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Introduction. Chronic graft versus host disease (GVHD) is a frequently occurring complication after transplantation of allogeneic hematopoietic cells associated with a decrease in the quality of life and long-term administration of immunosuppressive drugs. Extracorporeal photopheresis (ECP) is a second line of therapy after treatment failure with glucocorticoids.Aim — to evaluate the effects of ECP treatment in patients with glucocorticosteroids (GCS)-refractory, GCS-dependent or GCS -intolerant chronic GVHD.Materials and methods. 24 patients with GCS-refractory, GCS-dependent or GCS-intolerant chronic GVHD were included in the therapy with ECP. Nine patients had moderate chronic GVHD, and 15 had a severe chronic GVHD. Skin and mucous membranes were the most frequently targeted organs, 21 and 20 of 24 patients respectively, liver damage was detected in 8 patients. The maximum duration of treatment was 33 months (median — 8.5 months). The number of procedures of ECP ranged from 6 to 48 (median — 22).Results. A response was determined in 23 patients with one patient being excluded from the assessment due to a relapse of acute leukemia. 16 (69.5 %) patients achieved an overall response to ECP treatment. Three patients had complete response and full reduction of immunosuppressive therapy. When assessing organ-specific response, the most notable improvement was observed in the mucous membranes of 17 patients (89.4 %), skin — 17 (85 %), and liver — 7 (75 %). Along with achieving a general overall response, 78.2 % of patients partly reduced or completely canceled immunosuppressive therapy.Conclusion. ECP is an effective and promising second line treatment method for chronic GVHD in patients with GCS-refractory, GCS-dependent or GCS-intolerant forms.

Cognitive and value dissonances of the modern world, as well as the shifting balance in the “Technology-nature-society-man” system cause the need to rethink key development strategies, determine the guidelines that education should be guided by in order to be able to respond to the growing global challenges of modernity. The special acuteness of the modern formulation of this problem is due to the new format of the geopolitical life of the Russian Federation and the associated restructuring of many social institutions of the country, in particular, science and education.The article raises the question of the leading paradigm of domestic engineering education, considered in the prism of a specialist-engineer model that meets the requirements of the modern stage of society.Education standards have changed dramatically and repeatedly in their target characteristics over the past twenty years. The article considers the features of the competence model of specialist presented in the modern version of the Federal State Educational Standards of higher education (FSES HE). It is shown that the existing version of FSES does not fully meet the requirements for specialists in the modern world. In addition to highly professional knowledge and skills, future engineers need contextual, meta-professional and soft knowledge and skills for life and successful professional activity.World practice shows that one of the promising areas of training engineers is a project-oriented approach, which emphasizes the practical orientation of higher education. The authors have shown that the recognized international standards of engineering education in the fields of technology, natural and applied sciences (CDIO, STEM education) basically coincide with the world-known and repeatedly tested “Russian method of training engineers”, integrating broad fundamental education in the field of natural sciences and humanities and technological practice at advanced innovative enterprises. This experience which has already given the world great engineers and adapted at the same time to the modern technological capabilities of its transmission can become a fulcrum in a transitive world.

Introduction. The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs).Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs.Materials and methods. This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated.Results. From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 106 /kg (from 0.1 × 106 /kg to 3 × 106 /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %. There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days.Conclusion. CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

Introduction. One of the main causes of treatment failure after allogeneic hematopoietic stem cells transplantation (alloHSCT) for acute leukemia (AL) is disease relapse. In recent years, multiparameter fl ow cytometry (MPC) has been widely used to detect minimal residual disease (MRD) because of its capacity to identify patients with a high risk of relapse due to availability and the ability to obtain results in a timely manner.Aim — to evaluate the prognostic value of MRD status before allo-HSCT and the effect of donor type and conditioning intensity on long-term results of allo-HSCT of MOB-positive patients.Patients and methods. The analysis included 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL) who underwent allo-HSCT between September 2015 and June 2020. All patients were in complete morphological remission before allo-HSCT. At the time of allo-HSCT 91 patients with AML and 37 patients with ALL were in the first complete remission (CR), in their second and more than two CRs were 16 and 26 patients, respectively. The median follow-up was 18 (1.5–48) months for AML and 14 (1.8–60.1) months for ALL. Immunophenotypic study was performed before allo-HSCT. MRD was detected using a combination of the “different from normal” method and the search for cells with a leukemia-associated immunophenotype.Results. The disease status at the time of transplantation and the presence of MRD before allo-HSCT were independent factors infl uencing the probability of relapse (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304) and post-transplant mortality (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304). In univariate analysis, the relapse-free survival of MRD+ patients with AL in the first CR was significantly worse than in MRD– (AML: 23 % versus 57 %, p < 0.0001, ALL: 34 % versus 61.7 %, p = 0.0484), and the probability of relapse in MRD+ patients was significantly higher (AML: 75 % versus 12 %, p < 0.0001, ALL: 57 % versus 7 %, p = 0.0072). Pre-transplant MRD status was not prognostically significant for AL-patients in the second and third remission. The development of chronic GVHD reduces post-transplant mortality if it does not require systemic therapy with glucocorticosteroids (HR = 0.006, 95% CI: 0.008–0.446).Conclusion. Testing for MRD of patients with AL in the first CR before allo-HSCT is necessary for risk stratification and identification of patients who will need preventive post-transplant therapy in order to prevent disease relapse.

Lysobacter capsici VKM B-2533 T and Lysobacter gummosus 10.1.1 are promising strains for use in biomedicine as sources of new antimicrobial agents. Here, we report the whole-genome sequences of both strains (total lengths, 6,239,188 bp and 6,056,609 bp, respectively), obtained using the Illumina and Nanopore platforms.

