Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.

Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patients

Methods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.

Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.

Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.

Background. Gender has now been proven to have a significant impact on the development, course and outcome of a large number of diseases, including alcoholic liver disease. Alcohol consumption is one of the leading risk factors for various diseases. Alcohol-related diseases cause 10% of all deaths worldwide among young and middle-aged people. The occurrence of renal dysfunction in cirrhosis of the liver is an integral part of the natural course of the disease. At the moment, the diagnosis of gender-specific renal dysfunction that occurs against the background of liver cirrhosis is essential for the development of effective treatment strategies and the improvement of survival.

Objectives. The study is aimed at identifying the features of the gender-specific renal function and urinary syndrome in patients with liver cirrhosis of alcoholic etiology and assessing the comprehensive prognostic significance of the indicators of common urine analysis in the diagnosis of renal dysfunction.

Methods. An observational study was carried out using data from medical records of 158 patients with alcoholic liver cirrhosis (95 men and 63 women), aged 36 to 72 years, who were inpatients between February 2016 and March 2020. Physical examination and laboratory diagnostic data were taken into account. Binary predictors of renal dysfunction progression in patients with alcoholic liver cirrhosis were determined based on the analysis of descriptive statistics. Statistical data processing was performed using computer program Statistica 10 (StatSoft, Inc., USA) and standard Microsoft Excel software package (Microsoft Office 2016). Non-parametric statistical methods were used to describe the results. Quantitative results were analyzed using the Mann-Whitney test; comparison of two samples by a qualitatively defined feature was performed by means of the Fisher angular transformation method. Differences were considered significant at p ˂ 0.05. A multilayer neural network function from the Statistica 10 Neural Networks software was used to construct a classification scheme for renal dysfunction (yes/no). Neural network performance was assessed using descriptive and inductive statistics, calculating sensitivity, specificity, performing ROC analysis and constructing cumulative gains charts.

Results. A renal function test revealed a significant decrease in glomerular filtration rate (p = 0.029) and a significant increase in urinary albumin/creatinine ratio (p < 0.0001) in women with alcoholic liver cirrhosis as compared with men. Women are also reported to have a high incidence of proteinuria, leukocyturia and bacteriuria. According to ROC-analysis, the urinalysis indicators have a high prognostic significance in identifying renal dysfunction in men and women with alcoholic liver cirrhosis (AUROC = 0.902 and sensitivity 81.82%, AUROC = 0.881 and sensitivity 75.00%, respectively).

Conclusion. Renal dysfunction develops earlier and occurs twice as often in women with alcoholic cirrhosis than in men of the same age. The application of a neural network mechanism to predict renal dysfunction in men and women with alcoholic liver cirrhosis according to the indicators of urinalysis provides a high prognostic ability.

Background. Currently accepted risk assessments of periodontitis progression are determinants of indirect stability: periodontal pockets, persistent bleeding of the gums, tooth mobility, local risk factors. In the era of case-oriented medicine, a relevant solution would be to choose periodontal therapy according to one-time consideration of the maximum available range of individual risk factors rather than on general clinical guidelines.

Objectives. The study was aimed at determining the relative risk of periodontitis progression after active basic therapy using neural network modeling.

Methods. A cohort retrospective study was performed on 109 patients of both sexes, aged 30 to 70 years, after basic treatment of chronic periodontitis (mild, moderate and severe) in the period from 1999 to 2016, who were on supportive periodontal therapy (SPT) for 5 years ≤SPT≤ 20 years. The authors considered data from objective examination of the periodontium and categorical indices (24 in total) assessed before treatment, 4–6 months after basic (active) treatment and 5 years ≤SPT≤ 20 years. Following the analysis of descriptive statistics, target quantitative indices were determined for prognostic modeling of treatment outcomes in periodontitis patients and calculating the residual risk of disease progression. Statistical processing of obtained data was carried out using the Statistica 13.3 package (Tibco, USA). Mean values of the indicators at different time points were compared by means of Wilcoxon’s and Signs criteria; Spearman’s rank correlation coefficient was used to evaluate relevance between predictors and target indicators. The level of statistical significance p = 0.05 was accepted in all cases of analysis. DataMining, an automated neural network of Statistica software, was used as a tool to build neural network models. The task of classifying the level of risk of disease progression was solved by means of ROC analysis. The prognostic potential of the model was assessed using sensitivity and specificity measures.

