STATE INSTITUTION «NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE¼ - RESEARCH ACTIVITIES AND SCIENTIFIC ADVANCE IN 2022. / РЕЗУЛЬТАТИ РОБОТИ ДУ «ÐÐÐ¦Ð†ÐžÐÐÐ›Ð¬ÐÐ˜Ð™ НАУКОВИЙ ЦЕНТРРАДІАЦІЙНОЇ МЕДИЦИНИ НАЦІОНАЛЬНОЇ АКАДЕМІЇ МЕДИЧНИХ НАУК УКРАЇНИ¼ У 2022 РОЦІ.

Research activities and scientific advance achieved in 2022 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problems of the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaboration with the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annual report. The report presents the results of fundamental and applied research works of the study of radiation effects and health effects of the Chornobyl accident. The report also shows the results of scientificorganizational and health care work, staff training. The Scientific Council meeting of NAMS approved the NRCRM Annual Report.

STATUS OF THE CURRENT DOMESTIC REGULATORY BASE FOR ENSURING RADIATION SAFETY AND ANTI-RADIATION PROTECTION OF MILITARY PERSONNEL DURING THE PERIOD OF MARTIAL STATUS. / СТАН ЧИННОЇ ВІТЧИЗНЯНОЇ НОРМАТИВНОЇ БАЗИ ЩОДО ЗАБЕЗПЕЧЕННЯ РАДІАЦІЙНОЇ БЕЗПЕКИ ТА ПРОТИРАДІАЦІЙНОГО ЗАХИСТУ ВІЙСЬКОВОСЛУЖБОВЦІВ НА ПЕРІОД ВОЄННОГО СТАНУ.

Prerequisite. In the conditions of a full-scale invasion, the issue of radiation safety and anti-radiation protection in the Armed Forces of Ukraine (AFU) occupies a special place, since the aggressor country violated global geopolitical international decisions, occupied civilian nuclear facilities, in the process of their liberation servicemen mayhave to act in conditions of increased radiation risk, the possibility of using tactical nuclear weapons also is not excluded. OBJECTIVE: to investigate the state of the current national regulatory framework for ensuring radiation safety and anti-radiation protection of military personnel during the period of martial law. METHODS: bibliographic, analytical, historical, systematic approach. RESULTS: The main normative document on the organization of radiation safety and anti-radiation protection of both personnel and the population in Ukraine, as well as military personnel, currently in everyday conditions and in case of radiation accidents since 1998 and until now, are the State Hygienic Standards «Radiation Safety Standards of Ukraine (NRBU-97)¼. But neither in this document, nor in the transition to NRBU-2021-P, the issue of exposure to such a category as military personnel during the performance of combat (special) tasks is considered. The system of monitoring the radiation situation in Ukraine, documents on the organization of medical support for military personnel, including the Guidelines on the Medical Support of the Armed Forces of Ukraine for a Special Period (2019)and the Guidelines on the Organization of Radiation Safety in the Armed Forces of Ukraine (2020), were analyzed.modules of radiation safety principles in the Armed Forces of Ukraine were proposed. CONCLUSION: The unsolved problem of normalization of the radiation factor in the case of man-made and socio-political emergencies can create significant problems in the organization of anti-radiation protection of troops and the population in the case of the use of nuclear weapons or radiation accidents in a special period and requires anurgent solution. It is obvious that there is a need to develop regulatory documents regarding the response and planning of continuous activities to respond to potential nuclear and radiation threats during martial law, including relationships at all levels of the management vertical and methods of communication in the event of a threat.

THE COURSE OF CHRONIC LYMPHOCYTIC LEUKEMIA AFTER SARS-COV-2 VIRUS INFECTION. / ПЕРЕБІГ ХРОНІЧНОЇ ЛІМФОЦИТАРНОЇ ЛЕЙКЕМІЇ НА ТЛІ ІНФЕКЦІЇ ВІРУСОМ SARS-COV-2.

