Journal «MEDICINA» 3/2024

Introduction. Motivation for treatment is a complex and multidimensional phenomenon significantly impacting the effectiveness of medical assistance for patients with addictive disorders. An integrative assessment of biopsychosocial functioning and systematic analysis of the factors determining readiness for treatment are important directions of research aimed at understanding the formation of motivational processes in patients with alcohol dependence. Aim of the study is to determine sociodemographic, clinical, psychological and emotional characteristics of patients with alcohol dependence and with varying levels of motivation for treatment, as well as to identify predictors of readiness for change and treatment. Methods and Materials. A total of 138 patients with alcohol use disorder (F10.20; F10.21) were recruited for this cross-sectional study. Research instruments included: patients’ clinical charts, «The Stages of Change Readiness and Treatment Eagerness Scale» (SOCRATES), Differential Emotions Scale (DES), The State-Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HDRS), and State-Trait Anger Expression Inventory (STAXI), Attitude toward the disorder (TOBOL), Toronto Alexithymia Scale (TAS), Tests of anticipatory validity (TASPK), and Purpose-in-Life test (PIL). Results. The median age of the subjects was 27.0 years [20.0; 35.0]. Patients with low motivation for treatment (LMT), compared to subjects with medium (MMT) and high (HMT) motivation scores, were younger, displayed greater negative attitudes toward relatives, had shorter durations of substance use disorder and withdrawal symptoms, and reported fewer treatments and spontaneous remissions (p≤0.05). HMT patients had skilled jobs, longer duration of remission after treatment, and a higher ratio of remission duration to disease duration compared to LMT and MMT patients (p≤0.05). In contrast to the MMT group, the LMT participants demonstrated significantly higher levels of the emotion of contempt, alexithymia and a neurasthenic attitude toward the disorder (p≤0.05). Subjects with HMT, as opposed to LMT and MMT, had significantly lower levels of «depression», «trait anger», «trait anxiety»; while the levels of the emotion «surprise», «trait-situational anticipatory validity», «general anticipatory validity», «life performance», «I-locus of control» were significantly higher (p≤0.05). The following predictors for the readiness for change and treatment were identified: ratio of remission duration to disease duration (B1 = 57.05), skilled occupation (B2 = 2.10), emotions «surprise» (DES) (B3 = 1.81) and «contempt» (DES) (B4 = -1, 11), «trait anger» (STAXI) (B5 = -1, 72), neurasthenic attitude toward the disorder (TOBOL) (B6 = – 0.31), «general anticipatory validity» (TASPK) (B7 = 1.93), (B1, B2, .... , Bn – numbers and coefficients of predictors; multiple regression equation constant B0 = 92.35; adjusted R² = 0.753). Conclusion. A benign course of alcohol use disorder progression, employment in a skilled job, prognostic abilities in assessing the development of life situations, and personal responsibility for one's life, as well as higher level of the emotion of surprise and low levels of anxiety, depression, anger, contempt, alexithymia, and neurasthenia, increase motivation for change and treatment in individuals with alcohol dependence.

Key words: alcohol dependence, motivation for treatment, emotions, clinical and social factors

Introduction. The problem of latent alcohol consumption in groups of certain professions, in particular among railway engine crews, still exists, despite the fact that admission to train operation is carried out by a medical expert commission and railway engine crews undergo mandatory breath alcohol testing. An association between an excessive alcohol consumption, in the doses exceeding safe limit, and cardiovascular diseases and mortality of this professional group has been established, that is directly related to the safety of train operation. However, the dose of latent excessive alcohol consumption that can cause specific cardiovascular diseases and a fatal outcome remains unknown. Aim. To find out the effect of latent excessive alcohol consumption on cardiovascular morbidity and mortality among railway engine crews, determine the exposure to this factor in the observation group. Materials and methods. Based on the material of the 2008-2013 study of a natural group of initially healthy 7,959 male railway engine crew members of the Trans-Baikal Railway aged 18-66 years, predictors of acute coronary syndrome, cerebral stroke, of coronary heart disease and sudden cardiac death were established using multivariate statistical analysis. Cardiovascular diseases had a common predictor – latent excessive alcohol consumption, the characteristics of which as a screening tool were assessed using the quality control method of a verifiable diagnostic test with binary outcomes. By determining the sensitivity value of latent excessive alcohol consumption, the exposure of the predictor in the observed group was determined with this method. Results. The latent excessive alcohol consumption determined the occurrence of acute coronary syndrome, of coronary heart disease, cerebral stroke and sudden cardiac death in the 7,959 railway engine crew members, in the exposure of 0.13; 0.03; 0.10 and more than 0.24 respectively of the total population studied. Cardiocerebral morbidity in the railway engine crew members involved in latent excessive alcohol consumption and mortality from all causes constituted 1.6% and 1.2%. Acute cardiovascular diseases – 0.7% Conclusion. It is necessary to monitor latent excessive alcohol consumption determined in railway engine crews. The data obtained can be used in planning the range of preventive measures and medical care among the railway engine crews or in other socially significant groups of the population, as well as in scientific studies aimed to determine the effect of the exposure of excessive alcohol consumption on the formation and development of cardiovascular events.

