EDITOR-IN-CHIEF'S PREFACE
DISCUSSION PAPERS, LECTURES, NEW TRENDS IN MEDICAL SCIENCE
Pharmacogenetics aims to investigate the correlation between patient genetic characteristics and the efficacy of pharmaceutical agents, while concurrently evaluating the risks of adverse reactions. This field of research necessitates the application of complex statistical analysis methodologies, and artificial intelligence (AI) capabilities are increasingly being leveraged for such analyses. AI represents an advanced technology employed to automate the execution of tasks that traditionally demand substantial human intellectual effort. A review of scientific literature on the application of machine learning models in pharmacogenetic research has demonstrated that AI is a highly sophisticated and flexible tool capable of facilitating the widespread implementation of pharmacogenetics in clinical practice. A promising area for the application of AI in pharmacogenetics involves the integration of this technology into tasks related to the analysis, detection, prediction, and support of pharmacogenetic information and decision-making systems. The utilization of deep learning technologies has the potential to expand the understanding of drug pharmacodynamics, indications, and contraindications, which may potentially lead to the updating of educational and methodological literature on pharmacology and substantially advance the quality of patient pharmacotherapy. However, the implementation of AI technologies may be hindered by factors such as a shortage of qualified personnel, ethical disagreements, and complexities in legal regulation of this domain. Nonetheless, the application of AI technologies in pharmacogenetic research demonstrates high effectiveness and expediency, despite the existing challenges.
Background. The prevalence of cervical cancer (Cca) in Russian women makes it crucial to study modern epidemiological characteristics and adjust control measures accordingly.
The aim. To analyze trends in the incidence of cervical cancer in the Russian Federation.
Materials and methods. A retrospective epidemiological study was conducted on cervical cancer incidence in Russian Federation from 2008 to 2021. The materials of annual statistical data “Malignant neoplasms in Russia (morbidity and mortality)” and “Status of oncological assistance to the population of Russia” (2008–2022), data of the federal statistical reporting form No. 5 “Information about preventive vaccinations” (2021), data on the number of studies conducted (cytological study and HPV-test based on RT-PCR) in the clinical diagnostic laboratory of Central Research Institute of Epidemiology of Rospotrebnadzor (2013–2021) were used.
Results and discussion. The trends of Cca incidence varied depending on the women’s age. Starting in 2016, there was a stabilization of the level of morbidity in women aged 30–49 with the subsequent decrease from 2019 due to the strengthening of secondary prevention measures, including the active introduction of HPV-test into the diagnostic schemes conducted in the Russian Federation. Increased control of cervical cancer caused a rise in the proportion of cases diagnosed at an early stage (carcinomas in situ and I–II stages Cca), the increase of detection rate of in situ carcinomas per 100 cases of Cca, the growth of the proportion of carcinomas in situ to I–II stages Cca, rise of the percentage of the cases detected actively, decrease of the number of Cca cases detected at later stages and one-year mortality index.
Conclusion. The epidemiological analysis of cervical cancer incidence shows that preventive measures are effective and that there is a need to intensify and increase their coverage.
OBSTETRICS AND GYNAECOLOGY
Background. COVID-19 negatively impacts pregnancy progression and outcomes. However, data regarding pregnancy complications related to prostaglandin activity during COVID-19 remain insufficient.
The aim. To assess markers of metabolic processes related to prostaglandin metabolism in the blood of pregnant women depending on the severity of COVID-19 and to explore associations with the development of pregnancy complications.
Methods. The study included 109 pregnant women in their third trimester (28–30 weeks), 36 of whom had mild COVID-19, 38 had moderate COVID-19, and 35 were not infected with SARS-CoV-2. The concentration of prostaglandins E2 and F2α, phospholipase A2 (PLA2), cyclooxygenase 2 (COX2), and arachidonic acid (AA) were measured in the blood using enzyme-linked immunosorbent assays and gasliquid chromatography for AA.
Results. Comparative analysis showed that pregnant women with moderate COVID-19 had significantly higher levels of AA, COX2, PLA2, prostaglandins E2 and F2α (p < 0.0001) compared to those with mild disease. These women also experienced more frequent complications, such as chronic placental insufficiency, preterm labor, and premature rupture of membranes. Regression analysis revealed associations between chronic placental insufficiency and prostaglandin E2 levels (p < 0.0001), preterm labor, AA (p = 0.001) and COX2 (p = 0.001); premature rupture of membranes and PLA2 (p = 0.025), COX2 (p < 0.001), AA (p < 0.001).
Conclusion. Moderate COVID-19 during the third trimester of pregnancy is associated with increased levels of AA, COX2, PLA2, and prostaglandins E2 and F2α in the blood. The most significant factors increasing the risk of pregnancy complications in women with moderate COVID-19 were elevated levels of AA, COX2, and prostaglandin E2 in the blood.
Background. Hypertensive disorders during pregnancy, such as gestational hypertension and preeclampsia, pose significant health risks. They require a personalized treatment approach due to their multifactorial nature. The presence of subclinical hypothyroidism may exacerbate these risks, making thyroid function monitoring before and during pregnancy particularly important.
The aim. To investigate the clinical features and severity of hypertension in newly diagnosed subclinical hypothyroidism among women in Andijan.
