[Predictors of thromboembolic complications in patients with severe SARS-CoV-2 coronavirus infection].

AIM: To identify predictors of the development of thromboembolic complications (TECs) in patients with severe SARS-CoV-2 coronavirus infection. MATERIALS AND METHODS: A single-center observational retrospective study included 1634 patients with a confirmed diagnosis of SARS-CoV-2 coronavirus infection. The patients were divided into 2 groups depending on the availability of the feasibility study. The criterion for inclusion of patients in the main group was the presence of venous feasibility studies in 127 patients (group I), the comparison group consisted of 1507 patients in whom the course of COVID-19 was not complicated by the development of feasibility studies (group II). RESULTS: When performing computed tomography of the chest organs, it was revealed that patients with a feasibility study had a higher percentage of lung tissue damage than patients in the comparison group: 55% [37.5; 67.5] and 37.5% [25.0; 47.5], respectively (p<0.001). The average values of C-reactive protein in I patients group were 129 [60.1; 211] ng/l, which was significantly higher than in II patients group - 41.0 [12.2; 97.6] ng/l (p<0.001), interleukin-6 - 176 [52.9; 471] pg/ml and 39.4 [11.0; 107] pg/ml (p<0.001), respectively. A one-factor regression analysis proved a significant contribution of comorbid pathology to the development of feasibility studies in patients with COVID-19. The presence of three nosologies at the same time: arterial hypertension, coronary heart disease (CHD) and chronic kidney disease increased the probability of a feasibility study by 4.81 times (odds ratio 4.8117, 95% confidence interval 3.2064-7.2207), in patients with arterial hypertension, CHD, chronic kidney disease and type 2 diabetes - by 5.63 times (odds ratio 5.6321, 95% confidence interval 3.1870-9.9531). CONCLUSION: The presence of severe comorbid pathology significantly increased the risk of developing a feasibility study in patients with COVID-19. The most significant predictors of the development of feasibility studies in patients with severe SARS-CoV-2 coronavirus infection. They are: CHD, arterial hypertension and type 2 diabetes.

[Association between cardio-ankle vascular index and markers of thrombosis in hospitalized patients COVID-19].

AIM: To evaluate the relationship between the cardio-ankle vascular index (CAVI) and the marker of procoagulant state - D-dimer in hospitalized patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This cross-sectional study involved adult patients admitted to the University hospital with clinically diagnosed or laboratory-confirmed COVID-19. We compared groups of patients with normal and elevated CAVI. Univariate and multivariate logistic regression analyses were performed to assess the association between risk factors and elevated D-dimer levels; odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to determine the strength of association. A p<0.05 was considered statistically significant. RESULTS: The study included 152 patients [64 (42.1%) men and 88 (57.9%) women], mean age 59.10±12.74 years. 45 (29.6%) had elevated CAVI. Patients with elevated CAVI were older, had more comorbid diseases, a higher Charlson comorbidity index and D-dimer levels. Age, the comorbidity index, and CAVI above 9.5 were associated with elevated D-dimer levels in patients with COVID-19. In a multivariate logistic regression, CAVI above 9.5 was an independent predictor of increased D-dimer in patients with COVID-19 (OR 2.513, 95% CI 1.050-6.012; p=0.038). CONCLUSION: In this study, for the first time, the association between a vascular stiffness marker, elevated CAVI, and increased D-dimer levels in COVID-19 patients was shown. This relationship may be a consequence of endothelial dysfunction and can be used as an additional marker of coagulopathy developing as part of COVID-19.

Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer.

Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship between these parameters and the main clinical morphological characteristics of the disease was analyzed. Plasma levels of the proteins were measured using standard direct ELISA kits. The level of MMP-7 in patients with gastric cancer was significantly higher than in the control group (medians 2.7 and 1.2 ng/ml, respectively; p<0.01), but only in 51% patients this parameter surpassed the upper threshold normal value (2.35 ng/ml; 95% percentile of control). The level of MMP-9 in gastric cancer patients was lower than in control group by 1.6 times (medians 167 and 267 ng/ml, respectively; p<0.01). Plasma levels of MMP-2 and TIMP-2 in patients with gastric cancer and healthy subjects were similar. No appreciable associations of plasma matrixins and TIMP-2 with the main clinical morphological characteristics of the disease were detected. The patients were followed up for 8 to 85 months (median 70.8 months). Low level of MMP-2 and high level of MMP-7 in the plasma proved to be unfavorable prognostic factors for overall survival. At MMP-2<268 ng/ml, the 5-year overall survival was 32% vs. 60% for patients with the marker level higher than this threshold value (p=0.016). The differences in overall survival in relation to their MMP-7 levels for 5-year observation did not surpass 16% (39% at marker level >2.7 ng/ml and 55% at lower level; p=0.048). Plasma levels of MMP-2 and TIMP-2 were not significantly associated with overall survival. Multivariate analysis showed that only T index (p=0.034) and plasma MMP-7 level (p=0.007) were essential for overall survival. The increase in plasma or serum MMP-7 levels is a universal phenomenon in tumors of different histogenesis, which precluded the use of this parameter as a specific diagnostic marker of gastric cancer. At the same time, it could be useful for monitoring the treatment efficiency and detection of relapses. In addition, high plasma level of MMP-7 remained an independent factor of unfavorable prognosis for overall survival of patients with gastric cancer.

Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air.

Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion.

Review of the correlation between results of cytogenetic dosimetry from blood lymphocytes and EPR dosimetry from tooth enamel for victims of radiation accidents.

The goal of this study was to compare dose estimates from electron paramagnetic resonance (EPR) dosimetry with teeth and cytogenetic dosimetry with blood lymphocytes for 30 victims of radiation accidents. The whole-body exposures estimated by tooth enamel EPR dosimetry were ranging from 0.01 to 9.3 Gy. Study group comprised victims exposed to acute and prolonged irradiation at high and low dose rate in different accidents. Blood samples were taken from each of them for cytogenetic analysis. Aberrations were scored and analysed according to International Atomic Energy Agency (IAEA) guidelines for conventional and FISH analysis. Tooth samples were collected in dental clinics after they had been extracted during ordinary practice. EPR dosimetry was performed according to the IAEA protocol. EPR dosimetry showed good correlation with dosimetry based on chromosomal analysis. All estimations of cytogenetic dose below detection limit coincide with EPR dose estimates within the ranges of uncertainty. The differences between cytogenetic and EPR assays may occur in a case of previous unaccounted exposure, non-homogeneous irradiation and due to contribution to absorbed dose from neutron irradiation.

[Methods of individual retrospective physical dosimetry in the problem of estimation of consequences of accidental irradiation].

The overview of the results of development, verification and application of the methods of individual retrospective physical dosimetry among population of settlements contaminated with radionuclides, which suffered from irradiation as a result of the accident in Chernobyl NPP, and among the population located in the vicinity of the Semipalatinsk nuclear test site is presented in the paper. The estimations of sensitivity of the methods of physical retrospective dosimetry are shown. The data on individual doses among population, which was irradiated as a result of accidental irradiation are presented as well.

Dental enamel EPR dosimetry: comparative testing of the spectra processing methods for determination of radiation-induced signal amplitude.

The aim of this investigation is to find out the optimal algorithm for mathematical processing of the EPR spectra of irradiated tooth enamel for estimating the amplitude of the radiation-induced signal, which is used for determination of the absorbed dose in enamel for retrospective individual dosimetry. A recently developed analytical model, which takes into account the line shape variation of the enamel EPR spectral components registered at different microwave power, was applied to spectra processing in various operation modes to simulate spectra processing techniques differing by the number of fitted parameters. The precision of dose determination at spectra processing was assessed by the root mean square deviation between experimental and nominal doses for sets of spectra of enamel samples irradiated in different doses and measured at different microwave power. It is shown that in the case of pooled enamel samples prepared as a mixture from different teeth, the higher precision of spectra processing is obtained using a model with fixed native background signal line shape (characterized by width and asymmetry parameters). In case of individual samples prepared each from a different tooth, better results are obtained using a model with variable background signal line shape.

