Objectives To estimate and improve Ukraine's health sector's preparedness to respond to radiation and nuclear emergencies.Methods Field expert assessments and analytical methods were used.Results In September 2022, the WHO evaluation mission to Ukraine visited several critical regions to review the current state of health sector preparedness for a nuclear emergency and revealed many defects and items for improvement. The provision of radiation control equipment was considered for ambulance teams, admissions departments/emergency departments in designated hospitals, and tertiary level hospitals, and for National and Regional Public Health Laboratories. For cases of mass casualty, WHO procured 20 decontamination tents for the country. Training courses for medical specialists and decision-makers were launched.Conclusions The WHO mission was crucial in assessing the overall state of preparedness for CBRN threats and directing forces and resources to improve it. Donor assistance in the form of equipment for dosimetric monitoring and diagnostics of emergency-related disorders contributes to improving the preparedness of the health system of Ukraine to an adequate response to the threats of radiation and nuclear emergencies.

Radiation exposure is a well-established risk factor for leukemia. Clonal hematopoiesis (CH), the expansion of mutated hematopoietic cells, is also associated with increased leukemia risk and its frequency is higher in cancer patients following radiotherapy and chemotherapy. We investigated whether low to moderate environmental ionizing radiation determined by state-of-the-art dosimetric analysis was associated with CH in the Chornobyl Family Study (CFS). Our study conducted targeted high-depth sequencing and array genotyping to identify and characterize clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) in 882 participants from 292 CFS families. Fathers had mean bone marrow radiation doses of 0.24 Gy (range: 0-3.86) and mothers had mean doses of 0.009 Gy (range: 2 × 10-5-0.63). The expected relationship between increasing age and CHIP was observed. No detectable effect of red bone marrow radiation dose was observed for CHIP risk (Fathers: Excess OR (EOR)/Gy = 0.41; 95% confidence interval (CI) = -0.57,1.39; P-value = .42; Mothers (categorical model due to limited dose range): odds ratio (OR)0.01-0.09 versus <0.001 Gy = 0.73; 95% CI = 0.39,1.38; P-value = .33) and the distribution and types of CHIP and mCAs detected in CFS participants did not differ from that seen in previously published studies of unexposed populations. No transgenerational effect of parental gonadal radiation exposure was detected in the children (Fathers: P-value = .08; Mothers: P-value = .67). Our findings suggest the type and levels of radiation exposure investigated in CFS families are unlikely to be strong contributors to CH risk, which could have important implications for public health concerns following environmental exposure to low to moderate ionizing radiation.

Вступ. Збереження життя та здоров’я військовослужбовців в умовах радіаційних і ядерних загроз на період воєнного стану є одним з актуальних завдань сьогодення. Управління в умовах виникнення таких загроз має певні особливості, тобто має характерні риси, що відрізняють його від управління у звичайних повсякденних умовах. Мінімізувати наслідки та певною мірою попередити катастрофічні явища можна лише на підставі наукового прогнозування, яке базується на наукових дослідженнях в галузі медичній, державного управління, національної безпеки оскільки згадані вище події можуть виникати з різних причин та бути зумовленими різноманітними факторами, їх різними комбінаціями та взаємодією. Сьогодні в Україні не існує відповідної нормативно-правової бази, що регулювала б сценарії радіаційно-ядерних загроз в умовах війни та стосунки між органами військового управління з державними органами самоврядування. Мета. Проаналізувати чинну нормативно-правову базу в Україні щодо протирадіаційного захисту та радіаційної безпеки військовослужбовців. Матеріали та методи. Бібліографічний метод з можливістю так званого «згортання інформації»: на підставі бібліографічного вивчення інформації, яка існує у вигляді документів у відкритому доступі, аналітична обробка. створення нової, вторинної інформації. Системний підхід – один з спеціальних способів наукового дослідження, за яким досліджуваний об'єкт розчленовують на елементи, що їх розглядають в єдності, тобто як систему. Результати. В статті розглянуто питання необхідності розробки ключових документів, що підтримують готовність до реагування на можливі сценарії ядерних та радіаційних загроз у період воєнного стану. Крім того, необхідно відзначити, що принципи організації державного управління у звичайних умовах також відрізняються від аналогічних принципів в умовах радіаційно-ядерних подій у період воєнного часу. Це пов’язано з особливостями, до яких слід віднести слабку передбачуваність дійсного масштабу та часу їх виникнення; складність та багатоваріантність взаємозв’язків між процесами; часткову передбачуваність сценаріїв подальшого розвитку; надзвичайно високий рівень невизначеності. Висновки. Доведено необхідність розробки нормативних документів щодо реагування та планування безперервної діяльності з реагування на потенційні ядерні та радіаційні загрози у період воєнного стану, включаючи взаємозв’язки на всіх рівнях управлінської вертикалі та способи комунікації в разі реалізації загрози.

