According to the available data, the effect of high doses of ionizing radiation on the human central nervous system (CNS) takes form of cognitive dysfunction and increased risk of development of malignant neoplasms. At the same time, there is a growing concern about the possible effects of low, moderate doses of ionizing radiation and chronic irradiation, on cognitive functions, as well as their potential long-term consequences manifesting as neurodegenerative diseases. There is both epidemiological and experimental evidence confirming that low and moderate doses of ionizing radiation affect cognitive abilities. The underlying mechanisms include disruption of normal neurogenesis in the hippocampus, development of long-term sustained neuroinflammation, disorders of synaptic plasticity, energy metabolism, and oxidative status. On the part of CNS, the body is most sensitive to radiation during the period of active formation of the brain. Irradiated at that time, people may suffer consequences thereof for several months and years, or have them manifesting only much later, in old age. Improvement of radiation safety and development of means and ways of prevention and treatment of radiation-induced CNS disorders require further research efforts aimed at establishing causal relationships between chronic exposure to radiation and low-dose irradiation and their adverse effects on the part of CNS in the long term post-exposure.

The review is dedicated to matters related to epidemiology and pathogenesis of multisystem inflammatory syndrome associated with SARS-CoV-2 in children (MIS-C). The majority of the reviewed reports are focused on immunopathogenesis of the disease. The causes of the syndrome related to the features of the virus are listed in the paper, the association with circulating variants is described. The role of the SARS-CoV-2 surface protein as superantigen is considered. The literature data on the likelihood of MIS-C development according to the antibody-dependent enhancement pattern are discussed. The factors of cellular and humoral immune response contributing to hyperinflammation are addressed. Sporadic papers describing genetic mutations that can play a certain role in the MIS-C pathogenesis are provided. Furthermore, the association of vaccination against novel coronavirus infection with the likelihood of MIS-C in vaccinated individuals is discussed.

Transcranial magnetic stimulation (TMS) stands out among the rapidly developing methods for clinical rehabilitation of patients after cerebral vascular accidents. The method is widely used not only in post-stroke rehabilitation, but also in sports medicine, psychiatry and other fields of medicine. However, there is an unresolved issue related to precise targeting and holding the magnetic field focus on the points of interest in the brain when performing TMS. Unprecise magnetic field focus localization may result in the emergence of side effects during the TMS session. The review provides the existing solutions of these problems, comparison of the commercially available navigation devices for TMS, analysis of their composition and operation algorithms; promising directions of developing hardware for TMS navigation are proposed.

Factors of the immune system, including secreted pro-inflammatory interleukins, enable tumor control. However, against the background of prolonged chronic inflammation, they can trigger oncogenesis. Polymorphic variants in the coding and regulatory regions of cytokine genes can affect gene expression, mRNA stability, structure and activity of the protein product, with consequences on the levels of cells and body as a whole. This study aimed to search for the relation between polymorphic variants of interleukin genes IL1b (rs1143634), IL2 (rs2069762), IL4 (rs2070874), IL6 (rs1800795), IL8 (rs4073), IL10 (rs1800871) and risk of cancer, and to analyze the effect of polymorphic loci on concentration of serum interleukins. The study involved 585 persons chronically exposed to radiation. We established association of polymorphic IL4 site (rs2070874) with concentration of serum IL4 in individuals with chronic low dose-rate exposure of the red bone marrow 1.17 to 3507 mGy (mean value — 566 mGy). The content of serum IL4 in people with C/T and T/T genotypes (as per the dominant model) was significantly lower than in those with C/C genotype (p = 0.02). Polymorphic sites rs1143634, rs2069762, rs2070874, rs1800795, rs4073, rs1800871 were not found to be associated with the risk of malignant neoplasms in exposed individuals.

