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The authors of this work recall the most popular method of architectural reflection at the end of the twentieth century, which is again becoming relevant in the modern world of modernity. The presentation of the theoretical foundations of the philological metaphor in architectural practice is illustrated by the actual design experience, inspired by a literary work.

The aim of the study was to determine the comorbidity index in geriatric patients of a neuropsychiatric hospital and to assess its impact on their survival. A pharmacoepidemiological study was conducted to assess comorbidity and its effect on survival in geriatric patients of a neuropsychiatric dispensary. There were analyzed 90 inpatient records of geriatric patients, men and women in equal numbers. The average Charlson index in the study group of patients was 13 %, which shows a low survival rate of geriatric patients with significant concomitant pathology. In addition, the average index of the Charl-son index was determined depending on the number of concomitant diseases and it revealed a tenden-cy to decrease the probability of survival of elderly patients over a 10-year period, with an increase in the level of comorbidity.

Dementia is a debilitating condition characterized by memory decline, impaired cognitive functions, behavioural changes, and difficulties in performing daily activities. It predominantly affects older individuals and is a leading cause of disability. The global prevalence of dementia is on the rise, primarily due to population aging. Many individuals with dementia are cared for at home by their family members, who face the potential risk of caregiver burden and psychological stress stemming from the changing psychological state of the dementia patients. Providing daily care for individuals with dementia necessitates caregivers' active engagement in personal adaptation processes and the utilization of psychosocial resources. The purpose of this study is to determine the peculiarities of character accentuations of caregivers for patients with dementia. The study demonstrated that approximately 80% of patients with dementia receive care from their relatives. We conducted a comprehensive examination encompassing sociodemographic, clinical-psychopathological, psychodiagnostic, and statistical analyses. The methodology of K. Leongard - N. Schmieschek (1970) allowed us to establish a profile of personal accentuation of the studied groups, which took into account the presence of a certain type at the level of a sign, tendency or clearly present characteristic. Our findings revealed a statistically significant predominance of anxious (χ2=10.759, p=0.002) and stuck (χ2=4.166, p=0.042) accentuation types among individuals in Group I who possessed caregiving skills, compared to those in Group II. Conversely, caregivers in Group II exhibited a prevalent tendency towards demonstrative behaviour (χ2=8.028, p=0.005). Through this study, we established characterological profiles with pronounced accentuations for individuals fulfilling the role of caregivers for dementia patients. This enables us to consider the unique personal characteristics when developing psychocorrective measures for caregivers. For this particular category of individuals, counselling assistance is recommended, along with psychoeducational measures aimed at raising awareness and enhancing the quality of life.

Many insect subspecies are described without a statistical assessment of differences. In this work, an attempt is made to statistically process the morphological differences of some recently described subspecies. In this regard, a taxonomic review of Entomoscelis adonidis (Pallas, 1771) (Coleoptera, Chrysomelidae) and related taxa described from European Russia and the Caucasus is presented. Statistical processing of numerous materials (782 specimens) from type localities of the nominal taxa adonidis, spuria Jacobson, 1896, caucasica Kippenberg, 2020, and bashkiriae Kippenberg, 2020, and their environs showed the presence of geographical variability in several characters, which, however, does not reach the level of species or subspecies. For subspecies, the classic “75 %” rule is applied. Therefore, all these specimens are considered to belong to the same species and subspecies. For nomenclature stability and to clarify the taxonomic position of closely related taxa, the neotype of Chrysomela adonidis Pallas is designated from the type locality; the neotype is in accordance with the currently used interpretation of E. adonidis adonidis. Besides that, the lectotype of Entomoscelis adonidis var. spuria Jacobson is designated. The paratypes of E. adonidis caucasica Kippenberg and E. dorsalis bashkiriae Kippenberg were studied. The following new synonyms are proposed: E. adonidis adonidis (Pallas, 1771) = E. adonidis caucasica Kippenberg, 2020 (syn. nov.) = E. dorsalis bashkiriae Kippenberg, 2020 (syn. nov.). The status of E. adonidis var. spuria Jacobson, 1896 as a junior synonym of E. adonidis adonidis is confirmed. The endophallus, particularly, flagellum of E. adonidis was studied for the first time. Several Brassicaceae species, namely Berteroa incana, Barbarea vulgaris, Sisymbrium officinale, Capsella bursa-pastoris, and Thlaspi arvense, as well as Adonis vernalis (Ranunculaceae) are confirmed as host plants of the adults of E. adonidis in cages.

Background. The need to use BRAF and MEK inhibitors in the treatment of patients with metastatic and/or unresectable BRAF + melanoma in certain clinical situations is beyond doubt nowadays. The medical community need more information about the new combination of targeted therapy approved in Russia, further details on the expected efficacy and tolerability, potential differences from the existing combinations. Aim. To present of the study results and demonstration of our experience with the new generation of targeted therapy encorafenib and binimetinib combination in the treatment of patients with metastatic and/or inoperable BRAF+ melanoma. Materials and methods. We present the clinical case of BRAF+ advanced melanoma patient with multiple metastases in the liver, spleen, mediastinal and abdominal lymph nodes, stomach and bones who is being treated with encorafenib and binimetinib since 2015 with the treatment efficacy and tolerability described in details, as well as the published data on the efficacy and tolerability of this combination from the pivotal phase III study COLUMBUS. Results. High immediate and long-term efficacy, satisfactory tolerability of encorafenib and binimetinib combination are presented. Updated data on progression-free and overall survival in the COLUMBUS study confirmed the long-term efficacy of COMBO450 therapy in patients with advanced melanoma with BRAF V600 mutation. Conclusion. New generation of BRAFi and MEKi combination expands options of systemic therapy for patients with metastatic and/or inoperable BRAF+ melanoma.

BACKGROUND: Currently there are practically no works in the literature to assess the outcomes of systemic therapy in patients with solitary, single and multiple metastases of renal cell carcinoma. AIM: The aim of the study was to analyze the outcomes of systemic drug therapy of the first line in patients with solitary, single and multiple metastases of renal cell carcinoma. MATERIALS AND METHODS: The data of 981 patients with metastatic renal cell carcinoma who underwent systemic therapy of the first line at the City Oncological Hospital No. 62 in Moscow and the City Oncological Dispensary in St. Petersburg from 2006 to 2022 were retrospectively analyzed. All patients underwent clinical, laboratory and pathomorphological examination. 90 (9.2%) patients had solitary metastases, 252 (25.7%) single metastases and 639 (65.1%) multiple metastases. An analysis was made of the outcomes of 1st line therapy, which were conditionally divided into favorable, including all cases of complete response, partial response and stabilization, and unfavorable progression during treatment, death or deregistration. Subsequently patients who had previously received chemotherapy or cytokine treatment were excluded from the analysis. RESULTS: Complete response (3.3%) and deregistration (5.56%) were more often observed in patients with solitary metastases, stabilization more often occurred in patients with single metastases (51.1%), partial response (9.4%) and death (6.2%) in patients with multiple metastases. In patients with multiple metastases treated with immune checkpoint inhibitors a partial response was observed in almost half of the cases. Stabilization and progression were observed in almost the same percentage of cases (about a quarter of cases), and only two patients had a fatal outcome, which is slightly lower than in patients receiving tyrosine kinase inhibitors. Frequent outcomes when using tyrosine kinase inhibitors were stabilization of the process (40.72% of cases) or progression (38.72%), a complete and partial response was rarely recorded. Significant differences in the occurrence of favorable and unfavorable outcomes were revealed in patients with multiple metastases, depending on the number of affected organs and the prescribed drug. When comparing the results of systemic therapy of the first line, a higher efficiency of tyrosine kinase inhibitors was observed in solitary metastases of tumors with a high and moderate degree of differentiation. Systemic therapy of G3 tumors with solitary metastases had low efficacy in the appointment of tyrosine kinase inhibitors in 27.27% of patients. Higher efficiency was noted in single and multiple metastases. The effectiveness of immune checkpoint inhibitors was revealed in 70.6% of patients with single and multiple metastases. CONCLUSIONS: When choosing systemic therapy for metastatic renal cell carcinoma in clinical practice, it is necessary to take into account such prognostic factors as histological variants, the degree of differentiation of the tumor and the number of affected organs.

