The review is devoted to long-term genetic and epigenetic disorders in exposed individuals and their descendants,namely to cytogenetic effects in the Chornobyl NPP accident clean-up workers and their children, DNA methylation as an epigenetic modification of human genome. Data presented in review expand the understanding of risk of the prolonged exposure for the present and future generations, which is one of key problems posed by fundamental radiation genetics and human radiobiology.
Objective: To describe the status and results of thyroid disease screening and assessment of reliability of radiationthyroid doses in the Belarusian in utero cohort of 2,965 individuals exposed to Chernobyl (Chornobyl) fallout.
Materials and methods: Thyroid screening examinations are currently underway including thyroid palpation by anendocrinologist, ultrasonographic examination by an ultrasonographer and analysis of blood samples for diagnosisof hypo- and hyperthyroidism, autoimmune thyroiditis, thyroid function tests (thyroid-stimulating hormone [TSH],thyroxine [T4], thyroid peroxidase antibody [anti-TPO], and thyroglobulin antibodies [anti-TG]). Reliability of (i)information from 780 pairs of questionnaires obtained during the first and second interviews of the mothers and (ii)thyroid doses, which were calculated for the cohort members using this information, is evaluated.
Results: As of 15 August 2021, 1,267 in utero exposed study subjects had been screened. A single thyroid nodule wasdiagnosed in 167 persons (13.2 % of the total) and multiple thyroid nodules in 101 persons (8.0 %): 189 (14.9 %)persons had nodules detected for the first time at the screening while 79 (6.2 %) persons had nodules detected pre-viously (pre-screening nodules). Fifty-nine out of 268 subjects (22.0 %) with a suspicious thyroid nodule werereferred to fine needle aspiration biopsy, and among them 33 (55.9 %) were biopsied. Reasonable agreement wasobserved for modelqbased doses calculated for the Belarusian in utero cohort members using data from the two inter-views (Spearman's rank-correlation coefficient rs = 0.74, p < 0.001), while measurementqbased doses yielded almost per-fect agreement (rs = 0.99, p < 0.001).
Conclusions: During the thyroid screening, at least one thyroid nodule was identified in 268 of 1,267 (21.2 %) inutero exposed cohort members. Seven thyroid cancer cases were identified in the cohort, including 5 pre-screeningcases and 2 cases detected during the screening. Ongoing research on this unique cohort will provide importantinformation on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocesium iso-topes, for which available epidemiological data are scant.
Objective: to determine the place of health in the system of values of the population of the surveillance zone (SZ)of nuclear power plants (NPPs) and its importance in the perception of emergency risks (ER).
Materials and methods: To determine the place of health in the value system, a survey of the able-bodied popula-tion of satellite cities of Rivne (RNPP) and South Ukrainian (SUNPP) nuclear power plants was conducted using non-repetitive sampling, where the sampling error does not exceed 7,0 %. The motivational and behavioral componentthat determined health in the individual hierarchy of values of the subject according to the questionnaireBerezovskaya R. A. was studied. Statistical and mathematical methods were used in the research process.
Results: The array of respondents was conditionally divided into 4 groups according to their attitude to humanhealth. And the group where a person's life position is focused exclusively on health is the most common - 77,0 %.Group IV, which wants to live without limiting itself, is 8,1 %. The component integrity of values-goals and values-means among the urban population of the SZ of both nuclear power plants is the same: the main goal in life is health,happy family life, and as a means - perseverance, diligence and health. Goal values in groups I and IV have somedifferences: in the first group of respondents the main goal in life is health, and in the fourth, where a person's lifeguidelines exclude any restrictions - a happy family life. Values for these populations have some differences, but inboth groups health appears to be the main means to an end. There is a close correlation between the core of termi-nal values and the average indicators of the state of concern about the risk of emergencies.
Conclusions: Identified hierarchy of values: a group of stable dominant values; average status values; group of leastsignificant values. The values of the highest status among the values-goals are - health, happy family life and inte-resting work. Most respondents plan to achieve them through values such as «health», «perseverance and hardwork». There is a close correlation between the core of terminal values and the average indicators of the state ofconcern about the risk of emergencies.
