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The article is devoted to the analysis of the current state of regenerative and rehabilitative treatments of skeletal muscles, the possibilities of restoring the functioning of tissue lost due to aging, injuries or diseases. The study of the molecular genetic basis of mechanotransduction and mechanotherapy will allow the identification of genes and molecules, the expression levels of which can serve as biomarkers of the effectiveness of regenerative-rehabilitation measures. These mechanisms are potential therapeutic targets for stimulating of regeneration of skeletal muscles. The focus of the article is on the choice of an individual approach, both when conducting basic scientific research and developing rehabilitation programs. All this will significantly improve patient outcomes.

The review presents the pathogenetic, diagnostic, therapeutic and rehabilitation aspects of computer visual syndrome. The importance of an integrated approach to the implementation of treatment and rehabilitation measures is emphasized. The promising directions of scientific and practical activity on the problem of treating patients with computer visual syndrome symptoms from the standpoint of modern requirements for medical rehabilitation have been determined.

Despite the high level of modern technologies in the field of laboratory methods and imaging of the respiratory system, the problem of early and accurate differential diagnosis of inflammatory lung diseases remains important in practical medicine. It leads to improved treatment results and a reduction in the number of complications (pleural empyema, fistulas, mediastinitis, sepsis, etc.), and in some cases allows suspecting the presence of a primary purulent source in the body, such as that in the case of septic pulmonary embolism. The review covers the Staphylococcus aureus specifics as a pathogen of lung diseases, relevant epidemiology, pathogenesis, clinical features and imaging diagnostics of various types of inflammatory changes in the lungs with a focus on destruction.

Altres ajuts: Sponsorship for this study and the Rapid Service Fee were funded by JSC BIOCAD, Ul. Italianskaya 17, St Petersburg, Russia, 191186 Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. Clinical Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101).

Here, we review an overall effectiveness of interferon-based preparations and interferon biosynthesis inducers for treatment of feline leukemia, as well as development of methodological approaches to improve efficacy of interferon therapy. Feline leukemia is a systemic hematopoietic malignancy caused by a single-stranded RNA retrovirus called Feline Leukemia Virus (FeLV) that leads to lethal outcome within about 3 years after the onset. FelV is widely distributed in population of domestic cats worldwide, being often detected in the blood of wild cats, including those of rare and endangered species. In some regions, FeLV prevalence may be high not only among domestic cats, but among wild as well. Currently, there are several commercially available vaccines to protect cats from FeLV infection (e.g., inactivated whole-virion vaccines such as Nobivac adjuvanted Feline 2-FeLV, two-adjuvant subunit vaccine FeLV-derived protein antigens as well as non-adjuvanted vector DNA vaccine). However, none of such vaccines provides durable protection. In addition, vaccination of cats against FeLV is often associated with development of diverse inflammatory, allergic and shock complications, and highly serious side effects such as developing vaccine-associated sarcoma at the injection site that some researchers connect with use of adjuvants like aluminum salts etc. We briefly describe FeLV virus, pathogenetic parametersassociated with FeLV infection as well as current technologies for preventing and treating feline leukemia. A historic background and current state of interferon therapy for FeLV infection as well as associated neoplastic processes in domestic cats and some wild species are evaluated. Possible interventions aimed at improving efficiency of interferon therapy of feline leukemia based on using new recombinant interferon preparations of various types and subtypes, as well as interferon inducers are discussed. In conclusion, it is noted that another interesting and potentially highly promising option in defining strategy of biotherapy associated with modulating IFN system in FeLV-infected animals might be to use of synthetic inducers triggering endogenous IFN production.

The aim of the study was to obtain and characterize a recombinant vaccine for the immunoprophylaxis of infections caused by Pseudomonas aeruginosa. A set of two highly immunogenic P. aeruginosa recombinant proteins was used to create related vaccine. The first vaccine component was presented by recombinant outer membrane protein F (OprF), whereas the second one — by recombinant atoxic exotoxin A (toxoid). These antigens allowed to develop vaccine inducing immune response against the surface bacterial cues and promote production of neutralizing antibodies against exotoxin A, one of the most dangerous P. aeruginosa pathogenicity factors. Recombinant proteins were synthesized in Escherichia coli cells and isolated by two-step purification. In case of recombinant OprF protein, it was initially (stage 1) isolated as a precipitate containing hydrophobic fraction of producer cell-derived proteins, whereas for recombinant toxoid we purified inclusion bodies. At stage 2, a Ni Sepharose column affinity chromatography was performed. Next, purified recombinant proteins were dialyzed against buffer solution containing 50 mМ Tris-HCl (pH 9.0) and 0.01% Tween 20 followed by filtration sterilization. Three lots of the Pseudomonas Recombinant Vaccine (PRV) were obtained for the study, wherein the recombinant antigens were absorbed with aluminum hydroxide. Recombinant OprF and toxoid protein in vaccine formula were used at a dose of 25 μg and 50 μg, respectively. Absorption completeness of the recombinant antigens within the vaccine was evaluated by polyacrylamide gel electrophoresis with PRV preparations concentrated by ultrafiltration in spin columns. Authenticity of recombinant vaccine was assessed by using customized method by desorbing antigens followed by ultrafiltration concentration in spin columns. Final concentrated desorbed vaccine preparations were analyzed by polyacrylamide gel electrophoresis and immunoblotting, which allowed to confirm presence of specific recombinant antigens in the vaccine. The experimental PRV series demonstrated specific activity (protective properties) after inoculation in animals (mice) by using a dual vaccination protocol, wherein mice were immunized intraperitonially twice with a two-week interval. Next, two weeks later mice were infected by toxigenic P. aeruginosa strain PA-103 culture cells. The index of protective efficiency (IE) for experimental vaccine series was at least a value of three (IE: 3.0–3.3) that was by 1.5-fold higher than that for using single vaccine components (IE: 2.0–2.3). Thus, we confirmed an additive effect of using a set preparation to protect against infection caused by toxigenic Pseudomonas aeruginosa strains.

Introduction.Pathology of the inferior turbinates (IT) was found in 76.1% of patients with difficulty in nasal breathing. If nasal breathing cannot be restored with conservative measures, surgical intervention becomes the method of choice.Materials and methods.Under local infiltration anesthesia, the IT is fractured and retracted medially (medialization). In the anterior section of the HHP, a vertical incision 0.5 cm long to the bone is made, through which the mucosa is peeled off from the bone base of the concha with a raspator-suction and a small tunnel from 2 to 3 cm long is created. shell surfaces and a small area of the mucosa of the lateral surface of the IT and the lateral wall of the nasal cavity. After insertion into the created tunnel of the required size of the "spreader-implant" plate, treated with a thin layer of LTK glue, the shell is slightly pressed with a self-inflating latex-foam rubber swab introduced into the IT for 10–15 minutes. At the end of the operation, after removing the tampon, the edges of the incision are processed with LTK glue.Results.The results of the study demonstrate the effectiveness of the developed method for the rapid restoration of nasal breathing after rhinosurgical interventions. We use this technique in the overwhelming majority of cases of fibrous and bone forms of IT hypertrophy. In cases of the cavernous form, we perform a submucous conchotomy with a shaver, which makes it possible to very accurately remove exactly that part of the concha that violates the patency of the nasal cavity. In all cases, we consider it compulsory to carry out the IT lateroposition according to our method, which significantly improves the result of the operation. The surface of the shell remains completely covered with mucosa and as a result of matching the edges of the incision, the wound surface is absent. At the same time, after the operation, the shell remains full anatomically and functionally, i.e. consists of the bone skeleton and the corresponding volume of soft tissues.Conclusion.The question of how to predict in the long-term postoperative period the normal size of the modeled IT, apparently, is currently not answered even by highly qualified rhinosurgeons. In this regard, there remains a need to search for new technologies for treating patients with chronic hypertrophic rhinitis.

Colorectal cancer occupies one of the leading positions in the world in the structure of cancer incidence. The vital processes of cancer cells largely depend on the production of growth factors and their receptors. One of these is epidermal growth factor (EGFR), which is a tyrosine kinase receptor for cell membranes. Normally, binding of EGFR ligands and transforming growth factor alpha (TGFα) induces receptor activation, which triggers ERK and PI3K signaling pathways that control cell proliferation, migration, invasion, and many other processes. It was found that in 80% of cases, colorectal cancer occurs as a result of EGFR overexpression, which leads to increased growth and division of tumor cells due to hyperactivation of the RAS-RAF-MEKERK signaling cascade. The RAS-RAF-MEK-ERK cascade is a pathway that regulates cell proliferation, cell cycle, and cell migration. In the development of human cancer, mutations of the RAS/RAF family are most often the cause of dysregulation of signal transduction through this pathway. According to current data, about a third of all malignant neoplasms are associated with mutations in the genes of the RAS family, which include HRAS, KRAS, NRAS, RRAS, and other homologous proteins. Proteins of the RAS family are involved in the activation of tyrosine kinase signaling pathways, which leads to gene mutations. This process determines proliferative activity, ability to differentiate, metastasis, avoidance of apoptosis, induction of angiogenesis. Permanent RAS activation leads to malignant cell degeneration. Thus, the expression and mutation of the EGFR gene are associated with various variants of tumor progression and poor prognosis in malignant neoplasms of various localizations. Over the past decades, significant advances have been made in the treatment of metastatic colorectal cancer. However, the expansion of the spectrum of effective anticancer drugs also creates a number of difficulties in choosing the optimal drug therapy regimens in patients with metastases of colorectal cancer.

