducting media. In addition, he initiated research in a new branch of today’s solid state physics, specifically investigation of plasma instabilities in semiconductors that occur because of heating of conduction electrons by the existing elecromagnetic fields.

Aim: to present the results of the Expert Panel with a discussion of modern concepts of the pathogenesis of functional gastrointestinal diseases and the possibilities of multitarget therapy with trimebutine. Key points. Low-grade inflammation can be considered as a morphological substrate of functional diseases with an increase in activated mastocytes and eosinophils, T-helpers 2 and T-helpers 17 in the gastrointestinal mucosa. In the development in the content of visceral hypersensitivity, the functional connection between mastocytes and TRPV1-positive sensory endings of the vagus nerve is of great importance. Proinflammatory cytokines and matrix metalloproteinases can enter the systemic circulation, provoking the development of systemic manifestations. Increased levels of proinflammatory cytokines are supported by altered intestinal permeability and microbiota. Functional diseases are believed to modify the symptoms and course of concomitant organic diseases of the gastrointestinal tract (for example, functional diseases of the biliary tract may contribute to the development of cholelithiasis, pancreatitis). The peripheral μ-, κ- and δ-receptor agonist trimebutine (Trimedat®) regulates the production of enterohormones, modulates motility throughout the gastrointestinal tract and normalizes visceral sensitivity. The effectiveness of trimebutine in the treatment of functional disorders has been shown in various studies. Trimebutine helps reduce the production of proinflammatory cytokines, including interleukin-6. Conclusion. In the treatment of functional diseases of the gastrointestinal tract, trimebutine can be considered as a multitarget agent, since the drug helps to normalize motility, reduces the degree of visceral hypersensitivity, exhibits anti-inflammatory and neuroregenerative effects, and can also increase the effectiveness of treatment of concomitant diseases.

Aim: Diagnostic criteria for functional disorders of the biliary tract are presented in the materials of the Rome IV consensus, as well as expert councils of Russian and foreign specialists. Episodes of functional biliary pain are caused by a violation of bile outflow through the cystic duct and sphincter of Oddi. It has been suggested that there is a “biliary continuum” in which in some patients’ biliary dysfunction is transformed into cholelithiasis. Key points. Lithogenic bile is considered as the pathophysiological basis for the development of biliary dyskinesia and cholelithiasis. Lithogenic bile provokes inflammation of low grades in the mucous membrane of the biliary tract, decreased contractility of the gallbladder and impaired relaxation of the biliary sphincters, impaired physiological response to cholecystokinin. Changes in motility of the biliary tract may be associated with the influence of hydrophobic bile salts and impaired eicosanoid metabolism. Hyperplasia of the epithelium and muscle layer, hypersecretion of mucin and cholesterol precipitation further impair the outflow of bile. Experimental data and some clinical observations indicate the possibility of transformation of biliary dysfunction into cholelithiasis. Dysfunction of the sphincter of Oddi is one of the possible consequences of cholecystectomy and, in fact, acts as a variant of postcholecystectomy syndrome. The basis for the treatment of biliary dysfunctions are antispasmodics of different classes, which can be combined with ursodeoxycholic acid. The biliary tract-selective antispasmodic hymecromone has shown high effectiveness in relieving biliary pain, which also has a moderate choleretic effect and the ability to prevent the crystallization of cholesterol in bile and can be used both for functional diseases and for cholelithiasis. The domestic drug hymecromone “Odecromone” entered the pharmaceutical market. Conclusion. There is no doubt that the relevance of further study of the patterns of development of biliary dysfunctions and GI is obvious. The study of this problem will contribute to the development of effective preventive approaches, including in the field of nutraceuticals.