Objective: to investigate the structural and morpho-functional changes in test systems of malignant (A-549 cellline) and normal (fibroblasts of the 6th passage) human cells during incubation with gadolinium-containing pho-ton-capture agent «Dotavist» and photosensitizer «Fotolon».
Methods: The passaged (continuously interweaved) cell culture technique on normal human fibroblasts and malig-nant human cells; cytological, biophysical, statistical methods.
Results: The cytotoxic properties of «Dotavist» gadolinium-containing photon-capturing agent and «Photolon»photosensitizer in a wide range of concentrations (5, 10, 25, 50, 100 and 200 μl/ml) were studied by the morpho-functional characteristics (growth kinetics, proliferative and mitotic activity, presence of atypical cells) in the invitro test systems of malignant (non-small cell lung cancer cell line A-549) and normal (6th passage fibroblasts)human cells. It was found that the cytotoxic properties of «Dotavist» in test systems of malignant and normal cellsare expressed under its administration in high concentrations (100 and 200 μl/ml). During incubation with«Photolon» photosensitizer the cytotoxic effect on malignant cells was determined at the lowest concentrations (5and 10 μl/ml). Photosensitizer administration in the increasing concentrations has lead to genotoxic effects.Cytotoxic effect of photosensitizer on the normal human fibroblasts was evident in the 5-200 μl/ml concentrationrange. There was a moderate decrease in mitotic activity along with increasing concentration. Genotoxic propertiesof photosensitizer were evident at 25 μl/ml concentration and above.
Conclusion: Study results of the effectiveness of neutron-capture and photon-capture technologies by the sensi-tivity assay in the in vitro test systems of human malignant cells (non-small cell lung cancer cell line A-549) andnormal cells (transplantable human fibroblast culture, the 6th passage) to the gadolinium-containing photon-cap-ture «Dotavist» agent and «Photolon» photosensitizer in different concentrations provide the basis for pre-clinicalstage of evaluating the effectiveness of medications used in binary technologies.
One of the current problems of modern radiobiology is determine the characteristics of the manifestation of radiation-induced effects not only at different dose loads, but also at different stages of development of the organism. In previous reports, we have summarized available evidence that at certain ages there is a comparative acceleration of radiation-induced pathological changes in the eye and brain, and the study and assessment of the risk of possible ophthalmic and neurological pathology in remote periods after contamination of radioactive areas. Data of irradiated in utero individuals are possible on the basis of observation of the state of the visual analyzer in persons who underwent intrauterine irradiation in 1986. Therefore, a parallel study of retinal morphometric parameters, amplitude and latency of components of evoked visual potentials in irradiated in utero individuals was performed.
Objective: to evaluate the retinal morphometric parameters, amplitude and latency components of the evoked visual potentials in intrauterine irradiated persons.
Materials and methods: The results of surveys of 16 people irradiated in utero in the aftermath of the Chornobyl disaster were used; the comparison group were residents of Kyiv of the corresponding age (25 people). Optical coherence tomography was performed on a Cirrus HD-OCT, Macular Cube 512x128 study technique was used. At the same time, the study of visual evoked potentials on the inverted pattern was performed, and occipital leads wereanalyzed. Visual evoked potentials were recorded on a reversible chess pattern (VEP) - an electrophysiological test, which is a visual response to a sharp change in image contrast when presenting a reversible image of a chessboard.
Results: In those irradiated in utero at the age of 22-25 years, there was a probable increase in retinal thickness in the fovea, there was a tendency to increase the thickness of the retina in the areas around the fovea. When recording visual evoked potentials on a reversible chess pattern in this group, there was a tendency to decrease the amplitudes of components (N75, P100, N145, P200) in the right and left parieto-occipital areas and asymmetric changes in latency of these components.
Conclusions: Early changes of fovea recorded in OCT and decreasing amplitudes of components of visual evoked potentials on the reversible chess pattern at the age of 22 25 years may indicate a risk of development in patients irradiated in utero, early age-related macular degeneration, as well as increased risk and increased risk structures of the visual analyzer.
The objective of the study was to improve the biological dosimetry approach among patients with acute radiationsickness of various degrees based on the analysis of radiation-induced chromosome aberrations in peripheral bloodlymphocytes of the victims.
