Features of Cytokine and VEGFA Gene Expression Modified with SARS-CoV-2 Virus in an In Vitro Experiment (Using the Example of the SARS-CoV-2 Vaccine Antigen).

The influence of SARS-CoV-2 antigen on the cytokine-producing function of immune cells was studied. We observed suppression of the production of proinflammatory cytokines by 11-46% relative to the spontaneous level under the influence of SARS-CoV-2 antigen vaccine simulator, as well as when it was co-administered with cortisol (IL-6 by 1.8 times and IFNγ by 1.57 times) compared with control samples. IL-8 production was reduced by 1.72 times relative to its spontaneous level. IL-8 production was reduced by 1.72 times relative to its spontaneous level. Under conditions of SARS-CoV-2 stimulation with the vaccine antigen in vitro, an increase in the relative scaled expression of the VEGFA gene by 2.16 times relative to the spontaneous level was observed, which can be regarded as a model "cytokine storm" scenario. The obtained experimental data verify the ideas about the pathogenetic mechanisms of the COVID-19 and can contribute to the development of new approaches to the correction of its complications.

Indicators of Immune and Neurohumoral Profile in Women of Fertile Age with Functional Disorders of the Autonomic Nervous System Associated with Polymorphic Variants of the HTR2A (rs7997012) and TP53 (rs1042522) Genes.

In women of fertile age with functional disorders of the autonomic nervous system (ANS), a complex of indicators of the immune and neurohumoral profile associated with polymorphic variants of the HTR2A (rs7997012) and TP53 (rs1042522) genes was revealed. In patients with the diagnosis "G90.8. Other disorders of the autonomic nervous system", the neurohumoral profile is characterized by excessive content of cortisol and serotonin (p<0.05), which indicates the development of the hypersympathicotonic variant of autonomic regulation disorders. The cellular immune profile in the examined individuals was characterized by a significant decrease in the content of CD3+CD4+ and CD3+CD8+ lymphocytes (p<0.05). At the same time hyperactivation of the humoral immune response was observed. In particular, we revealed enhanced production of IgG and IgM antibodies accompanied by increased count of CD19+ lymphocytes (p<0.05), which characterized clinical and laboratory manifestations of the asthenic syndrome. The women with ANS disorders had increased frequency of the G allele (OR=3.00; 95%CI 1.20-7.47) and GG genotype (OR=3.91; 95%CI 1.00-15.24) of the HTR2A (rs7997012) serotonin receptor gene, as well as the G allele (OR=1.93; 95%CI 1.04-3.57), CG genotype (OR=2.38; 95%CI 1.02-5.53) and the GG genotype (OR=1.48; 95%CI 0.42-5.24) of the TP53 (rs1042522) oncosuppressor protein gene (p<0.05). The polymorphic G allele and GG genotype variants of candidate genes (HTR2A (rs7997012) and TP53 (rs1042522) genes) in women with ANS pathology are associated with an imbalance of the neurohumoral (excess of cortisol and serotonin) and immune regulation (deficiency of the CD3+CD4+ and CD3+CD8+, excess of CD19+, IgG and IgM). These parameters form a complex of the immune, neurohumoral, and genetic profile indicators in women of fertile age that characterize functional disorders of ANS manifestations by hypersympathicotonic type with an asthenic component.

[Diagnostic significance of clinical and laboratory indices in predicting non-alcoholic fatty liver disease during screening studies].

