Background. Copper ions are necessary for maintaining basic physiological processes in the mammalian organism. However, their excessive absorption or accumulation in cells can lead to the development or exacerbation of various pathological processes. The  cytotoxic and  genotoxic effects of  high concentrations of  copper compounds are  currently well studied in  various cell cultures, whereas the  effect of non-toxic amounts of copper ions on physiological processes in cells, including during their cultivation, has been extremely poorly studied.

The aim of the study. To investigate the effect of copper ions on changes in the intracellular amount of mitochondrial cytochrome C oxidase and glutathione synthetase.

Materials and methods. A primary culture of hepatocytes was obtained, which was exposed to copper acetate at a concentration of 200 µg/ml in terms of copper content for 24 hours. After fixation, the samples were stained immunocytochemically using antibodies to  cytochrome  C oxidase (CcO) subunit  I and  glutathione synthetase (GS).

Results. In  hepatocyte culture, a  significant increase in  the  intensity of  fluorescent staining of the two analyzed enzymes was demonstrated both after 6 hours and  after  24  hours of  exposure to  copper ions, which indicates a  change in  their number in  cells. At  the  same time, the  increase in  the  amount of  CcO was more intense in the first 6 hours of incubation with a microelement, whereas in the next 18 hours, changes in the intracellular content of CcO were less pronounced. The increase in the intensity of the GS fluorescent stain was more active and was observed throughout the entire cultivation period.

Conclusion. From the  results obtained, it  can  be concluded that copper ions in  non-toxic concentrations are  able to  influence key indicators of  cell viability in culture by changing the amount of one of the main energy metabolism enzymes and the enzyme that provides synthesis of the most important low-molecular antioxidant glutathione.

Epigenetics plays a critical role relative to other branches of genetics, as it makes it possible to regulate gene expression without changing the nucleotide sequence of DNA molecules. This process allows cells to respond to external signals and adapt to  changes in  the  environment while keeping their genetic information intact. The  main mechanisms of  epigenetic regulation include DNA methylation, posttranslational modifications of  histones, chromatin remodeling and  regulation through non-coding RNAs. These processes play a key role in fundamental biological processes such as cellular differentiation, organismal development, and adaptation to environmental conditions.

Disturbances in epigenetic mechanisms can lead to various pathologies, including cancer, neurological and  autoimmune diseases. Understanding the  mechanisms of  epigenetic regulation opens new avenues for  the  development of  targeted therapies that can correct abnormal epigenetic profiles without changing the DNA structure itself.

In  recent years, the  development and  application of  innovative technologies, such  as  the  CRISPR/Cas9 genome editing system, have significantly expanded the ability to study epigenetic mechanisms and their relationship with diseases. These technologies allow not only a deeper understanding of epigenetic changes, but also the development of new therapeutic approaches, especially in the field of oncology. Research in  epigenetics is  also focusing on  the  interaction between epigenetic changes and the immune system, which opens new perspectives for the development of immunotherapies. The search for new markers of epigenetic disorders and therapeutic agents may lead to the development of individualized treatments that take into account the unique epigenetic profile of each patient.

The role of epigenetic modifications in the development of diseases and the creation of new therapeutic strategies cannot be overestimated. Recent research in this area is revealing the potential of epigenetic approaches to treat a wide range of diseases, ushering in a new era in medicine where understanding and correcting epigenetic changes will be the key to effective treatment.

Background. The pandemic of COVID-19 raised safety concerns for healthcare workers while non-medical personnel were left unattended. Comparing the levels of seroprevalence to SARS-CoV-2 and vaccination in different employee groups will allows us to assess the risk of infection and develop a strategy to minimize the spread of infections in medical institutions in future.

The aim. To identify the level of seroprevalence to SARS-CoV-2 for seven groups of medical center workers. Methods. The seroprevalence to SARS-CoV-2 was analyzed in 361 employees of the ophthalmology center in mid-2021. Data on the level of specific IgM and IgG antibodies were compared with questionnaire, including occupation data.

Results. Depending on occupation, workers were divided into seven groups. The average seroprevalence rate for all employees was 82.3 %, and the percentage of vaccinated employees was 27.4 %. The lowest level of seroprevalence was found in the group of maintenance staff (55.0 %) which is significantly lower (p ˂ 0.05) than in the groups of doctors (84.4 %), nurses (85.6 %), administrative stuff (82.6 %) and cafeteria stuff (77.7 %). The seroprevalence rate for cleaning staff was 84.6 % and for pharmacy workers it was 80 %. The highest vaccination coverage was among doctors – 50.0 %, the lowest was among cafeteria and kitchen staff – 7.4 %.

Discussion. We believe the high seroprevalence is associated with asymptomatic spread of SARS-CoV-2.

Conclusions. High seroprevalence was among doctors and nurses, pharmacy workers, canteen workers, cleaners, as well as administration workers. Anti-epidemic measures for these groups will reduce the spread of  infectious diseases and help retain staff during the seasonal increase in incidence.