The neutron dose conversion coefficients calculation in human tooth enamel in an anthropomorphic phantom.

In the present study, MCNP4B simulation code is used to simulate neutron and photon transport. It gives the conversion coefficients that relate neutron fluence to the dose in tooth enamel (molars and pre-molars only) for 20 energy groups of monoenergetic neutrons with energies from 10-9 to 20 MeV for five different irradiation geometries. The data presented are intended to provide the basis for connection between EPR dose values and standard protection quantities defined in ICRP Publication 74. The results of the calculations for critical organs were found to be consistent with ICRP data, with discrepancies generally less than 10% for the fast neutrons. The absorbed dose in enamel was found to depend strongly on the incident neutron energy for neutrons over 10 keV. The dependence of the data on the irradiation geometry is also shown. Lower bound estimates of enamel radiation sensitivity to neutrons were made using obtained coefficients for the secondary photons. Depending on neutron energy, tooth enamel was shown to register 10-120% of the total neutron dose in the human body in the case of pure neutron exposure and AP irradiation geometry.

[Influence of the environmental hygienic state on the intellectual development of Voronezh schoolchildren].

Voronezh belongs to the areas that have a poor hygienic situation in the environmental pollution with heavy metal compounds. The subject of the studies was pupils from 2 Voronezh schools situated in the areas hygienically contrast in the ambient air and soil pollution with heavy compounds. Their intellectual development was studied. A total of 245 pupils from the 2nd, 7th, and 10th forms were examined. The best intellectual development indices were recorded among all age groups of children living in the hygienically favorable areas. The findings are in agreement with the data published by Russian and foreign investigators.

ESR investigation of joint use of dentin and tooth enamel to estimate photon and neutron dose components of a mixed field.

In the case of mixed photon and neutron field, estimation of photon and neutron dose components from the ESR signal of tooth enamel alone is impossible. To differentiate neutron and photon components using the method described in ICRU 26 for twin chambers, enamel and dentin sensitivities to photon and to neutron were investigated. Enamel and dentin relative sensitivities were, respectively, estimated at 0.03 +/- 0.02 and 0.14 +/- 0.10 for fission neutrons. Basing on this result, calculation of neutron and photon doses was performed in realistic case of criticality accident. Estimation of neutron and photon dose components was found in good agreement with reference dosimetry.

The Third International Intercomparison on EPR Tooth Dosimetry: part 2, final analysis.

The objective of the Third International Intercomparison on EPR Tooth Dosimetry was to evaluate laboratories performing tooth enamel dosimetry <300 mGy. Final analysis of results included a correlation analysis between features of laboratory dose reconstruction protocols and dosimetry performance. Applicability of electron paramagnetic resonance (EPR) tooth dosimetry at low dose was shown at two applied dose levels of 79 and 176 mGy. Most (9 of 12) laboratories reported the dose to be within 50 mGy of the delivered dose of 79 mGy, and 10 of 12 laboratories reported the dose to be within 100 mGy of the delivered dose of 176 mGy. At the high-dose tested (704 mGy) agreement within 25% of the delivered dose was found in 10 laboratories. Features of EPR dose reconstruction protocols that affect dosimetry performance were found to be magnetic field modulation amplitude in EPR spectrum recording, EPR signal model in spectrum deconvolution and duration of latency period for tooth enamel samples after preparation.

The 3rd international intercomparison on EPR tooth dosimetry: Part 1, general analysis.

The objective of the 3rd International Intercomparison on Electron Paramagnetic Resonance (EPR) Tooth Dosimetry was the evaluation of laboratories performing tooth enamel dosimetry below 300 mGy. Participants had to reconstruct the absorbed dose in tooth enamel from 11 molars, which were cut into two halves. One half of each tooth was irradiated in a 60Co beam to doses in the ranges of 30-100 mGy (5 samples), 100-300 mGy (5 samples), and 300-900 mGy (1 sample). Fourteen international laboratories participated in this intercomparison programme. A first analysis of the results and an overview of the essential features of methods applied in different laboratories are presented. The relative standard deviation of results of all methods was better than 27% for applied doses in the range of 79-704 mGy. In the analysis of the unirradiated tooth halves 8% of the samples were identified as outliers with additional absorbed dose above background dose.