Methods. A case-control study conducted from November 2022 to April 2023 included 272 pregnant women aged 18 to 40 years without chronic diseases. The main group comprised 88 women diagnosed with hypertension after the 20th week of pregnancy. The control group consisted of 184 women without hypertension. The study excluded HIV-positive women, as well as those with congenital anomalies or who had undergone surgical interventions on the genitourinary and cardiovascular systems. Socio-demographic and lifestyle characteristics of the participants were studied. The analysis revealed significant differences in age, activity level, place of residence, employment, and education, as well as a correlation between body mass index, health status, and hypertension severity.
Results. The findings underscored the importance of thyroid function monitoring during pregnancy, linking hypertension to age, activity level, and obesity. This confirms the necessity for a comprehensive approach to pregnancy management, including thyroid function and lifestyle modifications.
BIOLOGY AND MEDICAL BIOLOGY
Currently, chimeric antigen receptor (CAR) T-cell therapy is an effective treatment method of hematological malignancies. However, T-lymphocyte-based immunotherapy has certain limitations for the scope of application of this approach. A promising alternative is CAR therapy based on natural killer (NK) cells, since it does not require detailed donor selection according to the human leukocyte antigen system; NK cells have a unique mechanism for recognizing and destroying tumor cells. In addition, NK cells do not cause severe toxic reactions when infused. The creation of a CAR NK product is a complex task includes cell culturing, using genetic engineering methods, and quality control testing of the resulting biomedical cell product (BMCP). For proliferation and effector function enhancement, NK cells require the presence of interleukins, feeder cells or their components, and immune system activators in the nutrient medium. This review focuses on various approaches to the activation and expansion of natural killer cells during cultivation, and also addresses the issues of the advantages and disadvantages of the chosen therapy and the regulatory aspects of creating a full-fledged BMCP.
Graves’ orbitopathy (GO) is an extrathyroid complication of thyroid dysfunction characterized by chronic autoimmune inflammation of soft retrobulbar tissues. The data on the role of oxidative and hypoxic stress in GO are heterogeneous, which necessitates further research.
The aim of the study. To evaluate the indicators of oxidative stress and tissue hypoxia at various phases of Graves’ orbitopathy activity.
Material and methods. Examination of patients with GO (n = 32), with autoimmune thyroid pathology (n = 18) and healthy individuals (n = 15) was performed. The study included ophthalmological examination and blood sampling to determine the concentration of antibodies to the thyroid-stimulating hormone receptor, interleukin 17A (IL-17A), hypoxia inducible factor 1a (HIF-1a), TBK-active products and calculation of total antioxidant activity.
Results. An increase in the concentration of TBK-active products in the clinical group was revealed compared with the control (p < 0.001). The total antioxidant activity was reduced at all phases of GO activity than in the control (p < 0.001). The level of HIF-1α did not differ in the study groups (H = 3.29; p = 0.51). Direct moderate correlations were found between the concentration of IL-17A and the level of TBA-active substances (p = 0.001), as well as inverse moderate correlations with the value of total antioxidant activity (p = 0.007). The activity of GO had weak correlations with total antioxidant activity (p < 0.001). Significant correlations between indicators of oxidative stress and tissue hypoxia were not found.
Conclusion. In GO, regardless of the activity phase, there is an imbalance between the parameters of the “lipid peroxidation – antioxidant protection” system, which is manifested by an increase in TBA-active substances while reducing the total antioxidant activity. The indicators of tissue hypoxia did not differ in the study groups. The revealed correlations between the autoimmune inflammation activity in the orbit and oxidative stress emphasize the pathogenetic conditionality of the antioxidant drugs appointment in the therapy of GO.
GENETICS, PROTEOMICS AND METABOLOMICS
Background. Methionine aminopeptidases (MAPs) are a class of enzymes that catalyze the removal of the N-terminal initiator methionine from a polypeptide chain. Bacterial MAPs are considered as targets for the development of broad-spectrum antibacterial drugs, and using MAPs in biotechnology necessitates the search for new MAPs and the study of their functioning and inhibition mechanisms.
The aim of the study. To identify methionine aminopeptidase in the Thermus thermophilus genome (Tt-MAP) and to confirm its functional activity.
Materials and methods. To identify Tt-MAP, we analyzed the Thermus thermophilus genome in the GeneBank database. Modern genetic engineering techniques (polymerase chain reaction, restriction, transformation, heterologous expression) were used to clone the putative open reading frame (ORF) encoding Tt-MAP in the pHUE vector. Various chromatography techniques (affinity, ion exchange, and size-exclusion) were used to obtain a purified enzyme preparation. The fluorogenic substrate L-methionine 7-amino-4-methylcoumarin (Met-AMC) was used to confirm the specific functional aminopeptidase activity of the enzyme.
Results. An ORF encoding MAP was identified in the Thermus thermophilus bacterium genome. Oligonucleotide primers were designed based on the nucleotide sequence. The ORF was cloned in the vector, and the recombinant enzyme was produced in E. coli cells. A method for purifying the enzyme to a homogeneous state was developed using a series of sequential chromatographies, allowing up to 30 mg to be obtained from 1 liter of culture. Using the fluorogenic substrate Met-AMC, the specific functional activity of the enzyme was demonstrated (the enzyme cleaves methionine from the substrate).