The purpose and objectives of the study: is to create an experimental model of a chemical burn of the esophagus with alkali to study the pathological transformation of the tissues of the upper gastrointestinal tract.Materials and methods. On the basis of the Department of Experimental Medicine with a vivarium of the Privolzhsky Research Medical University, the study of a chemical burn of the esophagus was carried out on 15 sexually mature male Wistar rats. The burn was simulated by exposure to caustic soda (NaOH) with a concentration of 20 %, 15 %, 10 % and 5 % in a volume of 1 ml. As part of the morphological study, the experimental material was fixed in 10 % formalin. After fixation, the preparations were sent to a standard histological wiring using an Excelsior ES apparatus (Thermo Scientific). Pouring into paraffin blocks using the “HistoStar” filling station (Thermo Scientific), staining with hematoxylin and eosin. For morphometric processing and creation of a video archive of the obtained material, a Leica 2500 microscope, ×4, ×10, ×20, ×40, objective, ×10 eyepiece based on the morphology department of NIITO PIMU was used.Results. Seeding with a 20 % alkali solution for animals turned out to be incompatible with life, since a day after the injection of the substance, 3 rats died, 2 were in an agonal state. Morphological examination revealed total necrosis (100 %) of the epithelial lining up to the muscle layer and partially in the muscle layer. When burned with a 15 % NaOH solution, the males were in a very serious condition, out of 5 inoculated in 2 cases, a lethal outcome was noted on the 1st day. Histological examination revealed massive necrosis (70 %) of the epithelial lining. The effect of 10 % alkali on the general condition of the animals did not show a pronounced severity of injury. Necrosis was diagnosed on 15 % of the area of the epithelial lining. A burn with 5 % sodium hydroxide solution did not provoke a severity incompatible with life. In this condition, focal necrosis was revealed, occupying about 5 % of the organ area.Conclusion. Seeds with 10 % and 5 % caustic solutions are relevant for further experimental research, since they make it possible to test different methods of diagnostics, treatment and prevention of scarring at different depths and morphological features of damage.

Isolated neuropathy of the superficial peroneal nerve (SPN) is a relatively rare type of peripheral neuropathy. It is linked to the mechanical entrapment of the SPN in predisposed locations of its anatomical pathway. Associated clinical findings are insufficient lifting of the latero-dorsal part of the foot, stepping on the lateral border of the foot, and commonly, a strong pain localized in the nerve dermatome.Case report. We describe a case of a 14-year-old female patient with right leg pain lasting 24 months. Repeated neurological examinations with negative findings on electromyography (EMG) were performed. The patient underwent a Steindler surgery for a suspected diagnosis of a heel spur, without any improvement. Despite complex pharmacotherapy, chronic pain developed. The patient was unable to walk, being bound to a wheelchair. Amputation of her lower limb under the knee was also considered. SPN entrapment was diagnosed at a physical examination at EuroPainClinics. Decompression of the SPN under local anaesthesia was performed at the clinic.Results. The symptoms improved immediately after the procedure, and following 2 months of rehabilitation, the patient was completely symptom-free. Her clinical state remains unchanged until this day.Conclusions. SPN entrapment is not a common diagnosis in the group of pain syndromes. Regarding the lower limb, it is imperative to include it on the list of differential diagnoses in cases of pain and functional disorders of the lateral muscle groups of the calf and leg. In the case of SPN entrapment, EMG findings may be negative.

The paper evaluates the effectiveness of the use of therapeutic laser exposure (photobiomodulation therapy – PBMT) to minimize acute pain in the early postoperative period in patients after septoplasty. The study included two groups of patients. Patients of the first group (31 patients) underwent septoplasty with standard management in the postoperative period. Patients of the second group (31 patients) also underwent septoplasty, and then added PBMT to the standard measures of the postoperative period at 3, 6 and 24 h after septoplasty (λ = 0.890 μm, P = 10 W, 2 min) and then intranasally 48 h after septoplasty (λ = 0.630 μm, P = 8 W, 2 min). In patients of both groups, heart rate variability and pain were assessed using a visual analog scale within 48 hours after septoplasty. In patients of the second group, after the use of PBMT, the indicators of heart rate variability had a significantly lower total power, compared with patients of the first group. So, after PBMT, the ultra-low-frequency component of the spectral analysis of heart rate variability in the first group was 18580 ± 2067 ms2, which is significantly higher than in the second group (8086 ± 3003 ms2) (p 2) compared to the second (1095 ± 190 ms2) (p

Despite the active introduction of surgical treatments for cardiac pathology and new synthetic cardiotonic drugs, cardiac glycosides (CG) remain an important component of the pharmacological treatment of heart diseases. Moreover, interest in this group of drugs is only increasing with the discovery of new pharmacological effects, such as antitumor and antiviral. However, despite many years of experience, the issue of managing patients with symptoms of both acute and chronic poisoning with cardiac glycosides remains one of the leading ones. The literature review provides a brief historical outline of cardiac glycoside poisoning and comprehensively describes the pharmacokinetics and pharmacodynamics of this group of drugs. The clinical picture of intoxication is described. We analyzed modern ideas and limitations of using antidote therapy such as digoxin immune Fab-antibody fragments, as well as the features of pathogenetic and symptomatic treatment of patients with acute glycoside poisoning.

Early prediction of disease severity helps clinicians prevent adverse events and/or minimize losses in the event of a life-threatening complication. This provision fully applies to refractory septic shock, in which norepinephrine administration at a dose exceeding 0.5 μg/kg-1/min-1 is needed to maintain mean arterial pressure.The objective: to determine predictors of lethal outcomes in patients with refractory septic shock.Subjects and methods. A retrospective study included 79 patients with refractory septic shock aged from 42 to 74 years (59.7 ± 7.8), with severity of the condition as per SOFA varying from 8 to 16 scores. The predictive value of indicators was assessed using univariate and multivariate analyses.Results. In multivariate analysis, the only significant predictor of an unfavorable outcome was the SOFA score (adj. OR: 1.626 [95% CI: 1.313; 2.014], p < 0.001). Other putative indicators (age, oxygenation index, lactate and procalcitonin concentrations, and norepinephrine dose) had no predictive value.Conclusion: The SOFA score is an independent predictor of lethality in adult patients with refractory septic shock (аdj. OR: 1.26 [95% CI: 1.313; 2.014], p < 0.001). According to the results of the ROC analysis, along with SOFA, norepinephrine dose was also a significant predictor (AUC 0.989 [95% CI 0.934; 1.000], p < 0.001).

The work is devoted to one of the actual problems of modern strabismology — the study of the ability to stereo perception in children with non-paralytic strabismus.Purpose: to study the capability to stereovision with alternating presentation of stereostimuli in children with functional scotoma in non-paralytic strabismus.Patients and methods. 113 children with functional scotoma (FS) in non-paralytic strabismus were observed. We used stereostimuli with different characteristics in the following regimes of presentation: 1) the regime of simple monocular alternating (alternate presentation of an image for the right eye and the left eye); 2) the regime having an “empty” interval (black background) between monocular phases; 3) the regime having a binocular phase (a binocular image containing details corresponding to the stimuli for the right eye and the left eye) between monocular phases.Results. It was found that in 23 (20,3 %) children, the ability to stereo perception was completely absent. All these children had stable total FS (monocular vision). In the remaining 90 children (with unstable or regional FS), the ability to stereo perception was shown with some stimuli in some modes of their alternating presentation. For stimuli with a central arrangement of linear parts, the stereo effect was possible when they were presented in an alternating mode with an “empty” interval lasting from 20 to 70 ms in combination with the duration of monocular phases from 30 to 90 ms. For stimuli with a peripheral arrangement of linear elements, 22.1 % of children were able to stereo perception not only in the “empty” interval mode, but also in the simple alternation mode. At the same time, the greatest number of children capable of stereo perception was detected when using the mode with an “empty” interval of 30–60 ms and a duration of monocular phases of 40–60 ms. With random-dot stimuli, none of the children in this group were capable of stereo perception.Conclusion. Our results suggest that even in patients with FS in non-paralytic strabismus, stereo perception is possible under the conditions of alternating presentation of stimuli with certain characteristics. In this case, the most likely appearance of a stereo effect with stimuli containing peripheral linear elements that create a stereo effect when presented in an alternating mode with an empty interval between monocular phases.