Objective - to investigate the course of B-cell chronic lymphocytic leukemia (CLL) in patients after SARS-CoV-2 virus infection taking into account anamnestic exposure to the ionizing radiation (IR).Methods. The study was performed in a group of 51 CLL patients who were admitted to the Department of Radiation hematology of the National Research Center for Radiation Medicine of NAMS of Ukraine, Kyiv, from January 2020 (the beginning of SARS-CoV-2 epidemic) to August 2023. The group included 19 (37.3 %) clean-up workers of the Chornobyl NPP accident, 15 (29.4 %) inhabitants of radionuclide contaminated areas and 17 (33.3 %) IR non-exposed patients. The diagnosis of CLL was based on clinical history, lymphocyte morphology, and immunophenotypic criteria. Statistical studies were performed using the SPSS software package, version 20.0.Results. The diagnosis of CLL was established for the first time in 14 patients, in seven of them, CLL was diagnosed after 2-17 months after SARS-CoV-2 infection. In contrast to patients who did not suffer from a coronavirus infection, they had pronounced lymphadenopathy, which in some cases was accompanied by hyperleukocytosis, and needed early treatment. Thirteen patients with a previously established CLL were diagnosed with COVID-19 by PCR test. In seven of them (53.8 %) starting treatment was needed, or CLL has progressed. Seven of 51 patients (13.5 %) were vaccinated against SARS-CoV-2. Then, four of them were diagnosed with SARS-CoV-2 infection, confirmed by a positive PCR test, and two patients had a relapse of CLL within 1-2 months after vaccination. Most of patients with signs of the influence of SARS-CoV-2 infection on CLL belonged to sufferers of the Chornobyl NPP accident Conclusions. The clinical features of CLL that developed after SARS-CoV-2 were characterized firstly. The negative impact of SARS-CoV-2 infection on previously established CLL was established. The question about vaccination of CLL patients remains debatable.

SLEEP QUALITY OF SCHOOLCHILDREN - RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS DURING THE COVID-19 PANDEMIC. / ЯКІСТЬ СНУ У ШКОЛЯРІВ ­ МЕШКАНЦІВ РАДІОАКТИВНО ЗАБРУДНЕНИХ ТЕРИТОРІЙ ПІД ЧАС ПАНДЕМІЇ COVID-19.

OBJECTIVE: to assess the sleep characteristics of middle school children during the COVID-19 pandemic. MATERIALS AND METHODS: Cross-sectional study of sleep characteristics of children - residents of radioactively contaminated areas of Zhytomyr and Rivne regions, who underwent a routine examination in June-July 2020, after their stay from March to June 2020 in conditions of home isolation due to quarantine restrictions during the COVID-19 pandemic. Ninety six students of comprehensive public schools, aged 10-16, took part in the study. Sleep characteristics were assessed using the Pittsburgh Sleep Quality Index (PSQI-U indicator), translated into Ukrainian. RESULTS AND DISCUSSION: During the period of the introduction of restrictive measures due to the COVID-19 pandemic, certain disturbances of sleep characteristics were observed, the imprint of which was a moderately increased total PSQI-U indicator, which was (3.89 ± 3.20) points. It was established that 19.79 % of children had insufficient total sleep time, and 2.08 % had significant sleep deprivation. The quality of their sleep was described as «rather bad¼ by 32.29 %, and as «very bad¼ by 4.17 %; 35.42 % of children complained about sleep disturbances, 67.71 % of children had signs of daytime dysfunction, 18.75 % had symptoms of insomnia. In the logistic regression model, quite significant prognostic factors of insomnia were: female gender (OR = 2.487; 95 % CI: 1.407-4.397); subjective determination of the negative impact of the pandemic on health, regardless of whether the respondent had COVID-19 or not (OR = 1.166; 95 % CI: 1.112-1.222), as well as living in the city (OR = 1.183; 95 % CI: 1.065-315). CONCLUSIONS: The introduction of restrictive quarantine measures as a result of the COVID-19 pandemic led to a violation of the daily routine of schoolchildren, which modified the characteristics of sleep. In almost a third of the examined children, the duration and quality of night sleep was insufficient for the physiological restoration of the body's reserves. A late choice of the start of sleep and violations of his hygiene had a critical impact on these indicators.