Background. Research results on the immune response and cytokine profile in children with the new coronavirus infection SARS-CoV-2 are contradictory and insufficient, which necessitates the need to understand the nature of the course of the disease depending on age and severity of the infection. The importance of assessing risks and predicting the consequences of a new coronavirus infection in childhood makes the study of serum concentrations of pro-inflammatory and anti-inflammatory cytokines relevant.

The aim. To study the level of pro-inflammatory and anti-inflammatory cytokines in newborns during the acute period of a new coronavirus infection to determine the characteristics of the immune response and identify prognostic criteria for the course of the infectious process.

Materials and methods. The article presents the results of a study of the level of pro-inflammatory, anti-inflammatory cytokines and C-reactive protein (CRP) in newborns (n  =  44) hospitalized with a confirmed new coronavirus infection of varying severity. The study was conducted during the acute period of COVID-19.

Results. Cytokine concentrations in the blood serum of newborns were determined by enzyme immunoassay. In newborns in the acute period of a new coronavirus infection, regardless of the severity, there is a decrease in serum concentrations of interleukin-1β, interleukin-4, interleukin-6, interleukin-8, tumor necrosis factor α, interferon (INF)  γ and  CRP compared with the control group. The level of INF-α in the blood serum of newborns of both the main and control groups did not have significant differences.

Conclusions. The cytokine profile in newborns with the new coronavirus infection SARS-CoV-2 may be due to inhibition of the innate immune system, which requires further research in this direction and increased pediatric attention to this category of children.

Background. The antiviral drug Remdesivir has been widely used for etiotropic treatment of COVID-19. The incidence of adverse reactions during Remdesivir therapy reaches 66.2 %, the most common one being an increase in hepatic transaminases.

The aim. To develop a machine learning model for predicting the risk of drug-induced liver damage in patients with COVID-19 when prescribing Remdesivir therapy.

Materials and methods. This prospective open-label observational study was conducted between November 2021 and February 2022, including 154 patients receiving Remdesivir therapy. Patients were divided into two groups: group 1 (n = 45), in  which patients developed signs of liver damage during Remdesivir therapy; group 2 (n = 109) – patients without this adverse reaction. All patients underwent pharmacogenetic study and retrospective analysis of medical histories, database with  the results of the conducted studies was formed, basing on which machine learning models for predicting the risk of drug-induced liver damage were trained.

Results. The main prognostic factors included body mass index (relevance – 12.03 %) and carriage of AG genotype at polymorphic marker rs776746 of CYP3A5 gene (relevance – 10.04 %). Subsequently, for all obtained factors and based on Сategorical boosting a model for predicting the development of drug-induced liver damage with 57.8 % sensitivity and specificity of 80.7 % was developed.

Conclusions. A risk model for the development of drug-induced liver damage during remdesivir therapy was built using machine learning. Body mass index and carriage of AG genotype at polymorphic marker rs776746 of CYP3A5 gene turned out to be key markers. To improve the accuracy of the model, an increase in the proportion of patients with adverse reactions in the training sample is required. Further studies will improve the quality of the model and integrate it into clinical practice.

Treatment of Klebsiella pneumoniae infections is becoming increasingly challenging due to their multiple resistance to current antimicrobials. The ability to form biofilms is a critical virulence feature of K. pneumoniae. Biofilms are complex bacterial communities consisting of  one or  more species embedded in  an  extracellular matrix of  proteins, carbohydrates, and  DNA. Inhibition and  killing of  biofilm-producing strains with  antibiotics often requires higher concentrations than those required to suppress planktonic bacteria. Dosage increases can vary significantly depending on many of their virulence factors. Therefore, alternative treatments have been sought recently. In this review, the literature was analyzed to gain insight into the major virulence factors with an emphasis on the role of biofilms in enhancing antimicrobial resistance, highlighting the importance of this mechanism for bacterial adaptation. The literature search was conducted using the electronic information resources PubMed, Google Scholar and eLibrary. The search depth was limited from 2000 to the present, the  share of  literature for  the  last 5  years was  63  %. The  keywords used in the search were: Klebsiella pneumoniae, biofilm, virulence factors, infection treatment, combination therapy. The concepts of the difference between the pathotypes of K. pneumoniae, hypervirulent and classical, and their relationship with biofilm formation are revealed. The composition and regulation of biofilm are characterized, some factors influencing the  structure of  biofilm are  briefly described. Some new combination strategies for the treatment of infections caused by biofilm-forming K.  pneumoniae are also presented. Understanding the  effect of  antimicrobials on biofilms is of paramount importance for clinical practice due to the increased level of resistance and the spread of resistance among infectious agents.

The unfavorable epidemiological situation with tick-borne vector-borne infections may be characterized not only by an increase in the occurrence of already known diseases, but also by the identification of new infections and pathogens, the role of which remains poorly understood. An example of such pathogens is Yanggou tick virus (YGTV), which belongs to the group of segmented flavi-like viruses.

