Today, genetic studies yield quite a large amount of information about a person, which, in many cases, allows predicting the risks of certain diseases. This gives grounds to believe that such testing can also be applied in the field of manned spaceflights in order to identify candidates best adapted to specific risks. The article examines publications on genetic polymorphisms and their effects on the carrier phenotype, namely, on such manifestations that are of interest in the context of risks arising during long-term space flights. Specific genes are listed and examples of allelic variants are given. Publications describing new molecular methods of monitoring human health are also considered, biomarkers that can be used for research in the interests of regular examination of active astronauts are identified.

The paper provides the summary of foreign literature data on the organizational and methodological aspects of functioning of the bone marrow and hematopoietic stem cell donor registries, the issues of HLA typing, the technical algorithms for compatibility degree ranking. The changes in the citizens’ motivations in response to the bone marrow donating program popularization are described, along with the features of arranging recruitment, approaches to determining the requirements for the registry population considering the multinationality and heterogeneity of ethnic composition, and the statistical approximation algorithms. Furthermore, attention is paid to the so-called specific aspects of the functioning of bone marrow and hematopoietic stem cell registries and biobanks. The latter is important in terms of ensuring national security, adaptation of the population to the effects of the disasters, emergencies, and terrorist attacks associated with the development of bone marrow syndrome in a large number of victims.

The review is focused on essential tremor (ET), the most common extrapyramidal system disorder. Current understanding of the disease pathogenesis is provided; issues of classification and differential diagnosis are discussed. Modern ET treatment methods include therapeutic approaches and surgical interventions. The benefits of the new ET treatment method, the magnetic resonance-guided focused ultrasound treatment (MRgFUS), are described; the world’s experience of using the method, indications and contraindications are summarized.

Today, the cell-based technologies are one of the instruments used for the cartilage tissue repair. Creation of a universal hypoimmunogenic cartilage tissue graft from the differentiated derivatives of induced pluripotent stem cells (iPSCs) might solve the problem of the lack of the cartilage cell product. However, currently there is little data on immunogenicity of such tissue-engineered preparations. The study was aimed to create a cartilage implant from the differentiated derivatives of the B2M-deficient iPSCs and assess its immunogenicity. The previously developed protocol was used to ensure differentiation of both wild-type and B2M knockout iPSCs into chondrocyte-like cells. After quality control of the resulting cell lines by conducting polymerase chain reaction and immunocytochemical assessment, the resulting cell lines were co-cultured with the peripheral blood mononuclear cells of a healthy donor. When co-cultivation was over, activation and degranulation of CD8⁺ T cells was assessed by flow cytometry analysis based on the CD69 and CD107a expression on the cell surface, respectively. The iPSC-derived chondrocytes expressed the cartilage tissue markers. Flow cytometry analysis revealed no substantial differences in immunogenicity between the derivatives of wild-type and B2M knockout iPSCs, as well as from the cartilage tissue cells of a healthy donor. Immunogenicity of chondrocyte-like cells was higher than that of hypoimmunogenic non-edited iPSCs. The B2M knockout iPSCs demonstrated a trend towards greater activation of CD8⁺ T cells. Thus, the B2M knockout in the iPSC-derived chondrocytes had no significant effect on the tissue immunogenicity. It is necessary to further edit the genes encoding MHC II and CD47 to obtain a less immunogenic product.

Microtia is a combined congenital malformation with the prevalence of one case per 10,000–15,000 newborns, which accounts for 50% of all congenital malformations. Treatment of microtia is a challenging task. Numerous solutions have been proposed, however, none of these options guarantee good functional and aesthetic outcome. High hopes for solving the problem are placed on advances in reconstructive surgery. The study was aimed to determine the possibility of using advanced biocompatible endoprostheses manufactured using the tissue engineering technologies. Two closely related male 2-year-old minipigs of the Sus salvanius breed underwent implantation of bioengineered implants manufactured by combined 3D bioprinting with application of the collagen solution containing autologous cartilage tissue cells under the temporal fascia. The samples were collected 3 months later. Histological examination and immunohistochemistry showed that the implanted endoprosthesis initiated the development of regenerated connective tissue and its own vasculature in 100% of cases, thereby ensuring cell viability and integrity of biological structures; furthermore, no facts of the endoprosthesis rejection or resorption were reported. We have concluded that the developed implant manufacturing method is promising and can provide the basis for creation of domestic porous ear implants based on biocompatible polymeric materials, hydrogels, and autologous cellular material. It is necessary to further test the auricular implant using biological models.