Disruptions of the Treg differentiation and functioning processes can play one of the crucial roles in the pathogenesis of radiation-induced malignant neoplasms in residents of the Techa riverside villages, who were chronically exposed in the low-to-medium dose range with predominant damage to the red bone marrow (RBM). This study aimed to determine the effect of radiation exposure, gender, age at the time of examination, and ethnicity on concentration of FOXP3 protein in lysates of mitogen-stimulated peripheral blood mononuclear cells in chronically exposed individuals in the period of cancer effects development. The main group consisted of 30 people aged 67–80 years, predominantly female and Turks. The comparison group included 10 unexposed individuals of similar age, gender, and ethnicity. In the main group, the mean dose to RBM was 867 mGr, to the thymus and peripheral lymphoid organs — 125 mGr. After 24-hour in vitro PHA stimulation, mononuclears were lysed, and the concentrations of the total protein and FOXP3 (using quantitative enzyme immunoassay) were measured. Among the different dose groups, there were no significant differences in FOXP3 concentration in mitogen-stimulated mononuclears (prior to the stimulation: 0 pg/ml in the comparison group and 3.50 ± 1.50 (0–27.19) pg/ml in the main group at p = 0.349; after the stimulation, respectively: 1.54 ± 1.51 (0–15.16) pg/ml and 9.71 ± 3.86 (0–77.92) pg/ml, p = 0.512). The variability of individual values is slightly higher in the main group than in the comparison group. Preliminary results allow concluding that the dose to RBM, thymus and peripheral lymphoid organs, age at the time of examination, gender, and ethnicity have no statistically significant effect on the concentration of FOXP3 protein in the lysates of the mitogen-stimulated peripheral blood mononuclear cells of chronically exposed people.

For residents of territories along the Techa River that was contaminated with radioactive substances in the 1950s, bone-seeking beta-emitting ^89,90Sr were the main source of internal exposure of active (red ) bone marrow (AM). The dose of these radionuclides conditions the severity of leukemia risk for them. Improvement of the methods of internal AM dosimetry is an important task. Computational 3D phantoms of the skeleton sites are a component of the solution for this task. Simulation of radiation transfer in a heterogeneous bone model allows estimating the dose conversion factors from radionuclide activity to AM dose. This manuscript continues the series of papers covering the development of a set of computational phantoms of a reference human being of different age. The objective of the study was to develop a computational phantom of a one-year-old child skeleton for internal AM dosimetry (exposure due to incorporated beta emitters). Using the original SPSD (stochastic parametric skeletal dosimetry) model, we develop voxel 3D models of skeletal sites. Skeleton sites with active hematopoiesis were modeled as a set of phantoms of simple geometries. Distribution of AM throughout the skeleton and parameters of the phantoms were assessed on the basis of the published results of measurement done in real bones of children aged 9 months to 2 years. The generated computational phantom of a one-year-old child consisted of 39 segments. It simulates the structure of the bone tissue, location of AM, and population variability of the skeleton microstructure and size parameters.

Skin and soft tissue infections following surgical procedures are usually caused by a broad range of bacteria and are the major cause of septic complications and hospital mortality. Treatment of such wounds is a challenge often resulting from the transition from acute to chronic inflammation due to persistence of pathogenic microflora in the wound tissue. The study was aimed to assess the wound-healing activity of the ointment composition based on the dispersion of fullerene C60 (AFD) in the in vivo model of skin wound, to estimate the effects of AFD on the expression of cytokines as markers of regenerative processes, to determine antibacterial activity of the developed cationic peptides. AFD was obtained by tangential ultrafiltration and used to make an ointment composition. The BALB/c mice were used to model the skin injury. The cationic peptides (CPs) were synthesized by the solid-phase method using the Fmoc technology. Antibacterial effects of CPs and AFD were estimated by colony counting. It was found that the AFD-based ointment exerted wound-healing and anti-inflammatory activity. The minimum bactericidal concentrations (MBC) of the CPs most active against the E. coli Dh5 α strain, AB-1, AB-2, AB-3, and ST-10, were 1.15, 0.11, 0.74, and 0.74 mM, respectively, while MBC of ampicillin was 0.7 mM. We assume that constructing the hybrid compounds/fullerene C60 conjugates with active CPs will be a promising area of the development of drugs for treatment of wounds complicated by bacterial infection.