AIM: To study the significance of clinical and laboratory non-invasive indexes along with the insulin resistance index when carrying out diagnostic assessment of non-alcoholic fatty liver disease (NAFLD) during screening examinations. MATERIALS AND METHODS: The study involved 348 employees working at oil-production enterprises. An ultrasound scanning of the liver was carried out to assess the criteria of NAFLD. The following indexes were calculated: fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation products (LAP), and homeostasis model assessment of insulin resistance (HOMA1-IR). The prognostic significance of these indexes in relation to the probability of NAFLD diagnosis based on ultrasound data was studied using single-factor and multi-factor logistic regression models followed by ROC-analysis. RESULTS: The FLI, HSI, and HOMA1-IR indexes in single-factor logistic regression models showed a high statistical significance when carrying out diagnostic assessment the NAFLD with good model calibration capability. The percentage of correct binary classification regards the presence/absence of NAFLD amounted to 82.4% for FLI, 79.7% for HSI, and 72.7% for HOMA1-IR (p0.001). According to the ROC-analysis, the area under the curve (AUC) by the NAFLD diagnostic assessment was 0.917 (95% CI 0.8890.945); 0.880 (95% CI 0.8460.915) and 0.849 (95% CI 0.7640.934), respectively. The multi-factor logistic regression model with the inclusion of FLI and HOMA1-IR 72.7% enabled us to achieve the correct binary classification in terms of NAFLD in 84.2% of cases. When it comes to the ROC-analysis, considering the probabilities predicted in the multi-factor logistic model as the test variable and NAFLD in ultrasound examination as the state variable, it was possible to set the value of AUC 0.933 (95% CI 0.8820.985). CONCLUSION: The studied clinical and laboratory indexes (FLI, HSI, HOMA1-IR) have a high diagnostic significance regarding NAFLD diagnosed using ultrasonographic criteria. The application of the proposed two-factor logistics model makes it possible to predict the presence of NAFLD when examining a large number of patients, without involving additional ultrasound diagnostics specialists in order to use medical resources rationally.

[Prognostic significance of arterial stiffness parameters in the identification of very high-risk patients].

Over the past few decades, much attention has been paid to the study of the properties of the vascular wall and its role in predicting cardiovascular events. The testing of new indicators characterizing cardiovascular risk is being actively conducted. The study included 288 men aged 40 to 60 years (mean age 51.6 ± 6.2 years). Among the examined 133 people belonged to the category of very high cardiovascular risk (they suffered myocardial infarction for no more than 5 years before inclusion in the study), and 155 patients did not have a history of cardiovascular complications. Using the Fukuda denshi VS-1500 VaSera sphygmograph, a cardio-ankle vascular index (CAVI) and augmentation index (AI) were obtained. A model of multivariate logistic regression was constructed for the probability of assigning the patient to a group of very high risk, as well as ROC analysis. The study demonstrated the statistically significant role of CAVI in predicting the assignment of patients to a group of very high cardiovascular risk (after myocardial infarction). An increase in the odds ratio of assigning a patient to this group with an increase in CAVI per unit is 1.417. According to the results of ROC analysis, the prognostic role of CAVI (AUC 0.70) is slightly inferior to age (AUC 0.75), but exceeds AI (AUC 0.641). The share of variability in the probability of classifying patients as a very high risk group from the influence of the studied factors is 31%. The overall quality of the predictive model can be rated as good (AUC = 0.77).

[Informativity of Indicators of the Arterial Wall Stiffness for Screening Studies].

OBJECTIVE: comparative assessment of informativity of parameters of arterial wall stiffness - the cardio-ankle vascular index (CAVI), the augmentation index (AI) - for solution of problems of screening patients being under threat of realization of complex impact of metabolic syndrome (MS) and elevated vessel wall stiffness, both creators and markers of high risk of severe cardiovascular complications. MATERIALS AND METHODS: We examined mining industry employees (n=206) with cardiac risk factors (arterial hypertension, abdominal obesity, and smoking). Comparative group comprised 75 employees of the same enterprise without above-mentioned risk factors. Studies of arterial wall stiffness included determination of CAVI and AI. The sensitivity, specifcity and accuracy of the screening method were calculated. RESULTS: CAVI and AI parameters had different sensitivity, specifcity and accuracy for identifying patients at risk of cardiovascular complications. AI was 2 times more sensitive than CAVI during examination of patients with only clinical and anamnestic cardiovascular risk markers and patients with clinical-anamnestic and laboratory risk markers. Specifcity of AI was lower than specifcity of CAVI and atained only 34.4% in patients with clinical-anamnestic and laboratory risk factors. At the same time, specifcity of CAVI in these patients reached 86.2%. Accuracy of AI for screening study was 1.4 times higher than that of CAVI in patients with only clinical-anamnestic risk markers, and 1.6 times higher in patients with both clinical-anamnestic and laboratory risk markers. Moreover, after comparing patient groups with individually high and normal CAVI and AI, we found the differences in metabolic laboratory risk factors (glucose, total cholesterol, triglycerides and the Atherogenic Index) only for AI. CONCLUSION: Parameters of arterial stiffness have different informative value for screening of patients with clinical-anamnestic or laboratory risk factors. AI compared with CAVI is 2 times more sensitive and 1.6 times more accurate but has lower specifcity for risk factor screening among patients being under threat of realization of complex impact of MS and elevated vessel wall stiffness.