Stimulated Amplification of Propagating Spin Waves.

Spin-wave amplification techniques are key to the realization of magnon-based computing concepts. We introduce a novel mechanism to amplify spin waves in magnonic nanostructures. Using the technique of rapid cooling, we create a nonequilibrium state in excess of high-energy magnons and demonstrate the stimulated amplification of an externally seeded, propagating spin wave. Using an extended kinetic model, we qualitatively show that the amplification is mediated by an effective energy flux of high energy magnons into the low energy propagating mode, driven by a nonequilibrium magnon distribution.

EFFECT OF B. SUBTILIS ІМV B-7724 LECTIN ON THE ACTIVITY OF EFFECTORS OF CELLULAR ANTITUMOR IMMUNITY OF MICE WITH LEWIS LUNG CARCINOMA.

AIM: To evaluate the effect of B. subtilis IMV B-7724 lectin on the functional activity of macrophages (Mph), natural killer (NK) cells and cytotoxic lymphocytes (CTL) of mice bearing Lewis lung carcinoma (LLC). MATERIALS AND METHODS: The studies were performed on C57Bl/6J mice; LLC was used as an experimental transplantable tumor. The lectin from B. subtilis IMV B-7724 was administered to LLC-bearing mice subcutaneously at a dose of 1 mg/kg of body weight for 10 days. The immunological testing was performed on days 14, 21, and 28 after tumor grafting. The cytotoxic activity of Mph, NK, and CTL was estimated in MTT-assay; the content of the stable metabolites of nitric oxide (NO) was measured by a standard Griess reaction; the arginase activity (Arg) was determined based on the measurement of urea. RESULTS: The administration of the B. subtilis IMV B-7724 lectin to LLC-bearing mice exerted its antitumor and antimetastatic effects partially via a significant (p < 0.05) increase of Mph and NK activities after the completion of the treatment. In the group of animals injected with lectin, the NO/Arg ratio increased significantly, indicating the prevalence of Mph with proinflammatory and antitumor properties. The cytotoxic activity of Mph exceeded the indices of untreated mice and intact control by 1.8 times and 5.3 times respectively; of NK - by 2.8 and 1.3 times respectively. The effect of treatment on the CTL activity was less pronounced. CONCLUSION: Antitumor and antimetastatic activity of the lectin from B. subtilis IMV B-7724 ensured the preservation of the cytotoxic activity of the main effectors of antitumor immunity (Mph, NK, and CTL) throughout LLC growth.

IMMUNOPHENOTYPE OF LEUKEMIC CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS WITH NOTCH1 AND SF3B1 GENE MUTATIONS.

BACKGROUND: The typical chronic lymphocytic leukemia (CLL) immunophenotype is vital for diagnosis, but the expression of some antigens varies and has prognostic value. There are data that reduced CD20 expression is associated with NOTCH1 and SF3B1 gene mutations. AIM: To determine a high-risk group of CLL patients for prediction of unfavorable NOTCH1 and SF3B1 gene mutations based on immunophenotyping of leukemic cells. MATERIALS AND METHODS: Flow cytometric and molecular-genetic analysis (mutations of NOTCH1, SF3B1, and TP53 genes using the polymerase chain reaction followed by direct sequencing) was performed in a group of 86 previously untreated CLL patients. RESULTS: The immunophenotype of leukemic cells of all examined patients met the criteria of CLL diagnosis. NOTCH1 gene mutations were found in 21 patients (24.4%), and SF3B1 gene mutations - in 7 patients (8.1%). There were no TP53 gene mutations among the examined patients. A decreased number of CD20+CD5+ cells and a downward trend in the relative index of mean fluorescence intensity (iMFI) of CD20+ cells were found in patients with NOTCH1 and SF3B1 gene mutations. Based on the iMFI level (higher and/or lower than 3.0) and the number of CD20+CD5+ cells among all B-cells (higher and/or lower than 50%), we distinguished CLL cases with low and relatively high levels of CD20 antigen expression. Using ROC analysis and the parameter of low CD20 antigen expression, we could predict the presence of NOTCH1 and SF3B1 gene mutations in 73.3 ± 0.06% of patients (p = 0.001). The risk of NOTCH1 and SF3B1 gene mutations in cases with low CD20 antigen expression was 6.96 (95% CI = 2.53-19.18; p = 0.0001). The revealed regularities were statistically significant for patients in whom the diagnosis was established in all Binet - Rai stages except A0-AI. CONCLUSION: Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.

