mFISH analysis of chromosome aberrations in workers occupationally exposed to mixed radiation

We performed a study on the presence of chromosome aberrations in a cohort of plutonium workers of the Mayak production association (PA) with a mean age of 73.3 +/- 7.2 years to see whether by multi-color fluorescence in situ hybridization (mFISH) translocation analysis can discriminate individuals who underwent occupational exposure with internal and/or external exposure to ionizing radiation 40 years ago. All Mayak PA workers were occupationally exposed to chronic internal alpha-radiation due to incorporated plutonium-239 and/or to external gamma-rays. First, we obtained the translocation yield in control individuals by mFISH to chromosome spreads of age-matched individuals and obtained background values that are similar to previously published values of an international study (Sigurdson et al. in Mutat Res 652:112-121, 2008). Workers who had absorbed a total dose of >0.5 Gy external gamma-rays to the red bone marrow (RBM) displayed a significantly higher frequency of stable chromosome aberrations relative to a group of workers exposed to 1.48 kBq, mFISH revealed a considerable number of cells with complex chromosomal rearrangements. Linear associations were observed for translocation yield with the absorbed RBM dose from external gamma-rays as well as for complex chromosomal rearrangements with the plutonium-239 body burden

Results of studying pro- and anti-atherogenic immune factors in the persons chronically exposed to ionising radiation

It is well established that cohorts of individuals exposed to ionizing radiation exhibit increased risks for cardiovascular diseases. Currently, the role of immune system in pathogenesis of atherosclerosis is actively studied. Meanwhile, the immunomodulatory effects of irradiation in pathogenesis of atherosclerosis in the persons exposed to ionizing radiation still remain unclear. The aim of this research was to study the effect of ionizing radiation upon lymphocyte subpopulations involved in pathogenesis of atherosclerosis. The lymphocyte subpopulations were studied in peripheral blood of the workers chronically exposed to occupational combined radiation versus a control group. The study considered 72 workers of the Russian nuclear production facility, the Mayak Industrial Association (mean age of 72.1±10.9 years), and 72 control individuals (mean age of 70.7±9.2 years). All the workers were chronically exposed to combined radiation (external gamma-rays and internal alpha-particles). The mean cumulative dose absorbed by red bone marrow from external gamma-ray exposure was 0.750±0.699 Gy; the mean cumulative absorbed dose to red bone marrow from internal alpha-particles was 0.072±0.092 Gy. The relative and absolute numbers of lymphocyte subpopulations (total T-cells, T-helpers, T-cytotoxic, total B-cells, NK-cells and T-NK-cells) were detected by flow cytofluorometry. The absolute number of CD3+CD19+T-lymphocytes was significantly lower in the individuals exposed to chronic irradiation, compared with the controls (1658.8±694.3 x 106/l and 1988.4±1045.4 x 106/l, respectively). The relative number of CD3+CD4+T-helpers and CD3+CD8+T-cytotoxic lymphocytes was significantly higher in individuals exposed to chronic irradiation. Relative number of T-helpers in the main group was 42.4±8.8% vs 35.3±8.7% in controls; the relative number of T-cytotoxic lymphocytes was 27.6±9.5%, and 23.3±6.5%, respectively. A significant negative correlation was revealed between absolute number of T-lymphocytes and cumulative absorbed doses to bone marrow from external gamma irradiation (correlation quotient r = -0,53565, p = 0,000001) and internal alpha sources (r = -0.54804, p = 0.0000006). This correlation may indicate a relationship between these changes (decreased absolute numbers of T cells) and occupational exposure rates. The increased relative number of T-helpers and cytotoxic T-lymphocytes confirm an assumption that specific antigens may cause an enhanced immune response during the development of atherosclerosis in exposed individuals

Status of antioxidant and oxidant systems in rheumatic fever and hereditary collagen dysplasias