Introduction. This article analyzes the effectiveness and safety of complex treatment of children with diseases of the lymphoepithelial pharyngeal ring against the background of persistent allergic rhinitis.Objective. Study the efficacy and safety of adenotomy in children with persistent allergic rhinitis.Materials and methods. 124 children participated in the study. Two groups were formed: a control group of children receiving medical treatment and a main group – complex (medical and surgical treatment). When contacting the polyclinic, an examination was carried out by an otorhinolaryngologist. An allergist-immunologist confirmed the diagnosis of persistent allergic rhinitis, assessed the quality of life of children, using a questionnaire for patients with allergic diseases in pediatrics PRQLQ together with an otorhinolaryngologist. The condition of the dental system was evaluated by a pediatric dentist. A pediatrician conducted a physical examination of all children one, three and six months after the start of the study.Results and discussion. After comprehensive (surgical and drug) treatment, children experienced a significant decrease in nasal obstruction, a decrease in the incidence of respiratory diseases, as well as increased physical activity and improved emotional status, inflammatory phenomena in the pharynx and nasopharynx decreased by 70.9% according to visual analog scales compared to the day of discharge from the hospital. Analysis of the results of the study showed that conservative treatment in combination with surgical intervention on the lymphoid structures of the pharynx in the presence of indications in patients with persistent allergic rhinitis is safe and more effective than using only a therapeutic approach.Conclusions. Thus, the preliminary results of the observed period demonstrate the effectiveness and safety of surgical intervention on the lymphoid structures of the pharynx in children with persistent allergic rhinitis. The complex method of treatment of combined pathology is safe and effective and has a beneficial effect on the somatic status and quality of life of children.

Clinical case of an 85-year-old patient with Heid’s syndrome is being reported: recurrent gastrointestinal bleeding due to angiodysplasia of the stomach and intestines in combination with acquired destruction of large von Willebrand factor multimers in severe aortic stenosis. Actually it remains difficult to make a diagnosis in these patients and perform timely surgical intervention. Considering the age of the patient, severity of manifestations of heart failure and high risk of surgical complications, transcatheter aortic valve implantation (TAVI) was the method of choice. Surgical correction of heart disease in this case is aimed not only at treating its clinical manifestations, but also at eliminating the cause of recurrent gastrointestinal bleeding in Hyde’s syndrome.

The purpose of the article is to study the factors of the development of enterprises in the tourism industry of Ukraine and the formation of scenarios for their development in the conditions of martial law and after the end of hostilities. When conducting the research, the methods generally accepted in economic science were used: monographic, dialectical - in the process of researching the development of enterprises of the tourism industry of Ukraine under martial law and after the end of hostilities; analysis and synthesis, grouping - to determine the factors of development of tourism industry enterprises; generalization and analysis, economic-statistical, abstract-logical and system-structural - for the formation of scenarios for the development of enterprises of the tourism industry of Ukraine. The key problem of the study is russia's attack on Ukraine, which turned into a heavy blow to the country's tourism. The article proves that protectionism and international conflicts threaten freedom and freedom to travel. All these changes mean that we are going through a period of great destabilization. It is justified that the reality as we know it, with a Europe without border crossings, may soon disappear. Emphasis is placed on the fact that it is important to create such tourist programs now so that not only Ukrainians but also tourists from other countries understand what was happening in Ukraine and tell about the struggle of Ukraine. Four scenarios for tourism development in Ukraine have been proposed, each with a number of implications for stakeholders. Based on the conducted scientific research, it was concluded that one of the optimal approaches to the formation of scenarios for the development of tourism industry enterprises in Ukraine in the conditions of universal dynamism, unpredictability and variability of the business environment is recognized as strategic management and change management. The practical significance of the obtained results reveals the prospects for applying the main scientific provisions of the article in the practice of managing tourism business enterprises in Ukraine in the conditions of post-war reconstruction. The results of the study presented in the work can be used by economists, scientists and practitioners to implement scenarios for the development of tourism industry enterprises in Ukraine, each of which has a number of consequences for stakeholders.

Being overweight has serious health consequences for schoolchildren. Schools use different physical education (PE) programs for obesity prevention in children, but the overall positive impact of school-based interventions is questionable. This scientific work investigated the effects of high-intensity interval training (HIIT) intervention on physical fitness performance and body mass index (BMI) of overweight primary schoolchildren (seven years old males). Sixty-four boys, who had overweight, participated in this study. All participants practiced 44 PE classes. Control group (G1; n=32; mean age: 7.46±0.32 years; mean height: 123.35±3.28 cm; mean body mass: 27.81±2.32 kg; mean BMI: 17.82±0.11) performed curriculum PE during the investigation. The experimental group (G2; n=32; mean age: 7.54±0.27 years; mean height: 123.26±3.41 cm; mean body mass: 27.84±2.07 kg; mean BMI: 17.78±0.14) performed sixteen-week HIIT intervention in PE classes. Participants' height, weight, BMI, and physical fitness: push-up test, running sprint test, standing long jump test (SLJ), seat-and-reach test (SRT), and six-minute walk test (6MWT) were assessed in pre- and post-PE intervention. There were significant (p

The objective: analysis of clinical cases of tuberculous spondylitis in HIV-infected patients with the detection of HIV RNA in the focus of vertebral bodies destruction.Subjects and Methods. Medical records of 2 HIV-infected patients who underwent surgery for verified tuberculous spondylitis were analyzed. Parts of the vertebral bodies collected during surgery were examined (PCR, microbiological and histological tests), those were parts with destruction and fragments of healthy iliac bone necessary to fill the implant during corporodesis.Results. M. tuberculosis RNA was detected in the foci of bone destructionas as well as M. tuberculosis DNA. The viral load in the fragments of healthy iliac bone and peripheral blood of these patients was undetectable.