Materials and methods: The study was based on primary cytogenetic data obtained in May 1986 within examina-tion of the 30 clean-up workers («liquidators») having got stage I-III acute radiation sickness. Dose verificationwas performed using the cytogenetic dosimetry based on a culture of peripheral blood lymphocytes with metaphaseanalysis of chromosome aberrations.
Results: A new method of evaluating the results of patients' cytogenetic examination at the beginning of specifictherapy has been developed. Procedure was performed using a model of multiple linear regression (complex of cyto-genetic parameters) and provided a satisfactory diagnostic level (featuring a compliance with initially definedclinical and laboratory diagnoses). Overall frequency of the aberrant cells and radiation markers increased in high-er disease stages. There was a trend of the frequency growth of chromatid-type aberrations with increasing of radi-ation burden. Adequacy of the proposed method based on the regression analysis of cytogenetic results was con-firmed through the preservation of group differences in estimates of disease stage in subjects with verified diagnosis.
Conclusion: Cytogenetic dosimetry in the scope of examination of persons exposed to ionizing radiation is an oblig-atory component of radiation sickness stage verification. The recommended method of cytogenetic data evaluationbefore and at the beginning of detoxification therapy provides a satisfactory level of diagnostics.
Objective: The article attempts to analyze the nature of sexual dysfunctions in patients living in areas exposed toionizing radiation as a result of the Chornobyl accident.
Materials and methods: A study of sexual function was carried out in 186 people (group I) living in the territoriesof Kyiv (Polisske, Chornobyl, Ivankiv, Borodianka, Vyshhorod, Makariv districts) and Zhytomyr (Malyn and Korostendistricts) regions. The control group consisted of persons who were born and lived on the territory of Ivano-Frankivsk and Chernivtsi regions (group II, n = 123). Diagnostics was carried out on an outpatient basis in accor-dance with the standards of the WHO and the Ministry of Health of Ukraine.
Results: Analyzing the obtained research results, a significantly larger number of patients with sexual dysfunctionwas identified in group I (82.3 %) than in group II (44.7 %) (р < 0.01). Psychopathological disorders disturbed,respectively, 60.2 % and 41.4 % (p < 0.01). Complaints of decreased libido were presented by 25.8 % of the surveyedmen exposed to ionizing radiation, and 6.5 % of them were concerned about a sharp depression of libido. In groupII patients, this indicator was 14.6 % and 3.3 %, respectively. The integral index of «libido» of the ICEF question-naire revealed a statistically significant difference between the groups (9.23 ± 0.89 and 12.22 ± 1.26, respectively;р < 0.05). In patients exposed to ionizing radiation as a result of the Chornobyl accident, the concentration oftestosterone decreases, and the content of FSH, LH, as well as globulin, which makes sex hormones, increases.Erectile dysfunction in patients of group I was detected in 58.1 % of men, and in patients of group II - 35.0 % (р < 0.01).The difference in the integral indicators of the ICEF questionnaire between the groups was 1.3 times behind the«libido» domain. For other domains - by 1.5-1.6 times. In men living in the territories of Kyiv and Zhytomyr regions,erectile dysfunction occurs earlier and is characterized by a more severe course than in people born and lived in theterritory of Ivano-Frankivsk and Chernivtsi regions. Both in terms of low rates of normal erection (in patients ofgroups I and II, respectively 3.8 % and 13.3 %), and for high percentages of existing moderate/severe ED (respec-tively 71.0 % and 45.5 %), persons from group I are characterized by significantly worse data than persons fromgroup II (р < 0.01). Orgasm pathology was found in 40.3 % of patients in group I and in 25.2 % of patients in groupII (р < 0.01). The quality of life index according to the QoL index in the context of existing sexual disorders in groupI of patients was 4.7 ± 0.4, in patients of group II - 3.9 ± 0.2 (р < 0.05).
Conclusions: The data obtained indicate a tendency for a more significant violation of sexual functions in men whowere born and lived in territories exposed to radioactive contamination
Objective: building of a mathematical logit model for possible prediction of the outcome of surgical treatment bythe method of coronary artery bypass grafting (CABG) in patients of different groups with coronary heart disease(CHD) based on myocardial viability (MV) assessment.