When eliminating the consequences of large-scale radiation accidents, primary triage of victims is of key importance during the early phase of medical evacuation. Information about lymphocyte counts (blood test) per unit of peripheral blood volume can be used for this purpose. The study was aimed to validate the method of using a lymphocyte test for prediction of acute radiation injury severity in the first days after the exposure associated with the radiation mass casualty incident, given peripheral blood was tested once. We performed correlation analysis of the data of laboratory studies focused on quantifying lymphocytes in peripheral blood of victims during the first days following the Chernobyl disaster and other radiation accidents on the territory of the countries of the former USSR (115 individuals), including radiation accidents with gamma neutron radiation (20 individuals). It was found that with the lymphocyte concentration of 0.2–1.0 × 10⁹/L on day 2 after exposure, the absolute error of estimated dose was ±1.5 Gy in case of gamma exposure and ±1.3 Gy in case of exposure to gamma neutron radiation. When the lymphocyte concentration exceeds 1.0 × 10⁹/L, mild acute radiation syndrome (ARS) is predicted, given the average dose is below 2.0 Gy; when the lymphocyte concentration is less than 0.2 × 10⁹/L< the estimated average dose exceeds 4.0 Gy, which corresponds to severe or extremely severe ARS. Thanks to the lymphocyte test accessibility and simplicity, this biological dosimetry method can occupy a worthy position in the diagnosis of radiation injury associated with large-scale accidents, since the results of cytogenetic tests are not available within first days after the accident.

Knowledge about the specificity of changes in the activity of neural networks associated with realization of thought processes can be used to construct the personalized medical rehabilitation systems. This approach is of particular interest for people with the speech function disturbance due to stroke, since the development of aphasia with the loss of speech leads to severe social maladaptation that worsens the disease outcome. The study was aimed to assess the functional activity of individual neural networks based on the theory of combining the EEG microstate identification technique with the method of determining spatial localization by solving the EEG inverse problem in 27 individuals (15 males and 12 females) with an average age of 52 years, who had speech impairment due to acute atherothrombotic stroke. Mathematical analysis of the scalp bioelectrical activity multichannel recording from the system for EEG microstate model isolation was carried out under changing environmental conditions caused by the auditory-speech load together with the EEG inverse problem solution for each subject. It was found that the speech disorder development depends not only on the fact of damage to brain structures, but also on the deep functional restructuring of both neural streams involved in implementation of brain function and the entire speech connectome. The disease with a predominant motor disorder, that has shown the possibility of transferring functions to the intact hemisphere prefrontal structures, in contrast to sensory disorders representing global changes in the entire speech connectome, can probably be considered the most favorable variant of aphasia.

The model of severe poisoning with acetylcholinesterase inhibitors has shown the possibility of drug treatment of toxic effects with valproic acid containing a tertiary amino group. The study was aimed to assess potential mutagenic effects of the valproic acid derivative containing a tertiary amino group when studing its safety. Testing for toxicophores and assessment of the mutagenic effect probability were perfomed using the QSAR Toolbox offline software (v4.5 SP1). The Ames test with and without metabolic activation was used to estimate mutagenic potential of valproic acid containing a tertiary amino group in vitro. The computer prediction results predicted that the test substance would show no mutagenic effects in the Ames test. These data were confirmed by the in vitro Ames test for a broad range of concentrations of valproic acid containing a tertiary amino group (0.02–5.0 mg/mL). The concentrations of valproic acid containing a tertiary amino group exceeding 1.58 mg/mL have a bacteriostatic effect on the TA 100 S. typhimurium strain and the WP2 uvr A pKM 101с E. coli strain. Thus, the valproic acid derivative containing a tertiary amino group possesses no mutagenic effect, it can be recommended for further preclinical trials of therapeutic efficacy and safety.