Based on the revealed contradictions between the needs of the labor market and the level of qualification of personnel, the article attempts to comprehend the current situation of integration of the potentials of the educational and professional communities in building the trajectory of career growth of students. The current mechanisms of building an ecosystem of professional education organizations, general education organizations and the business community are considered. The “ecosystem of personnel partnership” is discussed as a social environment that is formed for the purpose of productive development of the potential of students. It is a collaboration of teachers, employees of manufacturing companies and organizations, people living in this territory, education authorities and the labor market. The article analyzes the possibilities of the digital educational space as a link in the process of community integration and professional self-determination and self-realization of young people. The main technologies implemented in the integration process are systematized.

Trombiculid mites are known as vectors of larvae of Ericotrombidium caucasicum Schluger, 1967, Lacertacarus latus Schluger et Vasilieva, 1977, and Schoengastia sp. chigger mites (Acariformes: Trombiculidae) were collected from lizards Lacerta strigata and L. agilis (Reptilia: Lacertidae) in the Caucasus and adjacent territory (Iran). Our record of Ericotrombidium caucasicum in Azerbaijan is the first finding of the species in this country. Also, results of E. caucasicum on L. strigata and Lacertacarus latus on L. agilis are new host-parasite associations. Schoengastia sp. has been reported from L. strigata for the first time.

Introduction. Communication complexities which often occur in interdisciplinary work gave rise to the studies on teaching interdisciplinary communication. A growing need to provide pedagogical solutions to facilitate teaching interdisciplinary communication stimulated the research into language as a social practice to better understand communication process for interdisciplinary purposes.Aim. This exploratory study investigates the concept of interdisciplinary communicative competence and proposes a framework of interdisciplinary communicative competence with the focus on three underlying components: knowledge, skills, and personal attributes of interdisciplinary team members.Methodology and research methods. Qualitative and quantitative methods were used. The data obtained from 24 in-depth semi-structured interviews with five groups of higher education stakeholders (employers, academic directors of the programmes, professors, students, and alumni) revealed the existing interdisciplinary practices in the university and cross-functional practices in the companies. The proposed framework was empirically tested using an online survey with 139 responses from professors, students, and employers. The data processing techniques included the use of Kendall’s concordance coefficient, Cronbach’s alpha, and the principal component analysis.Results. The study presents the authors’ conceptualisation of interdisciplinary communicative competence and its framework as the result of the literature analysis and the empirical research. The findings provided evidence on the importance of language skills for effective interdisciplinary communication as perceived by 5 groups of respondents. The choice of language skills as a basic component of interdisciplinary communicative competence is justified.Scientific novelty. The study contributes to the conceptualisation of a framework of interdisciplinary communicative competence. The elements of the framework are identified and their relevance is empirically tested.Practical significance. The results of the empirical part of the study can be applied in the design of interdisciplinary learning process in higher education, for example, in the design of interdisciplinary courses, and teaching materials.

Introduction. Preeclampsia (PE) is a serious complication of pregnancy that occurs in 3-8% of pregnant women and is the leading cause of maternal and perinatal morbidity and mortality.Aim. To evaluate the role of vascular homeostasis gene polymorphism in the formation of preeclampsia.Materials and methods. The sample for this study included 250 women with preeclampsia and 209 women with normal gestation (control group). Five polymorphic loci of vascular homeostasis genes were selected for analysis: α-adducin (G460W ADD1), β2-adrenoceptor (+46G/A ADRB2), endothelin-1 (Lys198Asn EDN1) encoding the β3 G protein subunit (G/A GNB3), cytochrome 3A5 (+6986G/A CYP3A5). The molecular genetic study of all SNPs was carried out by polymerase chain reaction.Results. It was found that genetic variants determine the risk of developing preeclampsia. The allelic variant 198Lys EDN1 (84.80%) occurs in women with a clinical diagnosis of PE significantly more often than in women of the control group (79.67%) (p = 0.05; OR = 1.43; 95%CI 1.01–2.03). At the same time, among pregnant women without PE, combinations of 198Asn EDN1 x +46 A ADRB2 (23.65%) and 198Asn EDN1 x 460 ADD1 x +46 A ADRB2 (23.65%) are registered 1.6–1.7 times more often than among women with PE (14.46 and 13.65%, respectively, рperm = 0.032). Conclusion. The risk factor for the formation of preeclampsia is the 198Lys EDN1 allele (OR = 1.43), and combinations of genetic variants 198Asn EDN1 х +46 A ADRB2 (OR = 0.55) and 198Asn EDN1 х +46 A ADRB2 х 460G ADD1 (OR = 0.51) have a protective value.

Актуальность. Разработка принципиально новых стратегий и технических решений, приводящих к повышению энергоэффективности и ресурсосбережения систем охлаждения энергонасыщенного оборудования невозможна без создания новых конструкционных материалов с целевыми функциональными свойствами. К перспективным системам охлаждения теплонагруженного оборудования, например, устройств связи пятого поколения 5G, с поверхности которых поступают тепловые потоки высокой плотности (до 1000 Вт/см2), относятся системы, базирующиеся на капельном орошении. Такое охлаждение позволяет повысить интенсивность и равномерность теплоотвода, значительно снизить расход теплоносителя. Но полученные к настоящему времени результаты показывают, что использование традиционных подходов (применение элементов систем охлаждения, изготовленных из стали, меди, алюминия и их сплавов, обработанных шлифовкой или полировкой) не позволяют решить задачу интенсивного охлаждения поверхностей, нагретых до высоких температур. Лазерные методы обработки теплопередающих поверхностей - один из наиболее эффективных способов интенсификации процессов испарения и кипения. В связи с развитием в последнее десятилетие лазерной техники стали доступны финансово возможные технологии создания целевых функциональных поверхностных свойств металлов. Использование на практике модифицированных лазерным излучением теплопередающих поверхностей систем охлаждения может решить ряд проблем, связанных с удовлетворением растущего глобального спроса на энергетические ресурсы, в частности, при интенсификации отвода тепловых потоков высокой плотности от элементов энергонасыщенного оборудования путем смещения кризиса теплообмена второго рода в область более высоких температур. Цель: оценка возможности смещения кризиса теплообмена (эффекта Лейденфроста) в область более высоких температур путем модификации теплопередающих поверхностей нагрева лазерным излучением наносекундной длительности. Методы. Методом лазерной обработки наносекундной длительности на типичных материалах, применяемых на практике при создании элементов систем охлаждения, созданы уникальные текстуры с заданными геометрическими характеристиками. Характеристики текстур определены с использованием оборудования конфокальной и электронной микроскопии. Регистрация эффекта Лейденфроста проводилась на специально изготовленной установке, оснащенной оборудованием теневого оптического метода и высокоскоростной видеорегистрации быстропротекающих физических процессов. Результаты. Установлены режимы воздействия одиночного лазерного импульса наносекундной длительности на поверхность нержавеющей стали и алюминия, гарантирующие образование абляционного кратера. Показана возможность применимости графоаналитической методики для формирования заданной микротекстуры при обработке поверхностей металлов лазерным излучением наносекундной длительности. Лазерная обработка поверхности металлов с энергией в импульсе до 0,6 мДж позволяет за счет формируемой текстуры и супергидрофильных свойств в достаточно широких диапазонах значений управлять характеристиками кризиса кипения 2 рода, а именно температурой Лейденфроста более чем на 110 °С на поверхности алюминия и более чем на 45 °С на поверхности нержавеющей стали в атмосферных условиях при использовании дистиллированной деаэрированной воды в качестве теплоносителя. The relevance. The development of fundamentally new strategies and technical solutions leading to an increase in energy efficiency and resource saving of cooling systems for energy-saturated equipment is impossible without the creation of new structural materials with targeted functional properties. Promising cooling systems of heat-loaded equipment, for example, 5G communication devices emitting highdensity heat fluxes (up to 1000 W/cm2), include systems based on drip irrigation. Such cooling makes it possible to increase the intensity and uniformity of heat removal, and significantly reduce the coolant consumption. However, the results obtained so far show that the use of traditional approaches (the use of surfaces made of steel, copper, aluminum and their alloys, processed by grinding or polishing) does not allow solving the problem of intensive cooling of surfaces that release high-density heat fluxes. Laser strategies for processing heat transfer surfaces are one of the most effective ways to intensify evaporation and boiling. In relation to the development of laser systems in the last decade, financially sound technologies for creating targeted, functional surface properties of metals have become available. The practical use of laser-modified heat-transfer surfaces of cooling systems can solve a number of problems associated with meeting the growing global demand for energy resources, in particular, when intensifying the removal of high-density heat fluxes from elements of energysaturated equipment by shifting the heat transfer crisis of the 2nd kind to higher temperatures. The purpose is to assess the possibility of shifting the heat transfer crisis (Leidenfrost effect) to higher temperatures by modifying heat transfer heating surfaces with nanosecond laser radiation. Methods. Using nanosecond laser processing, unique textures with specified geometric characteristics were created on typical materials used in practice in the design of heat transfer surfaces for heating cooling systems. Texture characteristics were determined using confocal and electron microscopy equipment. The Leidenfrost effect was recorded using a specially made setup with equipment for the shadow optical method and high-speed video recording of fast physical processes. Results. The modes of a single nanosecond laser pulse action on the stainless steel and aluminum surfaces were detected. These modes guarantee the formation of an ablation crater. We showed the possibility to apply the graphic-analytical technique for the formation of a given microtexture during the treatment of metal surfaces with nanosecond laser radiation. Laser treatment of metal surfaces with pulse energy up to 0,6 mJ makes it possible to control the boiling crisis characteristics (2nd kind), in particular, the Leidenfrost temperature, over a wide range of values by more than 110 °C on aluminum surface and by more than 45 °C on stainless steel surface in atmospheric conditions when using distilled deaerated water as a heat carrier due to the formed texture and superhydrophilic properties.