Results. The heterogeneous dynamics of predictor variables describing the state of the periodontium was determined. The outcomes of regenerative periodontal surgery, regardless of gender, age of patients and comorbidities, significantly outperformed those of other approaches, due to the formation of a new dentogingival attachment, although to different extent. Another positive functional outcome was recorded in restoring the dentition integrity by implantation, without any mutually damaging effects. Since revealing the interrelationships between indicators is not equivalent to the predictive value, prognostic models were built for target indicators and stratification of the relative risk of periodontitis progression using automated neural networks. The networks with the best prognostic properties were selected out of 1000 automatically built and trained neural networks — double-layer perceptrons. The sensitivity of the relative risk prognostic model on the training, control and test samples made up 90%, 67%, 80%; the specificity of the model made up 81.481%, 85.714%, 100%. Overall, in the cohort, the sensitivity and specificity accounted for 85.937% and 86.666%. The area under the curve (ROC AUC) is 0.859.

Conclusion. The use of an artificial intelligence algorithm for the construction of neural networks for target predictors and stratification of the relative risk of periodontitis progression has advantages over classical methods — it is instrumental in solving classification and regression problems with categorical and quantitative predictor variables using data of arbitrary nature of large and small volumes. The practical implementation of the study results is reflected in the development of a relative risk calculator based on a written computer program.

Background. The incidence of invasive mycoses is reported to increase among patients with a history of new coronavirus infection COVID-19. Adhesion and damage of endothelial cells by zygomycetes lead to fungus angioinvasion, release of a large number of fungal proteases, lipases and mycotoxins, as well as vascular thrombosis, subsequent necrosis of tissues.

Objectives. Improvement of the diagnosis and treatment for COVID-19 associated invasive mycosis.

Methods. Examination and treatment of 143 patients with invasive mycosis of the maxillofacial area in the period from August 2021 to May 2022 at the Maxillofacial Unit of Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, Russia. The diagnosis was confi rmed by cytological, culture-based methods, as well as pathomorphological study of surgical specimen. Follow-up monitoring was carried out in 1, 3, 6 months, with repeated CT and MRI investigations. The group under follow-up monitoring included 91 patients. The incidence of signs was determined via descriptive statistics methods in proportion of the total number of observations and expressed as a percentage. Statistika 12.5 and Excel 2010 (Windows 10) were used in the study, the graphical representation of the material was made in the same programs.

Results. Manifestation of invasive mycoses of the maxillofacial area occurred during the early convalescent period of coronavirus infection in specialized infectious hospitals or within two weeks after discharge from the hospital. A typical clinical picture includes rhinocerebral zygomycosis with the development of fungal osteomyelitis of the upper jaw, nasal bones, zygomatic bone, ethmoidal labyrinth bones, sphenoid bone, frontal bone. 17 cases (11.9%) had a lethal outcome as a result of disseminated form of fungal infection caused by Mucorales (14 patients), Aspergillus (3 patients) with damage to the brain, lungs, kidneys and fatal massive necrotic lesions of the craniofacial area. An integrated approach embraced early antifungal therapy (Amphotericin B) as well as surgical debridement of the lesions and provided a positive effect in treatment.

Conclusion. Invasive fungal infections require prompt diagnosis and early prescription of antifungal therapy (prior to histological confi rmation of diagnosis) to minimize consequences and prevent fatal outcome. Due to the nonspecifi c nature of clinical symptoms and diffi culties of early diagnosis of invasive zygomycosis and aspergillosis, it is necessary to be alert to potential invasive aggressive mycoses in immunocompromised patients who have a history of a new coronavirus infection COVID-19.

Background. Despite a variety of existing methods of surgical treatment for sacrococcygeal pilonidal cyst, a universal technique has not been developed yet, due to the large number of postoperative complications and recurrences.

Objectives. To improve the treatment outcomes of patients with pilonidal cysts through developing and implementing a new method for closure of the postoperative wound defect of the sacrococcygeal region.

