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Quality Risk Management (QRM) is an important aspect of pharmaceutical development in the Quality-by-Design paradigm, since it determines the Design Space, critical quality attributes and critical process attributes.The purpose of this review is to systematize and analyze the main aspects of the QRM system in relation to each element of pharmaceutical development. This review article discusses the following key elements of QRM such as: risk analysis, risk control, risk communication, risk verification. For risk analysis, the advantages and disadvantages of QRM tools such as Preliminary Hazard Analysis, Failure Mode Effects Analysis, Fault Tree Analysis are presented and analyzed, Hazard Operability Analysis and Hazard Analysis and Critical Control Points. In addition, a description of the methods of mathematical planning and design of experiments for pharmaceutical development and QRM is given and their significance for these systems is determined. Elements of QRM such as root cause analysis, brainstorming, and a corrective and preventive action procedure are given as risk control and mitigation tools.In this paper, the main stages of QRM are considered and conclusions are formulated regarding the main advantages and disadvantages of the methods of identification, analysis, control, risk reporting, and the main ways for further improvement of the presented system are proposed.

In the article, with the help of general scientific and linguistic methods, primarily linguostylistic and contextual analyses, the study of lyrical rock-discourse is continued. The emphasis is made on its hybrid nature, viz. Placement between rock, poetical and, perhaps, interactive (juvenile) discourses. It has been found out that among different tools of rhetorical influence, made use of in the studied variation of rock-discourse, tropes, the most common of which are metaphors and epithets, have an important role. In the research, the cases of pragmatic application of personal pronouns and graphics are considered. Attention is paid to the personality of the lyrical hero (heroine) that is shown to be a language personality as well.

Relevance. Assay of acute toxicity is a mandatory step in a preclinical safety study of medicines and pharmaceutical substances. The purpose of this study was to determine the parameters of acute toxicity of the substance GIZH-298. Methods. GIZH-298 was administered once orally to outbred mice of both sexes at doses of 350–550 mg/kg. Control mice received 0.5 ml of 1 % starch solution under the same conditions. During the experiment, the death of animals, signs of intoxication were observed, and the clinical picture was recorded. Pathological anatomical autopsy of the dead mice was performed as they died. Surviving mice were autopsied 14 days after the start of the experiment, immediately after their euthanasia. Results. The average lethal doses of the GIZh-298 substance when administered orally to mice were determined: LD50 in females was 356 mg/kg, LD50 in males was 438 mg/kg. Conclusion. Compound GIZH-298 for oral administration according to the classification of Sidorov K.K. (1973) is a moderately toxic substance and can be assigned to the 3rd class of toxicity, and in accordance with GOST 12.1.007-76 — to the 3rd hazard class.

Introduction. Rabbit hemorrhagic disease is an acute highly contagious infection associated with two genotypes of pathogenic Lagovirus. Antibodies to major capsid protein (Vp60) are protective. The aim of the work ‒ is an evaluation of antigenic and immunogenic activity of virus-like particles (VLPs) based on recombinant major capsid proteins of both genotypes of rabbit hemorrhagic disease virus (RHDV) (recVP60-GI1 and recVP60-GI2). Materials and methods. Baculovirus-expressed VLPs were evaluated using electron microscopy and administered to clinically healthy 1.53 month old rabbits in a dose of 50 g. Rabbits were challenged with 103 LD50 of virulent strains Voronezhsky-87 and Tula 21 days post immunization. Serum samples were tested for the presence of RHDV-specific antibodies. Results. VLPs with hemagglutination activity forming VLP 3040 nm in size were obtained in Hi-5 cell culture. Specific antibody titers in rabbits measured by ELISA were 1 : 200 to 1 : 800 on 21th day post immunization with VLPs. Immunogenic activity of recVP60-GI1 VLPs was 90 and 40%, while it was 30 and 100% for recVP60-GI2 VLPs after the challenge with RHDV genotypes 1 and 2 respectively. The immunogenicity of two VLPs in mixture reached 100%. Discussion. VLPs possess hemagglutinating, antigenic and immunogenic activity, suggesting their use as components in substances designed for RHDV specific prophylaxis in rabbits. Results of the control challenge experiment demonstrated the need to include the antigens from both RHDV genotypes in the vaccine. Conclusion. Recombinant proteins recVP60-GI1 and recVP60-GI2 form VLPs that possess hemagglutinating an antigenic activity, and provide 90100% level of protection for animals challenged with RHDV GI1 and GI2 virulent strains.

The emergence of new drug therapy regimens and the completion of several large randomized trials led to significant changes in the clinical guidelines of the Ministry of Health of Russia and the practical guidelines of the Russian Society of Clinical Oncology (RUSSCO) for the treatment of urologic oncology diseases. However, different interpretations of some studies by expert panels and requirements for these documents led to a divergence of some statements in these publications. The article presents executive summaries of the updated clinical and practical prostate cancer treatment guidelines.