Introduction Violation of mutual positioning and fixation of parts worsens the operation of the equipment. Traditional approaches to solving the problem under consideration have been sufficiently studied: interchangeability of parts and the use of special equipment. Both methods involve a significant number of additional elements and assembly operations. Fixation is often provided by means of force fitting and welding. Disadvantages of these methods include assembly, residual and other stresses, engineering constraints, etc. To solve these problems, alloys with thermoelastic phase transformations are used, which provide shape memory effects (SME) to manifest themselves. This article describes, for the first time, self-positioning and self-fixation using the example of parts specially made from an alloy with SME. Materials and Methods. The pin element under pressing mandrels the blind hole of the cup and enters the seat. The alloy with SME was Ti-55.7wt%Ni. The temperature of the onset of its austenitic transformation was As = 95°C ± 5°C. The elemental composition was determined by a Shimadzu EDX-8000 X-ray fluorescence spectrometer, the phase composition — by a Shimadzu XRD-7000 diffractometer. The temperature was specified through differential scanning calorimetry. The range was 20–300°C, the heating rate was 5 deg/min. A Guide T120 thermal imager and a RangeVision DIY 3D scanner with structured illumination were used. After pressing the pin into the cup at different angles, the alignment and deviations between the axes of the cup and the pin were examined. Then, the cup was heated to 110–120°C, cooled, and control measurements were taken.Results. Values of the deflection angle after pressing were 0.2–11°. With a rigid structure and an installation angle of 0°, the pin deflected in the mounting hole by 0.2–0.5°. The axes shifted and did not intersect. The pin was not always completely pressed in. This indicated uneven deformation of the metal and different stress values around the hole. Such a unit would soon fail. The pin took the required position after heating the cup to 110–120°C (this temperature was higher than at the end of the reverse martensitic transformation). The angular deviation of the axes was noted to be 0.03–0.1°. The maximum misalignment (0.04 mm) corresponded to high positioning accuracy. Heating during the reverse martensitic transformation created internal stresses that returned the initial geometry of the cup. They also formed the forces that positioned and fixed the pin in the hole. That is, it is the parts that provide positioning and fixation (this is selfpositioning and self-fixation).Discussion and Conclusion. For self-positioning and self-fixation of parts due to the shape memory effect, it is necessary to avoid sharp transition lines between the surfaces of parts during design, select rounded corners or fillets, and get a clean surface without burrs. Self-fixation and self-positioning reduce defects and inaccuracies during assembly. The use of certain alloys increases the profitability of equipment production.

Background. Acquired aplastic anemia (AA) is a non-tumor disease of the blood system and the pathogenesis is based on immune dysregulation directed against own hematopoietic stem cells, which leads to the development of bone marrow aplasia. Some modern research is directed to the study of intrinsic defects of hematopoietic stem cells, and one of which is the change in telomere length. Several large studies have shown the association of telomere shortening in AA patients with decreased overall survival, poor response to immunosuppressive therapy (IST), high rates of relapse and clonal complications.Aim. To study the influence of the initial telomeric DNA regions length in AA patients on the disease course.Materials and methods. 43 adult patients with acquired AA without previous pathogenetic therapy were included in the study. IST was performed according to a standard protocol including the use of hATG and cyclosporine. Flow-FISH was used as the method for measuring relative telomere length, and peripheral blood mononuclear cells were used as the study material.Results. Telomere length determined before IST did not differ between non-severe and severe AA, but there were significant differences depending on disease duration (p = 0.032). Initially short telomeres correlated with a lower rate of achieving hematologic improvement (53 % vs. 80 %; p = 0.059). In addition, significantly worse results were obtained in achieving partial and complete remission in patients with initially short telomeres compared to those with initially long telomeres (37 % vs. 62 % and 5 % vs. 23 %, respectively; p

Background. Aplastic anemia (AA) is a non-tumor and rare disease of the blood system, characterized by deep pancytopenia due to the development of bone marrow aplasia with immune-mediated damage of hematopoietic stem cells. Research results indicate the presence of antigenic effects leading to pathological activation and dysregulation of the T cells in the bone marrow with increased production of pro-inflammatory cytokines that damage hematopoietic stem cells. The triggering factor that initiates the cascade of immune reactions is currently unknown. The high efficiency of immunosuppressive therapy (IST), which allows achieving remission in the majority of AA patients, is evidence of the immune genesis of the disease. The pathogenesis of AA is currently being actively studied. The participation of T cell subpopulations in immune response is beyond doubt, but the issues of their significance in the AA pathogenesis have not been fully studied. A more detailed understanding of the AA development mechanisms is necessary for the development of long-term effective treatment.Aim. To investigate the T cells subpopulation in bone marrow of AA patients during IST.Materials and methods. The study included 41 patients over 18 years of age with newly diagnosed acquired AA without previous IST. Treatment was carried out according to a protocol including horse antithymocyte globulin and cyclosporine. Flow cytometry was used to detect T cell subpopulations. Bone marrow examination was performed at three time points: initially, 3 and 6 months after initiation of combined IST.Results. Multidirectional changes in the T cell subpopulations ratio before the start of IST were found in all AA patients included in the prospective study: most patients had a higher proportion of effector CD4+ and CD8+ T cells (61 and 83 % of patients, respectively), memory CD4+ T cells (63 % of patients), and a lower proportion of naive CD4+ and CD8+ T cells (81 and 51 % of patients, respectively) compared to donors (p