Detection of staphylococcal enterotoxins in food products is an important task of food poisoning prevention. The study was aimed to develop immunochromatography tests (ICTs) for detection of staphylococcal enterotoxins А (SEA) and be В (SEB), as well as to improve sensitivity of immunochromatography detection of staphylococcal enterotoxins (by the example of SEB) in dairy products relative to visual assessment by recording the analysis results with digital video recorders (DVR) using the principle of processing digital immunochromatogram images acquired using illumination in various spectral ranges. ICTs for detection of enterotoxins were designed as sandwich tests based on highly specific monoclonal antibodies (MABs) against staphylococcal enterotoxins. Milk, cream, sour cream, cheese artificially contaminated with SEB were analyzed. The analysis results were recorded visually or by DVR. DVR of immunochromatograms of the enterotoxin-containing dairy products acquired using illumination with white light in the wavelength range of 400–800 nm ensures a 4-fold increase in the SEB detection sensitivity, while that involving illumination with green light in the wavelength range having its maximum at 525 nm ensures a 4–8-fold increase relative to visual recording. The use of the “Reflecom” and “Zondazh” digital video immunochromatogram analyzers multiplies sensitivity of SEB detection by immunochromatography when assessing dairy products relative to visual recording.

The impact of coronavirus infection (SARS-CoV-2) on cardiac output in underage athletes is uncertain. The study was aimed to determine heart disease in young elite athletes having a history of COVID-19 (SARS-CoV-2). A retrospective analysis of the results of the developed three-phase medical assessment of 236 elite athletes aged 14–17 (16 ± 1), who had had SARS-CoV-2 infection, was performed. The first phase of assessment involved examination, ECG, ECHO, bicycle ergometry (BEM), creatine kinase and creatine kinase MB tests. During the second phase 22 athletes (9.3%) underwent a more thorough assessment that included Holter monitoring (HM) with heart rate turbulence (HRT), microvolt T–wave alternans (MTWA), heart rate variability (HRV) estimation, signal averaged ECG (SAECG), determination of myocardial damage biochemical markers (troponin, NТproBNP) due to alterations revealed. Seven athletes (32%) having alterations revealed during this phase were referred to gadolinium enhancement cardiac magnetic resonance imaging (MRI) (the third phase). Myopericarditis was diagnosed in four cases (1.7% of 236) based on the results. Thus, low myocardial involvement (below 2%) has been revealed in young elite athletes, who have a history of SARSCoV-2 infection. Cardiovascular assessment algorithm has been developed for such athletes. Detection of cardiac arrhythmias by ECG, BEM, and HM is the most informative. SAECG, HRV, HRT, and MTWA can be used as additional methods to determine indications for MRI as a gold standard of the diagnosis of myocarditis.

Intense physical work is characterized by activity of physiological mechanisms as interrelated components joint for physical exertion. Definition of a set of individual and typological patterns of the physiological mechanisms’ activity answers the questions related to improvement of the athlete’s potential realization efficiency, definition of the limiting components and body’s reserve capacity, training load management. The study was aimed to assess the relationship between the responses of physiological mechanisms associated with standardized physical exertion and the pre-start state parameters. The athlete was through the step incremental test with the treadmill involving recording of the gas exchange parameters and heart rate to study physiological patterns. The physiological response parameters were calculated relative to the key phases of the exercise test: pre-start state, aerobic and anaerobic thresholds, peak exertion, rapid and slow recovery phases. The mathematical model “Horseshoe of Rest” characterizing the athlete’s pre-start state before performing the test was constructed using the T-SNE dimensionality reduction algorithms. The model enables estimation of the release of non-metabolic СО₂ throughout the testing period (MIC — 0.29) and the exertion period (MIC — 0.35).