STATE INSTITUTION «NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE¼ - RESEARCH ACTIVITIES AND SCIENTIFIC ADVANCE IN 2021. / REZUL'TATY ROBOTY DU «NATsIONAL'NYI NAUKOVYI TsENTR RADIATsIINOÏ MEDYTsYNY NATsIONAL'NOÏ AKADEMIÏ MEDYChNYKh NAUK UKRAÏNY¼ U 2021 ROTsI.

Research activities and scientific advance achieved in 2021 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problems of the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaboration with the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annual report. The report presents the results of fundamental and applied research works of the study of radiation effectsand health effects of the Chornobyl accident.The report also shows the results of scientific-organizational and health care work, staff training. The Scientific Council meeting of NAMS approved the NRCRM Annual Report.

STEREOTYPED CASES IN UKRAINIAN COHORT OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS DEPENDING ON THE IONIZING RADIATION EXPOSURE. / STEREOTYPNI VYPADKY V UKRAÏNS'KII KOGORTI KhVORYKh NA KhRONIChNU LIMFOTsYTARNU LEIKEMIIu ZALEZhNO VID VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa.

OBJECTIVE: to analyze the stereotyped subsets in cohort of Ukrainian chronic lymphocytic leukemia (CLL) patients in general and depending on the ionizing radiation (IR) exposure. METHODS: Analysis was performed in the groups of 118 CLL patients irradiated due to the Chornobyl NPP accident (95 clean-up workers, 17 inhabitants of radionuclide contaminated areas, and 6 evacuees) and 294 IR non-exposed patients. The IGHV (immunoglobulin heavy chain variable region) gene mutational status, mutations of NOTCH1, TP53 and SF3B1 genes were studied by polymerase chain reaction followed by direct sequencing. Associations between clinical and molecular data of patients were analyzed with the SPSS software package, version 20.0. RESULTS: The incidence of stereotyped CLL cases in Ukrainian cohort was high (50.5 %) and comparable in IR-exposed and non-exposed patients. The ratio of major and minor clusters as well as the frequency of individual clusters was comparable with reported data with some exceptions: a low incidence of subset #2; absence of subset #8; high frequency of minor subset #V4|J4.5.6|18|5. The distinctive features of IR-exposed CLL patients found were:1) comparable frequency of stereotyped cases among mutated and unmutated (UM) IGHV genes cases (p = 0.557);2) lack of differences IGHV gene repertoires among stereotyped and heterogeneous cases (p = 0.508); 3) «heterogeneity¼ of stereotyped cases: all identified stereotyped clusters, with the exception of cluster #1, consisted of one case. Stereotyped cases with expression of UM IGHV clan I genes (except IGHV1-69 gene) were more susceptible to the appearance of NOTCH1 mutations. Patients of cluster #4 were younger, tended to have a longer time-to-treatment period and overall survival (OS) compared to subset #2. Patients of cluster #2 are more likely to have autoimmune hemolytic anemia (AIHA) and SF3F1 mutations. IGHV3-21 expression was associated with worse OS in univariate and multivariate analysis. AIHA was more common in patients with UM IGHV4-59 and IGHV3-11 genes. CONCLUSIONS: The revealed differences in distribution of stereotyped CLL cases in Ukrainian cohort are most likely to reflect variations in the genetic background, environmental factors (including IR exposure), and their interactions in different geographic areas.