OBJECTIVE:Evaluation of structural features and metabolic/biochemical abnormalities of the bone tissue and relevant regulation patterns in children, residing in the radiologically contaminated territories (RCT). MATERIALS AND METHODS:Children (n = 148) aged 7 to 18 years old were involved in the study. Bone mineral density (BMD) is given in 3 grades according to the mean square deviation values, namely Grade I - standard (n = 75),Grade II - reduced (n = 45) and Grade III - very low one (n = 28). Cholelithiasis, urolithiasis, cancer and endocrinediseases, as well as bone fractures in the family members of children were taken into account. Bone fractures in thehistory and jaw anomalies were evaluated in study participants. A spectrum of blood biochemical parameters, namely the serum content of total protein, alkaline phosphatase (APh), serum iron (SI), creatinine, calcium, vitamin D,parathyroid hormone, calcitonin, pituitary thyroid stimulating hormone (TSH), free thyroxine (FT4), and cortisolboth with urine content of amino acids were assayed. Radiation doses in study participants were calculated. RESULTS:Abnormalities of the bone organic component were diagnosed according to the reduced serum level of creatinine, decreased urine levels of glycine and lysine, and increased urine content of oxyproline. A direct relationshipwas established between the urine level of oxyproline and serum TSH content (r = 0.42; p < 0.05). Abnormalities inthe bone mineral component were accompanied by calcium deficiency, increased serum content of APh anddecreased BMD. A direct relationship was established between the serum levels of calcium and APh (r = 0.33) andan inverse one between the APh serum content and BMD (r = -0.60) (р < 0.05). An inverse relationships were established between the serum vitamin D content and APh activity (r = -0.34), between the serum levels of vitamin D andSI (r = -0.35) (р < 0.05). Incidence and patterns of the abnormal parameters depending on BMD grades were established. Biochemical parameters reflecting the state of bone organic and mineral components both with the level ofserum iron and hormonal regulation of bone formation were ranked. Individual radiation doses of children were(0.66 ∓ 0.04) mSv being not correlated with any other studied parameters. CONCLUSIONS:Evaluation of the structural and functional components of bone tissue sheds light on the mechanismsof bone formation processes, metabolism of biochemical cascade, and regulatory pathways aiming the timely correction of abnormalities.