Conclusion. We have identified the Thermus thermophilus MAP and tested its functional activity. It has been shown that the ORF product TTHA1670 encodes a methionine-specific aminopeptidase, i. e. methionine aminopeptidase. The enzyme can be used in various fields of biotechnology and scientific research.
Background. The molecular mechanisms behind the maintenance of zoonotic pathogens in nature can be better understood by examining the gene expression in host cells in response to the infection. Reverse transcription and quantitative polymerase chain reaction (RT-qPCR) is a powerful method to study gene expression, especially with the use of endogenous reference genes (RG) to normalize the data. Therefore, it is critical to develop the reliable qRT-PCR assay and validate that selected RGs are stably expressed in the studied organism or cell culture.
The aim. In this work, we aimed to develop the real-time qRT-PCR method for detecting mRNA of two candidate RGs, succinate dehydrogenase subunit A (SDHA) and beta-actin (ACTB), in the cell lines of mammalian hosts of zoonotic infections.
Materials and methods. The SPEV (porcine embryonic kidney cell line) and ApnK (Korean field mouse kidney cell line) cells were grown in 24-well culture plates. Total RNA/DNA was isolated from trypsin-detached cell monolayers. Genomic DNA in the samples was removed with RNase-free DNase I, and one-step RT-qPCR was performed using primers for SDHA and ACTB gene fragments and the corresponding TaqMan hydrolysis probes. The experiment was performed in 4 independent replicates.
Results. In the Korean field mouse cells, the linearity, efficiency, repeatability, and reproducibility of the RT-qPCR for ACTB gene mRNA corresponded to the modern requirements. However, RT-qPCR for SDHA exhibited good linearity and efficiency of the reaction, but CV values for repeatability and reproducibility slightly exceeded the recommended standards. In porcine cells, both assays had acceptable parameters. Thus, to use the SDHA as RG for ApnK cells, a detailed study of the stability of its expression in this particular model is required.
Conclusions. New qRT-PCR assay was developed to assess the expression of housekeeping genes ACTB and SDHA in the cells of the Korean field mouse and domestic pig. Further research is necessary to validate these genes as references for quantitative assessment of gene expression in the cells of mammalian hosts of zoonotic infections.
INFECTIOUS DISEASES
Background. T cell immunity is known to play a central role in controlling SARSCoV- 2 (severe acute respiratory syndrome-related coronavirus 2) infection, so it is critical to understand its role in recovery from COVID-19 (coronavirus disease 2019), especially in the unfavorable conditions of the North.
The aim. To assess the immune status of women after COVID-19 living in the subarctic region of the Russian Federation.
Materials and methods. We examined a total of 50 women aged 36–46 years, including 38 vaccinated women 6 and 12 months after recovery from COVID-19 and 12 women (control group) who had not had COVID-19 and had not been vaccinated (Arkhangelsk region). We studied leukocyte count, leukogram and lymphocyte phenotypes (CD5+, CD8+, CD10+, CD16+, CD95+).
Results. The contribution of monocytes to the formation of the adaptive immune response among female residents of the subarctic region decreases in those who have had mild COVID-19 and increases in those who have had moderate COVID-19. It was found that the imbalance in the formation of the immune response after COVID-19 is formed due to innate immunity (CD16+, neutrophils (r = 0.89; p < 0.001)), affects the adaptive immunity and depends on the severity of the disease and the time since recovery. The most significant contribution to the formation of the adaptive immune response was established due to cellmediated cytotoxicity (CD8+, CD16+) and the activity of apoptotic processes (CD95+) both after 6 and 12 months and does not depend on the severity of the COVID-19. The adaptive immune response formed 6 months after COVID-19 with a high level of cell-mediated cytotoxicity and activity of apoptotic processes prevailing over lymphoproliferation persists after 12 months, which indicates a tense state of immune homeostasis.
Conclusion. In the examined women who had recovered from COVID-19, cellmediated cytotoxicity (CD8+, CD16+) is associated with the activation of the monocyte system, has a prolonged effect of up to 12 months and depends on the severity of the previous COVID-19 in 66.7–90 % of cases.
Background. SARS-CoV-2 infection often results in olfactory disorder at different levels of the nervous system, which may persist as anosmia, parosmia, hyperosmia, hyposmia, cacosmia, and olfactory hallucinations after recovery.
The aim. To study the effect of essential oils on the restoration of the olfactory apparatus in patients with coronavirus.
Materials and methods. We examined 138 people (mean age 19.9 ± 7.05 years) with olfactory complaints, 60 of them underwent olfactory training with essential oils (EO) for 2 months. Olfactory function was assessed using the Hansen – Roseburg method before and after the training.
Results. After 3 months of using essential oil sets for olfactory training, 27 respondents noted an improvement in the quality of odours and the appearance of previously missing odours. When conducting the Hansen – Roseburg test, a statistically significant improvement in the indicators for determining the tested odorants was revealed: phenylethyl alcohol (PA) – 7 [5; 7]; benzyl acetate (BA) – 6 [4; 6]; formic acid (FA) – 6 [2; 7] (p < 0.05). When repeating the test in the control group of 30 people, only 4 respondents reported an olfaction improvement; the results of the olfactory assessment according to Hansen – Roseburg were as follows: PA – 5 [2; 6], BA – 4 [3; 5], FA – 2 [2; 4] (p > 0.05).