IDENTIFICATION OF MONOAMINOXIDASE-A GENE PROMOTER POLYMORPHISM (MAOA-UVNTR) AND THEIR RELATIONSHIP WITH AGGRESSIVE BEHAVIOR IN UKRAINIAN CHILDREN. / IDENTYFIKATsIIa POLIMORFIZMU PROMOTORA GENA MONOAMINOKSYDAZY-A (MAOA-UVNTR) TA IOGO ZV'IaZOK Z AGRESYVNOIu POVEDINKOIu V UKRAÏNS'KYKh DITEI.

Aggressive disorders have moderate heritability; therefore, identification of genetic influences is important. TheX-linked MAOA gene encoding the MAOA enzyme has a functional polymorphism of 30 bp repeats. in the promoter region (MAOA-uVNTR), which affects aggression. Stressful life events and family misfortune are also known correlates of behavior disorder in children. OBJECTIVE: to investigate the interactive effect of monoamine oxidase-A gene promoter polymorphism (MAOA-uVNTR) and environmental factors on the development of aggressive behavior. MATERIALS AND METHODS: Genotyping of the MAOA-uVNTR polymorphism was performed in 144 boys and girls aged from 10 to 16 years, genotypes were grouped by a high and low transcriptional activity. For the general assessment of the psycho-emotional sphere of children, the projective method «non-existent animal¼ was used, the indicators and forms of aggression were determined according to the method of A. Bass and A. Darky. RESULTS AND DISCUSSION: It was found the predominant allelic variants of the MAOA gene with 3 (S) and 4 (L) tandem repeats. The presence of close relationships between the dependent variable «aggressive behavior¼ and the predictor variables: «family disadvantage index¼ and «MAOA-uVNTR genotype¼ was established. It has been proven that the presence of the highly active allele (L) in the genotype reduces the chances of developing general aggression, delinquent behavior, physical aggression, open aggression, negativism, and externalization. CONCLUSIONS: The MAOA genotype of the high-activity allele (L) moderated the impact of stressful life events, and the low-activity allele S was associated with increased aggression in girls and boys who experienced severe stress.

EXPRESSION OF IMMUNOGLOBULIN SEQUENCES HOMOLOGOUS TO ANTI-SARS-CoV-2 ANTIBODIES AND HIV IN CHRONIC LYMPHOCYTIC LEUKEMIA CASES.

BACKGROUND: Identification of epitopes recognized by leukemic B cells could provide insights into the molecular mechanisms of B cell transformation in chronic lymphocytic leukemia (CLL). The aim of this paper was to compare nucleotide sequences of immunoglobulin heavy chain variable region (IGHV) genes in CLL with known sequences directed against antigens of different origins available in public databases. MATERIALS AND METHODS: Analysis was performed in the groups of 412 unselected CLL patients with productive IGHV gene using polymerase chain reaction followed by direct sequencing. RESULTS: Homology between CLL Ig sequences and antibodies directed against autoantigens was found in 12 patients (2.9%), homology between CLL Ig sequences and antiviral antibodies - in 35 patients (8.5%). Most of these sequences belonged to stereotypical clusters. Among the sequences that have homology to antiviral antibodies, the most prevalent were cases homologous with antibodies against HIV (14 cases, 3.4%) and SARS-CoV-2 antigens (10 cases, 2.4%). None of the patients in our cohort was HIV-infected and the study was conducted before the emergence of SARS-CoV-2 virus. CONCLUSIONS: Suggestions could be made about the possible impact of past infection of SARS-CoV-2 virus on the pathogenesis of CLL. In particular, an increase in the proportion of CLL cases with the expression of some stereotyped BCR and/or an increase of CLL risk in the long-term period after SARS-CoV-2 virus infection is not excluded. This assumption needs to be verified by epidemiological data.