The  aim. To  detect and  molecular genetic characterization of  YGTV found in Dermacentor nuttalli Ol. (1929) ticks on the territory of the Republic of Buryatia.

Materials and methods. The study analyzed 350 individual samples of adult ticks of D. nuttalli species collected in the spring-summer period of 2023 on the territory of five districts of the Republic of Buryatia. The detection of YGTV RNA was performed by PCR followed by nucleotide sequence determination and phylogenetic analysis for each of the 4 genome segments.

Results. In one sample of  the  tick D.  nuttalli, collected in  the  Ivolginsky district of the Republic of Buryatia, YGTV RNA was detected, which was further confirmed by sequencing of the obtained genome fragment. The incidence of YGTV RNA among the studied D. nuttalli ticks in Buryatia was 0.3 % (95 % CI: 0.1–1.6). Primers were designed to obtain fragments of all four segments of the YGTV genome. The identified genetic variant of YGTV, when analyzed phylogenetically across all four segments, clearly clusters with YGTV sequences found earlier in China and Russia (the Republic of  Altai and  Tyva). The  detected variant shows the  highest sequence identity with the prototype strain Erzin14-T20074.

Conclusion. The study shows for the first time the presence of YGTV in the territory of the Republic of Buryatia, which actualizes the need to monitor the circulation of this virus in natural foci of tick-borne infections in this territory, as well as to further clarify the boundaries of the spread of flavi-like viruses potentially dangerous for humans.

A literature search was made to study works devoted to the results of gonadotropinreleasing hormone agonists (GnRHa) using in  men in  clinical settings and  male animals in experiments. Almost all researchers claim that GnRHa suppress testicular function. But there is no clear opinion regarding the mechanisms of this effect: some scientists believe that a direct effect of drugs on testicular cells is possible, others believe that such an effect is indirect through other hormones, including pituitary ones. Most published articles provide evidence of a decrease in mass with atrophy of prostate and seminal vesicle tissue after the use of GnRHa. The effect is similar to surgical castration, but appears somewhat later and sometimes less pronounced, since testosterone synthesis is not completely suppressed. In the complex therapeutic treatment of prostate cancer, drugs of this group provide comparable effectiveness to orchiectomy or high doses of estrogens, while a lower frequency of side effects has  been recorded. GnRH has an  antiproliferative effect on  the  cells of  prostate carcinomas, but at  the  same time there is  an  opinion that GnRHa do  not inhibit the  proliferation of  prostate cancer cells, and that direct suppression of  mitotic activity is unlikely to be the main mechanism of the antitumor effect of such drugs. When studying the data on the protective effect of GnRH drugs on the cells and tissues of the genital organs during chemotherapy and radiation, attention is drawn to the obvious inconsistency of publications: from a good effect with a rapid restoration of functional activity, to weak or even completely absent positive dynamics. In any case, the inconsistency of publications on each aspect of the effects of GnRH indicates that they have been poorly studied, and the advisability of further continuing not  only applied research, but also fundamental research, due to  its possible high prospects.

Research points to the importance of circadian rhythms for health; their disruptions are associated with various diseases. This has led to the development of circadian medicine, which focuses on using knowledge of physiological rhythms to optimize treatment and  diagnostic methods. Our article highlights the  role of  actigraphy, a non-invasive method for assessing sleep-wake cycles, in the study and diagnosis of  sleep. Actigraphs, wearable devices shaped like watches, use motion sensors to monitor activity, providing important data on sleep quality. Particular attention is given to the methodology for obtaining actigraphy data and the analysis of sleep parameters, which includes the  assessment of  total sleep time, sleep efficiency, and frequency of awakenings. The importance of accurate methodology and validated algorithms for  actigraphy data analysis is  emphasized through a  review of various sleep assessment algorithms and their application in clinical and research settings. Additionally, the paper explores the potential use of artificial intelligence, including machine and deep learning, to improve sleep data analysis. The conclusion emphasizes that despite the reliability of actigraphy for determining sleep phases, additional studies are needed to validate it in clinical use. This highlights the potential of actigraphy as an important tool in circadian medicine and sleep studies, which requires its further development and integration with new technological advances.

Background. Acute kidney injury is one of the most serious complications of thermal skin burns; in most cases it remains undiagnosed in the first day after injury. Therefore, it is necessary to search for new biomarkers that can indicate the onset of renal damage. Lidocaine and matrix metalloproteinases are of the greatest interest. Currently, there is insufficient information about the participation of these proteins in the development of acute kidney injury in the pathogenesis of burn disease.

The  aim. To  evaluate the  dynamics of  changes in  the  levels of  lipocalin, matrix metalloproteinases 2 and 9 in blood serum in patients with thermal skin burns.

Materials and methods. The study included 74 patients with thermal skin burns of  I–III  degree with  a  skin lesion area of  more than 25  %, of  which at  least 15  % are  deep burns. Serum creatinine levels were determined using the  kinetic Jaffe method. The concentration of lidocaine and matrix metalloproteinases was studied by multiplex analysis on a flow cytofluorimeter.