OBJECTIVE:To conduct a comparative analysis of cardiovascular system state in emergency workers (EW) of theaccident at the Chornobyl NPP and servicemen (SM) of Ukraine Armed Forces (UAF) who took part in the fightagainst russian military aggression, and to assess the role of military service factors on the development of cardiac pathology. MATERIALS AND METHODS:The study included 81 male EW and 161 SM of UAF, who were examined and treated in thecardiology department of NRCRMHO from 2022 to 2024. The average age of the surveyed EW was (56.0 ∓ 2.5) years,and SM - (45.9 ∓ 8.8) years. According to modern standards, clinical examination, electrocardiography, Dopplerechocardiography (EchoCG) examination, and statistical analysis were performed. RESULTS:It was found that among the examined people of both groups, who are now aged 50 to 60 years, EW at thetime hypertensive heart disease (HHD) and coronary heart disease (CHD) onset were younger than SM on average of7.5 and 5.4 years, respectively. Among EW there were more patients with HHD of stage III, angina pectoris of functional class (FC) III and heart failure (HF) of stage II according to NYHA, while among the FC there was a higher proportion of patients with HHD of stage II, FC II and HF I. In addition, 42 % EW had a history of myocardial infarctioncompared to 14.8 % of SM (р < 0.001), and EW had a higher proportion of patients with AV blocks (41.3% vs. 16.7%,р < 0.001). Echocardiographic parameters showed that EW compared to SM had a higher incidence of left ventricular dilatation, posterior wall and interventricular septum thickening, and, as a result, myocardial hypertrophy, particularly eccentric hypertrophy. It was found that the risk HHD developing during the war was 3.32 times higher inmobilized SM compared to the regular UAF, 2.41 times higher in SM who participated in combat, and 5.27 times higher in SM with shrapnel or bullet wounds. The risk of developing CHD was associated only with UAF staff: in mobilizedSM it was 3.84 times higher than in regular officers. CONCLUSIONS:The EW group differed from SM in a more severe course of HHD, CHD and HF, they had more severechanges in the structure of left ventricular myocardium. Most likely, this is explained by the fact that the incidenceof HHD and CHD occurs at a younger age, and therefore by the longer duration of these diseases, which led to moresevere pathological myocardial remodeling.

OBJECTIVE:To determine the structure of abnormalities of bone tissue and substantiate the management tactics inacute lymphoblastic leukemia (ALL) pediatric patients and in children with no oncohematological disorders, livingin radiologically contaminated territories (RCT). MATERIALS AND METHODS:Children (n = 220) living in RCT were the study participants i.e. the ALL patients (n = 120,Group I) and ones with no oncohematological disorders but having got some abnormalities in osteon and ironmetabolism (n = 100, Group II). There were 81.7 % cases of the «common» ALL, 10.0 % of the pro-B-ALL, and 8.3 %of the T-ALL types. Incidence of the bone fractures and jaw anomalies were taken into account. Types ofdiseases/disorders in the children's relatives were identified. The hemogram and myelogram data were evaluated.Biochemical blood parameters, namely the total protein, creatinine, calcium, alkaline phosphatase, serum iron (SI),ferritin (SF), transferrin, and vitamin D serum content along with the amino acid content in urine, bone mineral density (BMD) value, serum level of pituitary thyroid-stimulating hormone (TSH), free thyroxine, and cortisol wereassayed. Individual radiation doses were calculated/reconstructed. Curative and preventive measures were developed and applied. RESULTS:Collagen degradation, increased urinary excretion of oxyproline and proline, and decreased level of glycineand lysine occurred in the Group I after the chemotherapy (ChT) administration. The number of patients with BMDlower than 65 relative units (RU) was increasing (p < 0.05) as well as the number of cases with body iron excess(41.7 %). Toxic hepatitis and fatal cases were more often observed (p < 0.05 and r = -0.38, p < 0.01 respectively)under the SF level above 500 ng/ml. A direct relationship was established between the serum levels of SF and cortisol (r = 0.55; p < 0.05), between the TSH levels (above 3.3 IU/l) in blood serum and oxyproline in urine (r = 0.39;p < 0.05) negatively affecting the state of collagen. An increased level of cortisol contributed to the abnormalitiesin bone tissue structure and to a worse prognosis of the ALL course (p < 0.01). In the Group II (subjects having gotbone structure abnormalities) the sum amount of amino acids was increased. In 30.0 % of them the SI level exceeded the normative range. Radiation doses were on average (4.5 ∓ 0.9) mSv in ALL patients and (0.78 ∓ 0.07) mSv inthe RCT residents with no correlation with either serum biochemical parameters or BMD values. Curative and preventive measures were aimed at correcting the protein deficiency and mineral component of bone tissue, removingexcess iron from the body, and normalizing of hormonal status. Positive effect was reached in 81.7 % of the ALLpatients 6 months after the end of ChT. Normalization of the studied parameters occurred in 80 % of children having no oncohematological disorders. CONCLUSIONS:Diagnosis of abnormalities in the bone tissue structure and correction of osteogenesis in childrenreveal the mechanisms of leukemogenesis, determine the algorithm for timely approaches in prevention of bloodsystem diseases, and improve the quality of life of children.