АNTIMETASTATIC EFFECT OF B. SUBTILIS IMV B-7724 LECTIN OBSERVED IN LEWIS LUNG CARCINOMA MODEL.

AIM: To study the antitumor and antimetastatic effects of B. subtilis IMV B-7724 lectin used in neoadjuvant and adjuvant settings in vivo. MATERIALS AND METHODS: Studies were performed on C57Bl/6J mice; Lewis lung carcinoma (LLC) was used as an experimental tumor. В. subtilis ІМV В-7724 lectin was administered to tumor-bearing mice or to mice which underwent surgical resection of the primary tumor. The lectin was injected subcutaneously, 10 times, at a single dose of 5 or 1 mg/kg of body weight. The standard indicators of tumor growth and metastasis were evaluated. RESULTS: Independently of the application settings, the lectin at a dose of 1 mg/kg of b.w. caused more pronounced effect than at a dose of 5 mg/kg of b.w. The administration of B. subtilis IMV B-7724 lectin to the mice with LLC in neoadjuvant setting did not cause notable antitumor effect but led to a significant decrease in the number and volume of lung metastases. The lectin administration in adjuvant setting significantly inhibited metastasis: the metastasis inhibition index reached 63.0% and 100% in the mice treated with the lectin at a dose of 5 mg/kg and 1 mg/kg respectively. The mean survival time of the treated animals significantly increased. CONCLUSION: A pronounced antimetastatic effect of B. subtilis IMV B-7724 lectin administered in an adjuvant setting was demonstrated.

STATE INSTITUTION «NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE¼ - RESEARCH ACTIVITIES AND SCIENTIFIC ADVANCE IN 2020. / REZUL'TATY ROBOTY DU «NATsIONAL'NYI NAUKOVYI TsENTR RADIATsIINOÏ MEDYTsYNY NATsIONAL'NOÏ AKADEMIÏ MEDYChNYKh NAUK UKRAÏNY¼ U 2020 ROTsI.

Research activities and scientific advance achieved in 2020 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problems of the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaboration with the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annual report. The report presents the results of fundamental and applied research works of the study of radiation effects and health effects of the Chornobyl accident. The report also shows the results of scientific-organizational and health care work, staff training. The Scientific Council meeting of NAMS approved the NRCRM Annual Report.

THE EXPRESSION OF THE MAIN AND ALTERNATIVE TRANSCRIPT (SORL1 Delta2) OF THE SORL1 GENE IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS AFFECTED BY THE CHORNOBYL ACCIDENT. / DOSLIDZhENNIa OSNOVNOGO I ALTERNATYVNOGO TRANSKRYPTU (SORL1 Delta2) GENA SORL1 U KhVORYKh NA KhRONIChNU LIMFOTsYTARNU LEAKEMIIu, POSTRAZhDALYKh VNASLIDOK ChORNOBYLSKA KATASTROFY.

OBJECTIVE: to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 genein chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe. METHODS: Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP acci-dent (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups ofpatients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main andalternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). TheIGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data wereanalyzed with the SPSS software package, version 20.0. RESULTS: Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57),did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expressionof B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relativeexpression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01-90.51). The expression of SORL1-Δ2transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmu-tated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene inpatients of the main and the control groups did not differ. CONCLUSIONS: Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients withunmutated IGHV genes can be considered as a negative prognostic marker.

SUBCLINICAL INFLAMMATION IN NON/ALCOHOLIC FATTY LIVER DISEASE AT THE REMOTE PERIOD AFTER THE CHORNOBYL ACCIDENT. / SUBKLINIChNE ZAPALENNIa PRY NEALKOGOL'NII ZhYROVII KhVOROBI PEChINKY U VIDDALENOMU PERIODI PISLIa ChORNOBYL'S'KOÏ AVARIÏ.