Results. It was  found that the  level of  lipocalin in  the  blood serum of  patients with thermal skin burns increased 5.5 times in relation to the control group during the shock period. During the period of burn toxemia and septicotoxemia, this indicator remained at a high level and exceeded the control values. The concentration of  matrix metalloproteinase  2 in  blood serum during burn shock was  4.3  times higher, with burn toxemia – 3.5 times and during septicotoxemia – 2.9 times in relation to the control group. Similar dynamics was observed in the study of the level of matrix metalloproteinase 9.

Conclusion. Lipocalin and matrix metalloproteinases 2 and 9 can be considered as early biomarkers of acute kidney injury in patients with thermal burns.

The pathogenesis of sepsis as a pathological process, which is based on the body’s reaction in the form of generalized (systemic) inflammation to an infection of various nature, leading to acute multi-organ dysfunction, includes changes in the immune response, imbalance of  pro-inflammatory and  anti-inflammatory mechanisms, hemostasis disorders, hemodynamic disorders, microcirculation, activation of the hypothalamic-pituitary-adrenal system, and disorders of delivery, consumption, and utilization of oxygen. The predominance of the pro-inflammatory component over the anti-inflammatory one and damage to the primary barrier structures in the area of inflammation predetermines the breakthrough of inflammatory mediators into the  systemic circulation. The  dominance of  the  destructive effects of  cytokines leads to a disorder of microcirculatory hemodynamics outside the primary focus, to the launch of disseminated vascular coagulation syndrome and organ failure. Sepsis is characterized by a hypercoagulable-hypofibrinolytic phenotype of changes in hemostasis, immunothrombosis as a result of endothelial dysfunction, platelet activation, autocoid-induced coagulation, activation of the external and internal coagulation pathways, and a decrease in the activity of the anticoagulation and fibrinolytic systems. Tumor necrosis factor α, interleukin (IL) 1β, IL-2, interferon γ, IL-10, HLA-DR (human leukocyte antigen – DR isotype), C3, C4, C5, C1 complement inhibitors, C3a, C5a, IgA, IgM, IgG, CD3⁺CD4⁺, CD3⁺CD8⁺, CD3⁺CD56⁺, CD3⁺CD19⁺ can be considered as biomarkers of changes in the immune response in sepsis. In order to detect hemostasis disorders in sepsis, promising biomarkers may be: total platelet count, von Willebrand factor, factor VIII, protein C, thrombomodulin, tissue factor pathway inhibitor, tissue-type plasminogen activator, plasminogen activator inhibitor 1, thrombin activatable fibrinolysis inhibitor. Further study of the immunological and coagulation links of the pathogenesis of sepsis will make it possible to determine the key diagnostic and prognostic biomarkers of sepsis. We  analyzed 125 literature sources on  the eLibrary, Medline, PubMed, RSCI sites, of which 64 sources met our criteria for use in a systematic review.

Background. Even small amounts of alcohol have an extremely negative effect on the fetus, especially in the early stages of gestation. It is known that ethanol promotes the formation of free radicals, but there is no data on the nature of the oxidative stress development in pregnant women depending on its blood level.

The aim. To assess the level lipid peroxidation products and superoxide dismutase activity in the first trimester of pregnancy for women, who consumed alcoholic bevera ges, depending on the phosphatidylethanol (PEth) level in the blood.

Materials and methods. The study included 165 women in the first trimester of pregnancy aged 18 to 40 years. To identify the fact and amount of alcohol consumption, the direct biomarker of alcohol 16:0/18:1PEth in blood plasma was performed using high-performance liquid chromatography with tandem mass spectrometry. Depending on the concentration of PEth, groups of women consuming different doses of alcohol were identified: group 1 – PEth concentration < 8 ng/ml (non-drinkers; n = 63); group 2 – PEth concentration from 8 to 45 ng/ml (drinkers of less than 1 dose; n = 66); group 3 – PEth concentration ≥ 45 ng/ml (drinkers of more than 1 dose; n = 36). The content of lipid peroxidation products and superoxide dismutase activity was determined by spectrophotometric methods.

Results. It was found that lipid peroxidation intermediates level in the groups of women who consume alcohol, regardless of PEth 16:0/18:1 level in blood plasma, was significantly higher compared with the control (p < 0.05). The superoxide dismutase activity was higher in the group of pregnant women who consumed less than 1 dose of alcohol compared with the control (p < 0.05) and the group who consumed one or more doses of alcohol (p < 0.05).

Conclusion. The obtained results indicate the activation of lipid peroxidation processes in the first trimester of pregnancy regardless of the dose of alcohol-containing products consumed.

Back and lower limb pain interferes with patients’ daily lives and ultimately reduces their quality of life. Many interventional treatments have been proposed to reduce and prevent the development of chronic pain syndrome.

The aim of the study. To evaluate the effectiveness of the simultaneous use of laser nucleoplasty and radiofrequency neuromodulation of radicular nerves and ganglia in the treatment of discogenic lumbar radiculopathy.