Purpose: an assessment of efficacy and safety of cabozantinib in unselected patients with metastatic renal cell carcinoma in the first and subsequent lines of therapy.Materials and methods. Russian multicenter observational study included 92 consecutive patients with morphologically verified metastatic renal cell carcinoma treated with cabozantinib (60 mg/d) in 16 Russian centers. Median age of the patients was 56 (19-79) years, a male-to-female ratio - 3:1. At the start of cabozantinib therapy 27.2 % of patients had ECOG PS 2. Most common histological type of kidney cancer was clear-cell RCC (90.2 %). Most patients were diagnosed with synchronous (71.7 %) multiple metastases (60.9 %). Previous nephrectomy was performed in 87.0 % of cases. Prognosis according to International Metastatic Renal Cancer Database Consortium (IMDC) score was assessed as favorable in 5.4 %, intermediate - in 58.7 % and poor - in 35.9 % patients. Cabozantinib as the first-line therapy was administered in 9 (9.8 %), following 1-5 lines of systemic treatment - in 83 (90.2 %) cases. Median follow-up was 11 (2.3-44.5) months.Results. In patients, receiving cabozantinib as the first-line therapy, objective response rate was 66.7 %, tumor control was reached in 100 % of cases. Median time to the objective response was 2.6 (1.9-3.6) months, median objective response duration - 13.2 (6.2-21.5) months. Median progression-free survival (PFS) and overall survival (OS) were not reached, 6- and 12-months PFS was 77.8 % and 77.8 %, 6- and 12-months OS - 88.9 % and 88.9 % respectively. Cabozantinib as the second and subsequent lines of therapy provided objective response rate of 34.9 %, tumor control rate - 97.6 %. Median time to the objective response was 2.5 (1.8-4.1) months, median objective response duration - 12.6 (5.5-27.3) months. Median PFS was not reached (6- and 12-months PFS - 92.5 % and 73.1 % respectively), median OS was 32.6 months (6- and 12-months OS - 97.4 % and 80.8 % respectively). Any adverse events (AE) developed in 88.8 %, AE grade III-IV - in 32.6 % of cases. Most frequent AE grade III-IV included arterial hypertension (18.5 %), diarrhea (6.5 %) and palmar-plantar erythrodysesthesia (6.5 %). Unacceptable toxicity demanded treatment cancellation in 2.2 %, therapy interruption - in 16.3 % and dose reduction - in 30.4 % of patients.Conclusion. Cabozantinib as the first and subsequent lines of therapy for metastatic renal cell carcinoma patients in the real world practice demonstrated high efficacy and better tolerability comparing with population assigned for cabozantinib monotherapy in the randomized phase II-III trials.

Background. In the JAVELIN Bladder 100 trial, 1st line maintenance with avelumab in combination with best supportive care significantly increased (9.2 months) overall survival compared to best supportive care in patients with locally advanced or metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy: 29.7 months versus 20.5 months, respectively. Trial results led to inclusion of avelumab into the international guidelines as a standard of care with the highest level of evidence. Combined therapy with avelumab + axitinib in patients with previously untreated metastatic renal cell carcinoma showed higher progression-free survival and objective response rate compared to sunitinib in all IMDC (International Metastatic Renal Cancer Database Consortium) groups. Avelumab + axitinib is one of the immuno-oncology combinations with proven effectiveness for progression-free survival and objective response rate.Aim. To evaluate the effectiveness of avelumab in treatment of oncological urological diseases in routine clinical practice. Materials and methods. At the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology - branch of the National Medical Research Radiology Center, 12 patients with locally advanced inoperable and metastatic urothelial cancer without progression after 1st line platinum-based chemotherapy in combination with gemcitabine received maintenance avelumab therapy. Median follow-up was 10 months. Primary endpoints were overall survival from the start of avelumab maintenance therapy and safety.Combined therapy with avelumab + axitinib was administered in 18 patients with metastatic renal cell carcinoma. Median follow-up was 9 (3-16) months. Overall survival, progression-free survival, response rate and safety in the overall population and according to IMDC groups were evaluated.Results. At data cut-off (March 2023) with median follow-up of 10 months, overall survival was 100 %, progression-free survival was 66.7 % (among patients who received more than 3 infusions - 100 %). Progression-free survival was higher in patients with tumors of the lower urinary tract compared to upper (72.5 % versus 60 %), complete response to induction platinum-based chemotherapy compared to partial response and stable disease (100 % versus 66.7 %) and presence of metastases in the lymph nodes only compared to visceral and bone metastases (100 % versus 66.7 %). Adverse events were observed in 4 (66.7 %) patients.Among 18 patients who received avelumab + axitinib, complete response was observed in 2 (11.1 %) patients, partial response in 6 (33.3 %) patients, stable disease in 9 (50 %) patients, disease progression in 1 (5.6 %) patient. Response to therapy was observed in patients of all prognosis groups; for large (>5 cm) metastases in the lungs, soft tissues, lymph nodes and bones response was observed 3 months after treatment start. Overall survival for this follow-up duration was 100 %, progression-free survival was 96.4 ± 11.2 %. Adverse events were observed in 8 (44.4 %) patients, and in 6 (75 %) of them they were grade I—II and did not require infusion regimen correction or axitinib dose reduction.Conclusion. Avelumab maintenance therapy in the 1st line is the standard of care for patients with locally advanced and metastatic urothelial cancer without disease progression during 1st line platinum-based chemotherapy. Maintenance therapy allows to achieve better overall survival and progression-free survival irrespective of the choice of platinum regimen (cisplatin or carboplatin), response to platinum-based chemotherapy, number of chemotherapy cycles, tumor localization and advancement.Experience of the N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology confirms results of the JAVELIN Bladder 100 trial on the effectiveness of avelumab maintenance therapy in routine clinical practice. Combination drug therapy with avelumab and axitinib in patients with metastatic renal cell carcinoma is an effective and safe treatment method which allows to achieve fast objective response and has good tolerability in patients irrespective of IMDC group or metastasis location. Effectiveness and favorable safety profile of avelumab + axitinib combination were proven in the context of routine clinical practice.