Recently, the interest in research on the role of free radical-induced lipid peroxidation reactions in pathogenesis of rheumatic fever and hereditary collagen dysplasias has considerably grown. The study tested blood plasma of 60 children: 18 carriers of hereditary collagen dysplasias and 42 children with rheumatic fever. Twenty healthy individuals have constituted control group. All patients have undergone complex clinical and laboratory examinations to evaluate process activity and disease stage, their familial and genealogical histories have been taken. Presence of rheumatoid factor was determined by latex agglutination test. Other rheumatic fever markers were tested by common methods. Status of the lipid peroxidation process was assessed by malondialdehyde content, using reaction with thiobarbituric acid and subsequent spectrophotometric measurement. Catalase activity was measured spectrophotometrically. To diagnosticate hereditary collagen dysplasias, hydroxyproline levels in blood and urine were assayed. Content of glycosaminoglycans was determined by electrophoresis, and levels of amino acids were measured chromatographically. In the majority of patients, the tests detected an increased daily urinary excretion of hydroxyproline and glycosaminoglycans what reflects the process of collagen metabolism disorders. The authors detected elevated levels of malondialdehyde, increased activity of superoxide dismutase and decreased activity of glutathione peroxidase and catalase. These three markers are sufficiently sensitive to assess affection of immunocompetent cells in rheumatic fever and hereditary collagen dysplasias

Is Lone Hypertension a Risk Factor for More Severe COVID-19 Outcomes?

Background Based on current evidence, it is not clear whether lone hypertension increases the risk for severe illness from COVID-19, or if increased risk is mainly associated with age, obesity and diabetes. The objective of the study was to evaluate whether lone hypertension is associated with increase mortality or a more severe course of COVID-19, and if treatment and control of hypertension mitigates this risk. Methods This is a prospective multi-center observational cohort study with 30-day outcomes of 9,531 consecutive SARS-CoV-2 PCR-positive patients ≥ 18 years old (41.9 ± 9.7 years, 49.2% male), Uzbekistan, June 1-September 30, 2020. Patients were subclassified according to JNC8 criteria into six blood pressure stages. Univariable and multiple logistic regression was conducted to examine how variables predict outcomes. Results The 30-days all-cause mortality was 1.18% (n = 112) in the whole cohort. After adjusting for age, sex, history of myocardial infarction (MI), type-2 diabetes, and obesity, none of six JNC8 groups showed any significant difference in all-cause mortality. However, age was associated with an increased risk of 30-days all-cause mortality (OR = 1.09, 95%CI [1.07-1.12], p < 0.001), obesity (OR = 7.18, 95% CI [4.18-12.44], p < 0.001), diabetes (OR 4.18, 95% CI [2.58-6.76], p < 0.001), and history of MI (OR = 2.68, 95% CI [1.67-4.31], p < 0.001). In the sensitivity test, being ≥ 65 years old increased mortality 10.56-fold (95% CI [5.89-18.92], p < 0.001). Hospital admission was 12.4% (n = 1,183), ICU admission 1.38% (n = 132). The odds of hospitalization increased having stage-2 untreated hypertension (OR = 4.51, 95%CI [3.21-6.32], p < 0.001), stage-1 untreated hypertension (OR = 1.97, 95%CI [1.52-2.56], p < 0.001), and elevated blood pressure (OR = 1.82, 95% CI [1.42-2.34], p < 0.001). Neither stage-1 nor stage-2 treated hypertension patients were at statistically significant increased risk for hospitalization after adjusting for confounders. Presenting with stage-2 untreated hypertension increased the odds of ICU admission (OR = 3.05, 95 %CI [1.57-5.93], p = 0.001). Conclusions Lone hypertension did not increase COVID-19 mortality or in treated patients risk of hospitalization