Key words: alcohol, locomotive crew workers, cardiovascular disease, risk factors, endothelial dysfunction, screening testing

Introduction. For the introduction of new medicines into medical practice, a mandatory stage is quality control, which includes determining the quantitative content of active components using modern methods of pharmaceutical analysis. Tizol gel, included in soft dosage forms, is an independent pharmacologically active agent, therefore it is important to evaluate its content in complex medicinal preparations. Aim. To develop a method for quantitative determination of tizol gel and metronidazole in a new semisolid dosage form «Metronidazole» using multiple-wavelength spectrophotometry. Materials and methods. Pharmaceutical substance metronidazole, tizol gel, «Metronidazole» ointment containing 5% nitroimidazole in a tizol base was used for analysis. The studies were performed on spectrophotometer SF-2000 by multiple-wavelength spectrophotometry in the UV region. On the basis of experimental data, the metrological parameters of the developed analytical technique were calculated. Results and discussion. Experimental studies allowed us to justify the use of an acetate buffer solution with pH = 4 as the optimum solvent for the spectrophotometric analysis of tisol gel and metronidazole in the mixture. Analytical wavelengths (238 nm for tisol gel, 316 nm for metronidazole) were selected according to the UV spectra of the drugs obtained. According to the results of quantitative determination of the components of the Metronidazole ointment, the content of medicines is within the limits: metronidazole from 0.4900 to 0.5219 g, tizol gel (in terms of the mass fraction of titanium) – 2.32–2.46%, which are acceptable according to regulatory documentation (FSF 42-3157-06, OFS.1.8.0001). Conclusion. Quantitative analysis of tisol gel in complex pharmaceutical preparations was proposed for the first time. The method of quantitative determination by multiple-wavelength spectrophotometry has been developed which allows to determine the content of tizol gel and metronidazole in a new semisolid dosage form «Metronidazole» with relative errors of the average result not exceeding ± 3.00%.

Key words: metronidazole, tizol gel, multiwave spectrophotometry, quantitative determination

Introduction. The article discusses the problem of using laboratory animals in preclinical research and, as a solution to this problem, the use of modern technologies like artificial intelligence. The aim of the work is to study the application of computer vision methods and large language models for preclinical research. Discussion. Nowadays scientists all over the world are actively trying to replace animal models in preclinical research with more modern solutions. Artificial intelligence plays an important role in this process. It allows us to make research faster and also to improve the quality of experiments, and therefore, it can lead to the decrease in the number of tests, that may turn out to be unjustified and, in most cases, fatal to animals. The use of AI in preclinical research makes it possible to conduct more accurate experiments, reduce the likelihood of unsuccessful research and increase the reliability of the results. It also allows us to reduce the number of animals which are used in experiments, which is one of the main aspects of bioethics. It is possible to reduce the suffering of animals and improve their protection from the negative effects of experiments by replacing them with computer models and AI-based virtual systems. Conclusions. The use of artificial intelligence in preclinical studies is one of the best ways to develop more ethical, accurate and effective scientific methods.