Purpose: The aim of this work is the construction of bridge structures on a soil foundation with physical and mechanical characteristics, often differing from survey activity parameters. Technical regulations of bridge supports envisage plate-bearing test of drilled pile foot.Design/methodology/approach: The quality improvement of not only plate-bearing test preparation, but also requirements for structural reliability, the approximated Ritter-Rassokhin method with different soil behavior under normal conditions with regard to foundation uplift, which allows calculating the maximum draft and other design parameters of soil.Practical implications: The obtained results make it possible to clarify the work regulations for plate-bearing test.

This article explores the theoretical foundations of calculating the user’s trust in Internet services. The author conceptualized trust as a rational action and used the metaphor of calculation to examine the main objective factors that affect trust in internet services. These factors were divided into three groups according to the evaluation object: winnings, risks, and trustworthiness. The increasing offer makes the user face the trust dilemma. Trust in Internet services depends on many interrelated factors that encourage users to turn to online services. The factor of winning is especially important: online services save time and are more user-friendly. The risk factor is associated with the personal data that the user has to provide. The research facilitates the processes of digital transformation in general and can help to increase public trust in specific Internet services.

Ti2AlNb-based alloys are promising materials for operation at high temperatures in aerospace industry. Meanwhile, the existing difficulties of weldability restrict opportunities of their application. This work is devoted to studies of welded joints from Ti2AlNb-based VTI-4 alloy, obtained using pulsed laser welding (PLW). The optimum PLW modes have been determined providing uniform faultless joint. The features of formation of external defects, internal pores, cracks and non-uniform penetration depth were detected depending on welding conditions. The main PLW parameters influencing on formation of welded joint are voltage and duration of laser pulse. It was demonstrated that at insufficient medium and high peak powers sawtooth seam roots and internal pores can be formed. However, at higher rates of energy input thermal hydraulic processes in welding bathe are violated, accompanied by metal splashing (spattering), heterogeneity of pulse imposition is observed. This leads to formation of cracks, higher porosity, heterogeneity of melting zone, and as a consequence, poor mechanical properties. Microstructure analysis of the welded joints obtained by means of PLW has demonstrated that the melting area is comprised of long dendritic grains of β phase, and the heat affected zone from two regions of β + α2 phases and β + α2 + O phases. Herewith, the achieved joint strength equals to ~80 % of the base metal produced using the optimum PLW mode.

The article is devoted to the study of the effect of a compound based on an aqueous solution of fullerene C60 on the hematological parameters of white rats. The experiment was carried out on three groups of animals. The first group served as a control. The second group was injected with 1 ml of an aqueous solution of Fullerene C60 (1 mg / ml of DV), 150 mg of resveratrol – 25 mg, betoin hydrochloride – 10 mg. The third group received 1 ml of an aqueous solution of Fullerene C60 (1 mg/ml of DV), 2500 mg of resveratrol, 1000 mg of betoin hydrochloride. It was determined that the animals of the second group had a significant increase in the number of erythrocytes by 11.8% and the hemoglobin content by 14.8% relative to the control values. In white rats of the third group, there were no significant differences with the control. In animals of the second group, the number of rod-shaped neutrophils and monocytes increased by 10 and 9.3%, respectively, relative to the control. No significant differences were found in animals of the third group. The number of segmented neutrophils after the introduction of an aqueous solution of fullerene C60 increased by 12.4% (group 2 animals) and 6.1% (group 3 animals). It was revealed that the compound based on an aqueous solution of fullerene C60 has a pronounced effect on the hematological parameters of the body of white rats. The most effective dose was 1 ml of an aqueous solution of Fullerene C60 (1 mg / ml of DV), 150 mg of resveratrol – 25 mg, betoin hydrochloride – 10 mg, after administration of which an increase in the number of erythrocytes by 11.8% and the hemoglobin content by 14.8% relative to the control values, the number of rod-shaped neutrophils and monocytes by 10 and 9.3%, respectively, and the number of segmented neutrophils by 12.4%.

The aim of the study was to analyse histologically and morphometrically the peribiliary glands of the extrahepatic biliary tract in the elderly and long-living people.Material and methods. The study included wholemounts of the gallbladder, the cystic, hepatic and common bile ducts obtained from the corpses of both sexes aged 22 to 35 years (n=16) and older than 76 years (n=39). Macro-microscopy was used to evaluate the number, localization, sizes and shape of the glands, the area of the lumen of the excretory duct orifices, the area of the initial section of the glands, the number of initial (terminal) parts and the proportion of epithelial parenchyma in their composition.Results. With age, there is a decreased proportion of "complexly branched" glands with a significant number of initial sections and excretory ducts of the 1st order. The proportion of "simple" glands, with one initial section increases to 70.2–78.3% in the senile age, while it is 41.0–52.1% in people of mature age. In long-living people, there is an increased number (up to 70–85%) of glands with ampullar extensions of the common excretory duct. The total number, density of gland localization, the length and width of the initial section of the peribiliary glands tend to decrease from the period of mature age to longevity. In senile age, the size and quantitative parameters of the glands stabilize, and do not modify in long-living people.Conclusion. The results of the morphological analysis demonstrate that there is no progression of involutive changes in the peribiliary glands of the extrahepatic biliary tract from senile age to the period of longevity. In some cases, long-living individuals manifest compensatory-adaptive reactions, such as an increased severity of the epithelial parenchymal component in the composition of the glands and an increased proportion of glands with an ampullar expansion of the common excretory duct.