Background: Most patients with severe respiratory failure in intensive care unit (ICU) require bed rest. The limitation of physical activity leads to some adverse consequences such as ICU Acquired Weakness (ICUAW). Progression of respiratory failure, including that caused by the new coronavirus infection (COVID-19), can lead to the development of acute respiratory distress syndrome, the treatment of which contributes to a combination of risk factors for the development of ICUAW. Traditional diagnostic methods have certain limitations. Muscle ultrasonography is a modern tool for early detection of muscle mass loss. Aims: To compare different methods of early ICUAW screening and to estimate the incidence and peculiarities of ICUAW in patients with respiratory failure of infectious genesis. Methods: 31 patients with severe coronavirus pneumonia (COVID-19 “+”) and 13 patients with viral and/or bacterial lung infection (COVID-19 “-”) were included in the study. The muscle mass loss percent from day 1 to day 7 was higher in the COVID-19 “-” group (p=0.022). These patients also had longer durations of the ICU and hospital stay but a significantly lower mortality (2.5 times). Results: The analysis of the parameters of deceased and living patients regardless of the lung damage etiology showed a correlation between the indices of hand grip strength dynamometry (handgrip test) and ultrasonography of the thigh muscles: F1 and D1 (rho=0.6, p=0.003), F1 and S1 (rho=0.6, p=0.005), D1 and F7 (rho=0.9, p=0.001). In addition, the examined levels of the ICUAW markers were associated with age - F1 (rho=-0.6, p=0.001), D1 (rho=-0.4, p=0.003), S1 (rho=-0.4, p=0.004). Conclusions: During the critical illness, ICUAW develops by the 3d day of bed rest in two thirds of patients with respiratory failure of different infectious genesis. The correlation between the investigated markers of ICUAW and age indicates that elderly patients are the most vulnerable category in respect to the formation and progression of muscle weakness in the ICU. The handgrip test can serve as a reliable and simple method of ICUAW screening. Early identification of patients with ICUAW should provide the improvement of nutritional support and individualization of rehabilitation.

Introduction. Endoscopic dextranomer/hyaluronic acid copolymer (DxHA) injection is the most commonly used minimally invasive method of surgical treatment of vesicoureteral reflux (VUR) in children.Purpose of the study. To estimate the accuracy of logistic prognostic models and artificial neural network for prediction a single endoscopic injection DxHA in VUR.Materials and methods. We used endoscopic DxHA in 582 patients (783 ureteric units) of all grades reflux (I - 20, II - 133, III - 443, IV - 187), 53 ureters had complete duplication. A total effectiveness of surgery was 53.2%. A binary logistic regression model and an artificial neural network (multilayer perceptron) were created, taking the following as independent variables: grade of reflux, the patient's age and sex, the ureteral duplication and ureteral dilatation index.Results. The univariate logistic regression showed that the selected predictors were strongly related to the outcome of the treatment. Binary logistic regression and neural network developed high accuracy of the predictions, area under ROC-curve was 0,7 for logistic regression model (a sensitivity of 70.7%, and a specificity of 66.3%) and 0.74 for artificial neural network (a sensitivity of 85.5%, a specificity of 65.3%). Synaptic neural network weights and logistic regression parameters were used in a scoring model to predict the outcome of a single endoscopic injection of DxHA in 2 independent hospitals. An outcomes analysis using predictive models in independent clinics showed a good quality of prediction both with the use of logistic regression (75% and 90% of the correct prognosis) and using a neural network (89.7% and 77% of the correct prediction).Conclusion. An artificial neural network and a binary logistic regression model are an effective tool to assist urologists in identifying and applying endoscopic treatments for VUR in children.

Introduction. Currently, a large number of techniques are used in the treatment of patients with ureteral stones: extracorporeal shock-wave lithotripsy (ESWL), retrograde ureterolithotripsy (RULT), laparoscopic and retro-peritoneoscopic ureterolithotomy.Purpose of the study. To evaluate the possibilities and effectiveness of percutaneous antegrade ureterolithotripsy in the treatment of patients with proximal ureteral stones in comparison with transurethral contact ureterolithotripsy.Materials and methods. Twenty-eight patients with urolithiasis were treated, who underwent percutaneous antegrade ureterolithotripsy (PAULT) and 27 patients of the control group, who underwent RULT. All patients included in the study underwent a standard preoperative examination: complete blood count and urine analysis, bacteriological urine culture, biochemical tests, and X-ray research methods. Plain urography, renal ultrasound, computed tomography were used as imaging methods. The OLYMPUS URF-V3 8.4 Ch (Olympus Europa SE & Co. KG., Germany) video uretero-renoscope was used for PAULT in patients of the main group; lithotripsy was performed using thulium laser. The results of the study were subjected to statistical processing in order to determine the statistical significance of the differences between the data obtained. Quantitative variables were described using the arithmetic mean (M) and standard deviation (5). Qualitative variables were estimated by absolute and relative frequencies (percentages). The data were considered reliable at p values < 0.05.Results. The average time of surgical intervention in patients of the main group from the moment of placement of the ureteral catheter was 47 ± 12 min, with access without preliminary renal catheterization: 28 ± 4 min. Average time of surgical intervention in patients of the control group: 42.0 ± 10.7 minutes. The presented data indicate a significant (p < 0.05) greater cases' number of complete stone removal among patients of the main group compared with patients in the control group (74.0%).Conclusion. PAULT is preferred among choice treatment methods for patients with proximal ureteral large stones, for whom RULT and ESWL cannot be performed with a high level of “stone-free” rate and a minimum number of complications.

The subjectof the research is the categories “the spirit of the law” and “the letter of the law” in their regulatory sense.The purposeof the research is to confirm or disprove hypothesis that the concept of “the spirit of the law” fundamentally impacts the methodology of legal research, legal con-sciousness and the mechanism of legal regulation.The methodologyfor researching the spirit of the law presupposes an adequate selection of means of knowledge. It is impossible to study the spirit of the law with the tools of ma-terialism or economic determinism. The spiritual-moral, axiological, metaphysical, systemic methods and the method of synthesis are preferred for the study of the spirit of the law. The legal system of society ceases to meet the elementary requirements of the formation of a person's legal consciousness, his improvement and spiritual health when the spirit of the law is denied. It is generally impossible to understand how law functions and achieves a regulatory effect using the dogmatic, positivist approach to law as a dominant method of cognition.The main results,scope of application. The problem of the operation of the spirit of the law is one of the ignored problems of legal practice. If the legal act is at odds with the spirit of the law, the law enforcer faces a difficult choice: either morality or law. This dilemma is fraught with serious conflicts both in the mental, psychological sphere of the law enforce-ment officer himself, and between all participants in the legal process. Every person has an internal imbalance if he makes decisions and performs actions that are contrary to his con-science. Jurisprudence, which adequately perceives the subordination between the spirit of the law and the letter of the law, warns against the temptation to consider law as a sphere independent of spiritual absolutes. The current law is not exactly what is set out in the texts of regulatory acts. Distinguishing between the spirit of the law and the letter of the law, therefore, requires special types of interpretation of texts (broad, restrictive), as well as analogies of legislation and analogies of law.