In this article we review the history of key epidemiologicalstudies of populations exposed to ionizing radiation. We high-light historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer andnon-cancer outcomes with emphasis on study design andmethods of exposure assessment and dose estimation alongwith brief consideration of sources of bias for a few of themore important studies. We examine the findings from theepidemiological studies of the Japanese atomic bomb survivors,persons exposed to radiation for diagnostic or therapeutic pur-poses, those exposed to environmental sources includingChornobyl and other reactor accidents, and occupationallyexposed cohorts. We also summarize results of pooled studies.These summaries are necessarily brief, but we provide refer-ences to more detailed information. We discuss possible futuredirections of study, to include assessment of susceptible popula-tions, and possible new populations, data sources, study designsand methods of analysis. @2024 by Radiation Research Society

Research activities and scientific advance achieved in 2023 at the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine» (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 institution has been reorganized and since December 2023 has been called the State Institution «National Research Center for Radiation Medicine, Hematology and Oncology» (NRCRM). 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.

OBJECTIVE:To assess the functional state and age-related characteristics of autophagy in peripheral blood leukocytes as a risk factor for the development of inflammaging using the example of the servicemen of the DefenseForces of Ukraine and clean-up workers of the Chornobyl accident. MATERIALS AND METHODS:A total of 103 male patients aged 28-77 (56,48 ∓ 9,05) years were examined. They included: the main group - 23 servicemen of the Defense Forces of Ukraine aged 44-59 (50,21 ∓ 5,13) years; the comparison group - 57 clean-up workers of the Chornobyl accident aged 56-63 (60,31 ∓ 1,78) years; and the control group -23 civilians aged 28-77 (53,26 ∓ 15,98) years. The individuals in the main and control groups were divided according to age into subgroups under 50 years and over 50 years. Clean-up workers were divided into 3 subgroups depending on the radiation dose: І - D < 100 mSv, ІІ - 100 < D < 500 mSv and ІІІ - D > 500 mSv. Analysis of autophagyparameters in peripheral blood leukocytes (PB) was performed using flow cytometry and polymerase chain reaction. RESULTS:In patients of the main group, the autophagy activity factor (AAF) of granulocytes and the expression of theSQSTM1 gene in PB leukocytes decreased. A decrease in chloroquine-induced accumulation of LC3B protein in leukocytes, AAF in PB monocytes and the expression of the MTOR, RB1CC1 and MAP1LC3B genes was revealed in servicemenof the Defense Forces of Ukraine under 50 years of age. The spontaneous levels of LC3B protein and AAF in monocytesand the expression level of PIK3C3, ULK1 and MAP1LC3B genes in PB leukocytes were increased in servicemen of theDefense Forces of Ukraine over 50 years of age. The clean-up workers of different dose groups showed a decrease inthe AAF in lymphocytes and granulocytes, the LC3B level in monocytes after incubation with chloroquine, the expression of the MTOR, RB1CC1, SQSTM1, ULK1, MAP1LC3B, BECN1 and PIK3C3 genes in PB leukocytes, and the AAF of monocytes was higher. Similar changes were revealed in the indices of chloroquine-induced LC3B accumulation in lymphocytes and monocytes of the clean-up workers and servicemen of both age groups, as well as the spontaneous LC3B protein level in PB monocytes of the clean-up workers irradiated at doses above 100 mSv and civilians over 50 years old. CONCLUSIONS:Unidirectional dysregulation of autophagy was established in the servicemen of the Defense Forces ofUkraine and the clean-up workers of the Chornobyl accident. The existing changes in autophagy parameters can leadto disruption of the functioning of the autophagic apparatus of leukocytes at the level of mRNA and protein, as wellas signaling pathways, and be associated with age-related changes at both the cellular and organismal levels. Theemergence of new and persistent earlier stress factors as a result of the war creates an additional load on the mechanisms of maintaining homeostasis, which is observed in individuals exposed to ionizing radiation more than 30years later. The found intergroup differences and similarities can activate the same or similar mechanisms of pathological processes, which will ultimately increase the risks of developing age-associated chronic somatic pathologyin younger age groups.