Key words: artificial intelligence, preclinical research, machine learning

Background. Nicotinamide adenine dinucleotide (NADN) is involved in many important biochemical reactions in human metabolism, including participation in mitochondrial energy production. Mitochondrial activity, which affects skin microcirculation and the efficiency of local blood supply, can be indirectly assessed by the fluorescence of NADH in its reduced form. Changes in major skin fluorophores have been studied in both animals and humans, at rest and under different conditions, using spectrofluorimetry. The purpose of the work is, based on scientific literature data, to evaluate the possibility of using a spectrofluorimetric study of NADH levels, as well as the NADH/FAD ratio when assessing the condition of both free skin flaps and pedicled flaps after reconstructive operations, in particular in ophthalmology. Materials and methods. A search of scientific publications in PubMed, Google Scolar and Elibrary was conducted, as a result 61 articles for the period of 1957-2022 were selected for the final scientific review. Results and discussion. A brief historical background of the first spectrofluorimetric studies is presented. A brief overview of spectrofluorimetric methods for studying the skin of both humans and experimental animals, as well as other organs and systems, is given. The disadvantages and advantages of various research methods are listed. A review of changes in spectrofluorimetric parameters of the skin in patients with various somatic diseases of organs and systems was carried out. Conclusion. A review of the abovementioned methods for assessing tissue metabolism is applicable in surgical treatment, plastic surgery and onco-ophthalmology. Of particular value for surgery will be research methods that make it possible to predict the likelihood of rejection of transplanted skin flaps and their cicatricial changes. The presented literature review confirms the effectiveness of spectrofluorimetry for assessing metabolic disorders in the skin. The relevance of the method for predicting cosmetic outcomes during plastic surgery, including on the adnexal apparatus of the eye, requires continued research into the main fluorophores of the skin.

Key words: cicatricial changes of the skin of the eyelids; NADH; skin; spectrofluorimetry, autofluorescence

Data on 7,236 patients with schizophrenic spectrum disorders (SSD) treated with long-acting injectable antipsychotics were studied, most of whom had paranoid schizophrenia diagnosis (F20.0 – 91.6%), the rest with SSD (F20.1-25.9) observed in 9.4% of patients. In the studied sample, the majority were men (53.9%). Cluster analysis allowed the formation of three cluster groups (CG) of patients, depending on the severity of psychopathological symptoms – positive and negative at the time of remission. The first group (n=4717) included patients with residual productive symptoms and pronounced negative symptoms (CG1); the second (n=1185) – patients with moderately pronounced positive and negative symptoms (CG2); the third (n=1334) – patients with mild positive and negative symptoms (CG3). The largest cohort (CG1) consisted of patients with the most severe register of mental disorders and the lowest social and labor indicators. Patients with CG3 had a mild register of psychopathological disorders and the highest rehabilitation level. Clinically and socially СG2 patients occupied an intermediate position. Thus, a large cohort of seriously ill patients with a predominance of pronounced negative symptoms (СG1) and patients with more favorable clinical and social characteristics and preserved rehabilitation potential (СG3) was identified. A clinical and statistical study has shown that the clinical and nosological heterogeneity of the isolated patients with SSD is dissonant with the approximate homogeneity of the therapy. Regardless of the clinical characteristics of the patients, about a third of them received therapy with prolonged preparations of haloperidol, a third – zuclopentixol, the proportion of long-acting injectable antipsychotics in the groups was also approximately the same and did not exceed 27.4%. It has been established that the subjective perception of psychopharmacotherapy, its direct and side effects is a significant factor influencing the characteristics of long-term antipsychotic therapy. The severity of the clinical course of SSD revealed a relationship with lower compliance, a relatively higher prevalence of episodic therapy intake disorders. It is concluded that pharmacotherapy with prolonged antipsychotics by itself does not determine pronounced shifts in the dynamics of psychopathological disorders and is not determined by clinical and social parameters, which determines the relevance of further catamnestic research of patients of the selected groups after optimizing pharmacotherapy and conducting psychorehabilitation measures taking into account their identified individual characteristics.

Key words: schizophrenic spectrum disorders, long-acting injectable antipsychotics, clinical and social factors, compliance, cluster of seriously ill patients, uniformity of therapy

Aim of the study. To analyze publications of scientific studies devoted to the study of biochemical and immunological aspects of the pathophysiology of acute respiratory distress syndrome. Material and methods. An analysis of 54 sources was conducted. The search for articles was carried out in the abstract databases Scopus and Web of Science, as well as in the search engines PubMed, eLIBRARY.RU and Google Scholar, from 2000 to December 2023. Conclusions. The immunological aspect of the pathophysiology of acute respiratory distress syndrome is characterized by the activation of the innate immune system and antigen-presenting cells, which contributes to the initiation of the immune response. In turn, neutrophils release cytotoxic molecules, active oxygen metabolites, bioactive lipids and proinflammatory cytokines and trigger an inflammatory cascade. Cytotoxic molecules cause tissue necrosis, initiate apoptosis and autophagy, which maintains and enhances inflammatory reactions and lung injury, as well as the formation of a vicious circle. Damage to vascular endothelial cells initiates coagulation, promoting the activation of platelets and procoagulant cascades, which leads to the formation of microthrombi in the pulmonary microcirculatory network and fibrin deposition in the intraalveolar and interstitial compartments. The interaction of platelets and neutrophils at the site of endothelial injury is considered a humoral regulatory process. Uncontrolled immunothrombosis can cause concomitant tissue damage and contribute to organ dysfunction.