Introduction. The issue of protection against vaccinepreventable diseases has acquired new urgency in connection with the decrease in the vaccination rate established by WHO against the background of the COVID-19 pandemic. This creates the conditions for outbreaks and puts patients with immunopathological diseases at particular risk, who are most often not vaccinated from the moment of diagnosis Purpose of the study – to assess the safety of specific antibodies to measles, mumps, rubella and diphtheria in children with JIA, depending on the duration of vaccination, the duration of the disease and the therapy received.Materials and methods. The vaccination rate of 171 children with juvenile idiopathic arthritis (JIA) aged (11,31±0,31 years) with the duration of the disease at the time of examination was 4,69±0,29 years, who had previously received 1-2 vaccinations against measles, mumps, rubella and 3-6 vaccinations against diphtheria. Antibodies to these infections were determined by ELISA.Results. 42.1% of children had no protective titers of antibodies to measles, 19,9% – to mumps, 9,4% – to rubella and 16,4% – to diphtheria. Among 93 vaccinated and revaccinated patients, there were no protective titers of antibodies to measles – 40,9% (38 children), mumps – 13,9% (13 people), rubella – 5,4% (5 children), and among 78 vaccinated once, respectively: measles – 43.6% (34 children), mumps – 25.6% (20 children), rubella – 14,1% (11). The level of protection against diphtheria was comparable for those who received 3-5 vaccinations. Depending on the therapy, 3 groups were identified: group 1-71 children received metatrexate and glucocorticosteroids, 2-82 children received modifying anti-rheumatic drugs (DMARD) and 18 children without this therapy (Group 3). Children of the 2nd group were on average older (12,48±0,42 years) than in the 1st and 3rd groups (10,04±0,48 and 10,96±0,96 years, respectively), they had significantly more frequent systemic variant and polyarthritis (64,6% compared to 36,6% and 16,7%, px2˂0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. The average level of antibodies to measles in children of group 2 (0,32±0,07 IU/ml) was 2,8 times less than in group 3 and significantly less than in group 1 (0,78±0,16, Pt=0.009), the average value of antibodies to rubella was also significantly less in group 2 (84,48±7,34 IU/ml) than in group 1 (109,73±8,09, Pt=0,022) and in group 3 (120,01±15,42, Pt=0,042). The analysis showed that the safety of antibodies to antigens of live vaccines, especially against measles, is negatively affected by the duration of the disease and the nature of therapy. Children who received combined therapy with anti-TNF, anti-IL-6 and anti-CD-80 drugs had a longer duration of the disease (7,5±0,97 years)=0,00082 compared to those who received only anti-IL-6 (2,9±0,7 years) and antiTNF therapy (6,1±0,5 years) and with a comparable number of vaccine doses received, significantly lower average values of antibodies and a larger number of unprotected ones.Conclusions. The duration of the disease, the lack of timely age-related revaccinations, as well as the presence of combination therapy aimed at suppressing various mechanisms of the immune response in children with JIA are factors that lead to an increase in the number of unprotected from controlled infections. Immunity to measles suffers the most – 40.9% of revaccinated people are unprotected.

The subject of this article is the norms of contemporary Russian law. The purpose of the article is the author's vision of the problem concerning the structure of the norms of contemporary Russian law. The following tasks were solved to achieve this goal: 1) to show the importance of the structure of the rule of law; 2) to analyze the arguments of both supporters and opponents of the three-tier structure of the logical rule of law; 3) substantiate the two-tier structure of prescriptive norms; 4) determine the status of specialized legal norms and their types; 5) to substantiate the author's vision of specialized legal norms.The author uses a system of methods such as: general philosophical (dialectical-materialistic), general scientific (analysis and synthesis, induction and deduction, etc.), special (philological, etc.), private scientific (formal-dogmatic, interpretation, etc.) methods. Conclusions. The author is not a supporter of the three-tier structure of the logical norm of law. It seems that theory and legal practice should focus on the structure of norms-prescriptions (regulatory and protective), respectively highlighting the hypothesis and disposition and the hypothesis and sanction. As for the specialized norms of law (declarative, norm-principles, definitive, operational), they include such structural components as a supposed hypothesis and a real disposition. Conflict norms as a kind of specialized norms include a real hypothesis and a real disposition.

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components.

Background. Arterial hypertension is a multifactorial disease accompanied by an increase in systolic and/or diastolic blood pressure above the established values. Uncontrolled blood pressure can cause various complications, which will lead to either disability or death of the patient. Aim. To assess the compliance of the level of doctors knowledge with current clinical guidelines in the treatment of arterial hypertension. Materials and methods. Within the framework of the PHYSTARH multicenter study, we presented the results of an anonymous prospective survey to assess the level of physicians knowledge and pharmacotherapeutic preferences in the treatment of arterial hypertension. Results. The study involved 425 physicians from 9 regions of Russia: Belgorod, Voronezh, Lipetsk, Chelyabinsk, Moscow, Krasnodar Territory, Primorye Territory, the Republic of Adygea and Tatarstan. In the course of the analysis, we revealed an insufficiently high level of the respondents knowledge in the treatment of arterial hypertension. Less than half of the respondents chose the indication of combination therapy as a therapeutic intervention in which the effectiveness of lowering blood pressure increases about 5 times more than when the dose of the original drug is doubled; correctly indicated the pharmacological group for the proposed drug (methyldopa), determined the indication for the use of aspirin in patients with hypertension, selected the optimal antihypertensive therapy for the proposed clinical situations, indicated absolutely contraindicated antihypertensive drugs in pregnancy and chronic obstructive pulmonary disease. Conclusion. The need for additional educational activities among physicians was established to improve the quality of knowledge on the basic aspects of hypertension, because a significant number of key questions on this topic cause difficulties for respondents.

Aim – to study the relationship between body composition and bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA).Material and methods. 68 postmenopausal women, median age 59 [54; 63] years, with RA were included in the study. Bone mineral density (BMD) and body composition were assessed with dual energy X-ray absorptiometry.Results. 33 (48.5%) women had osteopenia, and 17 (25.0%) – osteoporosis (OP). Low lean muscle mass was found in 10 (14.7%) patients. There were positive correlations between different areal BMD and body weight, trunk fat, trunk lean muscle mass and total lean muscle mass. In the multivariate linear regression analysis total lean muscle mass was associated with BMD of lumbar spine (β=0.638; p=0.001) and total hip (β=0.473; p=0.008), and appendicular lean muscle mass, estimated using the appendicular muscle index, with femoral neck BMD (β=0.360; p=0.014).Conclusion. 73.5% of patients with RA had a reduced BMD, and 14.7% women – low muscle mass. The revealed significant association between the lean muscle mass and BMD of lumbar spine and proximal femur indicates the importance of detecting and correcting low lean muscle mass, as well as preventing its decline in order to prevent loss of BMD and osteoporotic fractures.

The article presents a review of research conducted by foreign psychologists on the role of sign language in the communicative, cognitive and social development of children with hearing disorders. Each national sign language is a kind of linguistic system that has a complex grammar, specific vocabulary and syntax. The main problems that arise in deaf children in the situation of ignoring the possibilities of sign language are discussed. A number of studies have shown that deaf children of deaf parents are not inferior to hearing children in their cognitive capabilities, that the use of sign language has a positive effect on cognitive functions and leads to greater creative activity, a better understanding of spatial relationships, and greater flexibility in solving problems. Researchers recognize the need for early acquisition of sign language by deaf children, even in case of use of modern rehabilitation techniques. It is sign language that could make up for the lack of communication tools characteristic of the initial stages of a child's mental development, which would serve to develop the cognitive sphere and personality and create conditions for emotional well-being. The review focuses on the difficulties in using sign language that are observed when selecting diagnostic tools and conducting psychological examinations.

The views of Russian lawyers of the second half of the 19th century regarding the political and legal concepts of Catherine II are considered. Attention is paid to educational and scientific works on the history of Russian law and Russian state law, published in the second half of the 19th century. The author proceeds from the fact that professional and class factors influenced the assessment of the empress’s political and legal ideas by Russian lawyers. It is shown that the professional one consisted in the official introduction by Catherine II into the Russian political and legal turn of the achievements of European educators, contributing to the formation of a tendency towards the prevalence of the law over the will of the monarch. Particular attention is paid to the fact that most of the representatives of the legal profession were of noble origin, the 18th century was a relatively recent past for them, and family traditions and class identity formed a positive idea of Catherine’s rule and the empress herself. At the same time, it is shown that researchers associated with the merchants paid attention to the fact that the empress’s selective acquaintance with the works of European thinkers left her without attention to branches of law, for example, civil law, which was of fundamental importance for the estate employed in commerce and industry. The author notes that historians of law paid maximum attention to the state-legal concepts of the empress. It is proved that the conclusions made in the study correlate with the ambiguous assessments of Catherine II both among historians and Russian society as a whole.

The author examines the evolution of Cuban medical diplomacy under the governments of Raul Castro and Miguel Diaz-Canel. The author shows that the essence of the Cuban national health system, which developed after the 1959 Revolution, is its accessibility. At the time of collapse of the socialist bloc, the Cuban government managed to maintain and surpass the achieved level of development of medicine. The presence of a large number of medical specialists allows the socialist government of Cuba to organize cooperation with dozens of states around the world. Under the leadership of Castro, the export of medical goods and services has become the main source of foreign exchange earnings and a driver of economic growth, and medical diplomacy has become an important tool of soft power, which is used to form an attractive image of the state among the world community. In doing so, the government combines pragmatism, increasing the cost-effectiveness of the programs, and altruism, providing gratuitous aid to the countries most in need. The main difficulty in developing this direction in Cuba’s foreign policy is associated with the North American embargo. In 2018, the US government launched a large-scale campaign to discredit Cuban medical internationalism. This policy aims to further restrict already limited access to essential resources. The country was also negatively affected by the ‘right turn’ in the region: the neoliberal governments of several countries refused to continue medical cooperation with Cuba. At the same time, the trends of recent years indicate an imminent repetition of the shift to the left, which in the future can significantly strengthen the Cuban positions in the region. In addition, the coronavirus pandemic showed that the world community needs a rapid medical response force with Cuban missions serving as a basis thereof.