Comparison of three methods of numerical procedures for ESR dosimetry of human tooth enamel.

Three numerical methods were employed to examine how gamma ray doses ranging from 100 mGy to 1Gy could be reconstructed using five human molar teeth. For samples above 28 0mGy, the obtained doses are consistent with each other within the errors but slightly larger than actually given doses. Background doses range from 20 to 170 mGy depending on the methods and samples. Further precise studies would be needed to characterize each method, but it would be recommended to apply several methods to check the reliability of the obtained doses.

[Potency of peroral and parenteral administration of Zinc-DTPA for decorporation of 241Am from the gastrointestinal tract]. / Effektivnost' tsinkatsina pri peroral'nom i parenteral'nom putiakh vvedeniia v dekorporatsii 241Am, postupivshego v pishchevaritel'nyi tract.

An effect of cincacine at three doses (25, 150 and 300 mumol/kg) has been studied in rats receiving 241Am citrate intragastrically. The radionuclide was introduced every other day for 2 weeks. The total content was 925 kBq/kg. A cincacine administration leads to limitation of radionuclide accumulation in the major organs of deposition independent of the modes of intake. At gastrointestinal 241Am intake peroral cincacine administration is more effective in limiting this radionuclide accumulation in skeleton but less effective in reduction of its accumulation in liver compared to parenteral cincacine. No reliable dependence of cincacine efficacy on dosage has been revealed. A morphology study of organs has shown that cincacine ingestion at a dose of 150 mumol/kg for 4 weeks and at a dose of 300 mumol/kg for 2 weeks produces a toxic effect on the small intestine mucosa. 25 mumol/kg is the optimum dose and per os administration of higher doses is not expedient.

Calibration of EPR signal dose response of tooth enamel to photons: experiment and Monte Carlo simulation.

The experimental energy dependence of the electron paramagnetic resonance (EPR) radiation-induced signal at irradiation by photons in the energy range of 13 keV-1.25 MeV was analysed in terms of the absorbed dose in human tooth enamel. The latter was calculated using a Monte Carlo simulation of the photon and electron transport. The dependence of the calculated absorbed dose on the sample thickness was analysed. No energy dependence of the EPR signal on the absorbed dose in enamel was verified in the range of 37 keV-1.25 MeV. At 13 and 20 keV the EPR signal dose response was reduced by 8% probably due to sample powdering. Dose-depth profiles in enamel samples irradiated by 1.25 MeV photons in polymethylmethacrylate and aluminium build-up materials were calculated. It was concluded that secondary electron equilibrium conditions are better fulfilled for irradiation in aluminium, which makes this material preferable for calibration.

Dose reconstruction by EPR spectroscopy of tooth enamel: application to the population of Zaborie village exposed to high radioactive contamination after the Chernobyl accident.

Individual irradiation doses were determined by electron paramagnetic resonance spectroscopy of the tooth enamel of the inhabitants of Zaborie, the most contaminated inhabited settlement not evacuated after the Chernobyl accident. Dose determination was performed using a specially developed automatic spectrum processing procedure. Spectrum processing was carried out in different operating modes, and average results were taken in order to reduce the contribution of uncertainty in dose determination caused by spectrum processing. The absorbed doses determined in enamel were corrected to take into account the contribution of natural background radiation and to determine the individual excess dose due to radioactive contamination of the territory. Individual excess doses are compared to calculated individualized doses to teeth, estimated using the local radioactive contamination levels, dose rates, and information concerning individual behavior. The individual excess doses measured by electron paramagnetic resonance spectroscopy and the calculated individualized doses are fully independent. Mean square variation between results of two methods was found to be 34 mGy, which is consistent with error estimation for both methods. This result can validate both the methodology of signal processing presented here when using electron paramagnetic resonance dosimetry of tooth enamel for low doses and the methodology of individualized dose calculation.