OBJECTIVE: to evaluate the parameters of inflammatory reaction and oxidative stress in patients with non-alcoholicfatty liver disease (NAFLD) in the remote period after the influence of the Chornobyl accident factors. MATERIALS AND METHODS: Eighty two patients with NAFLD who had been exposed to ionizing radiation as a result ofthe Chornobyl accident and have concomitant cardiovascular pathology were examined. Hematological parametersand the level of highly sensitive C-reactive protein (hsCRP) were determined, and the content of products of oxida-tive modification of lipids and proteins was evaluated. RESULTS: Activation of the processes of oxidative modification of lipids and proteins was observed in most patientswith NAFLD. According to the level of hsCRP, the presence of subclinical inflammation and the risk of developingcomplicated cardiovascular pathology was found in 58 % of patients with NAFLD. The neutrophil / lymphocyte ratiocorrelates positively with hsCRP and can be used as an available routine clinical marker for selection among patientswith NAFLD persons with increased risk of cardiovascular complications. CONCLUSIONS: HsCRP, oxidative modification products of lipids and proteins, ESR, and leukograms should be used toassess the degree of systemic inflammation in people affected by the Chornobyl accident, suffering NAFLD with con-comitant cardiovascular disease.

Influence of bacterial lectin on key regulatory links of functional activity of macrophages in mice with Ehrlich carcinoma.

BACKGROUND: Recent studies have shown the potential of using different approaches for immunotherapy in cancer treatment. Macrophages (Mph) are one of the promising targets for immunotherapy. AIM: To investigate changes in the functional activity of Mph in mice with Ehrlich carcinoma by nitric oxide (NO)/arginase (Arg), IRF4/IRF5 and STAT1/STAT6 ratios caused by administration of lectin from B. subtilis IMV-7724. MATERIALS AND METHODS: From the 2nd day after Ehrlich carcinoma inoculation into female Balb/c mice, lectin from B. subtilis IMV B-7724 (0.02 mg/mouse) was administered for 10 days. The peritoneal Mph were isolated on days 14, 21, and 28 after tumor transplantation and their functional state (NO production, Arg activity and cytotoxic activity) was examined. The levels of mRNA expression of transcription factors STAT-1, STAT-6, IRF5, IRF4 were evaluated. RESULTS: In lectin-treated animals with Ehrlich carcinoma, the functional state of Mph (NO/Arg ratio, index of cytotoxic activity) was maintained at the level of intact mice exceeding the values in untreated animals with Ehrlich carcinoma at late terms of tumor growth (21, 28 days). Analysis of mRNA expression levels of transcription factors in these animals showed a significant increase (p < 0.05) in the ratio of STAT1/STAT6 on the day 21 and IRF5/IRF4 on day 28 of tumor growth compared to that in untreated mice. CONCLUSIONS: Administration of lectin from B. subtilis IMV B-7724 to mice with Ehrlich carcinoma led to the prevalence of Mph exhibiting the functional properties of M1 type at late-term tumor growth. The transcription factors of the STAT and IRF signaling pathways are involved in the process of Mph polarization induced by lectin from B. subtilis IMV B-7724.

Association of lipoprotein lipase expression with TP53 gene polymorphisms in chronic lymphocytic leukemia cells.