[Arterial bed stiffness in patients with different cardiovascular risk factors]. / Zhestkost' arterial'nogo rusla u patsientov s razlichnymi faktorami riska razvitiya serdechno-sosudistykh zabolevanii.

AIM: To investigate the specific features of changes in the arterial wall stiffness (AWS) parameters obtained by sphygmomanometry in patients with different risk factors (RFs) for cardiovascular events (CVEs). MATERIALS AND METHODS: A total of 208 mining enterprise workers who had cardiovascular RFs, such as hypertension, abdominal obesity, and smoking, were examined. A comparison group consisted of 75 workers of this enterprise who had no these RFs. AWS was examined using a VaSera VS-1500 (Fukuda Denshi, Japan) to determine CAVI, ABI, UT, %МАР, AI, tb, and tba. RESULTS: The group of patients with a combination of RFs versus the comparison group showed a statistically significant prevalence of virtually all sphygmomanometric indices characterizing AWS, which is suggestive of a less favorable long-term prognosis in this category of patients. CONCLUSION: The patients having abnormal AWS parameters should be included in a group at risk for cardiovascular diseases and CVEs and their existing RFs be further assessed in detail for a preventive purpose. It is appropriate to incorporate volumetric sphygmomanometry in screening examination programs.

Formation of metabolic syndrome as a risk factor of circulatory diseases in drivers.

The authors considered systemic approaches to disclosing factors that promote metabolic syndrome formation and associated risk of ciculatory system diseases in drivers. Examination covered drivers with metabolic syndrome and without it. Findings are that metabolic disorders developing in drivers are occupationally conditioned. Length of service can determine cases numbers of cardiovascular disorders, diabetes mellitus manifestations, more frequent combination of hyperglycemia and/or hyper-, dyslipidemia with abdominal obesity. The drivers with length of service over 15 years, aged over 35, demonstrated arterial hypertension in 35% of cases, postinfarction cardiosclerosis in 43% of cases, disorders of cardiac rhythm and conductivity in 55% of cases, and the number increases with length of service and reaches 80% of total examinees number by 55 years of age. Diabetes mellitus was diagnosed in 37% of cases (in 75% of the workers first diagnosed) with over 20 years of service, average age of 50 years.

Evaluation of health risk for workers engaged into processing of titanium-containing and rare-earth materials.

The authors defined occupational risk level and relations of health disorders in workers engaged into processing of titanium-containing and rare-elements materials with forecasting risk changes in accordance with length of service and its realization evaluation. Work conditions are characterized by exposure to chemicals (sulphur dioxide, nitrogen oxide, chlorine and hydrochloride, vanadium compounds), noise, general vibration, heating, work hardiness - and are evaluated as hazardous, jeopardy degree 3 and 4. Results of a priori assessment of occupational risk define it as high. Modelling of health risk evolution outlines that after 15 years of service (by 35 years of age) the share of cardiovascular disease will approach 65% in total workers' health risk. Prevalence of arterial hypertension in the studied group by 15 years of service equals 44,5% (p = 0,04), in the reference group no reliable prevalence of arterial hypertension with length of service was seen. Realization of health risk due to chemicals manifested with higher prevalence of upper respiratory tract diseases that were significantly more frequent (p = 0,037) among the studied group (62,23%), than in the reference group (38,30%). The authors determined length of service criteria and health disorders, that outline priority contribution into the health risk, to specify a system of preventive measures for risk minimization.

[New potential of MTHFR gene variations application as an individual sensitivity marker in evaluation of occupational risk of arterial hypertension under exposure to nose].