Conclusion. The data obtained after 3 months of olfactory training with a special set of essential oils and the subsequent olfactory testing indicate that olfactory training is a promising method for olfactory restoration, which can help many people regain the joy of perceiving odours and significantly improve their quality of life. The success of the method depends on the correct use of essential oils and compliance with the frequency of training.
CARDIOLOGY
The aim of this study was to determine the possibility of studying the nature of the influence of cardiocytoprotectors on energy metabolism in cardiomyocytes using a model of human peripheral blood leukocytes.
Materials and methods. Sixty Wistar rats were divided into groups: 1) intact rats; 2) rats with experimental myocardial ischemia; 3) rats with myocardial ischemia, which were injected with cardiocytoprotector – trimetazidine, 4) meldonium, 5) cytoflavin and 6) ethoxydol. Animals were taken out of the experiment 10 days after the administration of drugs by decapitation. The activities of pyruvate dehydrogenase and citrate synthase were determined in mitochondria of myocardial homogenates and in mitochondria of leukocytes by spectrophotometric methods.
Results. The decrease in pyruvate dehydrogenase and citrate synthase activity in cardiomyocytes and in leukocytes were revealed in case of myocardial ischemia modeling. The introduction of cardiocytoprotectors led to the activation of these enzymes both in heart cells and in blood leukocytes. Direct positive correlations were obtained between the activity of pyruvate dehydrogenase in the mitochondria of cardiomyocytes and in the mitochondria of leukocytes (r = 0.811; p < 0.0001); between citrate synthase activity in the mitochondria of cardiomyocytes and in the mitochondria of leukocytes (r = 0.909; p < 0.0001).
Conclusion. Changes in energy metabolism in blood leukocytes under the influence of cytoprotectors reflect similar changes occurring in heart cells.
MICROBIOLOGY AND VIRUSOLOGY
Background. Isolation of strains from tick-borne encephalitis (TBE) patients proved that the European subtype tick-borne encephalitis virus (TBEV-Eur) in Siberia is involved in regional human infectious pathology and causes a clinical picture similar to Western TBE. However, a comparative analysis of the genomes of TBEV-Eur strains isolated from TBE patients in Eastern Siberia and Europe has not been carried out.
The aim. Genome comparative analysis and search for virulence determinants in TBEV-Eur strains isolated from patients in Eastern Siberia and Northern and Eastern Europe.
Materials and methods. In current work, TBEV-Eur strain 1G-98 from the collection of Scientific Сentre for Family Health and Human Reproduction Problems (GenBank Acc. No. KY069119) was used. The analysis also included all complete genome sequences of TBEV-Eur strains from patients submitted in GenBank database at the time the study began. Complete genome sequencing of strain 1G-98 was performed using the Sanger method. The virulence of the strain was assessed by intracerebral and subcutaneous infection of laboratory mice.
Results. It has been shown that, according to the coding region of the genomes, the level of differences between TBEV-Eur strains from Siberia does not exceed the previously established maximum for this subtype of 3.1 %. The strain 1G-98, isolated from the blood of TBE patient from the Irkutsk region demonstrated high cerebral and peripheral activity. In this strain, D67G mutation in E protein DII domain was revealed, which could potentially be associated with virulence, and a long deletion in the variable part of the 3’-noncoding genome region, comparable in length to the highly virulent strain Hypr from Europe was found.
Conclusions. For the first time, a comparative analysis of the genomes of TBEV-Eur strains from TBE patients from the Asian part of Russia and Europe was carried out showing their genetic similarity, and potential virulence determinants were identified. Key words: tick-borne encephalitis virus, European subtype, genome, amino acid sequence, virulence determinants
Background. Antimicrobial resistance is one of the most serious threats to modern clinical medicine. Despite the significant successes of modern pharmacology, the search for effective antiseptics that can influence wound processes continues. In our study, an experimental study of the effect of Anolit solution on pathogenic microorganisms Pseudomonas aeruginosa and Proteus mirabilis was conducted.
The aim. To evaluate the antimicrobial activity of the domestic antiseptic “Anolit” against gram-negative pathogens of nosocomial infections using the example of P. aeruginosa and P. mirabilis.
Methods. To assess the quality of the effect of “Anolit” on the studied colonies of microorganisms, experimental studies were performed in vitro. The bacteriological study was carried out in three stages using the Koch method.
Results. “Anolit” is a modern antiseptic agent with a pronounced antimicrobial effect based on the electrolysis of aqueous solutions. Its ability to lyse pathogenic microorganisms (P. aeruginosa and P. mirabilis) has been confirmed by experimental research.
Conclusion. The bactericidal effect of “Anolit” on the growth of gram-negative bacteria is shown, proving its high antimicrobial efficacy.
MORPHOLOGY, PHYSIOLOGY AND PATHOPHYSIOLOGY
To assess the reserve capacity of the body from a physiological point of view, it is important to study the specific “northern” hormone metabolic profile of the body during critical (autumn and winter) periods in apparently healthy individuals born and living in the North.
The aim of the work. To study the main parameters of carbohydrate metabolism, as well as possible causes of its disorders in the dynamics of autumn and winter periods in men living in the North.