Study of the hygrometric condition of cement stone and concrete

Cement systems are thermodynamically non-equilibrium, non-linear systems. Since it is far from equilibrium, it must be characterised by structure formation processes. Here it is necessary to consider the definition of ‘structure formation’. This term is used in two meanings. The first is generally accepted in concrete science -the formation of mechanical bonds between the dispersed particles of a solidifying system as a result of ongoing chemical and physicochemical processes, culminating in the formation of a solid body -the cement stone and concrete. The second meaning of the term describes the emergence of dissipative structures, i.e. the destruction of the initial homogeneity of the system due to the emergence of streams, concentration gradients, chemical waves, etc. By measuring the parameters of the resulting dissipative structures of different formation methods, it is possible to assess the degree of disequilibrium in the solidifying system and hence the directed methods of structure formation and structure optimisation. It should also be noted that a non-linear, non-equilibrium hydration process leading to a concentration potential difference proceeds with equal probability in all directions. Applying a gradient of a high-intensity physical field to the disperse system, one should expect a synchronisation of the fluctuations of the concentration potential of local areas of the disperse system, which will result in a sharp increase of the physical and mechanical properties of the hydration products of the binder and of the concrete in general

Immunomorphological characteristics markers of apoptosis of pulmonary adenocarcinoma at workers of plutonium manufacture

This work is aimed to identify changes in levels of apoptosis and cell proliferation markers in pulmonary tumour tissues in workers following occupational radiation exposure. We analyzed immune and morphological specific characteristics of apoptosis system using autopsy samples of 40 pulmonary adenocarcinomas including 22 samples from Mayak PA radiation workers. Levels of apoptosis regulating proteins were shown to differ considerably in pulmonary adenocarcinoma foci of plutonium workers internally exposed to alpha-particles compared to those in occupationally unexposed individuals.Цель работы – определение и оценка изменений в содержании в ткани легочных опухолей маркеров апоптоза и клеточной пролиферации у лиц, подвергшихся профессиональному облучению. Изучены иммуноморфологические особенности системы апоптоза на аутопсийном материале 40 случаев аденокарциномы легкого, в том числе 22 работников ядерного предприятия По «Маяк». Показано, что содержание белков-регуляторов системы апоптоза в очагах аденокарциномы легкого у работников плутониевого производства, подвергшихся внутреннему альфа-облучению, значительно отличается от соответствующего показателя в образцах аденокарциномы легкого у лиц, не подвергавшихся профессиональному облучению

Динамика показателей заболеваемости раком толстого кишечника в когорте работников, подвергшихся профессиональному облучению

Colorectal cancer is one of the most common malignant neoplasms. Main causes inducing this type of cancer are factors related to the life style and occupational exposures to chemical agents. Some studies demonstrated an association of colorectal cancer incidence and mortality with ionizing radiation. The aim of the present study was to assess the trend in colorectal cancer incidence in a cohort of nuclear workers employed at the Mayak Production Association who had been exposed to ionizing radiation over prolonged periods. The cohort comprised 22,377 workers (25% of females) employed at one of the main plants (reactors, radiochemical and plutonium production plants) of the Mayak Production Association in 1948-1982 who had been externally exposed to gamma rays (cumulative absorbed colon doses were 0–5.85 Gy with the corresponding median dose of 0.16 Gy) and those who had inhaled aerosols containing plutonium particles had been also internally exposed to alpha radiation (cumulative absorbed colon doses were 0–0.18 Gy with the corresponding median dose of 0.0002 Gy). Over the period of 1948–2018, 239 colon cancers and 186 rectum cancers were diagnosed in the study cohort. The incidence of colorectal malignancies among workers of the study cohort was shown to increase with age above 50. Age-standardized incidence rates were higher in males than in females. The time trend analysis of age-standardized rates of colorectal malignancies among workers of the study cohort was performed using a spline regression. The trend of age-standardized rates of colorectal cancer incidence in the Mayak Production Association workers over the analyzed period was nonmonotonic. In general, the average annual percent change of incidence growth for colon cancer was less than 0.1% (for both sexes), while the corresponding estimates for rectum cancer were 1.1% in males and 30.3% in females. To assess the effect of occupational radiation exposure on the incidence of colorectal malignancies, a radiogenic risk analysis that would take into account non-radiation risk factors should be performed.Рак толстого кишечника входит в число наиболее распространенных злокачественных новообразований. Основными причинами возникновения опухолей этой локализации являются факторы, связанные с образом жизни, а также профессиональный контакт с некоторыми химическими агентами. В отдельных исследованиях установлено влияние ионизирующего излучения на заболеваемость и смертность от рака толстого кишечника. Целью настоящего исследования являлась оценка динамики заболеваемости раком толстого кишечника в когорте работников предприятия атомной промышленности – производственного объединения «Маяк»», подвергшихся пролонгированному профессиональному облучению. Когорта включала 22 377 работников (25% – женщины), нанятых на основные заводы производственного объединения «Маяк» (реакторный, радиохимический, плутониевый) в 1948–1982 гг., которые подвергались пролонгированному общему внешнему гамма-облучению (накопленные поглощенные в стенке толстой кишки дозы 0–5,85 Гр, медиана 0,16 Гр), а в случае ингаляционного поступления соединений плутония – также внутреннему альфа-облучению (накопленные поглощенные в стенке толстой кишки дозы 0–0,18 Гр, медиана 0,0002 Гр). В период 1948–2018 гг. в изучаемой когорте диагностировано 239 случаев рака ободочной кишки и 186 случаев рака прямой кишки. Показатели заболеваемости раком толстого кишечника у работников изучаемой когорты статистически значимо увеличивались с возрастом старше 50 лет, стандартизованные по возрасту показатели были выше у мужчин по сравнению с женщинами. Анализ временных трендов стандартизованных показателей заболеваемости раком толстого кишечника у работников изучаемой когорты была выполнен с помощью сплайн-регрессии. Динамика стандартизованных показателей заболеваемости раком толстого кишечника у персонала производственного объединения «Маяк» в изучаемый период времени носила разнонаправленный характер. В целом, в 2014–2018 гг. среднегодовой темп прироста заболеваемости раком ободочной кишки составил менее 0,1% (оба пола), аналогичный показатель для рака прямой кишки у мужчин был равен 1,1%, а у женщин достигал 30,3%. Для оценки влияния профессионального облучения работников на заболеваемость раком толстого кишечника требуется анализ радиогенного риска с учетом действия нерадиационных факторов