A classification of monocyte subpopulations developed in 2010 with coverage of the immunobiological properties of cells, their functional activity and participation in various pathological processes (inflammatory, cardiovascular diseases, strokes, myocardial infarctions, aortic aneurysms, surgical modification of heart valves, diabetes, burns, etc.). The diagnostic and prognostic aspects of the analysis of monocytic subpopulations are considered. The unique data obtained by the staff of the Gamaleya Institute of epidemiology and microbiology. They consist in the fact that various physical forms of unmodified native type 1 collagen are powder, i.e. crushed bundles of collagen fibers, a hydrogel or a solution of extracellular matrix peptides, as well as a suspension of collagen fibers obtained from a powder, when applied to the surface of acute and chronic and diabetic wounds, bedsores, trophic ulcers, etc., can provide a pronounced anti-inflammatory, reparative, remodulating and regenerative effect on condition of wounds, providing their accelerated healing due to the local accumulation of “regenerative” subpopulations of Mon3 monocytes, which can be most directly used in burn tissue lesions. In this case, the analysis of monocytic subpopulations is of paramount importance. Moreover, possible potentiating effects of additional use in burns under the control of the analysis of monocyte subpopulations of powerful modern pluripotent immunomodulators – polyoxidonium, galavit and their possible combination with local use of collagen preparations are discussed. Finally, we obtained preliminary data indicating the development in burned patients of a deficiency in the absolute and relative content of the most important “patrolling” non-classical subpopulation of CD14+CD16++ monocytes compared with healthy primary (non-professional) donors, which can be a very important finding in the diagnosis and prognosis and substantiation of new methods of treatment of burns.

The relevance of research: is due to the need to establish true causes and patterns of changes in the hydrometric characteristics of the global water balance as a whole and its components, natural media on Earth. Purpose of research: Establishment of patterns of mutual influences and causes of changes in the components of world water balance on Earth: settlement changes in thermal and water resources on the territory of sushi, clouds on continents, lake levels on continents, the Caspian Sea, Arctic Islands, Greenland and mountain glaciers. Objects: Temporary series of heliocosmic and global climatic variables constituting a global water balance. Methods of research: the method developed by the author of the calculation of the wavelet phase-frequency and phase-temporal characteristics of the group of the studied time series specified at equal intervals of time, with the calculation of their correlation matrices and the construction of the charts of the variables in two coordinate systems, comparative analysis. Results of research: It is shown that in cyclical climate change on land, global water balance as a whole and its components in different relative units and phase orientations, depending on the properties of components of water balance, natural environments, two groups of variables are studying: Helicosmic (Baricenric Sun Movements, Solar activity, long-term solar insolation, greenhouse gases, ozone concentration in the ionosphere, elements of the Earth orbit, geomagnetic field) and global temperature climatic variables caused by changes in the helikosmic factors leading from which is the barycentric movements of the Sun. There is a variability of the water balance depending on their geographic locations on continents. It is shown that the calculated changes in thermal and water resources on the territory of the sushi, changes in clouds and levels of lakes on continents at the observed time intervals is significantly interconnected in the phase-frequency domain, coordinated with changes in the heliocosmic variables leading from which is the barycentric movements of the Sun. It is shown that the change in the level of Lake Rudolf, located in Kenya, occurs in antiphase with changes in other lakes from the phase-frequency domain due to changes in the level of the lake in antiphase with changes in evaporation, evaporation and precipitation the calculated changes in thermal and water resources on land ; Such a phenomenon is observed in changes in Lake Neivasha (Kenya). Data analysis obtained at the East station in Antarctica, bottom sediments of the ocean, in 379.3-1.1 thousand years in the past, graphs of changes in the elements of the Earth orbit, established high consistency of changes in the Caspian level with changes in the angle of inclination, precession and eccentricity of the Earth orbits; In Holocene, agreed with changes in solar activity; coordinated with changes in earthquakes, the speed of rotation of the Earth and the duration of the earth's day, as well as the changes in YMO and the El-Nio phenomenon, with changes in evaporation and precipitation on land in the phase-frequency domain due to the influences of heliocosmic factors. It has been established that changes in the components of the water balance of the Arctic Islands, Greenland and the mountain glaciers are divided into two subgroups; The first includes changes in precipitation and drains, to the second, changes in the resulting and increments of balance sheets. The components of the first subgroup are strongly agreed with the changes in the helixosmic factors, the second, with changes in climatic variables with a negative sign in changes in the balances of the Arctic Islands and Greenland; The second subgroup in the balance of mountain glaciers is strongly agreed with changes in the helicosmic variables with a negative sign in the phase-frequency domain in the observed inter. In changes of phase-temporal characteristics of groups of factors are observed lattice structures of differently and unidirectional changes of variables, characterizing stochastic variability in natural environments.