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 Ukraine» (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. Key words: NRCRM, Chornobyl, radiation effects, epidemiology, radiation hygiene, treatment of victims, international cooperation, personnel. Key words: NRCRM, Chornobyl, radiation effects, epidemiology, radiation hygiene, treatment of victims, international cooperation, personnel.

Under the conditions of war in Ukraine, there remains a high probability that russia will use nuclear weapons or commit terrorist acts against nuclear power plants, which will lead to exposure of the population in doses that cause acute radiation sickness (ARS). In this regard, our medical service must be ready for the treatment of ARS of various degrees of severity under a mass influx of victims. In peacetime, ARS is a rather infrequent pathology, so most doctors lack experience in its treatment. This article, having the form of a lecture, presents material on the pathogenesis, classification, clinic, diagnosis and treatment of ARS, taking into account the modern achievements of radiation medicine. Treatment of ARS is based on the use of pharmaceutical drugs that are licensed in Ukraine. The article will be useful for doctors and medical workers of all branches and levels of health care, who will have to deal with irradiated persons in order to timely identify patients with ARS and provide them with effective treatment. Key words: acute radiation sickness, bone marrow syndrome, oropharyngeal syndrome, hematopoietic growth factor, antibacterial therapy.

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 may have 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)». 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 an urgent 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. Key words: radiation safety, anti-radiation protection, military personnel, martial law.

OBJECTIVE:identification of clinical and metabolic characteristics of osteogenesis and factors affecting bone mineral density (BMD) in children living in radioactively contaminated territories (RCT) after the ChNPP accident for the use of therapeutic and preventive measures aiming to reduce the incidence of disorders. MATERIALS AND METHODS:Children aged 4 to 18 years old (n = 539) were involved in the study within 4 age groups, namely under 7 years old, 7-10 years old, 10-14 years old, older than 14 years old. Studied parameters in children with a reduced BMD (85-65 relative units and under 65 relative units) were estimated vs. the normative BMD (100-85 relative units) cases. Diagnosis of osteopenia and osteoporosis in children was established according to the BMD T-index. Family history of the relatives of children was studied. Body weight at birth, fractures of the long bones, complaints of osalgia, jaw anomalies, dental caries, presence of obesity, and hypermobility syndrome (HMS) were assessed. Peripheral blood biochemical tests were performed featuring the serum total protein, alkaline phosphatase (APh), calcium, vitamin D, creatinine, serum iron (SI), ferritin, cortisol, pituitary thyroid-stimulating hormone (TSH), and free thyroxine (FT4) assay. BMD was measured and radiation doses in children were reconstructed. RESULTS:BMD depended on the age of children. A direct correlation was established between the cholelithiasis and urolithiasis incidence (р < 0.01), cancer and endocrine diseases (р < 0.05) in the relatives of children that had BMD under 65 relative units. Dental caries developed more often (р < 0.05), while obesity was less frequent (р < 0.05) in the subjects with BMD < 65 relative units. A direct correlation was established between the level of serum creatinine and BMD (р < 0.01), and there was an inverse correlation between the serum APh level and BMD (р < 0.001).Every third child had a vitamin D deficiency. Fractures of long bones and increased content of SI and TSH were characteristic for the children having got osteopenia (BMD within 85-65 relative units), while besides a predisposition to bone fractures the higher levels of SI, APh, cortisol both with calcium deficiency were found in children with osteoporosis (BMD < 65 relative units) compared to the general group with a similar BMD. An increased incidence of HMS was characteristic too. Radiation doses in children with osteopenia were higher than in those with osteoporosis: (1.17 ± 0.09) mSv and (0.92 ± 0.06) mSv respectively (р < 0.05). No correlation was found between the radiation doses and clinical signs, blood biochemistry or BMD. CONCLUSIONS:Study of the functional mechanisms of bone structures in children, depending on their metabolism, had made it possible to reveal the factors that affect bone formation in children living in RCT after the ChNPP accident, and to form the population groups for the timely application of therapeutic and preventive measures aiming to reduce the incidence of disorders of musculoskeletal system.