Introduction of point genetic associations into clinical and laboratory diagnosis will allow the physician to determine the risk of severe diabetes mellitus and its complications with a focus on detection of the genetically determined disorder. The study was aimed to identify the molecular genetic markers of severe diabetic nephropathy in patients with type 1 and 2 diabetes mellitus (DM) based on the GSTP1 (I105V) gene assessment. Genotyping of the GSTP1 gene I105V locus was performed in patients with type 1 and 2 DM. Then we identified the features of oxidative status, free radical oxidation, and renal function in patients with various polymorphic variants of the studied gene. Patients with type 1 DM, who were carriers of the GSTP1 heterozygous polymorphic variant (Ile/Val), showed higher activity of the oxidative stress enzymes (glutathione-S-transferase, catalase) and malondialdehyde compared to homozygous carriers (р < 0.001, р < 0.001, р < 0.05). They also showed a significant increase in the levels of triglycerides (1.6-fold) and the glycated hemoglobin levels (1.1-fold) (p < 0.05). Patients with type 2 DM, who were carriers of the GSTP1 polymorphism homozygous for allele 2 (Val\Val), had a higher level of malondialdehyde (100.5 µmol/L, (р < 0.001)), which was associated with the more severe diabetic nephropathy (average glomerular filtration rate — 48 mL/min/1.73 m², 24-h urinary albumin excretion — 0.9 g/L; р < 0.01). It has been proposed to assess the GSTP1 (I105V) gene in individuals with type 1 and 2 DM. This polymorphism that is heterozygous in individuals with type 1 DM and homozygous for allele 2 in individuals with type 2 DM is unfavorable in terms of the DM course and complications.

Lymphopenia is a condition in which there are lower than normal counts of lymphocytes in the blood. Combination of lymphopenia and prolonged exposure to low temperatures leads to a reduction of adaptive resources, increasing risks of chronic inflammatory processes and secondary environmentally induced immunodeficiencies. The aim of the study was to compare characteristics of immune reactivity in response to cold exposure depending on background level of lymphocytes. Changes in hematologic and immunologic parameters in 203 participants before and immediately after short-term cold exposure were studied. Measurements included skin temperature (forehead, backside of palm), blood pressure, heart rate, leukogram, and hemogram. Levels of ferritin, lactoferrin, transferrin, interleukin-6, interleukin-1β, TNFα, erythropoietin, and irisin were determined using the enzyme immunoassay method. Apoptosis and necrosis of lymphocytes were assessed by flow cytometry analysis using AnV/PI double staining assay. Regardless of the background level of lymphocytes in peripheral blood, same-type responses to short-term cold exposure were observed in cardiovascular system as well as in irisin and ferritin levels, providing an evidence of activating thermoregulation and thermal homeostasis mechanisms. Lymphopenia is associated with a decrease in activity of nonspecific defense - in response to cold exposure there were no changes in level and functional activity of circulating neutrophil granulocytes that can increase the risks of chronicization of infectious processes in this group.

The oxidative stress associated with ischemic stroke is a major factor damaging the nervous tissue. Thyroid hormones have a significant effect on the body’s redox status, however, the impact of their derivatives, thyronamines, considered as potential neuroprotectors, on the characteristics of lipid peroxidation (LP) is not clearly understood. The study was aimed to assess the impact of the Т0АМ thyronamine synthetic analogue on the main LP indicators in the model of acute cerebral ischemia. Permanent ligation of the right common carotid artery was performed to simulate acute cerebral ischemia in white rats. The animals were divided into two groups: the control group receiving no treatment and the experimental group, to which the Т0АМ thyronamine synthetic analogue was intraperitoneally administrated (75 mg/kg of the rat’s body weight). After 24 h the rat was decapitated, and the cerebral cortex tissue was extracted for biochemical analysis. The following LP indicators were determined by spectrophotometry: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx). When administering the Т0АМ thyronamine synthetic analogue, a significant (2-fold) decrease in MDA levels was observed in the ischemic hemisphere (р = 0.022), along with the 2.49-fold increase in the GPx activity in the brain tissue (р = 0.004) of the intact hemisphere and the 2.65-fold increase in its activity (р = 0.021) in the ischemic hemisphere, as well as the 1.23-fold increase in SOD activity in the ischemic hemisphere (р = 0.042). The Т0АМ thyronamine synthetic analogue has a great potential in terms of activation of the antioxidant protection mechanisms in the cerebral cortex of white laboratory rats under conditions of acute hemispheric ischemia.