Among the cardiological material of our Clinic, we encountered the following completely unusual case, which we had the opportunity to observe.

In 2 series of experiments, the influence of population density and substrates on the growth and development of microgreens in oil radish was studied. In the optimum zone were crops with a density of 5 and 7 g of seeds per container with an area of 144 cm2. At higher seeding densities, the plants lagged significantly behind in growth. Their average height was 1.5 times less, and the average mass of microgreens per 1 g of sown seeds decreased 2-2.5 times. A new inert substrate, foam glass, was tested. Possessing high porosity, it provided an optimal water-air regime for plants. Comparison of growing microgreens on soil and foam glass showed the advantage of foam glass — the mass of plants on it was slightly larger. Despite the optimal air-water regime created by the foamglass, the diameter of the stones of 1.5-3 cm turned out to be excessively large and created inconvenience for growing microgreens.

Indications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with primary myelofibrosis are intermediate-2 and high-risk group of DIPSS (Dynamic International Prognostic Scoring System), beginning of the disease in childhood. The other adverse factors affect engraftment and survival after allo-HSCT, example partialy matched donor. But the result of allo-HSCT from matched related donors and result of allo-HSCT from haploidentical donors are comparable. The method for haploidentical hematopoietic stem cell transplantation is T-cell-depletion. This is clinical case of T-cell-depleted haploidentical hematopoietic stem cell transplantation in patient with primary myelofibrosis, the diagnosis was established in childhood.Показанием к трансплантации аллогенных гемопоэтических стволовых клеток (алло-ТГСК) у пациентов с первичным миелофиброзом является их принадлежность к группе промежуточного-2 и высокого риска. Пациентам с низким или промежуточным-1 риском с дебютом заболевания в детском возрасте также целесообразно рассмотреть включение алло-ТГСК в программу терапии. Перед алло-ТГСК необходимо учитывать наличие других неблагоприятных факторов, которые могут повлиять на приживление трансплантата и выживаемость после алло-ТГСК, например выполнение алло-ТГСК от частично-совместимого донора. При этом результаты нескольких исследований свидетельствуют о том, что алло-ТГСК от родственных полностью совместимых и гаплоидентичных доноров сопоставимы. Одним из подходов к выполнению трансплантации гаплоидентичных гемопоэтических стволовых клеток является T-клеточная/CD19-деплеция. Представлен клинический случай алло-ТГСК с T-клеточной/CD19-деплецией больному первичным миелофиброзом, у которого диагноз установлен в детском возрасте.

Purpose. The present work investigates the impact of the pedagogy approaches in the teaching e-resource of low-motivated students.Materials and Methods. The pilot study involves about 1000 first-year undergraduates of the North-West Institute of Management of the Russian Presidential Academy of National Economy and Public Administration (NWIM RANEPA). Introductory part of the lecture is traditional. “Motivational” part varies depending on e-resource and includes a demonstration of all possible advantages for target audience — uniqueness, quality, advantages over open resources. In addition, the material is organized so as to provide multiple entries into the interface.Results. We studied statistics of visits to e-resources for 2 calendar years (before the introduction of new methods in 2016 and after — in 2017), and conducted surveys of students at the end of training. We got the apparent increase of visits when the pedagogical approach and the methods of training are changed.Discussion and conclusions. Research findings have illustrated the importance of support to the low-motivated students in their educational process by new approaches to the training. The librarian-teacher in this role is the link between the e-resource and the consumer, and their role is important for achieving the best results for both the organization and students. The authors are conscious that the interest in subscription resources would probably decline in the future. The keeping this interest is beyond the scope of this study. The data obtained and the conclusions made can be useful at all stages of the students’ training at any year of study.

Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

Background Chronic infection by HIV evolves with a vascular inflammatory action causing endothelial dysfunction. The action of the virus as well as the side effects of antiretroviral drugs contributes to the progression of cardiovascular diseases. The study aimed to characterise the changes of the structure of the coronary wall and the thickening of the intima by Optical Coherence Tomography in HIV-infected patients with or without symptoms of coronary heart disease. Methods Fifty-two HIV-infected individuals had a mean age of 49.8±11.4 years. There were 75% men, diabetes 30,8%, hypertension 30,8%, smokers 34,62% and 7,7% with cholesterol levels ≥99 mg/dl. Control group included 120 non-HIV-infected controls with coronary heart disease. All the participants from HIV-group receive ART, 100% of participants had plasma HIV RNA Results The average diffuse homogeneous thickening of the intima in patients with HIV was 0.67±0.24 mm, and 0.34±0.18 mm in control group, with normal values not exceeding 0.05 mm. There was impaired three-layer structure of coronary wall in 90,4% (47 of 52) HIV-infected participants and in 60% of control group, atherosclerotic plaque had only 34,62% of HIV group. All HIV-infected patients receive ART more than 5 years. Conclusion The coronary angiography and OCT demonstratedthat the inflammatory process resulting from HIV-infection or HAART may be relevant in the changes of coronary arteries in HIV-positive patients. The changes are predominantly represented by thickening of the intima, impaired three-layer structure of arterial wall and accelerating atherosclerosis. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Russian National Research Medical University named after N.I. PirogovCentral Clinical Hospital of Russian Academy of Science, Moscow, Russia

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria constitute important factors in defining interactions with the extracellular milieu. Lysobacter sp. XL1 produces OMVs capable of lysing microbial cells due to the presence in their cargo of bacteriolytic protease L5 (AlpB). Although protein L5 has been functionally and biochemically characterized (including aspects of its packing into OMVs), its role in vesicle biogenesis through genetic deletion of alpB had not been studied previously. Here, we have successfully deleted alpB by allelic replacement and show that the alpB deletion mutant produces a significantly lower amount of OMVs that lack bacteriolytic activity and display altered ultrastructural characteristics in relation to the OMVs produced by the wild-type strain. These results confirm that, as previously proposed, protein L5 participates in OMV production through a mechanism that is not yet fully understood.