The study of violations of the adaptive-compensatory mechanisms of patients with mental disorders makes it relevant to study the combined characteristics of gender, psychosexual sphere and response to stress in mental pathology. The aim of the study was to identify the relationship between the types and directions of frustration reactions as unconscious components of coping with gender and gender-role behavior. 183 patients with diagnoses of schizophrenia and schizotypal disorder, recurrent depressive disorder, bipolar affective disorder were examined. In the diagnostic groups, men and women were dominated by persons under the age of 30. The «Method of diagnostics of gender role behavior accentuations» and «Drawing Associations test» were used. The data obtained indicate that among patients with schizophrenia, men with cross-gender role accentuation better assimilate socio-normative patterns of behavior than women with cross-gender role accentuation; in women with schizotypal disorder, the presence of cross-gender accentuation of gender-role behavior is associated with a lower level of social adaptation compared to women without accentuation.Women with schizotypal disorder and more pronounced masculine gender role accentuation have a profile of the direction of emotional reactions in frustrating situations, characteristic of men with schizotypal disorder. In ontogenesis, the interrelationships of stereotypes of emotional response and the level of gender role accentuation change. The revealed sex differences in the profiles of frustration reactions among patients on the schizophrenic spectrum may be partially explained by the gender-role characteristics of patients. In conclusion of the analysis, it can be concluded that the stereotypes of a person’s emotional response and their formation are closely related to gender-role behavior. Knowledge of this kind of interrelationships enables the psychotherapist in the course of treatment to achieve the patient’s understanding of his behavior, including its unconscious aspects.

At present time widespread use of autonomous laser systems supposes reducing of supply energy, consumed by laser sources that are included in their composition and at the same time increasing of their output energy characteristics. The objective of this work was practical confirmation of possibility of laser beam combining in systems based on a ring delay line.The experimental setup that implements the principle of synchronous laser beam combining scheme on the ring fiber-optic delay line, developed by authors earlier, is made. The schematic diagram of the manufactured setup is presented, its operation principle is described in detail and its composition is considered. It is noted that in order to achieve the objective measurements of electrical signals received from the photodetector of the setup and measurements of the part of laser radiation power removed by the splitter and formed in the fiber-optic path of the setup are performed. Results of measurements are presented as the waveforms of electrical signals from the photodetector and of power values at the output of the splitter. Plots of dependence of the output power and the circulation power on the power of the initial laser beam introduced into the setup are presented.Analysis of results showed that the laser beam combining occurs in the ring fiber-optic delay line. Besides, it was found that the proposed scheme provides an increase in the power of the initial beam by 1.05…1.11 times.

Purpose. To analyze the literature data on the use of CT perfusion in kidney diseases and to assess the future prospects of using the technique in clinical practice.Materials and methods. In electronic databases (PubMed, E-library, Web of Science, Google Scholar), a search was conducted for published studies evaluating the possibilities of using CT perfusion in both neoplastic and non-neoplastic kidney diseases. The article analyzes the results of 40 most relevant works of Russian and foreign researchers devoted to this topic.Results. According to the analysis of the data obtained, perfusion CT is an effective diagnostic tool in oncology: the technique allows noninvasively assessing the nature of the tumour, including differentiating benign nodes (fat-poor angiomyolipoma and oncocytoma) from renal cell carcinoma; to establish the histological variant of renal cell carcinoma and Fuhrman grade, to characterize the effectiveness of ablative techniques and systemic treatment of renal cell carcinoma. Based on the correlation of CT kidney perfusion data and the results of various methods for determining organ function, the possibility of using perfusion CT as one of the prognostic factors for determining the tactics of treatment of patients with obstructive uropathies, aortomesenteric compression, and also shows the potential of using the technique in transplantology both in patients after surgery and during the examination of donors.Conclusions. Despite the fact that the role of CT kidney perfusion in various fields of urology and nephrology has been sufficiently studied, some important aspects of the likely application of this technique remain underestimated. Taking into account the high incidence rates and a significant percentage of localized forms of tumors, the study of the role of CT perfusion in planning and evaluating the results of nephron-sparing treatment of renal cell carcinoma may open up new prospects in optimizing surgical tactics.

Rationale. Atraumatic mesh bandages are most commonly used bandages for treatment of wounds and burns. To date, considerable experience has been gained in the use of Branolind N bandages in clinical practice in treatment of burn wounds.Aim. Comparative evaluation of the results of the use of various atraumatic dressings and evaluation of the effectiveness of the Branolind N bandage in treatment of patients with burns. Materials and Methods. In 222 patients with burns, the comparative clinical and laboratory evaluation of effectiveness of various atraumatic dressings (180 patients) and cotton-gauze dressings with hydrophilic-based ointment Levomekol (42 patients), in various clinical situations, was carried out.Results. All types of atraumatic dressings had similar clinical effectiveness and were most effective for treatment of superficial and borderline burns of I-II degree, as well as for limited burns of II-III degree after surgical necrectomy at the stage preparation of granulating wounds for skin grafting, starting from the second, and especially in the third stage of wound process. The best results were obtained with the use of Branolind N bandages. Conclusions. The use of atraumatic "mesh" bandages Branolind N allows to improve the results of medical care for patients with burns. Their use contributes to a favorable course of wound process, provides comfort to patients and convenience for work of medical staff in treatment of patients in hospital, and on outpatient basis.

Abstract A simple sublimation technology for the lutetium and ytterbium separation was proposed, which already at the stage of preliminary experiments showed effectiveness: (a) the completeness of Yb separation resulted in short-term thermal annealing is at least 98%, the distilled product is completely free from 177Lu, no additional preparation of ytterbium for repeated irradiation is required ; (b) traditional ion-exchange chromatography can be used for the final purification of 177Lu from ytterbium.