Materials and methods. The  study included 20  patients; the  mean age was 39 ± 9.1 years. All patients underwent laser nucleoplasty of the LIV/LV intervertebral disc and radiofrequency neuromodulation of the radicular nerve in the foraminal space of  the  level of  interest and  localization of  pain. An  assessment of  changes in pain intensity and quality of life was carried out according to scales in the preand postoperative period and a control magnetic resonance imaging (MRI) study at the time of discharge, 3 months of observation, with an assessment of the volumetric indicators of the intervertebral disc.

Results. Patients showed a decrease in pain intensity according to the Visual Analogue Scale and an improvement in quality of life assessed by the ODI (Oswestry Disability Index) and SF-36 (Short Form 36) questionnaires. According to MRI studies, volumetric indicators increased after surgery and subsequently decreased by the 3rd month of observation.

Conclusion. The study demonstrates the possibility of using several interventional treatment methods simultaneously with an impact on various morphological substrates that cause the  formation of  pain syndrome. It  is  shown that a  decrease in the intensity of pain syndrome correlates with an increase in the volumetric indicators of the intervertebral disc according to MRI data immediately after surgery, with a subsequent decrease by 3 months of observation. Simultaneous use of laser nucleoplasty and  radiofrequency neuromodulation is  justified in  the  treatment of radiculopathy, allowing reducing the intensity of pain syndrome and increasing the volumetric indicators of the intervertebral disc, which is a sign that increases the shock-absorbing properties of the intervertebral disc.

A patient with diabetes mellitus (DM) complicated by nephropathy and retinopathy has changes in hemostasis, which poses a serious problem during retinal surgery and anesthesia using regional blockades.

The aim. To determine the risk factors of undesirable hemorrhagic phenomena occurrence in DM patients being on programmed hemodialysis during regional anesthesia at the time of retinal pathology surgery.

Materials and methods. A retrospective analysis of medical histories (for 2021– 2023) was performed. Age, gender, DM type, ASA score, duration of renal replacement therapy, time after last and before next hemodialysis, insulin therapy duration, diabetic retinopathy proliferative stage, general blood test, creatinine, blood sugar, APTT, undesirable hemorrhagic phenomena during retrobulbar anesthesia were recorded. Spearman correlation analysis was used to assess the relationship between the studied signs and hemorrhagic complications.

Results. General blood test parameters evaluation revealed an average platelet count of 320 ± 47.5 × 10⁹. Creatinine levels exceeded the norm by 5–7 times, which is typical for terminal chronic kidney failure (tCKF). APTT results before surgery did not go beyond reference values. The most significant correlations with an average positive relationship were established between the presence of hemorrhagic complications and the duration of the proliferative form of diabetic retinopathy (r = 0.67; p < 0.05), blood platelets number (r = 0.3; p < 0.05), creatinine level (r = 0.64; p < 0.05).

Conclusion. During retinal pathology surgery, the duration of diabetic retinopathy proliferative form, uremic syndrome severity and thrombocytosis degree may be factors of undesirable hemorrhagic phenomena occurrence in patients with tCKF on programmed hemodialysis during regional anesthesia.

Early diagnosis of  ophthalmic manifestations of  multiple sclerosis (MS) is  quite complicated.

The aim. To assess the degree of impairment of the pathways of the visual analyzer in patients with MS, taking into account the data of structural optical coherence tomography and magnetic resonance imaging.

Material and methods. Four groups of  patients were analyzed: three groups of MS patients with various changes in visual functions and a group of somatically healthy patients. Structural changes of  the  optic nerve were assessed according to OCT and magnetic resonance studies.

Results. A decrease in the thickness of the nerve fiber layer was found in groups 2 and 3 in the lower temporal sector – to 29–44 μm, in the upper temporal sector – to 30–33 μm, in the lower nasal sectors – to 11–18 μm. The data of groups 1 and 4 were comparable (p = 0.22). MR tractography in  groups  2 and  3 determined the  MRI picture of  rarefaction and signs of interruption of the pathways, respectively. MR spectroscopy at the level of the visual cortex revealed: a decrease in NAA/Cho in groups 2 and 3 by 13–23 % (the  data of  groups  1 and  4 were comparable); a  decrease in  NAA/Cr by  17  % in group 1, and by 23 % in groups 2 and 3, a decrease in Cho/Cr by 21 % in group 1, by 13.4 % – in group 2 and by 8 % – in group 3. At  the  level of  visual radiance, a  decrease was observed: NAA/Cho by  31.5  %  – in  group  1, by  39.5  % – in  group  2 and  by  50  % – in  group  3; NAA/Cr by  21  % – in group 1, by 32–35 % – in groups 2 and 3, and an excess of Cho/Cr by an average of 22 % in all groups.

Conclusion. The  data obtained indicate degenerative changes in  the  pathways of the visual analyzer not only in MS patients with partial optic nerve atrophy, but also in patients with no complaints and clinically pronounced visual impairment.