Severe burn injury (BI) is accompanied by disturbed microcirculation, water-electrolyte and acidbase imbalance within 2-3 days after the accident, and the development of toxemia within 4-12 days. The severity of toxemia depends on the area and depth of the lesion, resorption of tissue decay products, and development of a systemic inflammatory response syndrome. In the patients suffering with deep BI sepsis, it develops in 15% of cases. Pathogenesis of critical conditions is related to the functional activity of myeloid cells, including neutrophilic granulocytes (NG). Тhe determination of NG’s dysfunctions in patients with BI is important, both for prediction of septic complications and administration of rational therapy. The aim of our work was to study the functions of neutrophils in patients with severe BI and to determine early predictors of burn-associated sepsis. The study involved 53 patients with severe BI at the mean age of 43 years (32 to 52); the area of damage was 43% (17 to 63) of the body surface, with deep-burn area of 17 (13 to 27) %. The severity of BI was assessed using the Frank index, at the average value of 74 conventional units (62 to 89). Тwo groups of patients were identified: 24 persons without sepsis, and 29 people with sepsis and severe sepsis. The studies were carried out upon admission, on the 1st, 3rd, 5th, 10th , and 20th day of the burn disease. We determined the numbers of NGs expressing CD18+, CD14+, defensin+; serum contents of soluble defensins (sDеf), IL-6, IL-8 levels (ELISA); procalcitonin, as well as luminol-mediated spontaneous аnd induced NG chemiluminescence. Тhe results of this study showed a relationship between the amounts of NGs containing antimicrobial peptides, contents of NGs expressing CD18+ adhesion molecules, activation of oxidative metabolism, IL-6 overproduction, and development of sepsis in patients with burn injury, as well as with severity of burn trauma.

Studies of real opportunities for physical skills of athletes sufficiently depend on their adaptive potential for increasing physical loads. Extreme physical and psychoemotional loads may lead to overwork and decreased physical ability in professional sportsmen. These adaptation processes are regulated by the main biochemical systems of the body. A special role belongs to the factors of humoral immunity, i.e., natural antibodies, which are a component of innate immunity. They circulate in blood of healthy persons in absence of obvious antigenic stimulation. Analytical techniques for measuring the level of natural antibodies that reflect the state of the system of endogenous bioregulators involved into the molecular mechanisms of adaptation process have been developed. An important role among them is played by the regulators of the opioid system β-endorphin and orphanin. The biochemical and immunological parameters were determined in 10 athletes active in figure skating (Master of Sports), whose average age was 16±0.4 years, and sport experience of 9±1 years. The duration of the study was divided into 5 stages and was 62 days. During the dynamic observations in the course of intensive training, no clear shifts in biochemical parameters were revealed towards adaptation stress and delayed recovery. The level of natural antibodies to orphanin and beta-endorphin was measured in the athletes blood serum by ELISA techique. It is found that each athlete is characterized by individual immune profile. At the initial stage of the examination, the level of antibodies to beta-endorphin was within normal ranges, except for its decrease in one athlete. The level of antibodies to orphanin in majority of cases was higher than normal, probably, due to inhibitory control of the pain signal. Further study in time dynamics revealed that the immunological parameters, natural antibodies to opioid peptides, change in accordance with the state of adaptation resources in the athletes. These indexes reflect psycho-emotional potential and pain tolerance threshold for athletes from the start of training and throughout the entire period. Therefore, from a prognostic point of view, it is important to monitor the content of natural antibodies to beta-endorphin and orphanin in athletes in the course of training. Such individual monitoring of the athlete’s immunological indices allows us to select a more effective, personal training program.

Fat of game animals is a prospective raw material for bioactive additives. Before such a product enters the market, food science has to make sure it is safe for consumption. This research featured subcutaneous adipose tissue of brown bears tested with standard methods for microbiological safety indicators. The microbial properties were studied on liquid and solid nutrient media. Staphylococcus was profiled using a VITEK 2 Compact biochemical automatic analyzer and Gram-positive cards (Bio-Mérieux, France). The analysis followed the Technical Regulations of the Customs Union TR TS 021/2011 On Food Safety (December 09, 2011). The microbial count for mesophilic aerobic and facultative anaerobic microorganisms was 1.5×103 CFU/g. The fat samples revealed no molds, yeasts, or Escherichia coli bacteria. Liquid and solid nutrient media made it possible to describe the qualitative profile and cultural properties of the bear fat microflora against pork fat, which served as control. The automatic system identified Gram-positive, coagulase-negative, and oxidase-positive Staphylococcus lentus and Staphylococcus sciuri. In line with the modern classification, they belong to the new genus of Mammaliicoccus, namely Mammaliicoccus sciuri. Subcutaneous adipose tissue of brown bears needs to undergo a microbiological safety test before consumption. Bear fat requires additional research in order to become a safe raw material for food products and bioactive additives.