Digital transformation affects all social spheres bringing to life interactive technologies and virtual reality. Since the virtual (digital) space depends on the digital and creative solutions that form its technological base, insofar the legal regime of copying creative solutions affects both the freedom of creativity necessary for sustainable development and public control which is significant for maintaining the manageability of sovereign states and integrational unions.Aim. Improving the legal regime for the protection of interactive works to create a universal and harmonious information space where the rights of authors and the economic interests of software developers are protected, as well as digital sovereignty is guaranteed.Tasks. The concept development for legal protection of interactive works and the political and legal modeling of the digital (information) space presuppose the implementation of international agreements in the field of intellectual rights, as well as solution of several tasks to formalize the results of the creative activity that are perceived through digital technologies.Methods. Political and legal modeling of the digital space is carried out by introducing terminological certainty and creating a system of the interactive works protection. Such legal construction should provide effective public control while preserving creative freedom in digital space.Results. The protection of the copyright and moral rights of the authors of interactive works differs significantly from the legal protection of audiovisual artworks and literature. While the form of objective expression in computer programs may be similar to a literary artwork, their perception by the target audience is fundamentally different in that it models a virtual (digital) space, which the state administration seeks to control in recent years.Conclusion. The state administration’s tendency to digital sovereignty makes sense only if the target audience demonstrates high demand for interactive artworks published under the state jurisdiction. Since the information space is universal, the digital sovereignty of the state is inextricably linked with participation in integration unions that ensure the p roper quality of the results of creative work and create the digital space that is necessary under digital transformation for the interactive art development and the prosperity of creative corporations.

Aim. The work was to compile a list of bird species and their status in the forest-steppe and steppe of the Middle Irtysh region at the present time and to analyse their potential ability in terms of the transmission of influenza viruses that pose a danger to humans and farm animals.Materials and Methods. The study of avifauna and their status in the forest-steppe and steppe of the Middle Irtysh region has been conducted by us from 1973 to the present. The analysis of literary sources has been carried out since the time of P.S. Pallas's travels in the region in 1871. In addition, information on the wetlands of the Irtysh region which is freely available on the Internet was used.Results. At the beginning of the 20th century, about 200 species of birds were recorded in the vicinity of Omsk, 125 of them being breeding species. At present about 150 species of birds have been recorded in Omsk and its environs. Of the 290 bird species of the Middle Irtysh region, 48 species (16.6%) belong among the natural hosts of influenza A viruses. Of these, at least 40 species are migratory and 25 species nest there. In addition to the prinicipal influenza virus host species, the list of birds of the Middle Irtysh region includes several species of scavengers and predators, as well as synanthropic bird species. These species may share habitat or food resources with the main host species of influenza viruses. Influenza A viruses can be transmitted between species either by direct or indirect contact through mechanical propagation or contamination of nutritional resources.Conclusion. As the 3 largest bird migratory flyways run through the Middle Irtysh region where there is a significant number of wetlands, the prerequisites are created for a mass simultaneous accumulation of different populations and species of migratory birds carrying viruses and, accordingly, a high probability of exchanging viral genomes with each other and their further spread to new regions.

The article presents a review of the literature related to the problems of the gastrointestinal tract in gynecological practice.Complaints from the digestive organs are interrelated with vaginal dysbiosis, a violation of the formation of the menstrual cycle. The main complaints presented by women with diseases of the female genital sphere, the causes of their occurrence and measures to eliminate these complaints are considered.

Background. The growing number of overweight children is an important problem of modern healthcare. Excess body weight causes the risk of severe metabolic disorders developing. Analysis of changes in the immune, metabolic, and genetic profile of overweight children as markers of the early development of metabolic disorders is an effective tool for the prevention, diagnosis, and treatment of these pathologies. Aim. To identify the features of the immune and metabolomic profile in overweight children aged 711 years associated with polymorphic variants of the IL-1B (rs1143634) and TP53 (rs1042522) genes. Material and methods. 132 children aged 711 years were examined: 54 children with overweight and 78 children with normal body weight. The lymphocytes subpopulation composition was analyzed by flow cytometry; the content of leptin, cortisol, superoxide dismutase, lipid hydroperoxide and interleukin-1 using enzyme immunoassay, immunoglobulin G using the method of radial immunodiffusion method by Mancini. Polymorphic variants of the IL-1B (rs1143634) and TP53 (rs1042522) genes were identified by real-time polymerase chain reaction. Statistical data processing was implemented in the Statistica 10, SNPStat and Gen-Expert programs. Results. The immune profile of the examined children was characterized by an increased content of CD3+CD8+-, CD19+-lymphocytes and immunoglobulin G against the background of CD3+CD4+-lymphocytes, p53 deficiency and a decrease in the number of CD4+/CD8+. The metabolomic profile of children was characterized by an excess content of leptin, cortisol, lipid hydroperoxides, and superoxide dismutase. The identified changes in immune and metabolomic regulation in overweight children were significantly associated with the G allele and GG genotype of the IL-1B gene (rs1143634), as well as with the C allele and CC genotype of the TP53 gene (rs1042522), which cause the initiation of inflammation and inhibition of apoptosis. Conclusion. The established features of immune and metabolomic regulation associated with the G allele and GG genotype of the IL-1B gene (rs1143634) and with the C allele and CC genotype of TP53 gene (rs1042522) represent a complex of markers of overweight formation in children aged 711 years.

A clinical case of the successful use of light-oxygen therapy is presented irradiation in the absorption spectrum of endogenous oxygen with its transfer to a singlet state in a patient with vulvar leukoplakia and lichen sclerosus. As a source of laser radiation, we used the domestic Super Sab diode laser with a wavelength close to 1265 nm (OOO New Surgical Technologies, Moscow), radiation power – from 0.9 to 1.2 W, power density – from 0.8 to 1.06 W/cm2, exposure dose – 200–250 J/cm2. The procedures were carried out 2 times a week with an interval of 3–4 days.As a result of the treatment (8 procedures), complete clinical remission was achieved.