Background. Learning difficulties among schoolchildren are an important issue in  both education and  health care. As  a  rule, the  understanding of  this problem is  ambiguous among different specialists (physicians, teachers, psychologists). Despite the fact that the medical view of these disorders is reflected in the International Classification of Diseases, 10th revision, in the section “Specific developmental disorders of  scholastic skills” (F81), it  often remains outside the  field of  attention of the pediatric service.

The aim. To consider the pediatric component of learning difficulties in schoolchildren and to propose methodological approaches to its possible solution by the efforts of a pediatrician.

Materials and  methods. A total of  360 literature sources published from 2006 to 2024, indexed in the RSCI, PubMed, Scopus, were analyzed. For the article, 30 literary sources were used.

Results and discussion. The  review presents modern ideas about learning difficulties in schoolchildren and the medical and biological causes of their formation. It is shown that the main causes of learning difficulties are hereditary polymorphisms of  various genes responsible for  the  development and  functioning of  the  body, which exhibit their altered function against the background of social and biological risk factors. The role of different specialists in the treatment and correction of these disorders is reflected. It is shown that currently known treatment methods are symptomatic and ineffective.

Conclusion. For the effective treatment, it is necessary to find out the cause of the formation of disorders associated with learning difficulties in schoolchildren. An important role in their diagnosis should be played by a pediatrician who has the opportunity to observe the growth and development of the child from the moment of his birth.

The prevalence of rotator cuff ruptures among injuries of the musculoskeletal system according to the literature is 20 %. Massive injuries to the rotator cuff of the shoulder are tears with  retraction of  more than 5  cm or  damage to  two or  more tendons. With massive injuries, the head of the humerus is decentrated, the biomechanics of the joint is impaired and, as a result, the progression of osteoarthritis occurs.

The aim. To analyze the literature data of foreign and domestic authors and to provide an overview of modern views on the surgical treatment of massive ruptures of the rotator cuff tendons.

Materials and methods. A search and analysis of the literature of foreign and domestic authors was  carried out using the  Internet resources PubMed, eLibrary in the period from 2010 to 2024.

Results and discussion. To date, in treatment of massive ruptures, much attention is paid to the reconstruction of the upper capsule of the shoulder joint. The biomechanical principle underlying the  reconstruction of  the  superior capsule involves the use of a graft to close a tendon defect. Today, the most commonly used grafts are allografts, autografts, xenografts, and synthetic materials. This review presents surgical techniques and results of surgical treatment using the broad fascia of the thigh, dermal allografts, peroneus longus tendon, biceps brachii longus tendon, and Achilles tendon, but there is no consensus on the choice of grafts and methods of their fixation.

Conclusion. An  analysis of  literature sources does not  provide a  clear answer to the question of choosing the most effective method of treating this pathology. The number of modern publications shows that the problem of improving the treatment of such patients is currently relevant and requires in-depth research.

Introduction. Aging is a complex process related with the gradual diminution in cellular and physiological functions. The geroprotective effect of 10 biologically active substances (BASs) – rutin, squalene, kaempferol, biochanin A, ursolic acid, chlorogenic acid, baicalin, mangiferin, quercetin and trans-cinnamic acid and 5 crude extracts (Ginkgo biloba L., Pulmonaria officinalis L., Scutellaria baicalensis Georgi, Hedysarum neglectum Ledeb. and Panax ginseng C.A. Mey) isolated from medicinal plants of Altai Region of Russia were evaluated for their influence on the accumulation of intestinal autofluorescence material (IAM) using Caenorhabditis elegans model.

The aim of  the  study. IAM facilitates age-related decline and is a non-intrusive biomarker of senescence. This study assessed the impact of different bioactive substances in reducing the build-up of IAM using C. elegans model.

Materials and methods. Gravid nematodes were synchronized, and then seeded in 96-well plates to develop to L4-stage. Each BAS in 200 µM, 100 µM, 50 µM and 10 µM concentrations and extracts with a tenth, hundredth and thousandth times-dilution were administered to each well in 6 replicates for each treatment group. On incubation days 1, 5, and 15, adult L4 nematodes underwent spectrofluorometric analysis to determine the effect of the BASs and extracts on IAM accumulation.

Results. It was found that quercetin, kaempferol, baicalin, mangiferin, G. biloba and P. officinalis extracts exhibited the most profound inhibition of IAM accumulation compared to the control. It was noteworthy that the 10  µM concentration of  mangiferin significantly inhibited IAM accumulation in a manner comparable to the 200 µM of baicalin and 100 µM of quercetin. In addition, the crude extracts of G. biloba and P. officinalis respectively exhibited 2.8- and 1.8-fold decrease in IAM accumulation.

Discussion. The accretion of IAM is inversely proportional to longevity. Thus, the BASs identified in this study to modulate IAM accumulation could serve as important precursors or active ingredients for the pharmacosynthesis of geroprotective drugs in future research.