The aim of the study is to analyse the advocate’s letter of enquiry as a means of obtaining information by advocates to carry out their professional activity in the conditions of military operations. Attention is drawn to a number of issues that complicate the process of submitting advocate’s letter of enquiry and the proper use of this mechanism and procedure by an advocate, namely, during the deployment of military operations. Ratification of the EU-Ukraine Association Agreement opens up new prospects not only for Ukrainian and European producers, but also provides for interesting objectives for advocates to consult the private sector in the process of building new markets. In this article, we propose to make a comparison and consider the issue of access to the advocate’s letter of enquiry of Ukrainian and Polish specialists during the protracted hostilities. As a result of the research, problems were identified and proposals were made for a simplified procedure for submitting an advocate’s letter of enquiry as a means of legal communication in the field of advocacy as a necessary condition for the period of military operations. El objetivo del estudio es analizar la carta consulta del abogado como medio de obtención de información por parte de los abogados para el ejercicio de su actividad profesional en condiciones de operaciones militares. Se llama la atención sobre una serie de cuestiones que complican el proceso de presentación de la carta de consulta del abogado y el uso adecuado de este mecanismo y procedimiento por parte de un abogado, a saber, durante el despliegue de operaciones militares. La ratificación del Acuerdo de Asociación UE-Ucrania abre nuevas perspectivas no solo para los productores ucranianos y europeos, sino que también proporciona objetivos interesantes para que los defensores consulten al sector privado en el proceso de construcción de nuevos mercados. En este artículo, proponemos hacer una comparación y considerar el tema del acceso a la carta de consulta del abogado de especialistas ucranianos y polacos durante las hostilidades prolongadas. Como resultado de la investigación, se identificaron problemas y se propusieron un procedimiento simplificado para la presentación de la carta de consulta del abogado como medio de comunicación legal en el c

Hydrogen has gained significant attention in recent years as a clean and sustainable energy source, with the potential to revolutionize the energy industry. However, one of the challenges associated with hydrogen as an energy source is its storage and transportation. Hydrogen is a highly compressible gas, making it difficult to store and transport in its natural state. The study presents different varieties of hydrogen tanks that are used for the storage and transportation of hydrogen gas. The methods for compressing hydrogen are described, with a focus on their advantages and disadvantages. The study concludes by comparing different methods for compressing hydrogen and discussing the factors that influence the choice of method for a specific application. The importance of continued research and development in this area is emphasised, as the efficient compression of hydrogen is crucial for the widespread adoption of hydrogen as a clean and renewable energy source. Life cycle cost analysis can evaluate the economic feasibility of using different hydrogen compressor technologies by estimating the total cost of owning and operating the compressors over their entire lifespan.

Currently, there is a significant shortage of donor materials for replacing corneal tissue that is why it is relevant to create xenomaterials, which are able to replace a donor cornea with various types of keratoplasty. “Corneoplast” is a new medical device, which is a devitalized, fixed by the method of double crosslinking (dehydrothermic + UV), pork cornea.Purpose: to assess the biocompatibility and ability to integrate with the recipient cornea of implants based on the xenomaterial “Corneoplast”.Materials and methods. The experiment was based on biomicroscopy examination, high-resolution optical coherence tomography and histological examination of the experimental rabbits’ corneas (group I–IV: total of 8 eyes were examined), where keratoplasty was performed with the “Corneoplast” material.Results. High biocompatibility and ability to integrate with the recipient’s cornea were observed in all types of keratoplasty: penetrating, superficial lamellar and intralamellar keratoplasty. On the next day, the implant was transparent with slight swelling of the recipient’s corneal stroma. A week later, the slight swelling of implant was recorded without cornea edema. Its transparency decreased. The recipient’s cornea was reactive. A month later, the moderate neovascularization was noted towards the sutures. After 6 months, the recipient’s cornea was clear, transparent. The implant was translucent and neovascularization was absent. The entire surface of cornea and implant was epithelialized. On the series of optical coherent tomograms, a normal thickness of the epithelium continuous layer was determined in 6 months after the surgery. The complete integration of material with the recipient’s cornea was noted. The layered structure characteristic of corneal tissue was preserved. The cornea retained a layered structure and the endothelium was preserved. On histological examination, there were no differences in the intact cornea and implanted material.Conclusion. The “Corneoplast” material is sufficiently biocompatible and capable of integration with the recipient’s cornea in an animal experiment. This allows, at a certain stage of preclinical trials completion, to use it for replacing corneal tissue in penetrating keratoplasty, intralamellar and superficial anterior layer-by-layer implantations and to cover purulent corneal ulcers of various depths.

Introduction: Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality. Using the evidence obtained about various clinical phenotypes of patients with the same disease allowed us to expand our understanding of the treatment of COPD. Nowadays the only option for solving the problem will be the definition of the clinical phenotype of COPD, and the receipt of expanded data on its correlation with respiratory and other significant biomarkers. Materials and methods: We analyzed the correlations between FKN, CRP and TBA-active lipid peroxidation products in 373 patients with various COPD phenotypes and 60 healthy volunteers. Enzyme immunoassay was used to study the levels of inflammatory biomarkers. Results: We have identified a statistically significant increase in the levels of inflammatory biomarkers in patients with COPD compared with the control. The FKN level in the group of patients with COPD was 1.3 ng/ml, which was higher (p

The realities of modern digital technologies in the cross-media global information environment are one of the most relevant topics of today. In light of recent military conflicts, our article attempts to identify and describe the most important aspects of digitization through the prism of contemporary military confrontations, including the Russian-Ukrainian conflict and global manifestations of civil activism. The study focuses on specific developments and innovations that demonstrate the impact of digitalization trends on Ukrainian resistance to aggression, as well as the course of other global military conflicts and civil resistance actions. To this end, technologies related to the tools used in the enemy’s resistance strategy are examined, including cutting-edge systems for information content production, search, acquisition, and processing, as well as analysis, verification, and visualization. Innovative digital developments for successful military operations, reliable defense capabilities during times of conflict, and digital communication tools and means that ensure human safety in such conditions are described. The level of reflection of the aforementioned aspects in the works of domestic and foreign researchers is demonstrated.