Продолжительность жизни у работников ПО «Маяк» после острой лучевой болезни разной степени тяжести

Assessment of the impact of radiation exposure on human lifetime is an actual problem in radiation medicine. The aim of the study was to assess lifetime in Mayak PA workers who had developed acute radiation syndrome following accidental acute high-dose external exposure and in those individuals who had taken part in nuclear accidents but had not developed the syndrome. Study analyses considered 58 deceased Mayak PA workers (50 males and 8 females) and were performed using STATISTICA 10 software. Five indicators of lifetime were studied: static – before and after acute exposure, total lifetime, as well as potential – potential years of life lost and the proportion of people who lived less than 35 years. The study demonstrated significant decrease in static indicators excluding lifetime before acute exposure and increase in potential indicators of lifetime in workers with severe and especially with extreme acute radiation syndrome compared to workers with moderate and modest acute radiation syndrome and to workers free of the syndrome. The reason for the decrease of lifetime in workers with extreme acute radiation syndrome was extremely severe course of the disease. Decrease of lifetime in cases with severe level of the syndrome was mainly due to early death from malignancies. A significant linear regression association with natural logarithm of acute radiation dose in Gy was observed for lifetime indicators. At 1 logarithm of the radiation dose, the lifetime after acute exposure was reduced by 8.3 years, total lifetime by 8.8 years, and potential years of life lost increased by 8.4 years. The relative risk of the increase of the proportion of workers with less than 35 years of life was considerably higher in workers with extreme and severe acute radiation syndrome and in workers with acute radiation doses above 10 Gy compared to other groups of workers: 26.8 and 18.8 (95% CI: 3.8–191.1 and 2.7–129.8; p&lt;0.001), respectively. Thus, for the first time, a reduction in lifetime after acute radiation syndrome was found among Mayak PA workers.Оценка влияния радиационного воздействия на продолжительность жизни человека – актуальная проблема радиационной медицины. Целью исследования явился анализ продолжительности жизни в группе работников ПО «Маяк» после острой лучевой болезни, подвергшихся в результате аварийных ситуаций острому внешнему облучению в значительных дозах, и участников аварий без заболевания. Анализ проведен у 58 умерших работников ПО «Маяк» (50 мужчин и 8 женщин) с помощью программы STATISTICA 10. Изучены 5 показателей продолжительности жизни: статичные – до и после острого облучения, общая продолжительность жизни, а также потенциальные – потерянные годы потенциальной жизни и доля лиц, проживших менее 35 лет. В результате исследования у работников с тяжелой и особенно крайне тяжелой степенью болезни относительно работников средней и легкой степени тяжести заболевания и участников аварий установлено статистически значимое сокращение статичных показателей, за исключением продолжительности жизни до острого облучения, и повышение потенциальных показателей. Причиной сокращения продолжительности жизни при крайне тяжелой степени заболевания было его экстремальное течение. При тяжелой степени тяжести сокращение продолжительности жизни было обусловлено, главным образом, преждевременной смертностью от злокачественных новообразований. Установлена статистически значимая линейная регрессионная зависимость показателей продолжительности жизни от натурального логарифма дозы острого облучения. На 1 логарифм дозы облучения продолжительность жизни после острого облучения сокращалась на 8,3 лет, общая – на 8,8 лет, а потерянные годы потенциальной жизни повышались на 8,4 лет. Относительный риск повышения доли работников, проживших менее 35 лет при заболевании тяжелой и крайне тяжелой степени тяжести, а также при дозах острого облучения более 10 Гр по сравнению с остальными работниками, был существенно повышен, составив 26,8 и 18,8 (ДИ: 3,8–191,1 и 2,7–129,8; p &lt;0,001) соответственно. Таким образом, у работников ПО «Маяк» впервые установлено сокращение продолжительности жизни после острой лучевой болезни