The aim. The synthesis of nanoparticles through green methods is a biologically safe, cost-effective and environmentally friendly approach. This study focuses on the green synthesis of copper nanoparticles using aqueous stem extract of Tinospora cordifolia. Additionally, this research explores the formulation of an acetyl amine-modified xanthan gum-based gel incorporating curcumin and a solution of Cu⁺⁺ nanoparticles, and investigates its wound healing activity.

Materials and methods. The shade-dried stem of Tinospora cordifolia was extracted with distilled water, which serves as a bio-reducing agent for the synthesis of Cu⁺⁺ nanoparticles. Copper sulphate was added to the extract at room temperature using a magnetic stirrer. The visual color change during the addition indicates the formation of nanoparticles, which was further confirmed by UV spectroscopy and particle size analysis. The  modified xanthan gum-based gel formulation was  prepared using curcumin and a solution of Cu⁺⁺ nanoparticles, and its wound healing activity was evaluated using the excision method, along with antimicrobial activity assessed by the cup and plate method.

Results and discussion. UV absorption was observed at 261 nm, and the particle size was measured at 188 nm, confirming the formation of nanoparticles. The gel containing curcumin and  Cu⁺⁺ nanoparticles was prepared using modified xanthan gum. The nanocomposite exhibited significant antimicrobial activity against gram-positive bacteria compared to gram-negative bacteria. The group treated with the modified xanthan gum-based curcumin and nano copper composite demonstrated significant wound closure by day 16±2.

Conclusion. The  synthesis of  Cu⁺⁺ nanoparticles using Tinospora cordifolia and the formulation of a gel with modified xanthan gum and curcumin as a drug were successfully achieved. The  gel formulation demonstrated significant antibacterial and wound healing activities, attributed to synergistic effect of Tinospora cordifolia, curcumin, and Cu⁺⁺ nanoparticles.

Background. Тhe problem of treating widespread purulent peritonitis and abdomi nal sepsis remains one of the most urgent in surgery. The use of vacuum-assisted laparostomy creates prerequisites for improving the treatment results of this group of patients. Conducting research in this direction is relevant and justified. 

The aim. To conduct an initial comparative analysis of the effectiveness of vacuum laparostomy and planned relaparotomy in widespread purulent peritonitis and ab dominal sepsis. 

Materials and methods. The study consisted of retrospective (17 patients with planned relaparotomy) and prospective (7 patients with vacuum-assisted laparostomy) parts, in which two options for stage-by-stage treatment of patients with widespread purulent peritonitis complicating the course of urgent abdominal pathology and abdominal trauma were compared. 

Results. When using vacuum laparostomy in comparison with planned relapa rotomy, the duration of treatment increases both in the intensive care unit (14.0 days [12.0; 15.0] vs. 4.0 days [2.0; 4.0]; p < 0.01) and in the hospital (36.0 days [20.5; 39.5] vs. 11.0 days [7.0; 17.0]; p < 0.01), more relaparotomies are required (p < 0.01),  while the mortality rate decreases, albeit statistically insignificantly (14.3 % vs. 35.3 %; p = 0.625). 

Conclusion. Conducting systematic reviews and meta-analyses based on ran domized clinical trials will provide data of a higher level of evidence and grade of recommendations.

Legg – Calve – Perthes disease (LCPD) is the most common femoral head osteonecrosis in children. Until now, the knowledge of etiology, pathogenesis and clinical signs is partial and does not provide a coherent view of the disease. Despite modern advances in understanding and diagnosing of the disease, surgical interventions and stress release remain the standard treatment methods. Now there is a need to develop both new strategies for studying the pathogenesis of the disease and choosing methods of its treatment.

The aim. Reproduction and development of morphological criteria for the early stage of Legg – Calve – Perthes disease (stages 1–2 by the modified Waldenström classification system).

Materials and methods. The research involved 6 young gray giant rabbits (Flandres) aged 3–4 months. The early stages of LCPD were simulated by the pathophysiological model of Kuzhelivsky I.I. et al. (2016) with paraarticular adrenaline injections along with physical activity. We  modified the  physical activity regime for the  subjects by daily free range for 1.5–3 hours.

Results. The  experiment confirmed the  validity of  the  modified simulation and designed its morphological criteria. The osteochondropathy process was verified histologically, we also revealed the  classic signs of  damage to  subchondral bone and hyaline cartilage as well as abnormal vascularization of cartilage sites and pathological neoangiogenesis.

Conclusion. The  technique of  non-traumatic osteonecrosis simulation in  young rabbits featured initial results in reproducing the pathological links of osteonecrosis process. The cartilage tissue featured the loss of isogeneity in chondrocytes structure and their column-like arrangement; its delamination and replacement with fibrous tissue, including fibroblast-like cells and collagen fibers; cartilage neovascularization and persistent mixed hyperemia. In the bone marrow, only the activation of the red blood cell line was noted. The  bone tissue featured the  abnormality of  osteon structure with a mosaic arrangement of trabeculae as well as lacunar resorption, and osteoblast degeneration.