The article describes results of a study on the level of mental abilities in mod- ern children and in their peers from the last third of the 20th century. It was assumed that the mental abilities of modern preschoolers differ from those of their peers who were brought up in the pre-digital era. Developmental levels of sensory and intellectual abilities of preschool children aged 6-7 years (N=156) (studies from the 1970s), preschool children aged 5-6 years (N=100) (studies from the 1990s) were compared to those of children aged 5-6 years (N=184) and children aged 6-7 years (N=236) who attended preschool departments in Moscow, Moscow region, Smolensk and Ivanovo in 2015-2020. The level of development of sensory and intellectual abilities was assessed using specific tests (“Standards”, “Perceptual modeling”, “Schematization”, “Systematization”). The data was processed using statistical methods: descriptive statistics, the Fisher test, the Student’s t-test for samples with equal variances and samples with different variances. The results of the study show that the level of some sensory abilities of 21st-century preschoolers is lower than that of their 20th-century peers. On the other side, the level of intellectual abilities of preschoolers who were brought up in the early 21st century is higher than that of their peers from the 20th century.

Purpose: to establish the frequency and clinical significance of mutant variations of the HFE gene polymorphism in chronic hepatitis B (CHB) in children with iron overload syndrome (IOS).Materials and methods: 60 children with chronic hepatitis B with iron overload syndrome (IOS) were examined. When distributing children into groups, we took into account the criteria we developed for assessing the degree of life expectancy in children with CHB: CST>0.5 – mild degree of life expectancy (43,3% of children), CST˃0.5 – mild degree of life expectancy (43,3% of children), CST˂0,5 – moderate severity of life expectancy (31,7% of children) and CST˂0,2 – severe degree of SPL (25,0%). Virological verification of HBV was performed by ELISA and PCR. Using PCR Real Time and molecular genetic analysis, HFE gene C282Y, H63D, S65C mutations were detected from amplified DNA using the PRONTO Hemochromatosis reagent kit (Israel). The transferrin saturation coefficient (CST) was calculated using the formula CST = sTfR / log10.Ft. Results:Results: The study of the hemochromatosis gene HFE showed that the overwhelming majority (84,0%) of children with CHB with IOS were carriers of heterozygous, phenotypically different, mutant types. And only 16,0% of sick children were homozites of the wild (normal) HFE gene. Analysis of the phenotypic polymorphism of the hemochromatosis gene HFE revealed the presence of three point heterozygous mutations: H63D, S65C and combined variations in H63D / S65C, the latter of which is associated with severe forms of CHB and severe IOS.Conclusion. Children with CHB with IOS are characterized by a high incidence of heterozygous mutations in the HFE gene, the phenotypic manifestations of which were S65C, H63D, H63D / S65C. The comparability of the heterozygous combined mutation H63D / S65C with severe forms of CHB and a severe degree of IOS gives grounds to consider this phenotype of the HFE gene as a factor in the progression of the disease.

The current paper has presented the estimation results of ecological adaptability of the alfalfa samples. The purpose of the work was to assess the productivity and quality of green mass of the alfalfa samples from the IPI plant genetic resources gene bank and to identify the most adaptive ones according to the trait ‘green mass productivity’ and ‘raw protein percentage’. The study of the collection alfalfa samples was carried out in the southern part of the Rostov region on the plots of the “ARC “Donskoy” in the breeding crop rotation of perennial grasses in 2016–2018. The objects of study were 30 alfalfa samples from the collection of N.I. Vavilov IPI from different countries (Canada, the USA, Peru, France). The variety ‘Rostovskaya 90’ was used as a standard one. The estimation of alfalfa samples on the presence of adaptive properties in them according to the trait ‘green mass productivity’ showed that the most valuable samples in present practical breeding work are the samples ‘K-32873’, ‘K-33299’, ‘K-42684’, ‘K-42249’, ‘K-78803’ with weak responsiveness to changes in environmental conditions; the samples ‘K-36104’, ‘K-48778’, ‘K-42694’, ‘K-45715’, ‘K-47800’, ‘K-47802’, ‘K-43260’ with high resistance to stress; the samples ‘K-43272’, ‘K-50545’, ‘K-47806’, ‘K-47807’ with genetically flexible genotypes. When breeding according to the trait ‘raw protein percentage’, the samples ‘K-47807’, ‘K-47804’, ‘K-42712’ possessing a high raw protein percentage and resistance to changes in this trait are important for further work.

The objective: to compare efficacy and safety of Intellivent-ASV® with conventional ventilation modes during weaning in the patients after cardiac surgery.Subjects and methods. In this randomized controlled trial, 40 adult patients were ventilated with conventional ventilation modes and 40 with Intellivent-ASV after uncomplicated cardiac surgery. Eight physicians were involved in the study.Care of both groups was standardized, except for the modes of postoperative ventilation.We compared:- The physician’s workload, through accounting number of manual ventilator settings and time they spent near the ventilator in every group,- Duration of tracheal intubation in ICU,- Evaluation of ventilation safety by considering driving pressure, mechanical power, positive end expiratory pressure, and tidal volume level,- The frequency of adverse events, postoperative complications, and lethality.Results. There were significant differences in the duration of respiratory support in ICU: 226 ± 31 min (Intellivent Group) vs 271 ± 78 min (Control Group) (p = 0.0013).In Intellivent Group, the number of manual ventilator settings and time spent by physicians near the ventilator before tracheal extubation were significantly lower: 0 vs 4 (2–6), and 35 (25–53) sec vs 164 ± 69 sec respectively (p < 0.001 in both cases).Intellivent-ASV provided significantly more protective ventilation through reduction in the driving pressure, tidal volume, FiO2 and PEEP levels but no difference was noted between paO2/FiO2 ratio. ∆P and Vt were significantly lower in Intellivent Group – ∆P on mechanical ventilation was 6 (5–7) cm H2O vs 7.25 (6.5–9.5) cm H2O (p < 0.001); Vt on mechanical ventilation was 6 (5.2–7) vs 7 (6–9.5) ml/kg/PBW (p = 0.000003). PEEP and FiO2 levels were also significantly lower in Intellivent Group, PEEP on mechanical ventilation was 5 (5–7.5) cm H2O vs 7 (5–11.5) cm H2O and FiO2 level was 26 (22–30) % vs 34 (30–40) %.There were no significant differences between the groups in frequency of adverse events and duration of ICU and hospital stay.Conclusion. Application of Intellivent-ASV mode after uncomplicated cardiac surgery provides more protective mechanical ventilation and reduces the physician’s workload without compromising the quality of respiratory support and safety of patients.

The subject of research is the concept of practical ethics by Anatoly F. Koni who was an outstanding Russian lawyer in the late 19th – beginning of 20th centuries. Particular attention is paid to his ethical research in the article. The interest in this area is not accidental. The principles of professional ethics formulated by Koni have become largely a model for Russian lawyers.The purpose of the article is to identify the stages of the formation of Koni’s ethical theory, its main elements and sources, which made it possible to reconstruct the ideas of the famous lawyer.As the main research methods the authors applied the problem-chronological approach and the systemic approach, considering Koni's ethics as an emerging theory, which turned into a complete concept in the 1920s. The structure of the ethical concept was outlined by Koni in 1919 in the Program "Ethics of Cohabitation".The main results, scope of application. It was revealed that for Koni issues of legal ethics were only part of his colossal work on ethics. He has been developing ethical themes since the 1880s. He formed the foundations of the theory, developed the main types of ethics at the beginning of the twentieth century, and the idea crystallized in the 1920s. In particular, he formulated the types of ethics: public order, financial, literary, public events, medical, conscience, national, personal behavior, etc. After going through three successive stages in the course of the study Koni developed the foundations of practical ethics, which could serve as a model for creating relations in a new society as he assumed. Koni chose ethics as the object of his scientific research. He made great efforts to develop his deontology, which we will not find any analogues of. He contributed to the philosophy and philosophy of law. He summarized all his works on deontology in the work "Ethics of the Cohabitation", which was prepared in 1927, but have never been published.Conclusions. Koni not only collected moments of crisis in contemporary ethical manifestations, analyzed the works of the main deontologists, analyzed in detail the types of ethics (some of which he formulated for the first time in science), but also formed a harmonious practical ethics of human personal behavior. At the same time Koni assumed such a development of a sensitive personality that would be able to take into account the smallest men-tal characteristics of other people and behave tactfully as much as possible. He returned to ethical issues in numerous works over and over again whether he wrote about social ills, about psychology, about expertise. He saw the main causes of deformations in the destruction of ethical principles. "Moral perversions" threatened the very existence of the state. He perceived the fall of Russia in 1917 as a logical completion of the disintegration of ethics. Koni saw a future salvation in the revival of Russia. His ethical ideal was Christian in nature in many ways, although Koni himself almost never connected ethics with religion in his works. Here he acted as a Kantian, as a supporter of the categorical imperative.