Characteristics of malignant neoplasms of the hepatobiliary system in the cohort of occupationally-exposed workers

The aim of the study was to describe cases of hepatobiliary system disease in the cohort of employees hired at the main plants of FSUE Mayak Production Association (PA «Mayak») in 1948- 1982, who were exposed to occupational chronic radiationЦель исследования — характеристика случаев ЗНО гепатобилиарной системы в когорте работников, нанятых на основные заводы ФГУП «Производственное объединение «Маяк» (ПО «Маяк») в 1948–1982 гг., подвергавшихся профессиональному хроническому облучени

Pulmonary extracellular matrix and cell turnover in nuclear workers with respiratory conditions

The study was aimed to define the composition of lung stroma and parenchyma and to assess a role of parenchyma-stromal interaction for plutonium-associated lung fibrosis, post-inflammatory fibrosis and lung cancer in workers occupationally exposed to ionizing radiation. Using lung tissues collected from 109 Mayak nuclear workers during autopsy examinations, we studied distinguishing morphological features of fibrosis taking into account cumulative lung absorbed doses from internal exposure to alpha radiation and duration of the exposure. Considerable difference in the compositional structure of the extracellular matrix and characteristics of cell turnover were observed among plutonium-associated lung fibrosis, post-inflammatory lung fibrosis and paracancerous regions of lung adenocarcinomas. These observations may demonstrate that mechanisms of lung fibrosis development are associated with a type of an affecting factorЦель работы – определение состава стромы и паренхимы ткани легкого и оценка роли стромально-паренхиматозных взаимоотношений в развитии плутоний-обусловленного пневмофиброза, поствоспалительного пневмофиброза и рака легкого у работников, подвергшихся профессиональному облучению. Изучены морфологические особенности пневмофиброза на аутопсийном материале 109 работников ядерного предприятия По «Маяк», с учетом суммарной поглощенной в легких дозы внутреннего альфа-излучения и продолжительности облучения. обнаружены существенные различия в структуре экстрацеллюлярного матрикса и состоянии компонентов системы клеточного обновления при плутониевом пневмофиброзе, поствоспалительном пневмофиброзе и в параканкрозной зоне аденокарциномы легкого. Полученные данные могут свидетельствовать о различных механизмах развития легочного фиброза в зависимости от характера повреждающего фактор