The article examines the legal and institutional mechanisms for integrating gender equality into the national security and defence sector of Ukraine. The analysis of the legal framework governing gender policy, in particular in the Armed Forces of Ukraine, is carried out. Particular attention is paid to the role of international standards, such as UN Security Council Resolution 1325 and the Istanbul Convention, in ensuring equal access of women and men to participation in defence processes. Based on theoretical analysis and empirical data, the article examines the impact of gender balance on the effectiveness of the national security sector, in particular its managerial, operational and strategic components, in the context of modern military challenges. It is found that the integration of gender equality contributes to the efficiency of the defence sector, but requires improvement of legal regulation and changes in institutional approaches. The results of the study indicate the need to revise legislative acts and introduce gender-sensitive approaches in the planning and execution of military operations. The article provides recommendations for strengthening the legal framework for gender equality in the security and defence sector of Ukraine. It is concluded that gender equality in the military does not mean mandatory establishment of equal obligations for both sexes. It is important to take into account the specifics and capabilities of each gender, ensuring equal access to military service on a voluntary basis, which is a more effective and fair approach. This allows to take into account the individual characteristics of women and men, thus ensuring the harmonious functioning of the Armed Forces of Ukraine in the context of modern challenges and needs of society.

The article deals with the issue of systematisation of by-laws and regulations resulting from the adoption of the Law of Ukraine “On Lawmaking”. It is noted that the adoption of the Law of Ukraine “On Lawmaking” has not fundamentally solved the problem of streamlining of regulatory legal acts. The unresolved nature of a wide range of issues related to the systematisation of legislation gives rise, in particular, to many debatable issues, such as: clarifying the admissibility and expediency of codification of bylaws and regulations; determining and regulating the most optimal forms of systematisation of bylaws and regulations, and the role and possibilities of consolidation as a form of systematisation of bylaws and regulations. Based on the analysis of the Law of Ukraine “On Lawmaking”, the article determines that the legislator, firstly, has not proposed a definition of codification as a form of lawmaking, and secondly, has not classified the types of codification by their legal force. Thus, the question of the potential existence of codification bylaws in the context of the Law of Ukraine “On Lawmaking” is left unsolved. Instead, the practice of subordinate legislation confirms the regularity of the existence of codification subordinate acts in the structure of the legislative system. The authors point out that the main form of subordinate legislation is resolutions of the Cabinet of Ministers of Ukraine. It is noted that the existing theoretical developments and foreign experience of regulating both formal and informal incorporation indicate that it is inexpedient to introduce it in Ukraine through amendments to the Law of Ukraine “On Lawmaking”, since incorporation does not have the features of lawmaking at all, and therefore it cannot be the subject of legal regulation by the Law on Laws. It is emphasised that, given the current doctrinal understanding of the peculiarities of alternative codifications of by-laws and regulations in Ukraine, it would be advisable to adopt a separate legal act (at the level of a resolution of the Cabinet of Ministers of Ukraine) which would regulate the rules for systematisation of by-laws and regulations in the system of executive authorities, based on the Law of Ukraine “On Lawmaking”. It is concluded that the issue of the subjective composition of public authorities with regard to the specific forms of systematisation of by-laws and regulations requires normative and doctrinal certainty, given the consolidation of legislation.