Skeletal muscle plasticity is the ability to change morphofunctional properties in response to changes in contractile activity. Strength training increases the size of muscle fibers and maximum strength with the activation of protein synthesis. Regulation of these changes at the gene level has not been investigated properly. This study aimed to identify transcription factors associated with changes in the transcriptome of the human skeletal muscle in the context of single and regular strength exercises. We assessed changes in the transcriptomic profile of m. vastus lateralis of 10 young men (mean age 23 (20.8 - 25.9) years) before and after 12-week leg extensor muscles strength training course, as well as before, 8 and 24 hours after a single exercise. Transcriptomic profiling involved RNA sequencing, search for binding motifs and the associated transcription factors. Bioinformatic methods of statistics, FastQC, GraphPad Prizm 8, DAVID, R enabled analysis of the data acquired. The strength training course resulted in the enrichment of the functional groups of genes "secreted proteins", "extracellular matrix" and "basal membrane" (p < 0.05). Transcriptomic responses and the associated transcription factors differed 8 and 24 hours after a single session as well as after regular training sessions. Transcription factors involved in adjustment to regular and one-time loads participate in myogenesis, angiogenesis, regulation of fiber phenotype, proteostasis and other processes. Thus, regulation of gene expression during adjustment to the resistance training loads is a complex process that involves many transcription factors with different functions. Investigation of the role played by these factors in the context of adjustment to exercising is a potentially rewarding task.

In the treatment of patients with cardiorespiratory pathology, it is often necessary to simultaneously administer drugs that affect β-adrenergic receptors: β1-adrenoblockers and β2-agonists. β1-blockers can trigger a bronchospasm in patients with bronchoobstructive diseases, therefore, practitioners often decide not to prescribe them. This work aimed to evaluate functional parameters of patients with cardiovascular and bronchoobstructive diseases in the context of different sequences of administration of selective β1-blockers (bisoprolol) and long-acting β2-agonists (formoterol). This prospective, single-center 2-week pilot study involved 30 individuals suffering the aforementioned diseases. Using the envelopes method, we divided the patients into two groups of 15 people each. First group started therapy with a long-acting β2-agonist, second group — with a selective β1-adrenoblocker. While taking the β1-adrenoblocker, patients underwent a four-hour spirometric test enabling assessment of the external respiration function parameters. The tests and assessments have shown that the value of FEV1 went down in 33.3% of those who started therapy with a selective β1-adrenoblocker (bisoprolol 2.5 mg), and in the group that first took a long-acting β2-agonist for a week and then added bisoprolol 2.5 mg to the regimen the said value dropped in 7% of patients only. Thus, preceding long-acting β2-agonists, formoterol in particular, reduced the risk of bronchospastic incidents triggered by selective β1-adrenoblocker (bisoprolol) in patients with cardiorespiratory pathology.

Acute blood loss is associated with deterioration of blood circulation, including microcirculation. Clinical and experimental studies are focused on the search for the possibility of neutralizing the consequences of such impairment. The use of hypothermia is considered not only as a method to improve survival, but also as a method to improve cerebral microcirculation in hemorrhage. The study was aimed to assess the state of the rats’ cerebral arteries in cases of mild hypothermic exposure after acute moderate blood loss. The study involving anesthetized Wistar rats was performed by vital microscopy. We assessed the responses of pial arteries (initial diameter 10–40 µm) in animals cooled to the rectal temperature of 34 °С under conditions of hemodynamic stability and when simulating blood loss (20% of total blood loss) in normothermic animals and animals with mild hypothermia. The findings showed that 3.5 h of exposure were associated with vasoconstriction in animals of all studied groups. Hypothermic state of the body was associated with initial decrease in the diameter by 9% of the baseline (24.9 ± 0.9 µm to 22.7 ± 0.7 µm; p < 0.05) followed by restoration of the diameter after 2 h (to 25.7 ± 1.7; p > 0.05). Blood loss was associated with the decrease in the diameter of cerebral blood vessels by 20–25% within the first hour (23.4 ± 0.7 µm to 17.6 ± 1.1 µm; p < 0.001) and no subsequent restoration (the diameter was 16.7 ± 0.8 µm after 3.5 h of monitoring). When using hypothermia, vasoconstriction following blood loss was 8–10% in the first 45 min of monitoring (22.6 ± 1.3 µm to 20.3 ± 1.2 µm; p < 0.05), then the constriction decrease was observed (the diameter was 21.4 ± 1.4 µm after 3.5 h of monitoring). It was concluded that the use of mild hypothermia resulted in the reduced vasoconstrictor effect of moderate blood loss on the pial microvessels.