Methods. We conducted a randomized trial, involving 60 patients with sacrococcygeal pilonidal cyst. The control and main groups consisted of 30 people each. The study was carried out in the Purulent Surgery Unit of the Regional Clinical Hospital No. 1 — Research Institute, Krasnodar. The inclusion of patients in the trial was organized within 2019–2022 period. The duration of each patient’s follow-up period was equal to the hospitalization duration. The control group underwent the surgical treatment in the Moszkowicz (Moshkovich) modifi cation. The main group was treated by means of our own developed method. Postoperative wound complications were assessed according to Clavien—Dindo classifi cation. Statistical data processing was performed using Microsoft Excel 2013 with the add-ins Analysis package and AtteStat for statistical data.

Results. The control and main groups included 30 participants each. The gender, age and body mass index (BMI) were not defi ned as statistically signifi cant. When analyzing the primary data, the treatment median time accounted for 10.5 (9.0; 13.8) days in the control group and 7.0 (7.0; 8.0) days in the main group, a signifi cant difference according to the Mann—Whitney test (p < 0.001). The number of postoperative complications (suture failure, wound abscess, necrosis of skin fl aps) in the control group was 16 cases, and in the main group — 1 case (signifi cance of differences under the chi-squared test p < 0.001). The number of recurrences in the control group comprised 7 cases, while in the main group there was 1 case (signifi cance of differences under the chi-squared test p = 0.023).

Conclusion. The application of surgical treatment for pilonidal cysts in the authors’ modifi cation made it possible to reduce the time of hospitalization, the number of such postoperative complications as suture failure, wound abscess and necrosis of skin fl aps. The number of recurrences has also decreased significantly.

Background. With the introduction of synthetic mesh implants into clinical practice, the recurrence rate of postoperative ventral hernias was signifi cantly reduced. The extensive use of synthetic implants led to the development of specifi c complications. The development of biological implants, based on extensively purifi ed decellularized collagen matrix of xenogeneic origin is highly relevant due to the fact that, unlike synthetic analogues, they have a biological origin and biodegrade in a natural way, gradually being replaced with newly formed connective tissue. The use of bioprostheses reduces the risk of complications.

Objectives. To conduct a comparative evaluation of the biomechanical characteristics of acellular dermal matrix, obtained by detergent-enzymatic decellularization, and commercially distributed Permacol™ matrix.

Methods. Acellular dermal matrix (ADM) was created by using samples of native skin of pig of Landras breed aged 4 months. The dermis was processed by means of detergent-enzymatic method. In order to evaluate and compare the mechanical properties of acellular dermal matrix, the biological samples were divided into 2 groups of 15 samples each. The fi rst group included acellular dermal matrix samples, the second group — native samples of pigs unprocessed dermis. The control group consisted of samples of PermacolTM Surgical Implant, xenotransplant for hernioplasty approved for use in the Russian Federation (Covidien, France). All samples were tested wet using universal testing instrument Instron 1122. MedCalc Statistical Software (Belgium) was used for statistical processing of the study results.

Results. In the present study, pig dermis was processed using a detergent-enzymatic method to produce ADM. Routine histological examination confi rmed the removal of all cellular elements, and at the same time it was proven that the native structure of the dermis remained intact during its processing. The mechanical characteristics of xenogenic ADM were further determined. Its tensile strength was 9.1 ± 0.6 MPa (910 N/cm2 ), elongation to break was 21.1 ± 2.3%, and elastic modulus was 50.0 ± 1.6 MPa. These characteristics largely corresponded to the strength characteristics of native pig dermis and far exceeded the necessary physiological parameters. PermacolTM control was tested in two directions (longitudinal and transverse). In the longitudinal direction, the sample had higher mechanical characteristics: strength — 12.0 ± 1.7 MPa, elongation to break — 29.7 ± 2.4%, stiffness modulus — 47.2 ± 6.5 MPa. In the transverse direction, all indicators were 1.5–2 times lower.

Conclusion. The developed xenogeneic biological implant in the form of ADM demonstrates rather good characteristics of plasticity, tensile strength and elasticity, to be used as a biological endoprosthesis for plasty of hernia defects of the abdominal wall of any size and shape.

Background. Schizophrenia is a socially signifi cant disease that takes a variety of forms. The form of the course determines prescribing antipsychotic drugs with a different range of clinical effects. The study of the pharmacological activity of neuroleptics involves an experimental model using animals which makes it possible to reproduce some aspects of schizophrenia.

Objectives. The study is aimed at evaluating the antipsychotic activity of 5-HT2A— RU-31 antagonist and atypical neuroleptic clozapine in behavioral tests and electroencephalography (EEG).