Materials and methods. The autumn (October) and winter (December) stages of the study included 45 men (mean age 40.0 ± 0.8 years) permanently residing in the Magadan Region. We used chemiluminescent immunoassay, enzymatic method and immunochromatographic assay.
Results of the study. It was found that the average values of carbohydrate metabolism parameters in the examined male northern residents are comparable with the standard ranges with a shift towards higher values relative to the established limits and do not meet the main criteria of the “polar metabolic type”. “Polar metabolic type” is characterized by hypoglycemia and hypoinsulinemia against the background of elevated serum cortisol values. It is shown that during the critical period of the year from October to December (temperature transition through zero) against the background of relative “hypercortisolism”, activation of the insular apparatus of the pancreas is observed, accompanied by an increase in the insulin level, as well as the development of insulin resistance in the absence of compensatory secretion of β-cells of the pancreas. At the same time, the presence of signs of insulin resistance in northern male residents in the winter period may be determined by an imbalance towards greater dominance of the sympathetic nervous system, formed as a response to the critical period of the year.
Conclusion. The obtained results indicate the formation of a transformed “northern” hormone metabolic profile of the body of a modern resident of the North, which should be considered as a certain adaptive response to the modern modification of the socio-economic lifestyle of northern residents (hypodynamia, overeating, etc.).
Background. Metabolic syndrome (MS) with hyperandrogenism comorbidity in women is considered a common concept; however, the contribution of the neuroendocrine regulation system indicators to this in reproductive age remains unclear.
The aim. To analyze the activity of neuroendocrine regulation system in women of reproductive age of different ethnic groups with metabolic syndrome associated with hyperandrogenism.
Materials and methods. The groups of women with MS of Russian (n = 209) and Buryat (n = 84) ethnic groups and a group of women with MS and polycystic ovary syndrome (PCOS) of Russian (n = 23) and Buryat (n = 10) ethnic groups were formed.
Results. In women of reproductive age of the Russian ethnic group with MS and PCOS the study noted higher levels of anti-Müllerian hormone (AMH) (p = 0.030), testosterone (Ts) (p = 0.026), free androgen index (FAI) (p < 0.0001), dehydroepiandrosterone sulfate (DHEA-S) (p < 0.0001), and reduced levels of sex hormone-binding globulin (SHBG) (p < 0.0001) in relation to the control; in relation to the group with MS, we discovered increased values of AMH (p < 0.001), Ts (p = 0.030), FAI (p < 0.001), DHEA-S (p < 0.0001), and decreased values of SHBG (p = 0.001). In women of the Buryat ethnic group with MS and PCOS the study recorded increased values of AMH (p = 0.045), Ts (p = 0.002), FAI (p < 0.0001), DHEA-S (p = 0.033), decreased SHBG (p = 0.016) and 17-OH-progesterone (p = 0.027) levels in comparison with the control; in comparison with the group with MS we noted a higher level of DHEA-S (p = 0.006) and a decreased level of SHBG (p = 0.028).
Conclusion. Women with metabolic syndrome associated with hyperandrogenism showed more intense changes in the neuroendocrine regulation system relative to control values regardless of ethnicity. In Russian women, the combined syndrome (MS with PCOS) was accompanied by a greater number of hormonal changes compared to the monosyndrome (MS) than in Buryat women. The data obtained indicate the need to assess and control the content of these metabolites in women with MS and PCOS, taking into account ethnicity.
Background. Radiobiological research on chemical radioprotectors is relevant in the study of radiation injuries and in practical medicine during radiation therapy of cancer patients. Selection of the optimal experimental model is necessary to assess the effect of radioprotectors on hematopoiesis and is an important task.
The aim. Analysis of the possibility of using Danio rerio fish as a test object for assessing the effectiveness of the protective effect of radioprotectors against ionizing radiation using an erythrocyte micronucleus test.
Material and methods. The work was carried out on Danio rerio aquarium fish. Seven groups of two-month-old zebrafish juveniles (n = 35), as well as adult fish, were exposed to X-ray radiation at doses of 0 Gy (control), 1.0 Gy, 2.0 Gy, 3.0 Gy, 4.0 Gy, 6.0 Gy, 8.0 Gy to determine the frequency of occurrence of micronuclei in peripheral blood erythrocytes 72 hours after irradiation.
Results. The frequency of occurrence of micronuclei in Danio rerio erythrocytes was dose-dependent. In juveniles, as in adult fish, the dose of ionizing radiation increased to 4 Gy led to a sharp increase in the frequency of occurrence of micronuclei in erythrocytes. Adult Danio rerio were more radioresistant; the number of micronuclei formed in erythrocytes in two-month-old juveniles exceeded the frequency of occurrence of micronuclei in adult fish.
Conclusion. A model using juvenile fish Danio rerio as a laboratory test object for assessing the effectiveness of the protective effect of radioprotectors against ionizing radiation using the erythrocyte micronucleus test can be recommended for testing the effect of medications in case of radiation injuries, as well as for assessing the possibility of their use in radiation therapy in cancer patients.