The article is devoted to two talented representatives of the Russian university philosophical community of the first quarter XX century: Vasily Sesemann and Ksenia Miloradovich. It’s shown that their university routes are very similar, as far as it was possible for male and female biographies of that time. The most complete list of their original works published before 1922 is given. The thematic focus of their publications and journals in which they were published is compared and the translation activity is analyzed. This allows us to see that in publications names of the “youth”: Vasily Sesemann, Ksenia Miloradovich, Sergey Hessen most often are supported by famous philosophers N.O. Lossky and S.E. Radlov. Based on the material of Ksenia Miloradovich's essay about the Philosophical Society, it’s emphasized that they were acquainted with each other in the philosophical workshop. The publications of Miloradovich and Sesemann made in the genre of reviews and not previously mentioned in their personal bibliographies, were revealed. It’s also shown that two historical events: the First World War (1914-1918) and the revolution of 1917 influenced the publishing capabilities of both philosophers. Nevertheless, until 1922 they continued to be active participants in the processes of reviving philosophical publications and the philosophical society. Lives of Sesemann and Miloradovich had the pathos of the drama of political arrests that trimmed their philosophical biographies, but both managed to make their contribution to the history of Russian philosophy. The article emphasizes that the enthusiasm of their creativity and the drama of their destinies can serve as an example of vitality and loyalty to the work.

Konstantin Dmitrievich Glinka made a major contribution to the development of such areas of soil science as genesis, geography, cartography and mineralogy of soils. He made the first world soil maps (1908, 1915, 1927), the first soil map of the Asian part of Russia (1927, jointly with L.I. Prasolov), classic studies of weathering processes and transformation of primary minerals into secondary, first studies of buried and relic soils, which laid the foundation for paleosoil science. Fundamental, encyclopedic textbook, written by K.D. Glinka “Soil science” went through six editions (1908–1936) and became a basic guide for many generations of soil scientists. The ideas of K.D. Glinka in the genesis of different types of soils, including gray forest soils, podzols, red earths, burozems (brown soils) have not lost their scientific value until the present day. His outstanding scientific, organizational and pedagogical contribution to the development of genetic soil science has earned K.D. Glinka a well-deserved fame as a scientist of world class.

The paper presents an analysis of the final stage assignments developed for the Russia-wide Olympiad in the Russian language for school students. The study identifies assignment types. Etymology and issues of the history of the language receive particular attention in designing such assignments. It is noted that participants are required to combine their knowledge of all Russian language course sections to complete most assignments rather than simply reproduce the material. The research highlights the main problems that students encountered when doing the assignments. The insufficient formation of reading literacy skills and decreased attention to studying and assimilating the language and its levels as systemic phenomena are among such challenges. At the same time, we conclude that many school students demonstrated a high level of language proficiency and general erudition.

Palliative care for neurological patients is an approach to patient care and assistance to their families facing chronic, progressive, life-limiting and disabling conditions. The peculiarity of palliative care in neurology is due to the signifi cant duration of the late stages of many neurological diseases and the distinctive features of some diseases (cognitive disorders, mental disorders, speech disorders, pelvic organ dysfunction, paresis, convulsions, contracture development, etc.), as well as the presence of concomitant common symptoms (eating disorders, pain, bedsores, respiratory failure, etc.). The symptoms developing in the advanced stages of neurological diseases requiring palliative care are described. Drug and non-drug methods of treatment are described, measures aimed at improving the quality of life and preventing complications are considered. The features of pharmacotherapy, taking into account their interaction with drugs for the treatment of concomitant pathology, are considered.

Introduction. On the territory of Russia four species of lyssaviruses (genus Lyssavirus) were identified, three of them caused human deaths. The aim of work: to characterize fatal cases in humans after contacts with bats in the Far East in 20182021 and to perform typing of isolated pathogens. Materials and methods. Lyssavirus infection was confirmed in samples of sectional material from people who died in the Amur Region in 2019, in the Primorsky Krai in 2019 and 2021. Diagnostics was performed by fluorescent antibody test (FAT) and RT-PCR using diagnostic kits of domestic production. Viruses were isolated in a bioassay. The nucleoprotein sequences were analyzed after 1st passage. The analysis of phylogenetic relationships and the construction of a dendrogram were performed using the MEGA7 software. Results. The viruses that caused the fatal cases in humans in the Amur Region and Primorsky Krai share more than 90% identity to Lyssavirus irkut detected in Russia and China. Together they form a separate monophyletic cluster with 100% bootstrap support. Conclusion. On the territory of Russia, monitoring of bat populations for infection with lyssaviruses is relevant. The material of people who died from encephalomyelitis of unknown etiology within 1015 days from the onset of the disease must be examined for lyssavirus infection. It is necessary to develop PCR assays that employ genus-specific primers. The use of molecular biological methods is promising for improving the diagnosis of rabies and epidemiological surveillance, as well as increasing the efficiency of the system of biological safety of the population of the Russian Federation.

Troubling disparities in COVID-19–associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. However, targeted studies on this vulnerable population are scarce. Here, we applied multiomics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, leads to persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1β, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to acute respiratory distress syndrome in a well-defined patient population disproportionally affected by severe COVID-19.

Monitoring results on undesirable South American weed Acanthospermum hispidum DC conducted in the Primorsky Territory in 2020-2021 are presented. The territories of the first detections of the species in the Far East, the sites of its probable introduction connected with imported products, crops and ruderal communities were examined. Regional and All-Russian floristic check lists published for the last 30 years as well as data on the contamination of crops were analyzed. The study confirmed the status of the species as being absent in the territory of the Russian Federation. However, high probability of the entering of the pest fruits as contaminant of imported agricultural products from the countries of wide pest distribution and its successful naturalization in suitable conditions remains.

Анотація. В статті досліджено напрями реформування освітніх процесів у підготовці сучасних фахівців в Україні на основі глобальних ініціатив щодо відповідального управління освітньою діяльністю та європейських принципів якості вищої освіти. Ціллю статті є реформування складових механізму впровадження компетентністного підходу для оновлення освітніх процесів та підготовки сучасних фахівців публічного управління та інших галузей економіки. Інформаційною та методичною базою дослідження є комплексний та системний підхід до впровадження компетентнісного підходу у закладах вищої освіти для підготовки фахівців. Глобальні ініціативи ООН, рекомендації Європейської асоціації із забезпечення якості вищої освіти. У результатах визначено основні напрями розвитку освітніх процесів в Україні, глобальні та євроінтеграційні цілі, принципи та методи реформування освітніх процесів для закладів вищої освіти. Визначено особливості впровадження компетентністного підходу закладах вищої освіти України у підготовці фахівців фармацевтичного сектору. Запропоновано механізм розвитку викладацького потенціалу, який сприятиме покращенню сучасної освіти в Україні в умовах сталого розвитку. У висновках зроблено фокус на аспекти розвитку публічної служби. Обґрунтовано актуальність Концепції утворення вищої школи публічного управління, виділено ключові групи стейкхолдерів щодо її реалізації та ключові вектори розвитку для забезпечення безперервного навчання державних службовців (навчання державних службовців за сім’ями та рівнями посад державно служби; індивідуальна траєкторія професійного розвитку осіб; стажування в органах влади). Визначено цільові орієнтири у підготовці фахівців в сфері публічного управління: наближеність та доступність освітніх послуг; навчання осіб, зарахованих до кадрового резерву; науково-методичне та експертно-аналітичне забезпечення системи професійного навчання; просвітницька робота з громадянами України щодо їх залучення до державної служби.