Objective. To analyze treatment results of 172 patients with acute myeloid leukemia (AML) aged 18-60 years in National Medical Research Center for Hematology of MHRF. Materials and methods. Inductive and consolidation program for 139 (80%) patients was based on a standardized protocol: 4 courses “7+3” with different anthracycline use (2 courses of daunorubicin, idarubicin, mitoxantrone) and continuous use of cytarabine on the second inductive course. In 20% of patients cytarabine courses at the dose of 1 g/m2 2 times a day for 1-3 days combined with idarubicin and mitoxantrone were used as two consolidation courses. Allogenic bone marrow transplantation was performed in the first complete remission (CR) period in 40% of patients. Results. The frequency of CR achievement in all patients was 78.6%, refractory forms were observed in 13.9% of patients, early mortality - in 7.5% of patients. Seven-year overall survival (OS) rate was 40.7%, relapse free survival (RFS) - 43.2%. When estimating effectiveness depending on cytogenetic risk group it was demonstrated that 5-year OS and RFS in patients with translocation (8; 21) cannot be considered as satisfying, it accounted for 50 and 34%, respectively. At the same time in patients with 16th chromosome inversion (inv16) these characteristics accounted for 68.6 and 63.5%. Acquired results forced reconsidering of the consolidation program in AML patients of this subgroup. The median time to allogenic blood stem cells transplantation (allo-BSCT) in patients with first CR was 6.5 months that was taken as a reference point in landmark analysis of patients in whom allo-BSCT was not performed. Landmark analysis showed that in AML patients of favorable prognosis group allo-BSCT does not significantly reduce the probability of relapse (0 and 36%) and does not influence RFS (33 and 64%). In patients of border-line and poor prognosis allo-BSCT significantly reduces relapse probability (26 and 66%; 20 and 100%) and significantly increases a 7-year RFS (68.7 and 30%; 45.6 and 0%). Allo-BSCT also results in significant RFS increase and reduces the probability of relapse (25 and 78%) in patients in whom CR was achieved only after the second induction course. At the same time allo-BSCT does not influence patients who achieved CR after the first treatment course: 55 and 50%. Conclusion. Multivariate analysis showed that cytogenetic risk group (HR=2.3), time of CR achievement (HR=2.9), and allo-BSCT transplantation (HR=0.16) are independent factors for disease relapse prognosis after achieving CR.

Context: The independent influence of pre-transplant MRD status on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is now being widely reported. The genetic and immunophenotypic diversity of AML is a problem for monitoring MRD in daily clinical practice. The most widely used methods for assessing MRD are multiparametric flow cytometry (MFC) and PCR. Objective: To assess the impact of pre-transplant MRD status determined by MFC or PCR on the long-term results of allo-HSCT. Patients and Methods: The study included 106 patients with AML in the 1st CR who underwent allo-HSCT in our center from September 2015 to December 2020. The median follow-up was 19.5 (1–50) months. Eleven-color MFC was performed on bone marrow samples obtained before allo-HSCT. In 46 out of 106 patients who had molecular markers (NPM1, FLT3, RUNX1-RUNX1T1, MLL, or CBFβ-MYH11), the MRD status was determined using PCR also. Cox proportional hazards models were used to assess the influence of various independent factors on the probability of relapse (PR). The factors included in the model were ELN risk, donor type, conditioning regimen, graft source, pre-transplant MRD status, and age. The probabilities of DFS and relapse were estimated using the Kaplan-Meier method. Results: Out of 106 patients, 22 were identified as MRD+ MFC, 84 patients were MRD- MFC, 16 patients were MRD+ PCR, and 30 patients were MRD- PCR. Statistical analysis revealed significant differences between MRD+ and MRD- patients, regardless of the research method: patients with MRD+ status had the worst DFS (MFC: 24% versus 64%, p 40 y (HR=7.006) were independent factors influencing the probability of relapse. Conclusions: MRD, regardless of whether it is determined by MFC or PCR, ELN risk, and older age are independent predictors of disease recurrence risk. The study of MRD in AML patients before allo-HSCT can be used to stratify the risk of allo-HSCT and identify patients who need prophylactic post-transplant therapy to prevent disease relapse.

The cortical formations of the brain involved in visual functions (the occipital and temporo-parieto- occipital areas, the oculomotor area of the prefrontal cortex), as well as the motor cortex in the representation zone of the arm and the medial region of the frontal cortex adjacent to the limbic lobe, were studied in post-mortem material. The thickness of the cortex and cortical layer III, the sizes of pyramidal neurons, the specific volumes of neurons and intracortical vessels were studied in subjects of both sexes, from birth to the age of 20 years, at yearly intervals (103 observations) using histological techniques, computer morphometric and stereological analysis. The thickness of the cortex of the cerebral hemispheres was observed to intensively increase from birth to the age of 3 years in the occipital, temporo-parieto-occipital and prefrontal cortical areas involved in visual recognition processes. The increase in thickness of the cerebral cortex continues until the age of 6 in the occipital cortex and in the oculomotor area, until the age of 7 years in the temporo-parietooccipital area and the medial prefrontal area, and until the age of 8–9 years in the motor cortex. The sizes of pyramidal neurons increase until the age of 6 years in the motor cortex, until the age of 8 years on the medial surface of the frontal lobe, and until the age of 9–10 years in the temporo-parieto-occipital area and in the dorsolateral area of the prefrontal cortex. The specific volume of neurons and blood vessels in the cortex of the cerebral hemispheres decreases and the volume of intracortical fibers increases throughout the ascending ontogeny, which is manifested most intensively in the prefrontal cortex.