Human brain is one of the most difficult organs to study. The possibility of developing the technologies that have sufficient scientific accuracy and economic accessibility and never violate the moral and ethical standards of human society is of great interest. The study was aimed to study the possibility of assessing the retrosplenial cortex (RSC) structures’ activity based on the EEG analysis of brain activity in the alpha frequency range in 36 healthy volunteers with an average age of 29.1 years, no acute central nervous system disorders or exacerbation of chronic central nervous system disorders, severe traumatic brain injuries, mental disorders or epilepsy. Significant source localizations were obtained by solving the EEG inverse problem that could be used for identification of the cerebral retrosplenial cortex structures’ bioelectric activity. The use of such technology will allow us to expand the scope of the research focused on assessing the brain functional activity in both research and clinical centers, thereby paving the way for understanding the features of the brain structures’ activity in physiologically normal conditions and in individuals with mental disorders caused by various functional alterations in the brain.

Cytomegalovirus infection (CMVI) continues to be a serious public health problem, being second to hypoxia and asphyxia in the list of reasons of morbidity and mortality of newborns. This study aimed to analyze therapeutic approaches to management of children with congenital cytomegalovirus with the regimens including an antiviral drug (direct action) and a specific anti-cytomegalovirus immunoglobulin (anti-CMV IG), depending on the clinical form of the disease. The total number of participants was 62, with the first group of children receiving the antiviral drug (n = 21), and the second group — an anti-CMV IG (n = 41). We analyzed the clinical, laboratory and instrumental research methods, and studied the catamnesis of children under 3 years of age. For statistical analysis, we used SPSS Statistics and StatTech v.3.1.6. In the first group, where the regimen included the direct action antiviral drug, the outcome was successful for 28.6% of the participants, and in the second group, which was treated with the anti-CMV immunoglobulin, this figure was 58.5%. Regardless of the regimen, by the age of 3, 50% of the children were practically healthy. Most of the participants tolerated the therapy satisfactorily. However, for 66% of the involved children, we had to shorten the direct action antiviral drug therapy to 14 days because of the problems with venous access, in 4.8% we registered thrombocytopenia, and in 9.5% — increased transaminase activity. Comparing the disease outcomes depending on the therapy initiation day, we established significant differences only for the specific antiviral therapy cases (p = 0.044).

Stagnation of the institution of assigning professional grades (categorization) draws increasing attention to the study of the opinions of physicians aimed at understanding and addressing the issues of this system. The study was aimed to get an estimate of the categorization system, the need for and directions of its transformation from physicians. The study involved an absentee poll of 64 physicians. Among then 48.4% had professional grades, 42.2% had scientific degrees, 51.6% were members of professional communities, 45.3% were engaged in teaching, 48.4% published scientific research results, 26.6% presented the results of their work during scientific and practical events. The average work experience as a physician was 13.8 ± 6.13 years. The questionnaire consisting of 21 statements with 5-point Likert scales was divided into four items: assessment of current categorization system; refusal of categorization; need to transform the system; directions of transformation. As a result, it was found that the respondents having professional grades, scientific degrees, who were members of professional communities engaged in teaching and scientific research, rated the existing categorization system lower (1.0 ≤ Ме ≤1.8 vs 2.6 ≤ Ме ≤ 3.0; 0.001 < р ≤ 0.034), they more often agreed that there was a need to transform the system (1.0 ≤ Ме ≤ 1.33 vs 2.7 ≤ Ме ≤ 3.0; 0.001 < р ≤ 0.013), than the respondents with no listed above traits. A total of 71.9% respondents agreed that there was a need for change, 1.6% agreed with the refusal of categorization. No correlation between work experience and the scores of items was revealed (0.144 ≤ р ≤ 0.627). Thus, despite the fact that the categorization system was rated low, the majority of physicians don’t want to abandon it seeing the need for transformation. The physicians’ beliefs are affected by the levels of their professional development.