Key words: Biochemical and immunological aspects, pathophysiology, respiratory distress syndrome

Introduction: Bacteria of the genus Serratia are an important group of microorganisms that are both of clinical and scientific importance. The study of the morphological and pathogenetic properties, as well as the determination of resistance to antibacterial drugs of these bacteria is important for the development of methods for treating infectious diseases and the use of this knowledge in biotechnological processes. Despite the fact that bacteria of the genus Serratia were previously considered to be relatively sensitive to most antibacterial drugs, in recent decades there has been an increase in the resistance of these pathogens, which complicates the course of the diseases they cause. Analysis of scientific data on the issues of antibiotic resistance of the studied bacteria will allow us to obtain reliable information about the mechanisms by which bacteria of the genus Serratia acquire resistance to antibacterial drugs, as well as make a choice regarding the optimal drug for the treatment of infectious diseases. Purpose of the study: To study the epidemiological features and resistance mechanisms of bacteria of the genus Serratia to antibacterial drugs. Materials and methods: A review and analysis of 20 sources was conducted. The search was carried out in electronic databases of scientific articles e-Library, Google scholar, PubMed, Web of Science, CyberLeninka. The materials studying the relationships between the epidemiological characteristics of bacteria of the genus Serratia and their mechanisms of resistance to antibacterial drugs were analyzed.  Results: In this narrative review, in the course of data analysis, it was noted that most Serratia isolates remain sensitive to some antibacterial drugs, but strains were also identified that exhibit resistance to various classes of antibacterial drugs, including penicillins, cephalosporins and aminoglycosides. The study of resistance mechanisms has shown that one of the key factors contributing to the resistance of bacteria of the genus Serratia is the presence of beta-lactamase enzymes, which destroy beta-lactam antibiotics. Efflux mechanisms have also been identified allowing bacteria to avoid the action of antibacterial drugs. There has been a trend towards increasing levels of antibacterial resistance in Serratia over recent years. This indicates the need for constant monitoring and control of the use of antibacterial drugs in hospital settings. Conclusion: An epidemiological analysis of the mechanisms of resistance of bacteria of the genus Serratia was carried out, and data were obtained confirming the need for in-depth planning before using antibacterial drugs in order to reduce resistance in various strains of bacteria.

Key words: Serratia marcescens, antibacterial drugs, aminoglycosides, antibiotic resistance, infection, microbiology, epidemiology

Aim: To analyze the potential impact of orthokeratological lenses when correcting myopia on the anatomical and functional state of the cornea. 160 eyes (80 patients) were examined – 60 eyes (30 patients) with mild myopia, 100 eyes (50 patients) with moderate myopia, average age 12.0 ± 0.38 years. Control group – 40 eyes (20 patients), with emmetropia, average age – 13.0 ± 0.45 years. All patients used reverse geometry orthokeratological lenses «Moonlens» from «Sky Optix» in night mode. Research methods. Special research methods were carried out: keratotopography, OCT of the anterior segment of the eye, autorefractometry, ophthalmometry, biometry, skiascopy against the background of cycloplegia, ultrasound of the eye, biomicroscopy, ophthalmoscopy. Results. After the use of orthokeratological lenses, flattening of the cornea from the center to the periphery was revealed with the formation of a negative value of the asphericity index «Q» – exactly (-) 0.57±0.054 (p <0.01); an increase in refraction in the middle and peripheral zones of the cornea with an increase in the asymmetry index «l-S» is 3.0±0.12D (p <0.01). According to the SimK1 and SimK2 meridians, the degree of weakening of refraction in the center of the cornea was revealed (-) 2.32±0.19D and the degree of enhancement of refraction of the cornea in the middle and peripheral zones – (+) 61±0.53D and (+) 0.97 0, 11D. Conclusion. Thus, the identified changes in the anatomical and functional state of the cornea during the treatment of myopia with orthokeratological lenses in the night mode indicate a transformation of the induced myopic defocus.