Acute Graft-versus-host-disease (aGVHD), the major complication and one of the main causes of poor outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nowadays there are no widely accepted cell, plasma or another biomarker that can be used for aGVHD prediction. We hypothesized that a level of Granzyme B-positive T regulatory (GZMB-positive Treg) cells on day+30 after allo-HSCT could be the measure of immune response suppression and could predict aGVHD development after day +30. We applied a widespread and easy-to-perform method of multicolor flow cytometry to measure level of GZMB-positive Treg cells. Levels of GZMB-positive Tregs on day +30 after allo-HSCT were significantly higher in those patients who never developed aGVHD in comparison with the other group of patient with aGVHD after day +30 (p=0.0229). We conclude that the level of GZMB-positive Treg cells is a strong predictor of acute Graft-versus-host disease after day +30 after allo-HSCT.

The use of complex non-drug technologies at the stage of rehabilitation of metabolic syndrome (MS) includes multifactorial correction of its main manifestations: abdominal obesity, insulin resistance, arterial hypertension and dyslipidemia. A prospective randomized study on the use of low-calorie diet (LCD) and nutraceutical correction of the nutritional status of patients with MS was carried out.To study the effect of a non-drug complex including LCD, physical exercises, as well as correction of the gut microbiome and hepatic protection in relation to reduction of visceral fat volume in abdominal obesity and the dynamics of lipid and carbohydrate metabolism hormones in metabolic syndrome.120 patients with MS were randomized into 2 groups: Group 1 received LCD, physical exercises in the gym, and physical activity like daily walking up to 3-5 km/day. Group 2 received LCD, physical exercises in the gym, physical activity like daily walking up to 3-5 km/day, as well as nutraceutical correction of increased appetite, gut probiotic composition, hepatic protection. The treatment duration was 4 weeks. Anthropometric methods in order to control the body weight, waist and hip circumferences and bioimpedansometry were used.As a treatment result, patients in group 1 represented a reduction in body weight, lean and active cell mass, a decrease in musculoskeletal mass and a decrease in total fluid due to extracellular fluid. A decrease in total cholesterol and blood triglyceride fraction was noted. Leptin decreased by 13.96%. Patients of the 2Thus, LCD accompanied by nutraceutical correction of the gut microbiota and hepatic protection can be effectively used in combination with physical training in order to reduce the fat mass without pre-sarcopenia development that was confirmed by positive dynamics of volume indices, bioimpedance measurements and reduction in leptin and insulin expression.Применение комплексных немедикаментозных технологий при метаболическом синдроме (МС) включает мультифокусную коррекцию основных его проявлений: абдоминального ожирения, инсулинорезистентности, артериальной гипертензии и дислипидемии.Изучение влияния немедикаментозного комплекса, включающего низкокалорийную диету (НКД), физические упражнения, а также нутрицевтическую коррекцию микробиома кишечника и гепатопротекцию, на редукцию висцеральных жировых отложений при абдоминальном ожирении и динамику гормонов липидного и углеводного обменов при МС.Обследованы 120 пациентов с МС, которые были рандомизированы на две группы: в 1-й группе применяли НКД, лечебную гимнастику в зале и ежедневную ходьбу до 3—5 км/день; во 2-й группе — НКД, лечебную гимнастику в зале, ежедневную ходьбу до 3—5 км/день, а также нутрицевтическую коррекцию повышенного аппетита, пробиотического состава кишечника, гепатопротекцию. Длительность курса лечения составила 4 нед. Использовали антропометрические методы контроля массы тела, окружности талии и бедер и биоимпедансометрию.В результате лечения у больных 1-й группы отмечены снижение массы тела, тощей и активной клеточной массы, уменьшение скелетно-мышечной массы, а также общей жидкости за счет внеклеточной. Выявлено снижение общего холестерина и фракции триглицеридов крови. Лептин снизился на 13,96%. У больных 2-й группы наблюдалось снижение массы тела, жировой массы, тощей массы, общей и внеклеточной жидкости. Зафиксированы статистически значимое повышение активной клеточной массы, скелетно-мышечной массы, снижение общего холестерина, триглицеридов, трансаминаз. В результате снижения массы тела и уменьшения жировой массы отмечено снижение экспрессии лептина на 29,85%, уровня инсулина крови на 11,2%.Таким образом, НКД в сопровождении нутрицевтической коррекции микробиома кишечника и гепатопротекции может эффективно применяться в комплексе с физическими тренировками с целью снижения жировой массы без риска развития пресаркопении, о чем свидетельствуют положительная динамика объемных показателей, показателей биоимпедансометрии и снижение уровней экспрессии лептина и инсулина.

Context One of the main causes of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia (AL) patients is the disease relapse. Minimal residual disease (MRD) detected by multiparameter flow cytometry (MFC) is a strong prognostic marker of increased risk of relapse. Objective To determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes of acute leukemia patients. Patients and methods To assess the impact of MRD status before transplantation we included 84 AML patients and 46 ALL patients in their first or second morphologic remission who underwent allo-HSCT between July 2016 and April 2020. 6-color MFC was performed on bone marrow samples obtained before allo-HSCT. Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. For patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR) were estimated using the Kaplan–Meier method. Results Among 84 AML patients before allo-HSCT 23 patients (27.4%) were identified as MRD+. 11 out of 46 ALL patients (23.9%) before allo-HSCT were MRD+. Subsequently, 9 out of in 23 MRD+AML patients and 4 out of 61 MRD−AML patients relapsed (CIR 50.6% vs. 10%, p Conclusions Despite the presence of morphological complete remission before allo-HSCT, MRD persistence before allo-HSCT influences OS and RFS in patients with AL. Because of the association between MRD and relapse risk, MRD-testing before allo-HSCT may help to identify a subgroup of acute leukemia patients who need preemptive treatment.