Background. Oxidative stress plays an important role in the development of peritonitis, which leads to a decrease in antioxidant level and an increase in oxidant production. Studying ATPase activity and lipid peroxidation when using new methods of treating experimental peritonitis is of interest for clinical practice.

The aim. To study the dynamics of ATPase activity and lipid peroxidation indicators in liver tissue in experimental peritonitis when using Serogard.

Methods. The study was conducted on male Wistar rats aged 6 months. All animals were subjected to experimental peritonitis using the method we developed. Animals in the control group (n = 20) were intraperitoneally injected with 3 ml of physiological solution one day after modeling peritonitis; animals in the experimental group (n = 19) were injected Serogard® (AO Pharmasintez, Russia). We determined the initial values of the indicators in healthy rats (n = 7). In animal liver tissue, total and mitochondrial ATPase activity was  studied, as  well  as the  content of  malondialdehyde (MDA) and diene conjugates (DC).

Results. It was found that the total and mitochondrial activity of ATPases was suppressed by the day 3 of experimental peritonitis. During 14 days of the experiment, ATPase activity did not reach normal levels in any of the groups. However, animals in  the  experimental group had dynamics of  a  more steady, significant increase in the total ATPase and the mitochondrial ATPase (ATP synthase) activity with a significantly higher level than in the control group. MDA and DC in the experimental group increased by days 7–14, which indicated the activity of free radical processes and was also an indicator of the dynamics of restoration of metabolic and energy processes.

Conclusion. Using Serogard in experimental peritonitis contributed to a more effective restoration of total ATPase activity and mitochondrial ATPase (ATP synthase) and on days 7–14 of the study led to an increase in the level of free radical processes activity that accompany and indicate the process of aerobic energy restoration.

Surgical treatment of  spinal diseases is  often complicated by  epidural fibrosis, which is one of the main causes of failed back surgery syndrome.

The aim. To evaluate the laminectomy zone and transformation of epidural fibrosis using original gels in an experiment.

Materials and methods. Laminectomy was performed on  male Wistar rats. The animals were divided into four groups. The original gels were tested. The group of intact (unoperated) rats served as a comparison group for the control and groups with the tested gels, carrying and not carrying the p38 MAP kinase blocker. On day 28, the deformation of the dural sac was assessed by measuring the transverse and longitudinal sections of the spinal canal, also the adhesion of the spinal roots to the inner layer of the dura mater in epidural fibrosis and its coverage with connective tissue along the perimeter of the laminectomy window were determined.

Results. In the control group, the pronounced deformation ofthe dural sac was observed. The use of all the studied gels reduced the deformation, bringing the shape ofthe dural sac closer to the norm. However, the gel with the p38 MAP kinase blocker significantly reduced the adhesion of the spinal roots to the dura mater.

Conclusion. For the first time, a pharmaceutical composition containing a p38 MAP kinase blocker was used andstudied ona laminectomy model forthe prevention of epidural fibrosis, and the relationships between the transformation and change in the shape of the dural sac with an assessment of the involvement of the dura mater in the formation of epidural fibrosis were presented. The results obtained show that a gel with a p38 MAP kinase blocker is more effective for the prevention of epidural fibrosis than a gel without a blocker.

Background. Piroplasmosis (babesiosis and theileriosis) is a group of natural focal infectious diseases of  humans and  animals caused by  intraerythrocytic parasites transmitted predominantly by ixodid ticks. In the Baikal region, despite the widespread foci of babesiosis and theileriosis, the data about these pathogen vectors is fragmentary.

The aim. To identify human and animal babesiosis vectors, study various Babesia spp. tropism to ixodid ticks common in the Baikal region.

Materials and methods. A total of 3,239 specimens of I. persulcatus, 1,795 specimens of D. nuttalli and 729 specimens of H. сoncinna ticks collected in natural habitats of the Baikal region from 19 districts of the Irkutsk region and six districts of the Republic of Buryatia, as well as 5 specimens of D. nuttalli ticks removed from horses were examined for the presence of Babesia spp./Theileria spp. DNA. For detection and typing of Babesia and Theileria, a nested PCR with genus- and species-specific primers corresponding to  18S  rRNA gene region was used. Selective sequencing of samples was performed to study the genetic diversity of the identified pathogens.

Results. Babesia spp. DNA was detected in three species of ixodid ticks in Irkutsk region and in one species in the Republic of Buryatia. In I. persulcatus ticks B. microti US-type, B. venatorum, B. crassa-like and a unique Babesia sp. Irk-Ip655 were found. DNAs of B. crassa-like, B. motasi-like and Babesia spp. were detected in H. concinna ticks. DNAs of Babesia spp. And T. equi were found in D. nuttalli ticks.

Conclusion. Vectors of  both human and  animal babesiosis pathogens were  detected in the Baikal region. Tropism of B. microti US-type and B. venatorum in relation to I. persulcatus ticks was established. The establishment of specific relations between other species of Babesia and Theileria and vector ticks in the Baikal region will be continued.