Objective To systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates. Design Systematic review and meta-analysis. Main outcome measures Excess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods. Data sources PubMed and Medline, Embase, Scopus, Web of Science Core collection databases. Eligibility criteria for selecting studies Databases were searched on 6 October 2022, with no limits on date of publication or language. Animal studies and studies without an abstract were excluded. Results The meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect). Population based excess absolute risks are estimated for a number of national populations (Canada, England and Wales, France, Germany, Japan, USA) and range from 2.33% per Gy (95% confidence interval 1.69% to 2.98%) for England and Wales to 3.66% per Gy (2.65% to 4.68%) for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations. Estimated risk of mortality from cardiovascular disease are generally dominated by cerebrovascular disease (around 0.94-1.26% per Gy), with the next largest contribution from ischaemic heart disease (around 0.30-1.20% per Gy). Conclusions Results provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which require further investigation. The observed heterogeneity complicates a causal interpretation of these findings, although this heterogeneity is much reduced if only higher quality studies or those at moderate doses or low dose rates are considered. Studies are needed to assess in more detail modifications of radiation effect by lifestyle and medical risk factors. Systematic review registration PROSPERO CRD42020202036

Summary. CD38 antigen is a negative prognostic marker of chronic lymphocytic leukemia (CLL). The question of what cut-off level of CD38 antigen expression should be considered as prognostically significant, remains debatable. Aim: to evaluate the optimal cut-off level for CD38 antigen in primary untreated CLL patients for the prognosis of disease and its association with the mutational status of immunoglobulin heavy chain genes (IGHV genes). Objects and methods: flow cytometric and molecular-genetic analysis (mutational status of IGHV genes using polymerase chain reaction followed by direct sequencing) were performed in the groups of 106 primary previously untreated CLL patients. Time-to-treatment, progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox regression. Results: The prognostic value of cut-off level CD38 antigen expression ≥ 20% or ≥ 30% does not differ significantly. Lowering of cut-off level to 7% or 5% was unsignificant. The specificity of the evaluation of the mutational status of IGHV genes based on CD38 antigen expression was low, since CD38 expression in almost half of CLL cases with unmutated IGHV genes not differ from CLL cases with mutated IGHV genes. Conclusion: the obtained data confirmed the prognostic value of CD38 antigen expression in patients at the initial stages of disease (A0-AI), primarily for assessing the duration of overall survival.