The study was focused on the features of spectral characteristics of the EEG alpha and theta ranges in the military academy cadets undergoing specific training to improve cold resistance (cold exposure training). The study was aimed to assess the impact of the military academy cadets’ incremental exposure to the graduated cold stress (cold exposure training) on spectral characteristics of the EEG alpha and theta rhythms. Students of the civil higher educational institution and military academy cadets were assessed (58 individuals in total). Cadets underwent a specific program focused on improving cold resistance (cold exposure training). Background EEG in the alpha and theta frequency ranges was recorded. Statistical data processing involved nonparametric comparison using the Mann–Whitney U test. The results were obtained suggesting that there were significant differences in spectral characteristics of alpha and theta rhythms between the group of foreign cadets and the controls. The cold exposure training program was effective in the group of Russian cadets, which had an effect on the cerebral homeostasis stability with some degree of instability of neurodynamic processes in the CNS. In foreign cadets, regular cold exposure training resulted in the pronounced disintegration of cortical-subcortical and intracortical interactions, as well as in the formation of binary alpha-theta structure of background EEG.

The onset and progression of various disorders, including chronic urticaria, are associated with stress. The gut-brain-skin axis is used to describe correlations among the nervous system, gastrointestinal tract states and systemic and skin inflammation. We have summarized inflammatory and immune mechanisms underlying chronic urticaria and stress in the context of the gut-brain-skin axis. The study was aimed to show the relationships between substance P, the neurotransmitter, and diamine oxidase, the enzyme disrupting histamine in the gut of patients suffering from chronic urticaria. A total of 165 adults aged 18–68 were enrolled; 97 patients had chronic urticaria, the comparison group was formed of 68 nominally healthy individuals. ELISA (Cloud-Clone Corp; China) was used to simultaneously estimate serum levels of substance P, diamine oxidase, and histamine. We revealed a significant positive correlation (ρ = 0.5; p < 0.05) between substance P and diamine oxidase in patients with chronic urticaria and in the comparison group, which confirmed the existence of the gut-brain-skin axis. The paper provides theoretical background and new targets for treatment of chronic urticaria. The possibility of prevention and treatment of these disorders by modulation of gut microbiota is discussed, the place of diet and the lifestyle modification contributing to improvement of general health are determined.

Based on clinical practice, some patients with lipid metabolism disorders (LMD) are resistant to lipid-lowering therapy (LLT) — in such patients, taking optimaldoses of LLT drugs does not reduce levels of cholesterol and its fractions to target levels and using LLT at higher doses is associated with increased odds ofadverse events. To optimize the treatment, 58 patients with ischemic heart disease with LMD resistant to LLT were examined. The patients were divided into twogroups: in the main group, 29 patients received laser therapy and unloading therapeutic gymnastics; in the control group, 29 patients continued to take theirusual medications. The obtained results showed a significant lipid-lowering effect of the treatment in the main group: we observed a significant decrease in totalcholesterol (by 27.7%, p < 0.01) as well as low-density lipoprotein cholesterol (by 34.7%, p < 0.01), a significant increase in high-density lipoprotein cholesterol(28.1%, p < 0.01), a significant decrease of atherogenic coefficient (by 50.2%, p < 0.01) and in the levels of triglycerides (by 49.6%, p < 0.01). At the same time,no significant positive changes in lipid profile were observed in the control group. In patients of the main group, tolerance to physical activity increased significantly,with statistically insignificant changes in the control group accordingly.

Hip dysplasia (HD) represents the congenital underdevelopment of the hip joint (HJ) being the most common orthopedic problem of newborns having the prevalence of 5–20%. Late HD detection is the main cause of coxarthrosis in young adulthood. The study was aimed to assess the results of ultrasound screening for HD in infants. The study involved 860 full-term infants aged 1–3 months (446 boys (51.9%) and 414 girls (48.1%)). All newborns underwent ultrasound imaging of the hip joint at the age of 1 month and the follow-up examination at the age of 3 months (Graf method). The χ² test and p < 0.05 were used to compare the data. In their first year of life, 685 newborns (79.7%) had joints of normal or transitory shape, 161 (18.7%) showed physiological immaturity and 14 (1.6%) showed the HJ abnormality; the HJ immaturity and abnormality were more prevalent in girls (113 cases (26.3%)) than in boys (62 cases (13.9%)). The relationship between the breech presentation and the likelihood of developing HD was revealed (p < 0.001). Spontaneous improvement by the age of 3 months took place in the majority of infants having the ultrasound signs of HD, the rate of normal HJ increased from 79.8 to 94.5%. Ultrasound screening is an effective method allowing one to detect HD starting from the first days of the child’s life. The risk factors of HD are still female sex and breech presentation, regardless of the number of births. Spontaneous improvement following prescription of relaxing massage occurs in the majority of children.