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p < 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p < 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p < 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.

The article considers a part of the essay “Coverage of classical sources on the history of Buddhism” by the outstanding Buryat scholar Lama Kensura Ngawang-Nima, dedicated to the history of the spread of Buddhist teachings in Mongolia. Some biographical information of the author of the essay is introduced. The materials of the fragment under study are presented, on the basis of which we can say that the author divides the spread of Buddhism in Mongolia, like many researchers, into three stages. Secular and religious figures who played an important role in the spread and formation of Buddhism among the Mongols are noted in the article. It is indicated that when writing his historical treatise, Kensur Ngawang-Nima relied on the works of his famous predecessors, such as the 5th Dalai Lama Ngawang Lobsan Gyatso, Taranatha Gunga Nyingbo, Thukwan Chokyi Nyima, etc., and a part of the essay devoted to the history of Buddhism in Mongolia, based on the work “Golden Book / Altan Debter” by the famous Mongolian scholar Lama Shagdaryn Zava Damdin. The peculiarity of the historical treatise under study is that it is the only known and published work written by a Buryat in the Tibetan language in the genre of Tibetan historical literature — choichzhun.

Annually, up to 300 thousand new cases of kidney cancer and more than 134 thousand deaths associated with this disease are registered in the world. In the Russian Federation in 2019, 20,758 patients with a newly diagnosed renal cell carcinoma were registered; it should be noted that at the end of 2019, 177,755 patients with this diagnosis were registered. The issue of renal cell carcinoma metastasis seems to be quite relevant. The most common organs for metastatic renal cell carcinoma are lungs (up to 55 %), lymph nodes (up to 34 %), liver (up to 32 %), bones (up to 32 %), adrenal glands (up to 19 %), contralateral kidney (up to 11 %) and the brain (up to 5.7 %). The incidence of skin metastases in renal cell carcinoma ranges from 2.8 to 6.8 %, according to various authors.Our publication presents a case of treatment of a patient with a rare localization of renal cell carcinoma metastases in the external genital organs. The patient underwent palliative nephrectomy and vulvectomy. Taking into account the data on the prevalence of the disease, therapy with cabozantinib is carried out. Cabosantinib is an inhibitor of the tyrosine kinase domains of a number of growth factors, angiogenesis, abnormal bone remodeling, metastasis, and drug resistance.

The aim of this work was to attempt to analyze the demographic structure, clinical and radiological forms of tuberculosis and COVID-19, as well as the course and outcome of the disease in patients with this coinfection in the light of a new and still poorly understood problem of the mutual influence of tuberculosis and COVID-19.Material and methods. Examination and treatment were carried out in the infectious-tuberculosis departments of the Botkin Clinical Infectious Disease Hospital. We examined 63 patients identified in the first seven months of the epidemic in the multimillion city of St. Petersburg (Russia). Tuberculosis, confirmed by conventional bacteriological and molecular genetic methods, had an active phase in all of them. The new coronavirus infection was verified by a positive polymerase chain reaction test for SARS-CoV-2.Results. Tuberculosis in 43 patients was detected simultaneously with COVID-19, in 20 people it preceded coronavirus infection. Disseminated forms of tuberculosis prevailed - 50.8%; in 36.5%, two or more organs and systems were affected, which is associated with a high proportion (54.0%) of HIV-positive patients with an advanced stage of the disease. Lung damage with COVID-19 was noted in 36.5%. Fatal outcomes ended in 20.6% of cases of coinfection, the structure of the causes of death is given.Conclusion. An assumption was made about the possibility of an aggravating effect of tuberculosis on COVID-19 in the case of severe or widespread forms of these diseases. The negative influence of HIV infection on the outcome of the disease has also been shown. Further follow-up is required to identify more reliable associations between tuberculosis and COVID-19.

This article presents data on clinical ophthalmological manifestations of COVID-19 described in the literature, clinical examples that we met in pandemic conditions, COVID-19 including early and late manifestations, as well as references to studies conducted decades ago and aimed to evaluate the effects of coronavirus infection on the visual organ. The purpose of the most studies was to study the effect of COVID-19 on the visual organ indicate that the most common ophthalmological manifestation of this disease is conjunctivitis, which occurs in 3–10 % of cases. Our observations showed that patients with COVID-19, when applying for an appointment with an ophthalmologist after 1–3 months, make complaints about the feeling of dryness, discomfort in the eyes, itching and redness of the eyelids. These complains arose immediately after the illness and persisted during the above terms. This phenomenon can be explained by the fact that any inflammatory process occurring on the eye surface disrupts the process of lacrimation and leads to the emergence of dry eye syndrome. It is necessary to pay close attention to complaints from the visual organ not only in patients with COVID-19 in the early stages of the disease, but also in the coming months after stopping the acute pathological process. As studies have shown, coronavirus can involve the posterior segment of the eye in the pathological process, since this virus has a retinotropic effect. This hypothesis can be confirmed by the reports of several authors who studied with optical coherence tomography (OCT) the state of the retina 11–33 days after the onset of symptoms in patients with COVID-19. OCT data indicate the presence of hyperreflexive zones at the level of the ganglion cell layer and the plexiform layer, the severity of these zones being greater in the papillomacular bundle region. In addition, cases of thromboembolic complications affecting the vascular system of the eye are described. Considering the fact that in the development of thromboembolism of the central artery and retinal vein, therapy is as effective as possible in the first hours from the beginning of this pathological process development, close attention should be paid to patients’ complaints to visual impairment occurred against the background of coronavirus infection. The data presented in this article open up a range of possibilities for conducting new scientific research that will help to preserve the vision and health of our patients as effectively as possible.

Aim: to assess a rate and range of genetic and acquired thrombophilia in onco-gynecologic patients with ovarian cancer, uterine corpus cancer and cervical cancer.Materials and Мethods. A prospective controlled cohort non-randomized interventional study was conducted: within the years 2014 to 2020, there were examined 546 women with genital malignancies, divided into 2 groups: group I – 155 cancer patients with former thrombosis, group II – 391 women with female genital cancer without former thrombotic complications. Control group consisted of 137 patients with benign female genital tumors. The spectrum of circulating APA was studied: antibodies to â2-glycoprotein I (â2-GPI), annexin V and prothrombin as well as genetic thrombophilia due to mutations genes encoding factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) including polymorphism in genes for prothrombin, platelet glycoproteins and plasminogen activator inhibitor-1 (PAI-1).Results. It was found that frequency of circulating APA as well as incidence rate of genetic thrombophilia between cancer patients from group I vs. group II significantly differed: APA in group I vs. group II was 86 (55.5 %; p < 0.01) vs. 92 (23.5 %) compared to 7 (5.1 %) in control group. Genetic thrombophilia was dominated in group I by mutated MTHFR (92.9 %), polymorphismin PAI-1 (28.4 %) and platelet glycoprotein (44.5 %) that were significantly higher (p < 0.05) compared to group II and control group. Hence, it allows to suggest that such identified thrombophilia markers are largely associated with a risk of developing thrombotic complications.Conclusion. Detected high percentage of patients with circulating APA and genetic thrombophilia among cancer patients with former thromboembolic complications corroborate a role for genetic and acquired thrombophilia in developing pre-thrombotic condition. Detecting a range of circulating APA and genetic thrombophilia allows to identify patients who might be referred to a high risk of thrombogenesis and require to preventive application of anticoagulant therapy.

The article outlines the theoretical basis of the competence approach in early intervention aimed to children and their families, developed by the author. The concept, structural and functional aspects of competence are considered from the perspective of the theory of procedural analysis. Seven levels of competence development are identified: situational interest, pre-competence, minimal, initial, extended, adaptive and advanced competence. The main types of competencies in young children have been determined, including individually oriented, socially oriented, executive, universal and complex ones. A description of the properties of competencies is shown, including spontaneous activation, associated positive affect, openness and flexibility, the tendency towards explicitness, the ability to combine with other competencies. The following principles of the development of competencies were revealed: naturalness, involvement, autonomy, explicitness, balance, complexity and de-contextualization. The application of the approach is illustrated by 2 cases. The possibilities and limitations of the approaches are being discussed.