The article deals with results of assessing risk of occupationally related hypertension among workers of sylvinitedressing works, with individual sensitivity consideration. Epidemiologic study proved correlation between occupational exposure to noise over 83 dB and hypertension and its predictors - increased activity of serum lipoprotein and homocystein. The studies determined an indicator of the workers' increased sensitivity to arterial hypertension development and to changes in parameters of disordered vascular tone regulation (increased activity of serum lipoprotein and homocystein) under exposure to noise - CT genotype of MTHFR gene. Workers with CT genotype of MTHFR gene, according to epidemiologic analysis, demonstrated increase in relative risk of vascular tone regulation disorders (hypertension predictor). Additional probability ofvascular tone regulation disorders under exposure to noise of 83 dB in sylvinitedressing workers with increased individual sensitivity is estimated at 3%.

[State of vegetative nervous system in workers engaged into multiple shifts work with night shifts].

Occupational activity with night shifts and length of service over 5 years is characterized by prevalent sympathetic influence on cardiac activity, vagosympathetic interaction index (LF/HF) is considerably higher than in workers with lower length of service and 1.5 times exceeding upper normal value. VLF indicator exceeds physiologic normal value due to increased activity of ergotropic and humoral metabolic mechanisms of cardiac rhythm regulation. Sympathetic regulation activity level (LF parameter) is also reliably higher than in workers with lower length of service (p = 0.024). Parasympathetic regulation activity level (HF parameter) is below normal value - that indicates decreased influence of parasympathetic vegetative system on cardiac activity (depression of defence mechanisms). Comparative analysis of vegetative regulation spectrum at rest, in accordance with length of service, demonstrated the most marked changes in workers with length of service over 5 years: lower total spectral capacity (TP, msz), lower share of high-frequency waves (HF, %), increase of average vagosympathetic interaction index (LF/HF) and higher share of very low waves (VLF, %) in the spectrum structure. Ihe data prove intensified ergotropic, humoral, sympathetic influences on cardiac activity and, as a result, higher risk of dysmetabolic processes and cardiovascular diseases.

[DETERIORATIONS OF HEALTH CONDITION IN FURNACE AND SMELTER EMPLOYEES OF THE TITANIUM AND MAGNESIUM INDUSTRY].

There is presented the assessment of the impact of occupational risk factors on the health status of workers, carried out on the results of hygienic analysis of working conditions and the clinical and laboratory examination of workers.

[OCCUPATIONAL HEALTH RISK ASSESSMENT AND MANAGEMENT IN WORKERS IN IMPROVEMENT OF NATIONAL POLICY IN OCCUPATIONAL HYGIENE AND SAFETY].

In accordance with the international documents in the field of occupational safety and hygiene, the assessment and minimization of occupational risks is a key instrument for the health maintenance of workers. One of the main ways to achieve it is the minimization of occupational risks. Correspondingly, the instrument for the implementation of this method is the methodology of analysis of occupational risks. In Russian Federation there were the preconditions for the formation of the system for the assessment and management of occupational risks. As the target of the national (state) policy in the field of occupational safety in accordance with ILO Conventions it can be offered the prevention of accidents and injuries to health arising from work or related with it, minimizing the causes of hazards inherent in the working environment, as far as it is reasonably and practically feasible. Global trend ofusing the methodology of the assessment and management of occupational risks to life and health of citizens requires the improvement of national policies in the field of occupational hygiene and safety. Achieving an acceptable level of occupational risk in the formation of national policy in the field of occupational hygiene and safety can be considered as one of the main tasks.

[Improvement of legislation basis for occupational risk analysis in occupational hygiene and work safety].

One among priority trendsin health care in Russian Federation and abroad is minimization of occupational risks. The authors present evaluation of legislation basis for occupational risk analysis. The most promising trend in improvement of national legislation is its development on basis of internationally accepted documents, that-provides legislation basis for analysis of workers' health risk. Findings are that complete evaluation of occupational risk requires combination of data on work conditions and data of occupational control, and sometimes--with results of special research. Further improvement is needed for justifying hygienic norms with applying criteria of allowable risk for workers' health. Now development of risk analysis methodology enables quantitative evaluation of health risk via mathematic models including those describing risk evolution.