Methods. The research methodology involved a dysontogenetic model of schizophrenia, implemented via aspiration destruction of the ventral hippocampus of rats on day 7 of postnatal development. The study was carried out on white outbred male rats selected from the offspring of females, represented by a simple random sample, provided by Rappolovo animal breeding facility of the National Research Center “Kurchatov Institute”. Injection of the studied substances was initiated on day 35 of postnatal development. Motor activity was assessed on day 54 of postnatal development in the Open Field unit and included assessing vertical motor activity, measured as the number of acts of verticalization in 5 minutes, and horizontal motor activity of rats, recorded as the number of crossed squares in 5 minutes. EEG signals were recorded on day 55 of postnatal development; thereafter the spectral density was calculated in the delta- (д) (0.4–4 Hz), theta- (и) (4.8–8 Hz), alpha- (б) (8–12 Hz) and beta- (в) (12–30 Hz) frequency ranges and the effect of the “operation” and “substance” factors on spectral density was evaluated in comparison with control groups. Statistical data processing was performed using GraphPad Prism 9 (Insight Partners, USA).

Results. The antipsychotic activity of 1-(2-diethylaminoethyl)-2-(4-methoxyphenyl)-imidazo[1,2-a] benzimidazole — RU-31 compound with 5-HT2A-antagonistic mechanism of action was evaluated. RU-31 compound (10 mg/kg, intraperitoneally (i.p.)) statistically signifi cantly reduced vertical and horizontal spontaneous locomotor activity in rats with psychotic disorder by 18.8% and 20.9%, while the atypical neuroleptic clozapine (2 mg/kg, i.p.) signifi cantly reduced these values by 41.15% and 27.67%, respectively. The 5-HT2A-receptor antagonist RU-31 increased EEG signal power in the delta range by 123.33% and decreased it in the alpha range by 41.86% in surgically operated animals (p < 0.05). Clozapine increased the EEG signal power in all studied frequency ranges: in delta — by 107.99%, theta — by 97.16%, alpha — by 41.86% and in beta — by 49.16% in animals with neonatal destruction of the ventral hippocampus (p < 0.05).

Conclusion. The studied substances contributed to the correction of behavioural disturbances associated with hypermobility as well as electrophysiological changes induced by a surgical operation, while similar activity was not observed (or was observed to a lesser extent) in healthy animals.

Background. The high number of stroke cases is predetermined by risk factors, pathogenetic heterogeneity, genetic predisposition to the disease. Neurovascular changes can serve as a marker for the severity of the patient’s condition. By means of cardiointervalography, the reactions of the autonomic nervous system in patients with ischemic stroke were studied, depending on the territory of the cerebral infarction and its period. With a favorable outcome of the disease, the detected changes in regulatory mechanisms can be considered adaptive, while with fatal outcome — disadaptive. Objectives. Determination of the state of the autonomic nervous system by means of cardiointervalography in patients with stroke in various pools of blood supply.

Methods. 52 patients with a verifi ed diagnosis of ischemic stroke in the acute and peracute periods were examined. All patients were divided into 3 groups. Group 1 — patients with ischemic stroke in the middle cerebral artery territory on the left. Group 2 — with ischemic stroke in the middle cerebral artery territory on the right. Group 3 — with ischemic stroke in the vertebrobasilar territory. Patients with a fatal outcome are separately described. The functional state of the autonomic nervous system was assessed by the method of mathematical analysis of heart rate variability according to R.M. Baevsky (1984). Cardiointervalography was performed in the morning on the 1st day from the onset of the stroke and on the 10th day.

Results. The state of autonomic regulation in patients with ischemic stroke depends on the localization and size of the lesion. According to cardiointervalography, parasympathetic effects on the rhythm of the heart prevailed in patients with ischemic stroke in the middle cerebral artery territory on the left and in the vertebrobasilar territory in the peracute period, while the sympathetic one predominated in patients with ischemic stroke in the middle cerebral artery territory on the right. In the acute period, the general tendency for the increase in activity of the opposite part of the autonomic nervous system was observed.

Conclusion. Statistically signifi cant changes in the indicators of the total power of the wave oscillation spectrum and the indicator of ultra-low-frequency waves in the peracute and acute periods of stroke in the examined patients indicate the importance of neurohumoral mechanisms of regulation in the dynamics of the pathological state