ASSESSING RISKS CAUSED BY NICKEL-CONTAINING NANOMATERIALS: HAZARD CHARACTERIZATION IN VIVO

Nanoparticles (NP) of nickel (Ni) and its compounds are promising materials for being used as catalysts in chemical, pharmaceutical and food industry; as construction materials in electronics and optoelectronics, in manufacturing current sources, medications, diagnostic preparations, and pesticides. Annual production volumes for these materials in their nano- form are equal to dozen tons and are expected to growth further. According to data obtained via multiple research nano- forms of Ni and its compounds are toxic to many types of cells; stimulate apoptosis; and can induce malignant transforma- tion in vitro. It indicates that this group of nanomaterials can possibly be hazardous for human health. Risk assessment in- cludes such a necessary stage as quantitative hazard characterization, that is, establishing toxic and maximum no-observed- adverse-effect levels (NOAEL) for a nanomaterial that penetrates into a body via inhalation, through undamaged skin, or the gastrointestinal tract. Experiments in vivo performed on laboratory animals with Ni-containing materials revealed overall toxic effects; toxicity to specific organs (including hepatoxoticity and cardiotoxicity); atherogenic, allergenic, and immune- toxic effects, as well as reproductive toxicity. There are multiple available data indicating that all Ni-containing nanomate- rials are genotoxic and mutagenic, though data on their carcinogenic potential are rather scarce. Factors that determine toxicity of Ni and its compounds in nanoform are their ability to penetrate through biological barriers and to release free Ni++ ions in biological media. The review focuses on analyzing and generalizing data on toxicity signs in vivo and effective toxic doses under various introductions of Ni and its compounds in nanoform into a body over a period starting predominantly from 2011.

ASSESSING RISKS CAUSED BY NICKEL-CONTAINING NANOMATERIALS: HAZARD CHARACTERIZATION IN VIVO

The paper dwells on examining mortality among men due to malignant neoplasms (MNs) in Russia and in Norilsk and Monchegorsk, two monotowns located in the Arctic zone with the only industry there being nickel production. Nickel is a well-known carcinogen. Given rather small population numbers in these two towns, the authors calculated mortality due to MNs that was aver- aged over 8 years (2010–2017) for 5-year age groups and standardized mortality ratios (SMR) for employable and post- employable ages as per this nosology in general and specific MNs localizations as well. Mortality was comparatively analyzed in two male populations in the following pairs: Monchegorsk and Russia, Norilsk and Russia; the analysis was based on data on climatic peculiarities in the towns, working conditions at industrial enterprises, ecological situation, and socioeconomic features including an existing situation in public healthcare. Socioeconomic welfare and public healthcare quality were close to average Russian ones in Monchegorsk, but SMR for employable population was higher than on average in the country: due to MNs in general, by 34.7 %; nickel-specific MNs such as MNs of the lip, mouth, and throat, by 2.2 times; MNs in the stomach, by 1.5 times. In Norilsk working conditions were similar to those in Monchegorsk but the environmental conditions were worse; still, mortality among employable population was lower: due to MNs in general, by 15.4 %; MNs of the lip, mouth, and throat, by 14.0 %; due to MNs in the stomach, by 39.3 %. In comparison with Russia as a whole, mortality due to MNs was also lower at employable age but higher by 21.6 % at post-employable one. A decrease in MNs-related mortality and carcinogenic effects becoming apparent at older ages were achieved due to organizing up-to-date oncologic aid in Norilsk including high-tech diagnostic, treatment, and rehabilitation procedures as well as due to higher living standards in the town.