[Prospects of occupational risk evaluation via modelling methods].

The article represents methodic approaches that enable quantitative evaluation of worker's health risk, forecast of changes in health state. Models application proved that integral risk of health disorders in workers exposed to occupational factors becomes unacceptable by the age of 45 years, without exposure to the factors - by 54 years. At work under existing levels of exposure to occupational factors, cardiovascular risk increases with length of service, and by 5 years of service, number of additional occupational cases in a studied group of workers approaches 11 per year. Solving effectively problems of health risk evaluation, evolution models consider specific conditions of workplaces contamination and describe influence of variable factors within work conditions on risk of various health disorders in dependence on length of service and exposure duration. Methodic approaches to health risk evaluation, based on evolution models of hazardous effects development under exposure to working environment factors, enable to follow dynamics of these effects development on background of natural ageing and to forecast health state of human and population under multi-factorial, multi-exposure load.

[Problems of occupational fitness conclusion on periodic medical examination].

Additional examination in Occupational Pathology Center are economic loss both for employer and employee, as the employee receives payment for those days when in the examination. Analysis of over 600 cases of occupational fitness examination in Occupational Pathology Center according to referrals given by medical institutions providing periodic medical examination shows that in most cases the conclusion was possible during periodic medical examination. Difficulties in conclusion on workers' fitness for occupation during periodic medical examination, according to our viewpoint, result not from limited diagnostic facilities for adequate examination and unfitness disclosure, but from lack of information in primary medical documentation and inadequacy of occupational factor and work characteristics presented by employer to actual working conditions.

[Hygienic features of work conditions and their influence on health of workers engaged in ferrovanadium production].

The authors present complex hygienic characteristics of work conditions for workers engaged into metallurgic process of ferrovanadium production. Chemical factors were shown as having complex influences. Occupational risk for the workers' health was estimated. Categories of a priori occupational risk for workers are valued from average (considerable) risk to very high (intolerable) risk. Factors that are priorities for development of occupationally induced diseases are disclosed. Reliable cause-effect relationships between working environment factors and the workers' diseases are determined. Work conditions appeared to play considerable role in respiratory tract diseases (average degree of occupational conditionality). Differences between workshops in fractional composition and concentration of dust, as major components of occupational factors complex, develop pathologic changes in various levels of respiratory system.

[Considering risk factors of arterial hypertension in workers exposed to occupational hazards, according to results of periodic medical examinations].

The article covers prevalence of risk factors concerning cardiovascular diseases and health disorders in workers due to occupational hazards of textile production, criteria for early diagnosis of arterial hypertension. To prevent arterial hypertension and its progress into severe cardiovascular diseases in the workers, the authors necessitated complex of medical and preventive measures.

[Influence of work intensity on development of arterial hypertension in metal-mining workers].

The article covers data on influence of working shifts duration and shift work intensity on cardiovascular system functioning in operators of mining excavators. Findings are that 8 hours shift with regular shift schedule (40 working hours per week) gives significant load on cardiovascular system of workers engaged into underground activities. 50% of mining excavator operators following this working schedule develop transitory arterial hypertension within 10 years. Longer work shift over 8 hours and more intensive shifting schedule over 40 hours per week causes stable arterial hypertension within 3 months in 60% of workers, in 10% of cases associated with lower functioning of sinus node.

[Social and behavioural factors of reproductive health in female workers (exemplified by textile factory)].

Based on analysis of sociologic poll results in a textile factory of Perm area, the authors describe main social and behaviour factors of reproductive health deterioration among female workers exposed to occupational hazards. Conclusion is high prevalence of behavioural factors of health deterioration, with occupational and household hazards in the studied group.

[Features of diurnal profile of blood pressure in workers having serum aromatic hydrocarbons level].

Features of diurnal profile of blood pressure in workers having serum level of benzol and ethylbenzene are high systolic and diastolic arterial blood pressure during the day, index of systolic arterial pressure time and index diastolic arterial pressure time was also high. These features should be considered in anti-hypertensives prescription.