The present state is investigated and the necessity of automation is substantiated accounting systems of budgetary institutions to ensure their effective operation. The main characteristics of accounting automation software in budget organizations are considered, as well as the main advantages of using these programs for optimization and adaptation of the accounting system of domestic institutions to contemporary challenges of the information society and international practice of budget accounting. The analysis of the functions of the most popular products used for accounting for labor remuneration for budget institutions, namely: “FIT–Budget”, “1С: Enterprise8”, “Sail–Wages”, “UA– Budget”, “IS–pro7”, “MASTER: Salary and Frames”, “Chiz–Bookkeeping: Wages”. The key requirements for companies producing software for accounting automation are substantiated. The paper deals with the problem of accounting for the calculation of wages in budgetary institutions and possible directions for solving this problem, in particular, automation of accounting systems. The advantages of the computer accounting system in the case of payroll and automation accounting in general are emphasized. Also, a list of budget institutions of Ukraine and their software is presented and the most important ways of solving the problem mentioned in the article., Исследовано современное состояние и обоснована необходимость автоматизации системы бухгалтерского учета бюджетных учреждений для обеспечения их эффективной деятельности. Рассмотрены основные характеристики программных продуктов автоматизации учета в бюджетных организациях, а также определены основные преимущества использования данных программ для оптимизации и адаптации учетной системы отечественных учреждений к современник вызовов информационного общества и международной практики бюджетного учета. Проанализированы функции наиболее популярных продуктов, которые служат для учета оплаты труда для бюджетных учреждений, а именно: "FIT-Бюджет", "1С: Пидприемство8", "Парус-Заработная плата", "UA-Бюджет", "ИС О7", " MASTER: Зарплата и кадры »,« Чиж-Бухгалтерия: Заработная плата ". Обоснованно ключевые требования к компаниям-производителям программных продуктов автоматизации бухгалтерского учета. В данные статьи освещена проблема учета расчета оплаты труда в бюджетных учреждениях и возможные направления решения этой проблемы, в частности автоматизации систем учета. Подчеркнуто преимущества компьютерной системы бухгалтерского учета в случае учета оплаты труда и автоматизации в целом. Также, приведен перечень бюджетных учреждений Украины и их программное обеспечение и самое главное пути решения указанной в статье проблемы., Досліджено сучасний стан та обґрунтовано необхідність автоматизації системи бухгалтерського обліку бюджетних установ для забезпечення їх ефективної діяльності. Розглянуто основні характеристики програмних продуктів автоматизації обліку в бюджетних організаціях, а також визначено основні переваги використання даних програм для оптимізації та адаптації облікової системи вітчизняних установ до сучасник викликів інформаційного суспільства і міжнародної практики бюджетного обліку. Проаналізовано функції найбільш популярних продуктів, які служать для обліку оплати праці для бюджетних установ, а саме: “FIT–Бюджет”, “1С: Підприємство8”, “Парус–Заробітна плата”, “UA–Бюджет”, “ІС ПРО7”, “MASTER: Зарплата і кадри”, “ЧІЖ–Бухгалтерія: Заробітна Плата”. Обґрунтовано ключові вимоги до компаній–виробників програмних продуктів автоматизації бухгалтерського обліку. У данні статті висвітлено проблему обліку розрахунку оплати праці у бюджетних установах та можливі напрями вирішення цієї проблеми, зокрема автоматизації систем обліку. Підкреслено переваги комп’ютерної системи бухгалтерського обліку в разі обліку оплати праці та автоматизації загалом. Також, наведено перелік бюджетних установ України та їх програмне забезпечення і саме головне шляхи вирішення зазначеної у статті проблеми.

In the diet of the population of Yakutia, the meat of 6-month-old and local herd horses is especially valued for its high nutritive value, excellent taste and dietary properties. In addition to meat, a number of other slaughter products, such as by-products, intestinal raw materials, internal fat, blood, etc., can be received during primary processing. Many of them are not fully used. The relevance of this work is to study the possibilities of waste-free use of the Yakut horse products. Biochemical investigation of the composition of the secondary products of slaughter (fat, blood, by-products, intestinal raw materials) was carried out, a concentrate from the internal fat of foals and dry blood were obtained. The inner fat of the Yakut horse in terms of the content of polyunsaturated fatty acids (PUFA) exceeded the PUFA level in subcutaneous fat. The content of linoleic acid was 10.91-12.25%. A low-temperature method for recovering fat has been tested, a fat-containing feed with a PUFA content of about 23% has been obtained. Slaughter blood is a high-value raw material for the production of functional food products as a source of iron, amino acids and other components. The iron content in the blood dried in the infrared dryer fluctuated in insignificant limits from 216.8 to 242.0 mg/kg that indicated a stable level of provision of horses with this trace element. The protein level in the dry blood of mature mares (8-19 years) was 87%. The results of the study of young offspring of the Yakut horse showed that such offal of the first category as liver, heart, kidneys were rich in protein (from 19.1±0.1 to 22.0±0.1%). The esophagus was high in fat (22.3±0.1%). The stomach and intestines were characterized by high ash content (from 3.2±0.2 to 8.0±0.7%).