It is shown that, as the result of developing alkali liquid metal coolants, including sodium, eutectic sodium-potassium alloy, lithium and cesium, the scientific basis has been established for their application in nuclear power. The paper presents data from investigations of thermophysical, neutronic and physicochemical properties and characteristics of various alkali liquid metal coolants, the content of solid-phase and dissolved impurities in coolants, mass transport of impurities in circulation circuits with alkali liquid metal coolants, development of systems for removal of impurities, and control of the content of impurities in alkali liquid metal coolants. Alkali liquid metal coolants are considered as a part of a system that includes a structural material in contact with the coolant, and a gas space that compensates for the thermal expansion of the coolant. The state of the system is defined by the physicochemical properties of the system’s components. And the coolant and the structural materials also represent subsystems consisting of a base material, a coolant and impurities contained both in the material and in the coolant. It has been shown that each alkali liquid metal coolant has its own set of impurities that define its technology. It depends on the physicochemical properties of the solution of the structural material impurities and components in the coolant. Objectives have been formulated for investigating further alkali liquid metal coolants, as stemming from the need to improve the efficiency, environmental friendliness, reliability and safety, and for extending the life of nuclear power plants in operation or under design. Alkali liquid metals are promising candidate materials for being used in thermonuclear power not only as the coolant but also as the tritium breeding medium. These include, first of all, lithium and its eutectic alloy with lead (17 at. % of lithium). The possibility for using lithium or a lithium-lead alloy as a coolant in the blanket of the international thermonuclear power reactor is compared.

The article discusses the main stages of development of the Sheskharis wine estate: from the early period of development of the Black Sea coast of the Caucasus - the creation of the first cultural sites, to the beginning of the Great Patriotic War. The analysis of small sources on this subject has been carried out. Archival documents of the Office of the Archives of the Municipal Formation of the City of Novorossiysk and the National Electronic Library were used. The types of economic activities are described in detail, as well as some ways of caring for the vineyards that took place during the heyday of the estate. The production of Sheskharis wines developed in parallel with similar activities of the specific estate of Abrau-Durso and the winery of M.F. Penchula "Myskhako". The production of the estate was repeatedly noted at foreign and domestic exhibitions of the late XIX, early XX centuries, incl. at the agricultural and cultural-industrial exhibition of the Black Sea coast of the Caucasus "Russian Riviera". After the revolution, the estate was nationalized and continued its activities as a state farm "Rosa Luxembourg". During the Great Patriotic War, the infrastructure of the state farm was significantly damaged. In the middle of the 20th century, on the site of the former vineyards, the Sheskharis oil harbor appeared, which is currently operating. This article provides an opportunity to see, on the example of the history of a single object, the contrast between its initial and subsequent purpose.

Currently, cervical cancer (CC) is one of the most common oncological diseases. In this regard, it is necessary to develop new research methods for a more detailed study of the occurrence and development of the disease at the molecular and cellular levels, as well as to improve the effectiveness of treatment and form a deeper understanding of the causes of relapses. The aim of this work was to study nanoparticles localized on the erythrocyte membrane—presumably HPV 16, 18, before and after radiation therapy, in patients with cervical cancer (CC). To study the surface of red blood cells by the SEM method, venous blood samples from 17 patients with a confirmed diagnosis of CC were prepared in thin layers evenly applied to a dry, fat-free glass slide, which was dried at room temperature. To detect nanoparticles on the surface of erythrocytes by the immunofluorescence analysis, we developed a special protocol for preparing erythrocyte masses from patients diagnosed with CC. As a result of using a new method of sample preparation for immunofluorescence assay and using SEM, the hypothesis of the viral nature of nanoparticles localized on the surface of the blood erythrocytes of patients with CC was confirmed: Particles of HPV 16 and 18 are located on the cytoplasmic membrane of erythrocytes. Studies suggest that viruses attach to the erythrocyte membrane, which seems to influence the development of CC, its recurrence, and metastasis.

The purpose of the article is a historical and anthropological reconstruction of the traditional economic practices of the Yakuts, in which the most important place was occupied by the exploitation of cryogenic resources (cold, snow, ice, "permafrost"). The work is based mainly on the analysis of observations by researchers of the second half of the XIX – first half of the XX centuries, who recorded in the course of their expedition surveys a number of stories concerning the practices of the use of cryogenic resources by the Yakuts in economic activities. Methodologically, the article is based on the principles of cryosophy, involving the study of the cold matter of the Earth through the prism of their role as an active element of the universe, a source of benefits and opportunities for humanity, as well as a historical and anthropological approach. The article for the first time shows a number of examples of successful and active exploitation of cold, snow, ice and "permafrost" in the traditional economic activities of the Yakuts within the framework of such a plan: cattle breeding and horse breeding, fishing and hunting, as well as in the organization of salt production. Based on accumulated materials, including documents from the Archives of the Russian Academy of Sciences and its St. Petersburg branch, the State Archive of the Irkutsk Region, the Scientific Archive of the Siberian Branch of the Russian Academy of Sciences, the Scientific Archive of the Russian Geographical Society and the Manuscript Fund of the Archive of the Yakut Scientific Center SB RAS, the authors conclude that cryogenic resources were one of the important adaptation mechanisms Yakuts to the natural and geographical realities of Yakutia.