NEUROLOGY AND NEUROSURGERY
As is known, the issues of pathogenesis, diagnosis and treatment of the new coronavirus infection COVID-19 are the most priority areas of scientific research in the modern clinic of internal diseases. The rate of emergence of new scientific data in the leading libraries PubMed, Medline, Cochrane Library and eLibrary, which can potentially be important in the correction of ongoing therapy for infection and its complications, is extremely high. In turn, this dictates the need for a comprehensive discussion of the results of newly published studies. These issues include clinical and neurological manifestations of COVID-19 and other coronavirus infections. The exact mechanism by which the SARS-CoV-2 virus enters the structures of the central nervous system is unknown. Thus, two pathways for the penetration of the COVID-19 pathogen are most actively discussed: the hematogenous pathway (through the systemic circulation into the vessels of the brain with a low linear blood flow velocity, which allows the virus to adhere to the surface of the endothelium and penetrate into the nervous tissue through damage to the latter) and the contact pathway (through the cribriform plate and the olfactory bulb). It should also be noted that a number of experimental works clearly demonstrate the pathogenic effect of other members of the Coronaviridae family on the neurons of the respiratory and vasomotor centers. The review presents an analysis of current literature data on the study of clinical and neurological manifestations of COVID-19 and other coronavirus infections. It is important to emphasize that patients with a severe course of COVID-19 deserve special attention, requiring observation in the intensive care unit in order to prevent the development of fatal neurological complications.
Background. Despite the comprehensive study of Parkinson’s disease (PD), studying the quality of life (QoL) of patients, especially the prediction of low QoL, remains an unresolved issue.
The aim. To create a prognostic model for low quality of life in patients with Parkinson’s disease by studying the severity of clinical features.
Materials and methods. The cross-sectional study included 104 patients diagnosed with PD (56 % of men, 48 % of women); the median age was 67.0 [60.0; 71.0] years; the median duration of the disease was 5.0 [2.0; 8.0] years. We assessed motor and non-motor symptoms of PD in all patients. The PDQ-39 (Parkinson’s Disease Questionnaire) scale was used to assess the patients’ QoL. We conventionally accepted a PDQ-39 score of 50 or more as a low QoL level in a patient. Binary logistic regression using the stepwise exclusion method was used to create a prognostic model for a low QoL level in a patient with PD.
Results. To predict the probability of low QoL in patients with PD depending on the studied clinical manifestations, we proposed a function according to which female gender has the greatest impact on low QoL (odds ratio – 20.0; 95% confidence interval (95% CI): 1.82–222.26). An increase in the PD stage according to the Hoehn – Yahr scale by 1 unit causes 8.77 times increase (95% CI: 2.11–36.49) in the probability of low QoL, an increase on the Epworth sleepiness scale by 1 point – 2.33 times increase (95% CI: 1.24–4.38), an increase in the level of depression according to the HADS (Hospital Anxiety and Depression Scale) by 1 point – 1.93 times increase (95% CI: 1.13–3.32). The sensitivity and specificity of the obtained function were 95.9 and 80%, respectively.
Conclusion. The proposed prognostic formula can be used in neurologists’ appointments to determine the probability of low quality of life in patients with Parkinson’s disease.
The prevalence of post-COVID syndrome in patients treated on an outpatient basis ranges from 10 to 35 %; it can reach 80 % in patients with severe coronavirus infection. It is currently hypothesized that long-COVID may be due to both the direct effects of the SARS-CoV-2 virus and the biopsychosocial effects of COVID-19.
The aim. To study the characteristics of damage to the central nervous system and mental sphere in patients with comorbid post-COVID syndrome.
Materials and methods. To study the clinical features of the course of post-COVID syndrome, 98 patients who had suffered COVID-19 were examined. Of these, 18 (18.4 %) were men, 80 (81.6 %) were women. The mean age in the group was 56.05 ± 1.27 years. The examination program included a questionnaire, clinical examination, pulse oximetry, and assessment of exercise tolerance using the Borg scale. Statistical processing was carried out using the Statistica software package, version 6 (StatSoft Inc., USA). The results of the study are presented as a median, upper and lower quartiles. After analyzing the compliance of the studied indicators with the law of normal distribution (Shapiro – Wilk test), the groups were compared using the Wilcoxon test for pairwise comparison of related samples. Differences were considered statistically significant at p < 0.05.
Results. Our studies of comorbidity and complications after COVID-19 infection revealed the most frequent involvement of three systems in the pathological process: cardiovascular, nervous and endocrine. Metabolic syndrome was detected in 67 % and involvement of the cardiovascular system was detected in 48.8 % of those examined.
One of the main manifestations of post-COVID syndrome is damage to the central nervous system and mental sphere in the form of mild cognitive and emotional-volitional disorders with asthenodepressive and anxiety-depressive disorders.
Conclusion. The health status of patients after COVID-19 is significantly lower than that of the general population. The study results indicate an urgent need to study the pathogenesis of long COVID and develop effective interventions to reduce the risk of its development.
OPHTHALMOLOGY
Accurate preoperative determination of biometric parameters of the eye is the key to successful lens surgery, achieving high and predictable functional results. At the preoperative stage of refractive and cataract surgery, special attention is paid to the study of corneal parameters, in particular, optical power – keratometry. Corneal power is one of the important parameters in calculating intraocular lens power, in the selection of patients for surgery, the diagnosis of corneal diseases, monitoring the dynamics of pathological processes in the cornea, and analyzing postoperative results. Keratometry is based on the fact that the anterior surface of the cornea has mirror properties, and the size of the image reflected from it depends on the curvature of the cornea, which indicates the possibility of calculating its refractive power based on the analysis of the displayed image size. However, the methods and principles of keratometry are diverse. In this review, an analysis of literature devoted to the study of methods for determining the optical power of the cornea is carried out in order to systematize the data. The review highlights the historical aspects of keratometry – from the first attempts to measure the radius of the anterior surface of the cornea to the first ophthalmometer, shows the evolution of ophthalmometry technology – from manual keratometry to keratotopography and keratotomography, separately reflects the principles and formulas for calculating the optical strength of the cornea.