The article is devoted to the development of innovative potential of the personnel based on knowledge management. The controversy surrounding the concept of innovative potential is highlighted. Current trends in human resources management are described. The interpretation of the aforementioned concept as a dynamic process of self-development of the personnel is substantiated. Key competencies, dynamic, organizational and absorbing capabilities of an enterprise that are being formed as part of the knowledge management system created at the enterprise are included in the list of the main characteristics of the stated potential. It is stressed that continuous staff training should be the main block of the system. The need to integrate the knowledge management system into the innovative business model of the organization is substantiated. Therefore, the company will transform into a self-learning one and eventually, with the maximum number of employees involved in the continuous training system, a company of intellectual resources that does not only accumulate but also capitalises knowledge. It is stated that corporate universities and educational centers established at organizations should become an effective way to accumulate and share corporate knowledge.

This Expert Council focuses on the meta-analysis of studies on the risk of atrial fibrillation (AF) in patients taking omega-3 polyunsaturated fatty acids (PUFA) and of data on the omega-3 PUFA treatment in patients with cardiovascular and kidney diseases.The major statements of the Expert Council: the meta-analysis of AF risk in patients taking omega-3 PUFA showed an increased risk of this arrhythmia. However, it should be taken into account that the risk of complications was low, and there was no significant increase in the risk of AF when omega-3 PUFA was used at a dose of ≤1 g and a standard dose of the only omega-3 PUFA drug registered in the Russian Federation, considering all AF episodes in the ASCEND study.At the present time, according to Russian and international clinical guidelines, the use of omega-3 PUFA can be considered in the following cases: • for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction as a supplement to the basic therapy (2B class of recommendations according to the 2020 Russian Society of Cardiology guidelines (RSC) and the 2022 AHA / ACC / HFSA guidelines); • for patients with hypertriglyceridemia (>1.5 mmol/l) as a part of combination therapy (IIb class of recommendations and B level of evidence according to the 2021 European guidelines on cardiovascular disease prevention, etc.); • for adult patients with stage 3-4 chronic kidney disease (CKD), long-chain omega-3 PUFA 2 g/day is recommended for reducing the level of triglycerides (2C class of recommendations). Data on the use of omega-3 PUFA for other indications are heterogenous, which can be partially explained by using different form and doses of the drugs.

AIM. To evaluate the efficiency of telemedicine technologies in the complex rehabilitation of patients after transpedicular fixation of the lumbar spine. MATERIAL AND METHODS. 64 patients (38 men and 26 females, age 31 to 67 years) after transpedicular fixation of the lumbar spine where included in the study. All patients underwent 2-weeks inpatient medical rehabilitation. The telemedicine platform «Steps Reabil» was used in the study group (35 patients) for home-based rehabilitation. Patients received e-mail links to the video recording of 10 home-based physical exercises. The control group (29 patients) received a leaflet describing similar 10 physical exercises. Rehabilitation diagnosis by ICF domains (b28013, b7303, b7600, d4500, e1151), backache on 100-mm visual analog scale (VAS) and on Roland-Morris Disability Questionnaire (RDQ), Health Assessment Questionnaire (HAQ), Spielberger-Khanin reactive anxiety test, Beck depression inventory (BDI), 10-meters walking test were evaluated before starting home-based physical exercises and after 1 month. RESULTS AND DISCUSSION. The best patient adherence (74 %) to regular home-based physical exercises using the telemedicine platform was observed after 2 weeks, by the 2nd month the adherence decreased. Telerehabilitation improved the values of the qualifiers of ICF domains, reduced backache on VAS by 43.2 % (p < 0.05), on RDQ by 47.8 % (p < 0.05), HAQ by 57.1 % (p < 0.01), 10-meters walking test by 39.0 % (p < 0.05), reactive anxiety level by 30.6 % (p < 0.05), subclinical depression symptoms on BDI by 44.2 % (p < 0.05), with statistically significant differences from the control group in most parameters (р < 0.05), excluding 10-meters walking test. These results are consistent with the data of numerous studies that have demonstrated the efficiency of technology-based distance telerehabilitation in patients with various diseases. CONCLUSION. Telemedicine technologies allow to conduct the individual home-based rehabilitation program, to control its efficiency, which ensures the continuity of rehabilitation activities at all stages.

Introduction. LHS-1269 is an indolocarbazole derivative with high antitumor activity. Due to the hydrophobic properties of the active substance, the use of organic co-solvents – dimethyl sulfoxide (DMSO) and ethanol – is required to obtain an injectable dosage form (DP). However, the inclusion of organic solvents in the composition of the DF carries a potential risk of side effects as a result of the use of the drug.Aim. Selection of auxiliary substances for obtaining an aqueous solution of hydrophobic indolecarbazole derivative, which allows minimizing the concentration of organic solvents in the composition of DF.Materials and methods. The object of the study is the active substance LHS-1269 series 010320, produced in the Chemical Synthesis Laboratory of the N. N. Blokhin National Medical Research Center of Oncology. The following auxiliary substances were used to obtain model compositions: Kollidon® 17 PF, Kollisolv® PEG-400, Kolliphor® P 188, Montanox™ 20, DMSO (p.a.), ethanol 95 % (standardized according to pharmacopoeia quality standard ФС.2.2.0019.18 of The State Pharmacopoeia of the Russian Federation). Analytical scales OHAUS Analytical Plus AP 100S and laboratory scales AND DL-120 were used for weighing LHS-1269 and auxiliary substances. The dissolution and mixing of the components was carried out on an IKA® C-MAG HS 4 magnetic stirrer.Results and discussion. In the course of the study, 2 groups of model compositions were obtained and estimated, comprising a complex of two or more auxiliary substances as a solubilizer. The first group of formulations contained DMSO at a concentration of 5 % and ethanol at concentrations from 0 to 15 %. The compositions of the second group included DMSO from 0 to 4 %. As a result, it was found that the addition of 5 % Kolliphor® P 188 to the composition of the solution reduces the content of ethanol to 5 %. In this case, with further decrease in ethanol, turbidity of the solution and precipitation are observed. Reducing the concentration of DMSO in the DF to 2 % was achieved by using a combination of 20 % ethanol and solubilizer complex – Kollidon® 17 (20 %), Kollisolv® PEG-400 (20 %) and Kolliphor® P 188 (5 %). In this case, the total dissolution of the active substance without DMSO was observed when compensating for the organic solvent by introducing additional auxiliary substances – Montanox™ 20 (5 %) and benzene (2 %).Conclusion. As a result of the research, the compositions of the auxiliary substances of solubilizers are selected, allowing to obtain an aqueous solution of the hydrophobic compound LHS-1269 with a minimum concentration of organic solvents.