У статті досліджено питання особливостей найменування та сприйняття професій галузі фрилансу в японській мові, що з’явилися в результаті впливу процесів інтернаціоналізації та глобалізації останньої чверті ХХ ст. на соціально-економічну сферу зокрема. Ключовими поняттями роботи є поняття 「内」uchi (“своє / старе / традиційне”) －「外」soto (“чуже / нове / сучасне”), що репрезентує японську традиційну культуру, та японська абетка катакана, що виступає як лінгвістичний (основною функцією є записування слів іншомовного походження), так і екстралінгвістичний чинник (лінгвістично уособлює концепт「外」soto (“чуже / нове / модернізоване / сучасне”). Ця функція катакани, виокремлена з-поміж інших, слугувала призмою, крізь яку розглянуто феномен фрилансу в Японії. У дослідженні також описано еволюцію катакани, зокрема нові риси, яких вона набула в контексті сучасних процесів інтернаціоналізації та глобалізації. Розроблені класифікації презентують явище фрилансу із взаємопов’язаних лінгвістичного (схеми номінації професій галузі фрилансу в японській мові, словотвірні моделі, етимологічний складник тощо) та екстралінгвістичного боків (типологізація професій за критерієм новизни / осучасненості та їхнє сприйняття з урахуванням семантико-стилістичного й етимологічного критеріїв зокрема). Інші наведені класифікації допомагають якомога повніше висвітлити феномен фрилансу в Японії та представити його в різних аспектах: і в лінгвістичному, і в соціально-філософському. Особливу увагу приділено так званим “катаканним” професіям, які сформувалися під впливом сучасних інтернаціоналізаційних і глобалізаційних процесів і більшість яких набули рис фрилансу.

Aim: to evaluate the relationship of body composition components with the development of ascites in patients with liver cirrhosis.Materials and methods. One hundred and ten patients (44 men and 66 women) with the established diagnosis of liver cirrhosis were treated at the University Clinical Hospital No 2 of the Sechenov University. The assessment of the component composition of the patients’ body was carried out using the ABC-01 “MEDASS” device (“MEDASS”, Russia). Ascites diagnosis was performed using ultrasound examination of the abdominal cavity and retroperitoneal space.Results. The values of body mass index (p < 0.001), fat mass (p = 0.002), active cell mass (p < 0.001), and phase angle (p < 0.001) were lower in patients with ascites than without it. Patients with a lower percentage of body fat mass had a more severe ascites severity and vice versa, and the proportion of fat mass was generally higher in women than in men (r = –0.290; p = 0.002). Patients with lower active cell mass had higher ascites severity (r = –0.380; p < 0.001). However, this indicator was lower in women than in men. Significant negative correlations were revealed between fat mass, active cell mass, phase angle (r = –0.395; p < 0.001) and the severity of ascites.Conclusion. Our study confirms the importance of body composition parameters in the development of ascites in patients with cirrhosis of the liver. Insufficient amount of fat and muscle mass, as well as low values of the phase angle according to the results of bioimpedance can become predictors of the development of ascites. Evaluation of these components can be used in prognostic models to identify patients with an increased risk of ascites. Further research in this area will help to better understand the mechanisms of ascites development and develop effective methods of prevention and treatment of this complication in patients with liver cirrhosis.

The aim of the work was to study the species diversity of pathogenic and non-pathogenic hantaviruses circulating in populations of small mammals in the Republic of Bashkortostan using molecular-genetic methods.Materials and methods. Individual samples from small mammals were tested by the nested PCR using genus-specific primers that amplify the L segment of hantaviruses. The resulting PCR products were sequenced by the Sanger’s method from internal nested PCR primers. For samples containing Puumala virus, fragments of the S, M, and L segments of the viral genome were sequenced using Sanger’s method. The construction of phylogenetic trees was carried out using the MEGA X software.Results and discussion. Out of 300 examined samples of small mammals collected on the territory of the Republic of Bashkortostan in 2023, 14 samples have been found positive for the presence of hantavirus RNA: Seewis (8), Tula (3), Puumala (3). The circulation of the non-pathogenic hantavirus Seewis and the opportunistic hantavirus Tula has been established for the first time in the Republic of Bashkortostan. The circulation of the Seewis hantavirus has been confirmed in populations of the common shrew (Sorex araneus) and the pygmy shrew (S. minutus); the Tula hantavirus – in populations of the common vole (Microtus arvalis). Results of phylogenetic analysis substantiate the reassortment origin of one of the genetic variants of the Puumala hantavirus on the territory of the Republic of Bashkortostan. The prerequisites for the formation of combined natural foci of hantaviruses Puumala, Seewis, and Tula on the territory of the Republic of Bashkortostan are discussed.