The feasibility of optimizing the electromembrane removal of carbon dioxide from an aqueous monoethanolamine (MEA) solution with a CO2/MEA molar ratio of 0.2 after the regeneration stage aimed to reduce the loss of MEA with the concentrate has been explored. The influence of the composition of the concentrate solution on the recovery of carbon dioxide and the specific loss of MEA (g MEA/g CO2 recovered) for a process duration of 1 h has been studied. The solution in the concentration cells was either distilled water or aqueous MEA solutions with a different carbon dioxide loadings. It has been found that the CO2 recovery ranges within 56.6–66.5%; the maximum and minimum specific losses of MEA make 4.80 and 1.49 g MEA/g CO2 recovered; and the specific energy consumption is 6.48–9.72 MJ/kg CO2 recovered.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) could be curative for acute myeloid leukemia (AML) patients. However, the disease relapse after allo-HSCT lead to poor outcomes almost in all cases. Minimal residual disease (MRD) is a strong prognostic marker of increased risk of relapse and reflects overall (OS) and relapse-free survival (RFS) in patients with AML. Immunophenotypic evaluation using multiparameter flow cytometry (MFC) is an important strategy for detecting MRD, because of its simplicity and wide availability. Aim. Determine the impact of MRD detected by MFC before allo-HSCT on clinical outcomes. Patients and methods. To assess the impact of MRD status before transplantation we include 56 AML patients who underwent allo-HSCT in National Research Center for Hematology between July 2016 and June 2019. Patient's characteristics are shown in table 1. All these patients were in first compete morphologic remission at the time of allo-HSCT. MRD was evaluated by MFC. Bone marrow samples were obtained before allo-HSCT and were analyzed by 6-color MFC (BD FACS Canto II, USA). Positive MRD was identified as a cell population deviating from the normal patterns of antigen expression on specific cell lineages at specific stages of maturation for all patients. In addition, for patients with LAIP at diagnosis, positive MRD was also defined as a cell population carrying LAIP markers at diagnosis. The probabilities of OS and RFS were estimated using the Kaplan-Meier method. Results. Among 56 AML patients before allo-HSCT (all were in CR at the time of MRD analysis). Median of follow-up was 9.3 months.11 patients (19,6%) were identified as MRD+ (0,011%-5,08%, mean 1%). And 5 of them relapsed (45,5%). Out of 45 MRD negative patients before HSCT relapse was registered in one (relapse rate 2,2%). Statistical analysis revealed significant differences between MRD- and MRD+ patients: MRD+ had much worse OS (22,9% vs. 85.5%, p=0.0047, Fig.1A) and RFS (26% vs. 97.4%, p Conclusions. Despite the presence of morphological CR before allo-HSCT, MRD persistence can lead to worse probabilities of OS and RFS, which is comparable to patients who were transplanted in relapse. Because of the association between MRD and relapse risk, it can be assumed, that testing for MRD before allo-HSCT may help to identify a subgroup of patients at high risk of relapse who might benefit from preemptive posttransplantation treatment. Disclosures No relevant conflicts of interest to declare.

Background: Nutritional problem is a key aspect of all severe diseases that always "keep in the shadows". There are different factors, such as intensive chemotherapy, constant nausea, severe infections, time for donor search that affect nutritional status in leukemia patients who underwent allogeneic stem cell transplantation (allo-HSCT). This study aimed to evaluate the impact of different "nutritional status assessment tools" on outcomes of allogeneic hematopoietic cell transplantation. Materials and methods: 307 leukemia patients who underwent allo-HSCT in National Research Center for Hematology from 2011-2019 were included on this study. Detailed patients' characteristics are given in Table 1. All data were collected directly before allo-HSCT conditioning regimen. Nutritional Risk Index (NRI) was calculated by NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight(kg)). Ideal body weight (IBW) was calculated by Lorentz IBW formula: for men IBW = (height, cm− 100) − ((height − 150)/4); for women: IBW = (height, cm − 100) − ((height, cm − 150)/2). All patients were stratified according to NRI: NRI < 83.5 - Major; 83.5 ≤NRI < 97.5 - Moderate; 97.5 ≤NRI < 100 - Mild; NRI≥100 - No risk group. Moreover all patients were stratified according to serum albumin level (more and less than 4.3 mg/dl ). Groups stratified by NRI and serum albumin was balanced for factors that can affect long-term results: disease type and status, graft source, conditioning regimen, donor's type, graft failure, acute and chronic GVHD. Data analysis was performed with R version 3.5.2 (Core Team, 2018). Chi-square and Fisher's exact test were used for contingency tables. Kaplan-Meier analysis was provided to assess the probability of overall survival. Log-rank test was used to compare two groups. Cox regression model was used to identify independent prognostic factors and its hazard ratio (HR) with a 95% confidence interval (95% CI). Age, sex, disease status before allo-HSCT (CR vs not in CR), serum albumin level (83.5 Results: As we can see on Figure 1A NRI-based stratification can't help us to predict long-term results in contrast with serum albumin level (Figure 1B). At the same time level of albumin >4.3 was associated with better results compared to serum albumin level Conclusion: These data showed that serum albumin level, but not NRI index, in leukemia patients before allo-HSCT can predict long term outcomes. Identification of these high risk patients could be a start point for future interventions and could change care protocols. Disclosures No relevant conflicts of interest to declare.