Relevance. The problem of respiratory diseases has been studied for a long time by many specialists and remains relevant to this day. This problem has been of interest to researchers for many years due to several factors. In many studies, it was demonstrated, that a signifcant relationship exist between the upper airway condition and jaw growth, craniofacial skeleton and TMJ dysfunction. Lateral cephalometric radiographs (LCRs) have been used to assess skull parameters, jaw bones and teeth, the morphology of the upper airway, the severity of airways obstruction and adenoid size. The present study aimed to determine the reliability of LCRs compared to CBCT in the assessment of the upper respiratory tract in order to determine which variables are reliable for potential use in clinical diagnosis.Aim. To analyze the literature on the effectiveness of the using Lateral Cephalogram in the assessment of the upper airway.Materials and methods. Electronic search of articles was carried out using search engines and databases: Cyberleninka, eLIBRARY, Google Scholar, Pub Med, SCOPUS. The publication date criterion was selected from January 2010 to January 2021. The electronic search was conducted using the following keywords: lateral cephalogram, upper airway, cone-beam computed tomography. A total of 10 studies from the literature met the selection criteria.Results. CBCT provides a good estimate of the transverse dimensions and volumetric measurement of the airway space. Linear measurements of CBCT and LCRs were quite reliable and reproducible. The most diffcult to study and differentiate area is the oropharynx, the variability of the pharyngeal segment cannot be predicted by LCs. LCRs method is advisable for adenoid pathology diagnosis due to its fnancial acceptability and availability. The cephalometric headflm provides a good general overall indicator for nasopharyngeal airway patency, adenoidal hypertrophy.Conclusions. The traditional lateral cephalogram remains not only a standard, reproducible and cost-effective diagnostic method in orthodontics, but also a reliable initial tool for screening upper airway obstruction, studying the nasopharyngeal morphology and assessment of adenoid size. Based on our results, the measurement of the nasopharyngeal space on lateral cephalograms can be used as an initial screening method to estimate the nasopharynx volumes. The results demonstrate that a lateral cephalogram can provide valuable information about the severe limitations and nasopharyngeal morphology

Gaucher disease (GD) is the most common lysosomal storage disorder, resulting from a deficiency in the activity of a lysosomal enzyme glucocerebrosidase, which is involved in the catabolism of sphingolipids. The phenomenal progress in understanding the pathogenesis and development of specific therapy of this disease over the past 60 years dramatically changed the clinical phenotype of GD, turning a severe progressive disorder into an asymptomatic metabolic defect. The evolution of the understanding of GD associated with fundamental discoveries in the field of cell biology, biochemistry and genetics may be of interest to a wide audience as a model of the effective work of the scientific community in the treatment of rare metabolic pathology.Болезнь Гоше (БГ) наиболее распространенное и хорошо изученное заболевание из группы лизосомных болезней накопления, возникающее вследствие наследственного дефицита активности лизосомного фермента кислой -глюкозидазы (глюкоцереброзидазы), участвующего в катаболизме сфинголипидов. Без преувеличения феноменальные успехи в изучении патогенеза и разработке специфической терапии данного заболевания во 2-й половине XX начале XXI в. кардинально изменили клинический фенотип БГ, превратив тяжелое прогрессирующее заболевание в бессимптомный метаболический дефект. Эволюция представлений о БГ, тесно связанная с фундаментальными открытиями в области клеточной биологии, биохимии и генетики, может представлять интерес не только для узкой группы специалистов, занимающихся диагностикой и лечением БГ, но и для более широкой аудитории как модель эффективной работы научного сообщества в лечении редкой метаболической патологии.

Aim.To provide a rationale for the feasibility of using the succinate-containing drugs to treat hypoxia associated with COVID-19 based on the analysis of experimental and clinical studies.Materials and methods. 84 Russian and international literature sources concerning the pathogenesis of COVID-19 and the pathogenetic role of succinate in the management of COVID-19 associated hypoxia, oxidative stress and diaphragmatic dysfunction were analyzed. The literature search was performed using Pubmed and ELIBRARY.ru databases.Results.The literature analysis showed that tissue hypoxia, triggering the pathomorphological cascade of events and resulting in multiple organ failure is a central element of COVID-19 pathogenesis. Experimental and clinical studies show the positive impact of tissue hypoxia correction using succinate in both adult patients and children with various conditions associated with acute respiratory failure.Conclusion.The literature data provide a rationale for using succinate-containing drugs in the treatment of severe COVID-19.

The report shows that V.A. Karlov proved at the current level of knowledge the correctness of the ideas of the great English neurologist John Hughlings Jackson, author of works on localization of the projection motor centers of the cerebral cortex, on aphasia, and others.

B7-H3, also called CD276, is a type I transmembrane glycoprotein that is encoded on human chromosome 15. It was discovered back in 2001. The original study described it as a positive co-stimulant, as it can stimulate T-cell response and IFN-y production. However, recent researches have shown that B7-H3 is involved in T-cell inhibition. A B7-H3 receptor has not been yet identified, and this may explain the complex immunomodulatory activity of B7-H3, as it can have more than one binding partner with different functions. Expression of the B7-H3 protein has been found on activated immune cells such as T-cells, NK cells and antigen presenting cells. Interestingly, it is overexpressed in a wide range of tumor cells and is associated with disease progression and outcome. The soluble form of this protein is also of particular interest. Increased sB7-H3 levels in the plasma of bone tumor patients might be their important diagnostic criterion.

Currently, there are negative trends in the incidence of cataract, which, along with glaucoma, is the most common cause of visual impairment in various countries. Cataract prevalence continues to be high, necessitating the search for new treatment technologies and criteria for assessing the health and quality of life of this population. The purpose: to study the quality of life of patients with cataract against the background of ultrasonic phacoemulsification with implantation of soft intraocular lenses. Nei-VFQ-25 quality of life was studied in 182 patients with nuclear–cortical form of cataract before and after ultrasonic phacoemulsification. The integral index and components of the quality of life of patients with cataract before treatment are significantly reduced. The quality of life of patients with cataracts significantly increases in 3 months after surgical treatment in all indicators. Especially vision significantly improved in the distance, near vision, General health. Improving the quality of life of patients with cataracts after treatment indicates the effectiveness of the used ultrasonic phacoemulsification. In this case, the cause is a violation in the field of role-playing physical and emotional functioning. In the long-term period (6 months after treatment) there is an improvement in the quality of life of patients with mechanical trauma in many respects, except for the role of physical functioning. This study for the first time revealed the effect of ultrasonic phacoemulsification with implantation of soft intraocular lenses on the quality of life of patients with cataract. For the first time using a specific questionnaire NEI-VFQ-25 revealed the scale on which there is an improvement in the quality of life after surgery. The leading indicators of quality of life of patients with cataracts, characterizing the effectiveness of treatment with high-tech method of ultrasonic phacoemulsification, were established for the first time.

The goal is to identify the epidemiological, territorial-epidemiological, environmental, clinical and features of hemorrhagic fever with renal syndrome in order to improve epidemiological surveillance in a large metropolis of the Northwestern Federal District.Materials and methods. An epidemiological analysis of cases of hemorrhagic fever with renal syndrome in St. Petersburg for 2005–2019 was carried out and the clinical and epidemiological characteristics of 135 patients hospitalized in the S.P. Botkin Clinical Infectious Disease Hospital were studied. 70 patients identified combined HFRS diseases associated with other pathogens of viral and bacterial nature. An epidemiological analysis of cases of hemorrhagic fever with renal syndrome in St. Petersburg for 2005–2018 and long-term monitoring of the zoological, epizootological state of small mammals in several districts of St. Petersburg and its suburbs were carried out. The clinical and epidemiological characteristics of 135 patients were studied, of which 70 patients identified combined hemorrhagic fever with renal syndrome diseases associated with other pathogens of a viral and bacterial nature. To assess the epizootological situation, trapped rodents were examined for the presence of viral antigen and antibodies using the method of indirect immunofluorescence with the Xantagnost diagnosticum and enzymelinked immunosorbent assay.Results. The long-term dynamics of the incidence rate in St. Petersburg had a fluctuant rising character with two peaks. The proportion of diseases during the first rise was 11,5%, the second – 44,2% of the long-term incidence. Men prevailed in the age groups of 20-49 years without changes in periods. The proportion of women 20–49 years old was 20,7%, increased to 52,8 % in age groups over 50 years old. When distributed by month in a period of high incidence, the seasonal rise began in September with a peak in October. Infection with hemorrhagic fever with renal syndrome patients – residents of the city occurred mainly (with 35.5%), in the nearby territories of the Northwestern Federal District with 8.9% - in remote areas and with 5,9% in the countries of near and far abroad. The epidemiological situation in places of temporary residence and infection of people was characterized by an increase in the number of small mammals (redbacked voles) and, in particular, infection from 2,9 to 4,4%. Hemorrhagic fever with renal syndrome diseases occurred in the form of moderate severity in 94,4% cases. Severe forms were found in only 5,6% of cases. In the structure of combined infection in 25,9–22,3%, there was a combination of hemorrhagic fever with renal syndrome with gastroenterocolitis and influenza, serologically confirmed. In 17,6% of cases, hemorrhagic fever with renal syndrome was combined with other zoonoses (Lyme disease, tick-borne encephalitis, pseudotuberculosis, leptospirosis, tularemia), in 17,6% with of various etiologies. The presence of combinations of hemorrhagic fever with renal syndrome with other infections complicates the clinical diagnosis.