SOCIETAL DETERMINANTS AS RISK FACTORS OF HIV-INFECTION SPREAD IN REGIONS IN THE RUSSIAN FEDERATION

The paper dwells on the results obtained via examining dependence between HIV-infection spread and factors related to social environmental and social structure of population in RF regions. These factors are considered to be potential health risk ones. The authors tested a hypothesis about influence exerted by demographic, economic, cultural and behavioral de- terminants and public healthcare availability on differences in territorial spread of the disease within social-epidemiologic approach. To solve the set task, data that characterized 85 RF regions were taken from official statistical reports. Descriptive statistic analysis was performed and regression models were built up; it allowed testing whether the analyzed factors had their influence in RF regions and selecting the most significant ones to be included into the overall regression model. The research revealed significant contextual differences in HIV-infection spread. Regression analysis showed that 22.0 % differences in a number of HIV-infected people detected in RF regions occurred due to differences in urban popu- lation numbers, provision with ambulatories and polyclinics, and unemployment rate. Moreover, a number of registered crimes committed by minors determined 32.5 % difference in a number of patients with the first diagnosed HIV-infection between the examined regions. These results allow assuming that the greatest influence on spread of the disease in RF regions is exerted by conse- quences of urbanization; this process is usually accompanied with a growth in a share of urban population in a given region, instability on the labor market there as well as related migration processes within the country and wider opportunities to pursue individual behavioral strategies including those that involve law violations and/or are destructive for people’s health.

ASSESSMENT OF THE CONTRIBUTION MADE BY ONCOGENIC FACTORS TO THE RISK OF MALIGNANT NEOPLASMS DEVELOPMENT FOR THE URBAN POPULATION OF WORKING AGE

High morbidity and mortality caused by malignant neoplasms in various age groups among urban population remains a pressing issue that public healthcare has to solve in contemporary megacities. This research concentrated on assessing significance of oncogenic risk factors that could cause malignant neoplasms (MNs) occurrence among urban population aged 18–64 inclusively. 766 people living in an administrative and industrial center in Siberia took part in the research; MNs were diagnosed in 367 out of them (the test group). The research involved calculating individual carcinogenic risks. Oncogenic factors, both environmental and occupational ones, were examined for each patient; attention was also paid to peculiarities of medical and biological characteristics as well as tobacco smoking and alcohol intake. Impacts exerted by the examined factors on risks of MNs occurrence were determined via odds ratios with estimated confidence intervals. First detected MNs frequency amounted to 638.9 ± 41.9 cases per 100 thousand people among women aged 18–64, and 532.6 ± 41.9 cases among men (p > 0.05). The following factors were determined as ones causing elevated risks of MNs occur- rence: carcinogenic hazards at a workplace; hereditary predisposition; tobacco smoking; alcohol abuse; female sex; living under exposure to chemical carcinogens in the environment. Women tended to have certain diseases that are conventionally considered possible risk factors (viral hepatitis B and C and pancreatic diabetes) 1.3 and 2.4 times more frequently than men. All the obtained data can be used for developing a targeted program aimed at malignant neoplasms prevention among urban population and they can also become a vital component in a system for managing risks of malignant neoplasms occur- rence on a given territory.

NEW APPROACHES TO ASSESSING AND FORECASTING MORBIDITY WITH ENTEROVIRUS (NON-POLIO) INFECTION IN THE RUSSIAN FEDERATION USING MATHEMATICAL MODELS

At present it is impossible to develop epidemiologic surveillance and control over any infection regarding studies on dynamics of morbidity, seasonality and periodicity without using mathematical modeling techniques. Our research goal was to study regularities in manifestations of epidemic process for enterovirus (non-polio) infection (EVnI) in the Russian Federation over 14 years (2006–2019) using mathematical models (linear, logarithmic, power, and exponential approximation).An optimal mathematical model was selected using three statistical parameters, namely determination coefficient, Fischer’s exact test, and standard error. Periodicity of rises and falls in morbidity was calculated with Fourier one- dimensional spectral analysis. Intra-year dynamics of morbidity with EVnI was estimated basing on monthly spread of the disease cases on the RF territory. Classic seasonal decomposition, Census I technique, was applied to analyze time series of monthly morbidity. It was determined that EVnI epidemic process was unevenly spread over years in the RF in the examined period of time (2006–2019) and there were two opposite trends in it; the first one lasted from 2006 to 2010 when morbidity was declining and the second was from 2010 to 2019 when it was growing. Having analyzed manifestations of EVnI epidemi- ologic process in long-term dynamics given its uneven spread as per years, we established that it was advisable to use mathematical models approximated as per separate time periods. Average long-term morbidity with EVnI amounted to 8.09 0/0000 in the RF in 2010–2019 with growth rate being equal to 17.7 %. Maximum value was registered in 2017 (16.32 0/0000). An unfavorable prediction for further epidemic situation development was revealed for the examined pe- riod. The epidemic process was characterized with 4-year periodicity and summer-autumn seasonality with peaks usually occurring in August and September. Rates that characterized intensity of the trends in long-term morbidity dynamics and were calculated with mathematical models differed authentically from those obtained via conventional calculations of average values (χ=11.08; d.f.=1; p=0.0009).