Julie J. Burtt, Suminori Akiba, Dimitry Bazyka, C. Norman Coleman, Maureen Hatch, and Jonine L. Bernstein Canadian Nuclear Safety Commission, Ottawa, ON, Canada; Hirosaki University Center for Radiation Support and Safety, Hirosaki, Japan; National Research Center for Radiation Medicine of the Academy of Medical Sciences of Ukraine, Kyiv, Ukraine; Radiation Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA; Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services, Washington, DC, USA; Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA

Objective: scientific substantiation of the new methodology for estimation of passport doses of the settlements which belong to Zone of Unconditional (obligatory) Resettlement, or 2nd zone and Zone of Granted Voluntary Resettlement, or 3rd zone in the framework of dosimetric passportization in accordance with the legislation of Ukraine. Materials and methods. 37 years after the accident, radioactive contamination of the environment has significantly decreased. However, it is still necessary to carry out ecological and dosimetric monitoring and apply countermeasures in certain territories of Ukraine affected by the accident at the Chornobyl Nuclear Power Plant: restriction of the consumption of locally produced milk, forest products, etc. The methodology, which was since 1996 used to estimate the passport doses of Ukrainian settlements, no longer corresponds to the current level of scientific knowledge about radioactive contamination of environment. The new methods of passport doses calculating presented in the work involves the use of a model whose parameters are determined by the types, quality and completeness of radioecological and dosimetric monitoring carried out on the radioactively contaminated territories in 1986–2013. The methodology takes into account the specific of radioactive contamination of each settlement. The passport dose of external exposure is reconstructed only from 137Cs radionuclide, because the contributions of other Chornobyl radionuclides influence the radiation dose only in the first years after the accident. The passport dose of internal exposure is formed as a result of the consumption of 137Cs contaminated food products. It is calculated depending on the availability in the settlement in the current year of the results of measurements of the 137Cs radionuclide activity incorporated in the human body using a whole body counter (WBC) and the activity of 137Cs in the private milk. At the same time, priority is given precisely to the results of WBC measurements of 137Cs. Results and conclusions. A new methodology (Methodology-2023) for passport doses calculation of Ukrainian settlements was substantiated. A comparison of passport doses based on the results of radioecological and dosimetric monitoring in 2011 calculated by Methodology-2023 and passport doses calculated by Methodology-96 was made. Passport doses calculated by Methodology-2023 increased by 40 % on average compared to doses calculated by Methodology-96. At the same time, passport doses of internal radiation calculated by the new methodology increased by 1.5 times, and passport doses of external radiation increased by 1.7 times. The passport dose of 2011, calculated by Methodology-2023, exceeds the legally established limit of 1 mSv in 71 settlements, most of which are located in Korostenkyi raion of Zhytomyr Oblast. Key words: internal radiation, external radiation, whole body counter, passport dose, radioactively contaminated territories, Chornobyl accident.

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.

Objective: to estimate the risk of thyroid cancer incidence in the population of Ukraine in connection with its exposure to radioactive iodine fallout of Chornobyl origin and the use of pesticides in agricultural production in the country. Object of study. Incidence rates of thyroid cancer in the population of Ukraine in 2001-2019, average regional radiation doses absorbed by the thyroid because of the Chornobyl accident, the volume of use of various groups of pesticides in the regions of Ukraine. Research methods: statistical, mathematical and cartographic. Results. The study covering the period of 2001–2019, revealed significant temporal and regional differences in the thyroid cancer incidence in the population of the Ukraine regions in 2001–2019. The existence of a significant correlation between the thyroid cancer incidence and the amount of radiation exposure to the thyroid associated with the Chornobyl accident was established. The existence of a significant correlation between the thyroid cancer incidence and the degree of pesticide use intensity in agriculture in the Ukraine regions was established. A significant value of multiple correlation r = 0.5866 (p < 0.05) was found between the thyroid cancer incidence in Ukraine and the average regional radiation doses and the pesticide use intensity in agricultural production in the country. Conclusions. A reliable value of the multiple correlation between the value of the average regional radiation exposure doses to the thyroid associated with the Chornobyl accident and the degree of pesticide use intensity in the national economy of Ukraine and the thyroid cancer incidence in the population was determined. Key words: ionizing radiation, pesticides, thyroid gland, morbidity, cancer.