Introduction In most cases, haploidentical stem cell transplantation (haplo-HSCT) with negative depletion of α/β(+) T cells and CD19+ B lymphocytes from the graft is used to treat pediatric patients. The results are promising. However, the results of this method in adult patients is controversial. The accumulation of experience in haplo-HSCT with TCRαβ / CD19 + depletion in the group of adult patients is relevant. Aim Evaluation of the effectiveness and characterization of the most frequent complications in adult patients with hematological malignancies who underwent allo-HSCT from a haploidentical donor with depletion of TCRαβ/CD19 + cells. Patients and methods The analysis included 32 patients (14 males/18 females) with acute myeloid leukemia (AML, n=12), acute lymphoblastic leukemia (ALL, n=11), myelodysplastic syndrome (MDS, n = 6), chronic myeloid leukemia (CML, n = 1), primary myelofibrosis (PMF, n = 1), lymphoproliferative disease (LPD, n = 1). Median age was 28 years (range, 17-58). Disease status of acute leukemia at the beginning of pre-transplant conditioning was first complete remission (CR1) in 14 patients, CR2 in 7 and active disease in 2 patients. Pre-transplant conditioning regimen: RIC (Treosulfan 42 g/m2, Melphalan 140 mg/m2, Fludarabine 150mg/m2), MAC (Treosulfan 42 g / m2, Thiophosphamide 10 mg / kg, Fludarabine 150 mg / m2). Immunosuppressive therapy: Rituximab, Bortezomib, Tocilizumab, Abatacept. Immunomagnetic separation was performed using a CliniMACS Plus device. Descriptive statistics methods were used for analysis. The probabilities of survival and graft versus host disease (GVHD) rate were estimated using the Kaplan-Meier method. Results Log of TCRαβ + depletion was 1.61-5.33 (Me = 3.66). The median dose of CD34+ cells in transplant was 6.8 * 106/kg (range, 2.0-10.8). The median time to white blood cells recovery was +13 days after haplo-HSCT (range, 9-26). Median follow-up was 6.4 months. Transplant related mortality was 3.1%. Primary engraftment - 96.8%. Graft hypofunction - 16.2%. The probabilities of overall and disease-free survival for 12 months were 94.1% and 70,5%, respectively. The probability of relapse was 24.4% (Fig. 1). The probability of developing acute GVHD was 25%, GVHD rate was 18,75% including grade I (n=1), grade II (n=2), grade III (n=3) (data not shown). In 4 cases complete response was achieved with administration of first line immunosuppression therapy. 1 case (grade III GVHD) required administration of second line immunosuppression therapy - methylprednisolone, and the response was complete. 1 patient developed chronic GVHD. Nonclassical infectious complications prevail: viral infections (CMV, HHV6 and EBV) was 58.8%, fever with an unverified infectious agent was 15.6%, and tuberculosis in two cases (6.2%). Immunological events not associated with GVHD - 21.8% (TMA, TTP, myasthenia gravis, AIHA, PRCA). Conclusion In some cases, haplo-HSCT is the only HSCT option for an adult patient. The frequency of viral infectious complications and relapses in adult patients after haplo-HSCT TCRαβ / CD19 + depletion is comparable to the results in the pediatric population. Haplo-HSCT with TCRαβ / CD19 + depletion is characterized by minimal toxicity and a short period of myelotoxic agranulocytosis. Among the undesirable phenomena in the first place are infectious complications and frequent immunological events that do not fit into the criteria for GVHD, but affect the patient's quality of life and length of hospital stay. Figure 1 Disclosures Maschan: Miltenyi Biotec: Other: lecture fee.

By comparison of peony and lotus embryos in in vitro culture we established differences in their morphogenetic potential. We traced in peony embryo culture: embryogenesis, embryoidogenesis, organogenesis and histogenesis, whereas the lotus embryo enhibited only one pathway of development - embryogenesis. At the critical stage the embryo becomes independent of the maternal organism, i.e, self-sufficient. Self-sufficiency of the lotus embryo on the 4O-11th day after pollination correlates with development and greening of the first -lead in the plumule, with a sharp increase in embryo dry weight and content of carbohydrates, decrease in the size of the endosperm, degeneration of the inner integument, appearance of starch in the embryo and ovary walls an Increase of its content in the outer integument.

Introduction Cytomegalovirus (CMV) reactivation is one of the main problems in allogenic hematopoietic stem cell transplantation (allo-HSCT). Standard of care for CMV-disease is still ganciclovir at 10 mg/kg b.i.d. Use of non-CMV specific intravenous immunoglobulin (IVIG) is still controversial and mostly determined by internal care protocols in every transplant center. Here we report data about impact of non-CMV specific IVIG during ganciclovir treatment in allo-HSCT CMV-patients. Patients and methods Thirty two patients with hematological malignancies transplanted in NRCH were included in this study. Detailed patients characteristics are listed in Table 1. All patients were CMV-positive by PCR (Amplisens EBV/ CMV /HHV6-screen-FL", InterLabService, Russia) and required to start therapy with ganciclovir 10 mg/kg when was included to this study. Patients in IVIG group also received non-CMV specific IVIG during ganciclovir treatment with a median total dose 20 g (7.5-90 g.). Kaplan-Meier estimator was used to determine probability of achievement of CMV-negativity from time of ganciclovir was started to CMV-negativity (by PCR) or last contact. The logrank test is used to compare differences between two groups. Fisher's exact test was used for 2×2 tables. P-value less than 0.05 was considered statistically significant Results Influence of IVIG in allo-HSCT patients on probability of achievement of CMV-negativity (by PCR) are shown in the Figure 1. As we can see there is no significant differences on the achievement of CMV-negativity (by PCR) in patients with/without IVIG during ganciclovir therapy. Conclusion The use of non-CMV specific immunoglobulins after allo-HSCT still lies in the plane of faith and the possibilities of the transplantation center than any evidence base. Using IVIG in patients after allo-HSCT is still not a routine in terms of CMV-reactivation/disease therapy and mostly based on an "experience" of every transplant center. According to our data there is no difference between IVIG/no-IVIG groups during ganciclovir treatment so use of IVIG, for our opinion, does not really make sense for CMV-disease treatment. Anyway a large randomized trial is required for determine indications for therapy with IVIG. Disclosures No relevant conflicts of interest to declare.