RISK FACTORS PROFILE FOR MYOCARDIAL INFARCTION: FOCUS AT A YOUNG AGE

The paper focuses on examining peculiarities of risk factors causing cardiac infarction at a young age. Although car- diac infarction primarily occurs among patients older than 45, its frequency at a young age has been growing recently. Risk factors that cause cardiac infarction at a young and old age are quite different. Examining risk factors profiles in different age groups provides wider opportunities for implementing primary and secondary prevention strategies aimed at reducing frequency and negative outcomes of ischemic heart disease.108 patients aged from 18 to 45 and 35 patients aged from 60 to 75 took part in the research; they all had confirmed cardiac infarction with or without rise in ST segment and were treated in a regional center for cardiovascular pathology treatment in a period from January 01, 2017 to January 01, 2019. Basic risk factors of cardiac infarction were assessed when a patient was admitted to a clinic for treatment. The research results indicate high prevalence of risk factors that could cause ischemic heart disease among young pa- tients. 92.2 % young patients have dyslipidemia, 70.2 % smoke, 68.5 have low physical activity, 68.2 % suffer from over- weight and obesity, 58.8 % have arterial hypertension, 7.4 % suffer from type II pancreatic diabetes, and disorders in toler- ance to carbohydrates was reveled in 15.7 % cases. Such factors as male sex (85.2 vs. 37.1 %, р=0,000), smoking (70.2 vs. 20.6 %, р=0.000) and burdened heredity as per early ischemic heart disease occurrence (54.6 vs. 16.0 %, р=0.001) were significantly more frequent among young patients than among older ones. Data obtained via the present research allowed creating risk factors profile for cardiac infarction associated with car- diac infarction occurrence at a young age; this profile included such factors as male sex, early ischemic heart disease occur- rence in family history, and smoking

MODIFICATION OF IMMUNOCYTES VIABLE PARAMETERS IN CHILDREN ASSOCIATED WITH COMBINED EXPOSURE TO CHEMICAL TECHNOGENIC AND EXTREME CLIMATIC FACTORS

The article dwells on results obtained via immunologic parameters of immunocytes death among children living and attending educational establishments in regions beyond the Polar circle where industry was developing rather intensely. Our research goal was to examine early disorders in immunologic profile as per immunocytes death among children living in Polar Regions under combined exposure to adverse chemical technogenic and extreme climatic factors. 75 children took part in the research (a test group); they lived and attended educational establishments in regions beyond the Po- lar circle where industry was developing rather intensely. Benzpyrene is a priority chemical exogenous factor in this region and a cli- matic one is extremely low temperature in winter (average temperature is -33,8 оС in this season). A reference group was made up of children (n = 35) who lived and attended educational facilities in Polar Regions where there was no exposure to technogenic chemical factors. The authors analyzed several immunogram parameters including CD3+CD95+, Annexin-V presenting cells, TNFRα, CD3+HLA-DR+, bax and p53. Cell death parameters were examined with fluorescent analysis via flow cytometry. Also, the authors assessed specific sensitivity of IgG to benzpyrene via allergosorbent testing with enzyme marker. The research revealed hyperexpression of lymphocytes-cellular profile parameters in children from the test group in comparison with the reference one. They had 1.4 times higher expression of immunocytes stained with AnnexinV and a num- ber of cells stained with PI (Propidium Iodide) was considerably higher than a number of cells stained with AnnexinV as well as the same parameters in the reference group(by 1.5 times) thus indicating that immunocytes predominantly die due to necrosis. There was hyperexpression of HLA-DR+ receptor on lymphocytes (both its relative and absolute quantity in 12.4–13.7 % children). Expression of CD95+ receptor (a membrane marker of immunocytes apoptosis) was 1.3 and 1.4 times higher (rela- tive and absolute value accordingly).The authors detected an authentically elevated contents of tumor necrosis factor recep- tor (TNFR) as well as intracellular anti-tumor antigen p53, and antiapoptotic protein bax that were by 1.5, 1.2 and 1.3 times higher accordingly (р<0.05) against the reference group. There was a significant difference in production of IgG specific to benzpyrene in children from the test group since its expression was 2.4 times higher than in children from the reference group (р<0.05). The authors detected elevated risks of excessive expression both for membrane factors of cellular death TNFR (RR = 12.17), CD3+СD95+(RR = 5.42), HLA-DR+ (RR = 4.80) that were apoptosis affectors and for intracellular transcription factors bax (RR = 4.55) and p53 (RR = 3.71) that modulated apoptogenic signals. This risk was associated with combined exposure to chemical tehcnigenic and extreme climatic conditions. It wasestablished that children living in the Polar Regions under combined exposure to chemical technogenic and ex- treme climatic conditions had imbalance in the immune status that became apparent via excessive expression of membrane (HLA-DR+, CD95+, TNFR) and intracellular (p53, bax) parameters with cell death program shifting towards necrosis (as opposed to the reference group that was exposed only to extreme climatic factors). These parameters indicate there is im- mune deficiency and a significant probability of viral infections and their complications.