Material and methods: To implement the set clinical tasks, 62 patients with coronary heart disease with preservedsystolic function and systolic dysfunction were examined. The mean age of the subjects was (59.6 ± 8.2) years. 35(56 %) patients had a variant of heart failure (HF) with an ejection fraction (EF) of 45 % or less. 27 (44 %) patientshad EF of 46 % or more. 5 (8.0 %) patients denied myocardial infarction (MI). Myocardial scintigraphy (MSG) wasperformed on Infinia Hawkeye combined gamma-camera (GE, USA) with integrated CT. The studies were performedin SPECT and SPECT / CT with ECG synchronization (Gated SPECT) modes. 99mTc-MIBI with an activity of 555-740 MBqwas used. MSG was performed in the dynamics of treatment (before CABG and after CABG) according to One Day Restprotocol. A total of 124 scintigraphic studies were performed.
Results: Samples of patients studied «before» and «after» the treatment were compared using nonparametricWilcoxon test (Wilcoxon Matched Pairs Test). A multivariate regression model, that reflects a statistically significanteffect on the treatment response (MV after treatment) of such cardiac activity indicators as LV EF (%), coronary bedlesion area and MV level (%) before treatment, was built. The above-described regression relationship between thethree above-defined functional factors of cardiac activity before treatment and the therapeutic effect in the formof the change in MV can be construed as a diagnostic model that predicts the treatment outcome.
Conclusions: This scientific study allows to build logit models to predict the expected outcome of coronary heartdisease surgical treatment in patients of different groups. The presented multivariate regression model is characterised by a sufficiently high for biostatistical studies adjusted coefficient of determination (Adjusted R2 = 0,893 (F = 173,4; p < 0,001)).
Objective: to analyze comorbid pathology by methods of its quantitative assessment in servicemen exposed toextreme factors of military service (a set of factors of radiation accidents, the influence of modern armed conflictsand modern combat trauma without blood loss).
Materials and methods: Studies of comorbid pathology were performed in 613 servicemen who were treated at theclinical base of the Ukrainian Military Medical Academy (UMMA) in National Military Medical Clinical Center «MainMilitary Clinical Hospital» NMMCC «MMCH» during 1989-2018 years. Soldiers who suffered from acute radiation sick-ness (ARS) in 1961 (n = 34), participants in the liquidation of the consequences of the Chornobyl catastrophe(PLCChC) 15 years after participating in the elimination of its consequences and in a later period (respectivelyPLCChC 1st group (n = 59) and the 2nd group (n = 337)). Soldiers are participants in the anti-terrorist operation(ATO)/Combined Forces (CFO) operation who did not receive modern combat injuries with blood loss (participants inthe ATO/CFO, n = 183). All servicemen did not have any diseases limiting their fitness capabilities for military serv-ice before being exposed to extreme factors of military service. A cumulative CIRS scale was used to comprehensive-ly assess comorbidity.
Results: With increasing time after participation in the elimination of the consequences of radiation accidents, thecourse of arterial hypertension (AH) is aggravated, but the dose-dependence of the severity of AH on the receivedradiation dose has not been established. The easier course of hypertension in ATO/CFO servicemen compared to ARSremote servicemen and group 2 PLCChC servicemen can be explained by their younger age at the time of the surveyand less time after exposure to extreme military service factors. In the military in the remote period after exposureto a complex of factors of radiation accidents, the frequency of diagnosing diseases by individual organs and bodysystem increases comparing to non-irradiated servicemen. The total number of disease severity scores on the cumu-lative scale of CIRS diseases is also higher. However, a dose-dependent effect of the severity of comorbid patholo-gy was also not found. These data indicate a higher prevalence of comorbid pathology in servicemen affected by acomplex of factors of radiation accf5idents, compared with participants in the anti-terrorist operation / environ-mental protection. However, the lower severity of comorbid pathology in ATO/CFO participants can also be explainedby their younger age at the time of the survey and less time after exposure to extreme factors of military service.
Conclusions: For servicemen, with increasing time after participation in the elimination of the consequences ofradiation accidents, the course of hypertension without its dose dependence becomes more difficult. The total num-ber of dise
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.
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