Background. Modern small incision surgery involves the use of injection systems for implanting intraocular lenses (IOLs) into a capsule bag. As with any other stage of cataract phacoemulsification, there are also risks of complications during implantation, consisting in damage to IOLs of varying severity from microcracks of optics to detachment of haptic lens elements. There is no convincing data on the effect of micro-destruction of the optical part of the IOL on the functional results of lens surgery, however, damage to the lens support elements affects the effective position of the IOL, which leads to visual defects (glare, flare) and the inability to achieve calculated refraction. Pinching and/or detachment of the IOL haptics during implantation is a rare situation that every ophthalmic surgeon can encounter. At the same time, there are isolated works on this topic in the literature that do not describe ways to prevent and resolve this complication.
The aim. To demonstrate, using clinical examples, surgical tactics for pinching and tearing of haptics of intraocular lenses during implantation. Material and methods. Clinical cases are presented using the example of patients with pinching and detachment of IOL haptics during implantation.
Results. The presented clinical cases reflect the features of surgery for damage to the supporting elements of the intraocular lens.
Conclusion. Pinching of haptic elements in the injector during implantation surgery can be resolved by simple dissection of the cartridge with a keratome knife. In the case of a haptic detachment, the use of the method of rear “capture” of IOL optics in the presence of a haptic stump of sufficient size (1 mm or more) allows the lens to be securely fixed in the central position.
PEDIATRICS
Juvenile idiopathic arthritis is a chronic inflammatory joint disease in children under 16 years of age associated with pathological immune response to various antigens. Probable factors are infectious and immunogenetic. The process begins with the activation of humoral immunity. One of the key components of juvenile idiopathic arthritis pathogenesis is damage to the vascular endothelium. Immune complex vasculitis develops with hemostasis and microcirculation disorders in synovial membrane. Proinflammatory cytokines are produced, causing the destruction of the synovial membrane of the joint, cartilage, bone, contributing to the chronicity of the inflammatory process. In patients with rheumatic diseases, hemostatic changes occur in 4.5–63 % of cases, especially with high activity of the inflammatory process. In juvenile idiopathic arthritis, hemostasis disorders include thrombinemia, decreased antithrombin III, increased D-dimer level, and decreased fibrinolysis activity. Thrombodynamics test in adults with rheumatoid arthritis has shown the presence of a chronic hypercoagulable state. Rheumatoid arthritis is a risk factor for thrombotic complications in adults. There are no data on the study of thrombodynamic parameters in juvenile idiopathic arthritis. Currently, the pathogenetic commonality between autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and immune-mediated antiphospholipid syndrome is known. The mechanisms of development of antiphospholipid syndrome are associated with an imbalance in the hemostasis system under the influence of autoantibodies to phospholipids of cell membranes, which can interact with endothelial cells, various components of the coagulation system, causing thrombotic complications. The importance of studying immune-mediated antiphospholipid syndrome in juvenile idiopathic arthritis is beyond doubt, but data on this issue in the pediatric population are extremely limited, including the relationship of antiphospholipid syndrome with immune hemostasis parameters. Single studies of immune-mediated antiphospholipid syndrome in children with juvenile idiopathic arthritis indicate that antiphospholipid syndrome markers are found in all variants of juvenile idiopathic arthritis, although thrombotic complications are rare.
Background. The issues of eating disorders among adolescents are currently becoming increasingly relevant. Eating disorders have an impact on a person’s mental and physical health. The aim. To identify the relationship between dietary habits and predisposition to eating disorders among rural schoolchildren.
Materials and methods. The study involved 106 adolescents aged 14–17 living in rural areas of the Irkutsk region. The assessment of individual actual nutrition was assessed using the method of “Analysis of the frequency of food intake”. To assess the risk of eating disorders, an Eating Disorder Inventory was used.
Results. The results of the study showed that eating disorders were detected both in boys and girls. Girls are less likely to consume meat and dairy products. Boys skipped breakfast more often. When analyzing correlations between scores on the Eating Disorder Inventory and the frequency of food consumption, a direct moderate relationship was revealed only in boys on the subscale “Drive for thinness” with rare consumption of chocolate and ice cream. Skipping breakfast for both boys and girls is associated with high scores on the subscales “Drive for thinness” and “Body dissatisfaction”, in addition, skipping dinners for girls is associated with the “Bulimia” subscale.
Conclusion. The prerequisites for the formation of eating disorders have been identified in both boys and girls. Eating disorders among adolescents is a complex problem that requires a comprehensive approach from society, healthcare institutions, educators and parents.
Background. Menstrual irregularities occupy a leading place among gynecological diseases in girls. It is assumed that there is a connection between reproductive system disorders and sleep in adolescent girls, but to date this issue remains poorly understood.
The aim. To study the subjective sleep quality of adolescent girls with irregular and regular menstrual cycles.