ON ESTIMATING THE ADDITIONAL INCIDENCE OF COVID-19 AMONG POPULATIONS EXPOSED TO POLLUTED AMBIENT AIR: METHODICAL APPROACHES AND SOME PRACTICAL RESULTS

This research is vital due to the considerable global medical and demographic losses during the COVID-19 pandemic and the latest research works providing evidence of a correlation between air pollution and spread of the disease, its sever- ity, clinical course and outcomes. Our research goal was to quantitatively estimate the influence of ambient air pollution on SARS-CoV-2 spread among populations in six cities in the Russian Federation. These cities were among priority ones as per air pollution and were in- cluded in the “Clean air” Federal project (Bratsk, Krasnoyarsk, Norilsk, Omsk, Cherepovets, and Lipetsk). Our hypothesis was that dynamic features of the infection spread would be different from an expected model of its epi- demiologic process under exposure to environmental pollution. Regression and correlation analysis was performed for rela- tionships between a daily deviation in actual incidence from a basic epidemiologic scenario and the average daily concen- trations of chemicals in ambient air. The initial data were results obtained from instrument measurements of ambient air quality in the examined cities (approximately 10.8 thousand measurements covering 29 chemicals) and the daily incidence of COVID-19 from April 18, 2020 to July 31, 2021 (77,337 cases). An authentic correlation between COVID-19 incidence and chemical concentrations in ambient air was detected in all six examined cities. The contribution of air pollution to COVID-19 prevalence amounted to 5.0 ± 2.6 % in five cities (Kras- noyarsk, Norilsk, Omsk, Cherepovets, and Lipetsk) over the examined period. In Bratsk, this value was about 33% and it requires additional research for either confirmation or correction. Growth in COVID-19 incidence in the examined territo- ries is associated with particulate matter (PM10, PM2.5) and some other chemicals that can irritate the airway directly or indirectly (sulfuric acid vapors, hydrogen chloride, formaldehyde, hydrogen sulphide, etc.). Target levels were substantiated for several priority chemicals; should these levels be achieved, one would predict a decrease in COVID-19 prevalence by more than 1-3% in the examined cities. We propose that population morbidity and mortality caused by COVID-19 require further studies, including those combined with medical and biological examination regarding efficiency of vaccination and post-vaccination immunity per- sistence on territories with elevated environmental pollution.