Aim. To characterize the influence of azoximer bromide (polyoxidonium, PO) in cultivation conditions on the morpho- and nanomechanical cell surface properties of Y. pestis EV NIIEG vaccine strain and its derivatives Y. pestis КМ218 (pYT–, pYV–, pYP–), Y. pestis КМ216 (pYT–, pYV–, pYP+), Y. pseudotuberculosis, Y. enterocolitica by atomic force microsopy (AFM), as well as on the adhesion of cells Y. pestis EV NIIEG to human collagen type IV.Materials and methods. The measurements were carried out using the Solver P47-PRO probe microscope (NT-MDT, Russia), standard methods of semi-contact AFM and AFM imaging analysis program. The adhesion of Y. pestis EV NIIEG to type IV collagen was determined by the number of cells binding to glass slides covered with human collagen type IV.Results. The introduction of PO in the cultivation environment caused changes in the morphometric parameters of the cells of Y. pestis EV NIIEG vaccine strain and its isogenic derivatives (increase in volume, flatten ingested (S/H), index I (W/H). These changes were accompanied by the transformation of nanomechanical properties of the cell surface (reducing the root mean square, adhesion force), which countenance was associated with the plasmid profile. The lesser decrease of adhesion force in the absence of changes of the index I was observed in cells Y. pseudotuberculosis and Y. enterocolitica with plasmid pYV. In the strain Y. enterocolitica KM383 (pYV–) PO did not induce significant changes in the indicators studied. The introduction of the PO into the cultivation environment decreased the ability of Y. pestis EV cells to bind to human collagen type IV. Modification by PO the adhesive properties of the vaccine strain Y. pestis EV NIIEG was accompanied by an increase in its immunogenicity.

The article provides brief information on the history of microRNA studies. Today, their role in human pathology is regarded as key regulators of the expression of genes and the proteins encoded by them: miRNA molecules perform important physiological functions in cells and tissues of various organs. The specific mechanisms of their participation in the pathological process are insufficiently known. MicroRNAs were the first to be studied in patients with spinal muscular atrophy and leukemia. Publications devoted to the study of miRNAs and their role in the life of the eye appeared in 2002. Initially, miRNAs were studied in the tissues of the animals’ eyes (mice and zebras), and later the role of miRNAs of retinal pigment epithelium in inflammatory changes was studied in the experiment. The first information on the searches and isolation of microRNAs, their quantitative characterization in patients with primary open-angle glaucoma, age-related macular degeneration, autoimmune uveitis was analyzed. Encouraging results were obtained and the prospects of such studies in revealing the pathogenesis and the possibility of targeted treatment. Preliminary judgments were made about the role of miRNAs in the formation of various clinical forms of Graves’ ophthalmopathy (endocrine ophthalmopathy), which also gives hope for the emergence of targeted therapy for this disease. More publications have been devoted to the importance of miRNAs in the development of primary malignant intraocular tumors (retinoblastoma and uveal melanoma). Considerable attention is paid to retinoblastoma: the results of a study of various miRNAs as biomarkers of this tumor for early diagnosis with final access to targeted therapy, both in case of local lesion and in conditions of its metastasis, are presented. Most studies are limited to the study of miRNAs in tumor tissues. Over the past 5 years, a number of studies have been performed to highlight the spectrum of circulating miRNAs that have potential diagnostic value for early detection of metastases of uveal melanoma. The number of observations or experiments in the analyzed works is small, the studies are exploratory in nature and the publications all end almost with the phrase: “Further research is required”.

Vertical transmission of viral hepatitis B (HBV) is one of the main transmission ways in endemic regions. There is a relationship between structural changes in the placenta and the clinical course of HBV infection. The risk of vertical transmission of hepatitis B depends on the condition of the placenta.The goal of this work was to study the relationship between HBsAg and / or HBcorAg expression in placenta on the one hand, and clinical parameters of mothers and newborns on the other hand.The study included 19 patients with CHB who gave birth at the Botkins infectious disease hospital in 2019. The first group included patients with markers of HBV infection (HBsAg and / or HBcorAg) detectable via immunohistochemical examination in at least one of the layers of the placenta. In patients from the second group, no markers of HBV infection were detected in any layer of the placenta. Inflammatory changes in placenta were detected in all women from the first group and in 9 (64%) women from the second group. HBsAg in umbilical cord blood was detected in 3 (16%) newborns. In two patients, whose children had HBsAg in the umbilical cord blood, no markers of HBV infection were detected in placenta. In the first group, only one newborn had HBsAg in umbilical cord blood. In two patients receiving an antiviral treatment during pregnancy, markers of HBV infection were identified in the placenta. Markers of HBV infection in placenta were also detected in women with undetectable viral load.ConclusionsMarkers of HBV infection can be found in placenta at low maternal viral load.HBsAg in umbilical cord blood can be detected even in patients with no markers of HBV infection in placenta.Antiviral treatment during pregnancy does not prevent the possibility of placenta’s infection with HBV.

Background. Urinary fistulas (UFs) are one of the most significant complications after partial nephrectomy. Placement of an ureteral stent eliminates urine extravasation in the majority of patients. However, some of them have persistent UFs despite upper urinary tract drainage. Such cases require retrograde injection of fibrin glue into the renal cavity through a ureteroscope or via the percutaneous approach. Some authors reported cases of simultaneous use of 2 stents and percutaneous cryoablation of the fistula, but these techniques are rare and, therefore, it is problematic to evaluate their efficacy.Objective: to evaluate the results of the new treatment method for the elimination of persistent UFs using the retrograde endoscopic percutaneous approach.Materials and methods. This study included 5 patients (3 males and 3 females) with UFs developed after kidney resection. Mean age of the patients was 55.8 years. The tumor size was 2.5 to 4.8 cm; mean R.E.N.A.L. score was 7.8. All patients had earlier undergone minimally invasive partial nephrectomy; the time between surgery and UF development varied between 3 and 10 days. Four out of 5 patients had a large amount of discharge from their paranephral drainage system, examination of which confirmed high creatinine level. Patients underwent flexible ureteropyelography in the lithotomy position. During this procedure, we identified the damaged calyx and then performed percutaneous puncture targeting the distal end of the endoscope at this calyx, ensuring that the tip of the needle appeared in the paranephral cavity in front of the injured calyx. Using the flexible ureteroscope, we inserted the needle into the pelvis, dilated the puncture opening along the string, and installed a nephrostomy drainage system (12 Fr). Then the endoscope was removed and the ureter was additionally drained with a stent. The stent was removed after 8-10 days with subsequent antegrade pyelography. If there was no extravasation, the nephrostomy tube was removed and the patient was discharged from hospital to continue treatment in outpatient settings.Results. All patients with UFs resulting from partial nephrectomy was successfully operated on. No complications were registered. The mean surgery time was 45.0 ± 20.5 min (range: 40-65 min). Only two patients had some discharge from the fistula within 1 day after nephrostomy tube removal and it stopped without any additional interventions. Three patients had their fistula healed immediately. The treatment efficacy during the whole follow-up period of 18 ± 4 months (range: 6-26 months) was 100 %.Conclusion. Ureteral stenting ensures elimination of UFs in the majority of patients after partial nephrectomy. In individuals with persistent UFs, retrograde endoscopic percutaneous drainage of the pelvicalyceal system is the method of choice, because it allows rapid and effective treatment of UFs.

To date, liver transplantation remains the only effective treatment for patients with cirrhosis. Due to lack of other effective, alternative therapeutic methods, the search and development of new treatment technologies is problem number one. The development of cellular technologies is promising for use in clinical practice. Using this observation as an example, the safety and efficacy of cell therapy technology for prolonged stay on the liver transplant waiting list by a patient with cirrhosis is shown. After intraportal injection of autologous bone marrow-derived mononuclear cells, liver cirrhosis stabilized on the CTP and MELD-Na scales for 22 months of observation, which allowed the patient to wait for an organ and successfully undergo liver transplantation.