Materials and methods. A survey of 461 teenage girls living in the city of Irkutsk and the Irkutsk region was conducted in the period from January 2023 to May 2024. Two groups were formed: group 1 – teenage girls with an irregular menstrual cycle (n = 121), group 2 – teenage girls without menstrual disorders (n = 340).
Results. Adolescent girls with irregular menstrual cycles had sleep disturbances more often and longer, falling asleep later and taking longer, waking up later, poor sleep and daytime sleepiness. The average duration of sleep on weekdays, regardless of the nature of the menstrual cycle, was below the normal values for this age, which indicates a sleep deficit in adolescent girls.
Conclusions. Poor sleep hygiene in adolescent girls, poor quality and short sleep cause disruption of the circadian rhythm that regulates the menstrual cycle. Increasing the duration and improving the quality of sleep are an important component of the formation and maintenance of reproductive health in adolescent girls. Further research is needed to better understand the complex relationships between circadian sleep-wake rhythms and the reproductive system in adolescent girls.
SURGERY
It is quite difficult to determine both the method and timing of healing of a burn wound in children at the initial stages of treatment and during a visual clinical examination. In the treatment of thermal burns in children, preference is given to conservative methods, although they do not always lead to optimal healing of the burn. The use of PRP (platelet-rich plasma) in the treatment of burn wounds can have a beneficial effect on the timing and quality of healing of burned skin. Also, in certain cases, it allows to avoid surgical intervention in order to restore damaged skin or helps to reduce the volume and number of surgical operations when there is a shortage of donor resources. We present three clinical cases of using allogeneic PRP for the treatment of thermal burns of different etiologies (flame, hot liquid, contact). The use of PRP of the allogeneic type is due to the fact that children with burn injuries have limitations and contraindications to the use of autologous PRP. Allogeneic PRP and its use allow to reduce the time of epithelization of burn wounds of IIIAB degree (2–3 degrees according to ICD-10) and in some cases avoid surgical intervention to restore damaged skin. Its main advantages are good tolerability, relative availability, absence of contraindications and ease of use. Presented clinical examples for the first time clearly demonstrate the high effectiveness of allogeneic PRP in the treatment of thermal burns of different etiologies in children.
EXPERIMENTAL RESEARCHES
Background. Among the environmental factors that influence the increase in the frequency of occurrence of psychoemotional states, great importance is attributed to the light conditions. However, the mechanisms of behaviour regulation in the mammals in non-standard light conditions and the role of melatonin in this process have not been fully studied.
The aim of the study. To assess the effects of specific northern light conditions and melatonin on the behavior of Mesocricetus auratus.
Methods. The animals were divided into 4 groups: LD (control), NL (northern light conditions), and LD + mel and NL + mel (melatonin, 100 μg/animal). The study of behavioral reactions, the level of emotional and phobic anxiety state of animals was carried out in the “Open field” and “Dark chamber with holes” installations.
Results. Keeping M. auratus in NL had a negative effect on their behavior – a decrease in motor activity (horizontal and vertical) and the “hole-exploratory behavior”, an increase in the number of freezing and grooming reactions and the time of the first peeking out of the upper hole were revealed. It was shown that melatonin contributed to an increase in exploratory activity and a decrease in the number of anxiety acts in NL + mel group compared to NL group; the opposite effect of the hormone on these parameters was observed in LD + mel group.
Conclusion. The obtained results indicate the important role of photoperiod and melatonin in regulating the behavior of seasonally breeding species.
EPIDEMIOLOGY
Background. Acute upper respiratory tract infections and influenza, while maintaining high epidemiological, social and economic significance, have a major effect on the public health of countries and individual regions.
The aim. To study the impact of influenza vaccination on the manifestations of the epidemic process of influenza and acute upper respiratory tract infections in the Irkutsk region.
Materials and methods. Epidemiological analysis of the incidence of acute upper respiratory tract infections and influenza, analysis of influenza mortality and the impact of vaccination on these infections were performed using continuous samples of statistical data from the Directorate of Rospotrebnadzor in the Irkutsk Region for the period of 2003–2022 (forms 2, 5).
Results. The intensity of the epidemic process of acute upper respiratory tract infections among the general population, children and adults during the observation period was characterized by an uneven course with a tendency towards increase. The dynamics of the incidence of acute upper respiratory tract infections in children and adults demonstrates multidirectional trends over the compared periods. The incidence of influenza in the general population had a steady downward trend, the decrease rate was –8.4 %. At the same time, there are significant changes in the intensity of the epidemic process in the compared periods. The proportion of adults increased in the structure of cases of acute upper respiratory tract infections, and the proportion of children increased in the structure of cases of influenza. Significant changes in the epidemic seasons of influenza are shown. Since the beginning of routine influenza vaccination in the region, the number of vaccinated people has increased annually – from 23.6 to 61.7 % of the population. Against the background of the influenza vaccination campaign, a statistically significant decrease in the incidence of acute upper respiratory tract infections among the general population and children under 14 years of age was registered (p < 0.01).
Conclusion. In the Irkutsk region, the epidemiological disadvantage for the studied infections persists. Increasing the regulated indicators of population coverage with preventive influenza vaccinations (75 % and more) will help reduce the incidence rate.
ISSN 2587-9596 (Online)