The hybrid high overtone bulk acoustic wave resonators (HBARs) consisting of a piezoelectric film transducers and gallium gadolinium garnet substrates with yttrium iron garnet films (YIG-GGG-YIG) are used for experimental excitation and detection of acoustically driven spin waves (ADSWs). Two types of HBAR transducers made of Al-ZnO-Al films (differed through the electrodes’ geometry) were deposited onto YIG-GGG-YIG trilayers with different YIG film thicknesses and doping levels and served for excitation of multimode HBAR at gigahertz frequencies. ADSWs were detected by measuring the shifts of resonant HBAR modes in a tangential external magnetic field when the conditions for magnetoelastic resonance (MER) were satisfied. It was shown that the design of the transducer with a continuous bottom electrode provides all acoustical excitation of spin waves (pure ADSWs), suppressing the additional inductive magnetic dynamics excitation due to the electrodes’ geometry. The theoretical study of the HBAR spectrum in a magnetic field showed that the resonance harmonics in the MER region can either almost continuously transfer from one to another, or decay and form an evident magnetoelastic gap. In this case, the shift of resonant frequencies can achieve several intermodal distances. The results obtained are important for applications of HBAR-based devices in spintronics and magnonics.

Methanol synthesis catalyst (MSC) waste was applied as the principal component (till 70 wt.%) of sustainable ceramics in composites with bauxite processing waste (RM), and waste foundry sand (FS). The results of the initial components' chemical interaction studies by a complex of methods (XRD, SEM/EDS/mapping, AAS and LAMMA) during heating demonstrated the synthesis of amorphous glasslike new formation, their filling of pores and compaction of the ceramic’s structure. In this case, a strong chemical and mechanical binding of all heavy metals and other hazardous elements of the initial industrial waste occurs with their transfer to an insoluble in an acidic environment. The materials with the highest MSC contents have the highest axial resistance values ill 25.98 MPa after firing at 1050°C.

This article presents a clinical case demonstrating the possibilities of MRI of the pelvic under the assumption of a histological variant of a prostate tumor. The main MR-patterns of the ductal adenocarcinoma, as well as the variants of their occurrence are considered. The authors present an analysis of data of differential diagnosis of various histological variants of prostate cancer.

The problem of developing a professional style of self-regulation among employees of the internal affairs bodies who are first recruited and undergoing training in vocational training centers is considered. The goal is to develop and test a specialized program for mastering the methods of arbitrary mental self-regulation, applicable in the conditions of the Center for Psychological Training. Materials and methods. The total sample of the study was 64 people aged 20 to 30 years. The experimental group of 20 people and the control group of 21 people were employees who were taking an initial training course at the Central Training Center of the Main Directorate of the Ministry of Internal Affairs in Moscow. An initial and final psychodiagnostic study was carried out using a test battery of the APPDK "Multipsychometer", sensorimotor and cognitive tests using a specialized space. An evaluation role at the final stage was also played by the data of expert surveys, self-reports of participants, and keeping a diary according to the model of A. V. Alekseev. At the stage of formative empirical research, complexes of methods of arbitrary mental self-regulation (PPSR) were used, as well as a set of lead-up exercises. Results and discussion. It was found that in the process of formation and development of the professional style of self-regulation among police officers, the most important factors are: the use of breathing, body-oriented and other lead-in exercises; the process of mastering voluntary self-regulation has a more stable result, provided that a certain algorithm for mastering the exercises of voluntary self-regulation is used, which involves a gradual acquaintance with entering an altered state of consciousness; such an algorithm makes it possible to carry out this work within the time frame determined by the duration of the training period for police officers in the framework of primary professional training. Conclusions. The ability for voluntary mental self-regulation is successfully developed among employees, provided that a targeted program is used, based on the idea of systematic mastering of an excessive set of self-regulation methods with gradual individualization and professionalization of the style of their implementation.

Restudy of Campyloprion annectans Eastman, 1902 from North America demonstrated that neither specimen included is diagnostic at the species level; thus, the species name is a nomen dubium. Since this species was designated as the type species of the genus, this requires suppression of the generic name also. Another species earlier assigned to Campyloprion, Campyloprion ivanovi Karpinsky, 1924 is used as a type for a newly established genus Karpinskiprion Lebedev et Itano gen. nov. The composition of the family Helicoprionidae Karpinsky, 1911 is reviewed, and a new family Helicampodontidae Itano et Lebedev fam. nov. is erected. A new specimen of Karpinskiprion ivanovi (Karpinsky, 1924) recently discovered in the Volgograd Region of Russia is the most complete Karpinskiprion specimen ever found. It unambiguously demonstrates the coiled nature of these tooth whorls and presents information on their developmental stages. During organogeny, cutting blades of the crown became reshaped, and basal spurs progressively elongated, forming a grater. Whorl growth occurred by addition of new crowns to the earlier mineralised base followed by later spur growth. In contrast to consistently uniform cutting blades, spurs are often malformed and bear traces of growth interruption. Both sides of the outer coil of the tooth whorl bear lifetime wear facets. The youngest (lingual) crowns are as yet unaffected by wear. The best-preserved facets show parallel radially directed scratch marks. The upper jaw dentition of Karpinskiprion is unknown, but we suggest that the faceted areas resulted from interaction with the antagonistic dental structures here. Three possible hypotheses for this interaction are suggested: (a) two opposing whorls acted as scissor blades, moving alternately from one side to another; (b) the lower tooth whorl fitted between paired parasymphyseal tooth whorls of the opposing jaw; or (c) the lower tooth whorl fitted into a dental pavement in the upper jaw.