Introduction. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for most leukemia patients. It seems that the bone marrow (BM) resident T-memory cells are the main pool for reconstitution of adaptive immunity, providing graft-versus-leukemia effect after allo-HSCT. However it has been shown previously that T-naïve cell subsets are responsible for acute graft versus host disease (aGVHD) onset. Here we report an impact of different GVHD prophylaxis on the BM resident memory T-cells recovery after allo-HSCT. Patients and methods. Our study comprised 39 leukemia patients (AML-26, ALL - 13) with a median age of 36 years (17 - 60 years old) who underwent allo-HSCT. Classical immunosuppressive regimen with CsA+MMF+MTX was applied in case of matched related (n=9) and matched unrelated (n=13) donors. Post-transplant high dose Cyclophosphamide (PT-Cy) on day +3, +4 as GVHD prophylaxis was used if allo-HSCT was performed from unrelated mismatched donors (n=8) or haplo-donors (n=4). Alfa/beta T-cells depletion was used as GVHD prophylaxis in young patients with a median age of 19 years (17-57 y.o.) who underwent haplo-HSCT (n=5). Acute GVHD grade II-III was diagnosed in 6 patients (27%) from the group with classical immunosuppressive regimen, in 2 patients (16,6%) from PT-Cy group. Acute skin GVHD grade II was diagnosed in 1 patient (20%) after T-cells depletion. Leukemia relapse was diagnosed after the day +100 in 4 patients (18%) after classic immunosuppressive regimen and 1 patient (8,3%) after PT-Cy. All 5 patients after T-cells depletion stayed in complete remission during follow-up period in 34 months after allo-HSCT. Bone marrow (BM) samples were collected on day +30, +60 and +90 after allo-HSCT in EDTA-tubes. Flow cytometry analysis was performed on BD FACS Canto II (Becton Dickinson, USA) to define T-memory subsets: T-naive and T-stem cell memory (Tnv+Tscm) - CD8+/CD4+ CD45R0-CCR7+CD28+; T-central memory (Tcm) - CD8+/CD4+ CD45R0+CCR7+CD28+; T-transitional memory (Ttm) - CD8+/CD4+ CD45R0+CCR7-CD28+; T-effector memory (Tem) - CD8+/CD4+ CD45R0+CCR7-CD28-; T-terminal effector (Tte) - CD8+/CD4+ CD45R0-CCR7-CD28-. Mann-Whitney U test was used for nonparametric data analysis. A p-value less than 0,05 was considered as significant. All data analysis was conducted utilizing SPSS ver. 23. (IBM, Chicago, Ill., USA). Results. The data are presented in the picture 1. According to our data the number of BM resident Tnv+Tscm CD8+ or CD4+ cells are much lower after alternative regimes of GVHD prophylaxis (PT-Cy or T cells depletion) on day +30 after allo-HSCT. Moreover on day +60 Tnv+Tscm CD4+ T-cells are still extremely low after T-cells depletion comparing to PT-Cy (p=0,03) and classical regimen (p=0,034). We didn't found any correlation between the number of Tnv+Tscm, Tcm, Ttm, Tem, Tte and the development of leukemia relapse or acute GVHD. Conclusion. New immunosuppressive approaches are now available for GVHD prophylaxis for patients who undergoes allo-HSCT from mismatched or haplo- donors that provides comparable results with classical immunosuppression in case of matched allo-HSCT. However Tnv+Tscm is the progenitor subset for all memory T-cells and its prompt recovery after allo-HSCT seems to be crucial for graft-versus-leukemia effect. Here we show the lowest number of Tnv+Tscm after alternative GVHD prophylaxis regimens that can be explained by more sever immunoablation. Through this it may lead to delayed reconstitution of adaptive immunity after alternative immunosuppression in patients after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Optical and electrical characteristics of different high-power multimode laser diodes with an emission wavelength of 835 nm are compared; the diodes were obtained on the basis of three systems of solid solutions: AlGaAS/GaAs, AlGaAs/GaAsP, and (Al)GaInP/GaInAsP. An output continuous optical power of 5 W is attained in lasers with a stripe width of 80 μm irrespective of the chosen material system. The highest optical power, 7 W, is attained in the lasers based on the (Al)GaInP/GaInAsP system.

The authors present the two-year follow-up of a female patient with severe pulmonary hypertension and a rare pathology – pulmonary veno-occlusive disease. Due to the treatment with low-dose prednisolone, in combination with warfarin, coraxan, and oxygen, the clinical status of the patient remains stable.

Results of an assessment of the actual food of the population in various medicoeconomic zones of the republic (industrial, agricultural, Arctic) by method of the frequency analysis of food consumption are presented in the article. The analysis of control of compliance of quality and safety of foodstuff in the Republic of Sakha (Yakutia), according to requirements of the legislation of the Russian Federation, acts of the Customs union has been made. Decreased consumption of such foodstuff as milk, fish and meat products including products from local food staples and national dishes has been established. The data obtained are medic-biological justification for search of ways of optimization of population nutrition, creation of specialized products with a functional purpose and for the prevention of the states and diseases connected with nutrition violation. They also define innovative development of the republic in questions of biotechnologies of the production of specialized foods for various groups of the population. Results of chemical composition research of the most used wild-growing food plants of Yakutia are given. The questions connected with the nutrition and biological value of the dairy products of a functional purpose with use of wild-growing food herbs and berries of Yakutia are discussed.

The reconstruction of photons in the ATLAS detector is studied with data taken during the 2004 Combined Test Beam, where a full slice of the ATLAS detector was exposed to beams of particles of known energy at the CERN SPS. The results presented show significant differences in the longitudinal development of the electromagnetic shower between converted and unconverted photons as well as in the total measured energy. The potential to use the reconstructed converted photons as a means to precisely map the material of the tracker in front of the electromagnetic calorimeter is also considered. All results obtained are compared with a detailed Monte-Carlo simulation of the test-beam setup which is based on the same simulation and reconstruction tools as those used for the ATLAS detector itself.