Shortcomings of the categorization system include weakness of the normative regulation oriented towards the outdated ideas about the qualification and formal features of professional development. It is often proposed to objectify measuring the professional competence of the subjects evaluated in order to improve the categorization system. The study was aimed to test the qualification requirements of physicians for the relationship with their qualification and the possibility of accurate full-fledged measurement of those in the evaluated subjects. We performed expert assessment of 22 requirements for grades approved by the Order of the Ministry of Health of the Russian Federation dated 31 August 2023 No. 458n relative to four items: their relationship with the physician’s qualification, feasibility of measurement (usability), relationship with the competence of the evaluation commission member (objectivity), possibility of determining the extent of the knowledge, abilities, skills required for each qualification grade. Assessment involving the use of the Stapel rating scale (“–5” to “+5”) was performed by seven experts. The sums of scores by items were as follows: relationship with qualification — 477, usability — 316, objectivity — ‒662, grade — –699. There are significant differences between the scores reported for all the requirements and pairs of all items (р ≤ 0.0001), except the objectivity–grade pair (р = 0.103). The total of the scores reported for the majority of requirements is negative due to the lowest possible scores of objectivity and grade. The experts believe that none of the qualification requirements approved by the Order enables accurate full-fledged determination of physician’s qualification during evaluation.

Retrocerebellar cysts of the brain represent the aspect that is important for determination of fitness for flight. The study was aimed to assess their impact on the pilot performance by conducting comparative analysis of MRI data of the first-year cadets and experienced pilots. We assessed the prevalence of retrocerebellar cysts among cadets and pilots, conducted non-contrast brain MRI, and compared the major academic and physical performance indicators, along with the results of professional psychological screen. The prevalence of retrocerebellar cysts among first-year cadets was 8.2%. High prevalence of asymptomatic retrocerebellar cysts among experienced pilots was revealed (two cases out of five). The intergroup comparison of indicators makes it possible to draw a conclusion about probable minor impact of such changes on fitness for flight. Further research is required to clarify the mechanisms underlying the impact of retrocerebellar cysts on the pilot performance and develop appropriate guidelines for medical boards.

The main causes of postoperative mortality associated with percutaneous coronary interventions involving the coronary artery stent insertion are perioperative myocardial infarction and acute heart failure due to inadequate protection of the myocardium against ischemia/reperfusion. The standard therapy includes beta blockers, anticoagulants, antiplatelet drugs. Two clinical cases of successful use of intravenous levocarnitine for cardioprotection in senile patients with acute forms of coronary heart disease with multivessel lesions are reported. The postoperative period went well, smooth dynamics of biomarker levels (troponin I, creatine phosphokinase, MB fraction of creatine phosphokinase) was observed, and ischemic ECG changes were relatively small. The expected results of the technique application include reduction of intraoperative and postoperative complications of ischemia/reperfusion and the increase in effectiveness of the stent insertion clinical outcomes in high-risk patients.

The development of complex criteria for the diagnosis, differential diagnosis, and optimization of treatment of infectious diarrhea associated with opportunistic Enterobacteriaceae is a pressing issue of pediatric research and practice. The paper reports a clinical case of protracted intestinal infection associated with Klebsiella pneumoniae in the form of moderate hemorrhagic enterocolitis in an infant, which is explained by the decrease in specific resistance due to unfavorable maternal obstetric and gynecological history, perinatal CNS injury, iron deficiency anemia, protein-energy malnutrition. The disease relapse associated with secondary norovirus infection was reported after the first hospitalization. Three courses of intestinal antiseptics and probiotics were required to achieve a beneficial treatment outcome, although usually in such a situation one course of such drugs is enough. The recovery process was accompanied by the nutritional status improvement, hemorrhagic colitis relief, normalization of gut microbiota.