Key words: myopia, cornea, radius of curvature of the cornea, refractive power of the cornea

Background. Macrolides are a class of broad-spectrum antibiotics used to treat a variety of infectious diseases, both local and systemic. Although the use of macrolides is generally considered safe, some patients may be at risk of dose-dependent adverse drug reactions (ADRs), which may reduce the safety of treatment for this category of patients. Purpose of the study. To investigate the influence of polymorphism of genes encoding transporter proteins and biotransformation enzymes of macrolide antibiotics on the safety of therapy in patients with bacterial complications of influenza. Material and methods. An open non-comparative prospective study was conducted in which 100 patients diagnosed with bacterial complications of influenza from the lower respiratory tract (ICD-10 diagnosis codes J10.0-J10.1), treated in an infectious disease hospital, received macrolide antibiotics (azithromycin or erythromycin) in tablet form for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. Results. The presence of statistically significant influence of the 3435C>T (rs1045642) polymorphic marker of the ABCB1 gene on the frequency of ADRs development in patients treated with macrolides was found: estimation – 0.751, OR = 2.12 (95% CI: 1.03 – 4.34), p = 0.043. In addition, the presence of a statistically significant effect of polymorphic marker C>T intron 6 (rs35599367) of the CYP3A4 gene on the overall incidence of ADRs in patients treated with erythromycin was revealed: estimation – 3.1781, OR = 24.0 (95% CI: 1.2775 – 450.9741), p = 0.0339; and on the incidence of abdominal pain and abdominal discomfort: estimation – 2.0794, OR = 8 (95% CI: 1.0377 – 61.7143), p = 0.046. Discussion: in patients carrying the CT and TT genotypes of the 3435C>T (rs1045642) polymorphic marker of the ABCB1 gene, a higher frequency of such ADRs as abdominal pain and discomfort in the abdomen and diarrhea was observed. Furthermore, the statistically significant influence of the C>T intron 6 (rs35599367) polymorphic marker of the CYP3A4 gene on the frequency of ADRs development against the background of erythromycin use was shown. Conclusion: the influence of ABCB1 genetic polymorphism on the safety parameters of macrolide therapy was demonstrated. It was found that carriage of the C>T intron 6 (rs35599367) polymorphic marker of the CYP3A4 gene may allow to predict the development of ADRs (and specifically abdominal pain) against the background of erythromycin use.

Key words: pharmacogenetics, adverse reactions, macrolides, biotransformation, personalized medicine

Background: The modern epidemic process of chickenpox is characterized by the involvement of all age groups and a high risk of forming epidemic foci in organized groups. The introduction of chickenpox into healthcare organizations and their further intra-hospital spread, especially in pediatric hospitals, requires adequate response and management decisions to minimize the risk of spread in a hospital environment. Objective: to study the frequency and risk factors of chickenpox cases in the hospital environment in a large pediatric multidisciplinary hospital to improve epidemiological surveillance. Materials and methods: The data of the epidemiological investigation reports of infectious (parasitic) outbreaks with establishment of a causal relationship for 2021-2023, medical records of inpatients and outpatients in a medical organization providing specialized, including high-tech, medical care were analyzed. The method of retrospective epidemiological analysis was used. The frequency of chickenpox (VO) inoculations in a medical organization (MO) per 1000 patients was determined. The index of focality was determined. A 95% confidence interval was calculated for relative values. Calculations were performed using the epidemiologic Confidence Interval Calculator. Quantitative indicators were evaluated for conformity to normal distribution using the Shapiro-Wilk criterion (number of indicators less than 50). The direction and strength of the correlation between two quantitative indicators in normal and non-normal distributions were evaluated using Pearson and Spearman correlation coefficients, respectively. When conducting correlation analysis, the direction of the relationship (direct or inverse) and the strength of the relationship according to the Chaddock scale were taken into account. Statistical data processing was performed using the Microsoft Excel program. Results: The highest risk of introducing chickenpox into the emergency department when providing emergency and urgent medical care in outpatient settings to emergency non-hospitalized patients has been established. Significant (p<0.05) differences in the frequency of registration of VO cases in somatic and surgical departments were determined. A low foci rate of 1.2 in the conditions of implementation of algorithms of personnel actions was determined. Conclusions: To reduce the risk of introducing chickenpox into a medical organization in the context of the development of digital technologies, synergy of actions of primary health care specialists in specific epidemic foci, even in single cases of the disease, is necessary. In a medical organization, the most important measures to reduce the risk of spread in the context of VO introduction are the development and implementation of algorithms of personnel actions and improvement of the level of professional competence of medical workers.

Key words: chickenpox, morbidity, transmission, pediatric multidisciplinary hospital, epidemic process