BACKGROUND: Expression of lipoprotein lipase (LPL) correlates with unmutated (UM) status of the variable region of the heavy chain of immunoglobulin (IGHV) genes, but the expression level of LPL in UM chronic lymphocytic leukemia (CLL) cases varies significantly. AIM: To study the association of LPL expression with the genetic variants of the TP53 gene since both genes are involved in lipid metabolism. MATERIALS AND METHODS: Expression of LPL mRNA was measured in peripheral blood mononuclears of 45 CLL patients with UM IGHV genes by real-time quantitative reverse transcription polymerase chain reaction. Mutational status of IGHV genes and TP53 genotyping (rs1042522, rs1642785, rs17883323, rs2909430, rs145153611, rs113530090, rs12947788, rs12951053, and rs17878362) were performed by polymerase chain reaction amplification followed by direct sequencing. RESULTS: Observed CLL patients were divided on groups with low (11.17 ± 2.66) and high (275.48 ± 39.37) LPL expression. In CLL patients with UM IGHV genes and low LPL expression we found an increased frequency of rs1042522 G (p = 0.0036), rs1642785 C (p = 0.0001), and rs17878362A2 alleles (p = 0.0091). The possible functional significance of these changes is discussed. CONCLUSION: Some polymorphic variants of TP53 may be genetic modifiers for LPL expression level in CLL leukemic B-cells. Further research is required in a larger cohort to confirm these findings.

Controlling the Nonlinear Relaxation of Quantized Propagating Magnons in Nanodevices.

Relaxation of linear magnetization dynamics is well described by the viscous Gilbert damping processes. However, for strong excitations, nonlinear damping processes such as the decay via magnon-magnon interactions emerge and trigger additional relaxation channels. Here, we use space- and time-resolved microfocused Brillouin light scattering spectroscopy and micromagnetic simulations to investigate the nonlinear relaxation of strongly driven propagating spin waves in yttrium iron garnet nanoconduits. We show that the nonlinear magnon relaxation in this highly quantized system possesses intermodal features, i.e., magnons scatter to higher-order quantized modes through a cascade of scattering events. We further show how to control such intermodal dissipation processes by quantization of the magnon band in single-mode devices, where this phenomenon approaches its fundamental limit. Our study extends the knowledge about nonlinear propagating spin waves in nanostructures which is essential for the construction of advanced spin-wave elements as well as the realization of Bose-Einstein condensates in scaled systems.

Macrophage polarization in dynamics of Lewis lung carcinoma growth and metastasis.

AIM: To assess the functional state of macrophages based on various manifestations of their activity at the different stages of metastatic tumor growth in C57Bl mice. MATERIALS AND METHODS: On days 7, 14, 21 and 28 after Lewis lung carcinoma transplantation to C57Bl mice, macrophages from various anatomic sites were isolated and tested on their cytotoxicity, metabolic activity, NO production and arginase activity. RESULTS: In the populations of peritoneal and splenic macrophages, on days 7 and 21 of tumor growth antitumor (M1) cells prevailed while on days 14 and 28 tumor-promoting (M2) macrophages predominated. In the population of lung macrophages, cells with M1 phenotype were in the majority in the early stages of tumor growth. On days 21 and 28, M1 cells were gradually substituted by cells exhibiting M2 phenotype. This shift correlated with metastasis to lungs. CONCLUSION: Lewis lung carcinoma growth is accompanied by the gradual change in macrophage polarization from antitumor (M1) towards tumor-promoting (M2) type. These changes were more evident in population of lung macrophages and correlated with the parameters of metastasis.

STATE INSTITUTION «NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY OF MEDICAL SCIENCES OF UKRAINE¼ - RESEARCH ACTIVITIES AND SCIENTIFIC ADVANCE IN 2019. / REZUL'TATY ROBOTY DU «NATsIONAL'NYI NAUKOVYI TsENTR RADIATsIINOÏ MEDYTsYNY AKADEMIÏ MEDYChNYKh NAUK UKRAÏNY¼ U 2019 ROTsI.

Research activities and scientific advance achieved in 2019 at the State Institution «National Research Center forRadiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) concerning medical problemsof the Chornobyl disaster, radiation medicine, radiobiology, radiation hygiene and epidemiology in collaborationwith the WHO network of medical preparedness and assistance in radiation accidents are outlined in the annualreport. The report presents the results of fundamental and applied research works of the study of radiation effectsand health effects of the Chornobyl accident.The report also shows the results of scientific-organizational and health care work, staff training.The Scientific Council meeting of NAMS approved the NRCRM Annual Report.