[Retrospective dose estimation in remote period after exposure using different biological methods]. / Retrospektivnaia otsenka doz v otdalennyi postraditsionnyi period raznymi biologicheskimi metodami.

Investigation of application of chromosome aberrations of lymphocytes in peripheral blood for biological dosimetry purposes in remote (up to 40 years) period after acute exposure to doses of 1 Gy and more was carried out. The comparative analysis of frequency of unstable and stable (using FISH and G-banding methods) aberrations was performed for 24 subjects accidentally exposed to radiation on nuclear submarines during 1961-1985. Statistically significant increasing of frequency of dicentrics and centric rings was determined in the exposed subjects in remote period after exposure to compare with controls. Their sum frequency in the exposed group varied depending on ARS heaviness from 0.1 to 1.0 aberrations per 100 cells. In control group it was from 0 to 0.2 correspondingly. Translocation frequency (complete + incomplete) fixed by FISH method (2, 4, and 12 chromosomes) varied within the limits of 0.2-16.0 for exposed subjects and 0.3-1.26 translocations per genome per 100 cells for controls. Some examined persons (5 subjects) exposed to accident in 1985 had results of analysis of unstable chromosome aberration in acute period after exposure that allow to estimate obtained doses by dicentrics frequency which having good correlation with ARS heaviness. Individual dosed using traslocation frequency were defined retrospectively in 11 from 21 exposed persons. They correlate with calculated physics doses and doses estimated by haematolotical parameters in acute period and also doses obtained by ESR spectroscopy of tooth enamel in remote period.

[Investigation of biologically active supplement Marinid as a prophylactic agent in ecologically unfavorable territory]. / Issledovanie biologicheski aktivnoi dobavki marinid v kachestve profilakticheskogo sredstva dlia ékologicheski neblagopoluchnykh territorii.

Physicochemical investigation of the biologically active supplement Marinid has been carried out. Biological accessibility of iodine containing in Marinid has been determined. About 60 micrograms of iodine can be assimilated by thyroid from one 0.5 g Marinid tablet. Daily iodine need for groups of different age can be satisfied by 1-4 tablets. Marinid reduces 90Sr resorption from gastrointestinal tract by 20-40%.

[Study of the influence of peroral zincacin on the removing of ingested Americium]. / Issledovanie vliianiia peroral'nogo primeneniia tsinkatsina na vyvedenie ameritsiia pri ego postuplenii v zheludochno-kishechnyi trakt.

Effect of different cincacine doses was studied in rats ingesting americium citrate during 2 weeks. As a result new data showing the possibility and efficacy of per oral cincacine administration at americium intake into digestive tract have been obtained. Dose dependence of cincacine efficacy has been stated for per oral 241Am intake. Preparation administration at a dose of 25 mumol/kg reduces amount of 241Am in skeleton, liver and kidney by 93, 90 and 33%, respectively and is optimum for radionuclide removal from the body and for the prevention of its deposition in organs. Digestive system organs and kidney structure at cincacine administration at a dose of 150 and 300 mumol/kg) to the rats ingesting 241Am have been studied.

Optimisation of recording conditions for the electron paramagnetic resonance signal used in dental enamel dosimetry.

Optimisation of the parameters for recording the electron paramagnetic resonance (EPR) spectra of dental enamel for absorbed dose reconstruction was performed for an EMX (Bruker) spectrometer supplied with a high-sensitivity microwave cavity. Dose determination was performed using a previously developed automatic spectra processing procedure, which uses the non-linear fit of a model spectrum. The experimental error was estimated as the standard deviation of the results from the nominal doses for the set of spectra recorded for 10 samples prepared from teeth of different persons and irradiated in the dose range 0-500 mGy. The microwave power and magnetic field modulation amplitude corresponding to the minimum of dependencies of the error on these parameters were adopted as the optimal ones. For the sets of spectra recorded at optimal parameters for sample masses 100, 50 and 30 mg, the errors of dose determination were obtained as 18, 27 and 37 mGy respectively.