DEOXINIVALENOL AS A RISK FACTOR OF FOOD GRAIN CONTAMINATION: MONITORING RESULTS OF 1989–2018 YEARS HARVESTS IN RUSSIAN FEDERATION

The paper dwells on the results obtained via long-term monitoring over food grain (wheat, barley, corn, oats, and rye) contamination with mycotoxin deoxynivalenol (DON). From 1989 to 2018 6,800 grain samples from Central, Southern, Volga, Ural, Siberian, North-Caucasian, Far Eastern, and North-western Federal Districts (FD) of the RF were analyzed. Depending on a year harvest, DON occurrence varied from 0 to 42 % and maximum toxin content reached 6.65 mg/kg. Over the whole examined period 10 % samples turned out to be contaminated and one forth of them contained the toxin in quanti- ties exceeding maximum permissible levels (MPL). DON occurrence amounted to 24–42 % in years of mass epiphytoties (1989, 1992 and 1993) as well as in crops gathered in 2014 and 2017; DON was detected in quantities exceeding MPL in 9–27 % of examined samples in those years. 78 % contaminated samples came from Southern and North-Caucasian FD and another 10 % were from Far Eastern FD. A significant correlation between DON occurrence and a number of rainy and sunny days in May was established on the example of wheat samples from Krasnodar region. Analysis of contamination dy- namics has revealed that over the last years there has been an ascending trend in frequency of DON detection in wheat that came not only from regions where Fusarium head blight was widely spread but also from regions in North-western, Siberian and Volga FD. Health risks related to DON intake with wheat grains processing products were assessed; the assessment revealed that DON intake higher than tolerable daily intake (TDI) for the residents of Southern and North-Caucasian FD in 1992, 1993, 2014 and 2017. Average occurrence of DON was 4.2; 11.9; 3.0 and 0.6 % for barley, corn, rye, and oats samples and its maximum contents amounted to 8.95; 0.95; 0.96 and 0.44 mg/kg accordingly. Just as it was the case with wheat, the most of contami- nated samples came from Southern, North-Caucasian and Far Eastern FD. Contamination tended to grow for all the exam- ined grains and it calls for relevant measures aimed at controlling food grains safety

REGULARITIES IN DISEASES OF THE MUSCULOSKELETAL SYSTEM DEVELOPING IN SCHOOLCHILDREN UNDER COMPLEX EXPOSURE TO ENVIRONMENTAL FACTORS AND FACTORS RELATED TO LIFESTYLE

The present research is vital due to diseases of the musculoskeletal system being widely spread and having great social significance as well as a variety of etiological factors that cause this pathology among schoolchildren. Overall, 339 school- children were examined; they attended secondary schools located on territories with different sanitary-hygienic conditions regarding ambient air. Hygienic, clinical-laboratory and instrumental procedures as well as mathematical data processing were applied to fulfill the research tasks. Average daily consumption of food products was estimated as per “Dairies of a weekly schoolchildren’s ration”; specific factors related to lifestyle were estimated via questioning performed with a specifi- cally designed authors’ questionnaire. Children who attended a secondary school in a city where metallic construction mate- rials were manufactured had manganese concentrations in their blood that were by 8–9 % higher than among their counter- parts from the reference group; lead concentrations in their blood were by 1.9–2.2 times higher than in the reference group and by up to 1.7 times higher than background levels. Priority factors that produce such negative effects on health as dis- eases of the musculoskeletal system include the following: school subjects with the same complexity do not interchange with simpler ones in schedules; breaks between classes do not conform to hygienic regulations; food rations are imbalanced as per milk products and eggs; physical training and doing sports are irregular; homework takes longer period of times than before. Average ionized calcium contents in blood of children from the test group were by 9.0–14.0 % lower and hydrocorti- sone contents were by 1.3–1.5 times higher than in the reference group (р=0.0001–0.01). Lower mineral density of bone tissues was by 1.6 times more frequent among children from the test group (р=0.04). Diseases of the musculoskeletal system were 4.6–15 times more probable and scoliosis was 8–11 times more probable due to persistent exposure to manganese and lead, violated hygienic principles of education process organization and food rations, and low physical activity of school- children. Changes in bone metabolism, activation of a stress-releasing system, and a decrease in bone mass are basic etiopa- thogenetic regularities in developing chronic pathology of the musculoskeletal system among schoolchildren associated with exposure to specific environmental factors and factors related to lifestyle.