Annotation. In the 20th century cardiovascular diseases (CVD) is remain a leading global public health problem. The aim of the study was to analyze the general trends and regional characteristics of mortality from CVD in Ukraine in 2010-2020. The dynamic analysis covered the period 2010-2020 and carried out using indicators of absolute growth and growth rate. Regional differentiation of mortality rates from CVD in Ukraine was assessed by the amplitude of a series of regional distribution of indicators, upper and lower quartiles, and the coefficient of regional variation. The stability of territorial characteristics of mortality from CVD was determined using the correlation coefficient (Pearson, r), calculated based on regional indicators in 2010 and 2020. Comparison of age-standardized mortality rates from CVD in Ukraine and countries of Europe and the European Union was carried out based on materials obtained from the statistical database of the international epidemiological study "Global Burden of Disease (GBD)", updated for 2019. It has been established that CVD cause 66.2% of all deaths and CVD are significant medical, social and economic problem for Ukraine. Every day more than 1000 people die from CVD, and 100 of them are of working age. In 2020 408,163 Ukrainians died from this cause, and during 2010-2020, Ukraine lost almost 4.6 million of its inhabitants due to this cause. Almost 70% of these losses are caused by coronary heart disease and 20% by cerebrovascular disease. Age-standardized mortality rates from CVD in Ukraine exceed similar indicators in European countries by 2.5 times, and in EU countries by 3.7 times, and from coronary artery disease – by 3.4 and 5.4 times, respectively. Ukraine lags far behind in terms of the rate of decline in standardized mortality rates from European countries. The regions of Ukraine are characterized by a significant regional variation and a stable territorial profile of mortality from CVD with the concentration of its maximum levels in the most demographically old regions in terms of age composition. The Ukrainian strategy for the prevention of mortality from CVD should be comprehensive, regionally differentiated, depending on the territorial characteristics of the morbidity and mortality from CVD, and combine population-based approach for controlling modified risk factors for CVD with modern methods of secondary and tertiary prevention of CVD, which proven to be effective in European countries with positive experience of prevention of premature death from CVD.

Background. Microembols detected during transcranial Doppler monitoring with microembolodetection (TCDM with MED) are different in nature and, accordingly, in structure, as well as in size and consequences of their impact on the cerebral vessels. The following biophysical characteristics of microembolic signals (MES) can be assessed during TCDM with MED: frequency, which indirectly reflects the structure of the microembolus, duration, which indirectly reflects the size of the microembolus, and power, which is an integral characteristic. The issues of the relationship between characteristics of MES and clinical indicators have been little studied according to literature. Aims study of the biophysical characteristics of microembolic signals recorded in patients with ischemic stroke, as well as the factors affecting these characteristics, the clinical and prognostic significance of microembolism. Methods. This is a cross-sectional observational study that is part of a prospective cohort study. Data on 28 patients in the recovery period of ischemic stroke are included, in whom the biophysical characteristics of MES were analyzed (the total number of cases in the cohort study was 1600), and who underwent: duplex scanning of the brachiocephalic arteries, transcranial duplex scanning, TCDM with MED, transthoracic echocardiography, magnetic-resonance tomography of the brain, electrocardiography. Study enrollment was carried out in the period from 2019 to 2021. The MES characteristics included frequency, duration, power, energy index (the product of power and duration), of which the MES power was the main one. Results. MES characteristics correlated with anthropometric parameters: average duration - with the patients age (r = 0.421; p = 0.029); average frequency with body surface area (r = 0.624; p = 0.010). The average power, duration and energy index of MES were significantly higher in persons with intraluminal masses in the carotid arteries (p 0.05). Correlations of biophysical characteristics of MES with blood flow velocities in brain vessels (inverse correlation between the duration of the MES and the value of the peak systolic velocity in the M2 segment of the right MCA r = 0.529, p = 0.02; correlations between the power of MES, as well as the duration of MES with peak systolic and end-diastolic velocities in the V4 segment of the right VA r = 0.4810.572, p = 0.0270.007), as well as with signs of atrophy of the temporal and occipital lobes of the brain were identified (inverse correlation between MES frequency and regional atrophy in the right temporal lobe r = 0.434, p = 0.038; inverse correlation between MES frequency and regional atrophy in the left temporal lobe r = 0.422, p = 0.045; inverse correlation between MES frequency and regional atrophy in the left occipital lobe r = 0.465, p = 0.025). Significant differences were found in the number of MES and their average power, duration, energy index in the presence and absence of atrial fibrillation (p 0.05). Conclusions. Age and, apparently, weight, as well as signs of atherosclerosis of the brachiocephalic arteries, influence the development of microembolism. In the presence of atrial fibrillation, material microembolism is observed predominantly, and the number of MES and their characteristics which reflect the size of microemboli are significantly higher. The relationship between the duration of MES and the characteristics reflecting the blood supply in the basin of the middle cerebral artery, as well as between the frequency of MES and the presence of regional atrophy in the temporal and occipital lobes of the brain according to magnetic resonance imaging was revealed.

Background. Novel agents immune checkpoint inhibitors fundamentally changed the prognosis for life in patients with metastatic and/or inoperable melanoma. The development, studies, and approval of a new original PD1 inhibitor in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess the real-world efficacy and safety of prolgolimab, as real-world patients differ from the refined population in clinical trials. Aim. To evaluate the real-world efficacy and safety of prolgolimab in patients with metastatic and/or inoperable melanoma. Materials and methods. From October 2020 to October 2022, the study enrolled 700 patients with metastatic and/or inoperable melanoma receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma, metastatic and/or inoperable type, use of prolgolimab outside of clinical trials, and signed informed consent by the patient. Objective response rate (ORR) was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 34 adverse events. Statistical analysis was performed using the SPSS 20.0 software package. Results. The ORR for patients with skin melanoma treated with prolgolimab in the first line therapy (n= 207/337) was 48.3% (n=100), the disease stabilization was reported in 30.4% (n=63), and progression in 21.3% (n=44) of patients. There were no significant differences in response to therapy between patients with/without BRAF mutation, although ORR was higher in patients with BRAF mutation: the ORR for patients with BRAF mutation was 57.9% (n=33), and for BRAF non-mutated patients, 44.4% (n=52; p=0.222). At a median follow-up of 5 months, the median PFS was 10 months (95% confidence interval 7.3512.64). The incidence of grade 34 treatment-related adverse events according to CTCAE 5.0 was 2% (n=12), and 12% (n=82) for grade 12 adverse events. Conclusion. The results confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with metastatic and/or inoperable melanoma in real-world settings. There were no significant differences in ORR between patients with or without BRAF mutation.

Biliary tract cancer (BTC) is a group of rare and aggressive types of malignancies that arise from the epithelium of the intra- and extrahepatic bile ducts (cholangiocarcinoma) and gallbladder. The prognosis of unresectable BTC is poor, and less than 5% of patients are alive at 5 years after diagnosis. Radical surgical resection remains the only potentially curative treatment for early stage BTC, and antitumor chemotherapy extends survival rates in patients with unresectable or metastatic BTC. With the emerging of monoclonal antibodies targeting immune checkpoints, the possibility of such therapy in first- and subsequent-line treatment of advanced BTC has been actively studied. The positive high-level results from the TOPAZ-1 Phase III trial showed durvalumab, in combination with standard-of-care chemotherapy (gemcitabine plus cisplatin), statistically improved overall survival versus chemotherapy alone and showed improvements versus chemotherapy alone in prespecified secondary endpoints including progression-free survival and objective response rate. Durvalumab plus chemotherapy was well tolerated, had a similar safety profile versus the comparator arm and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone. The U.S. Food and Drug Administration approved the combination of durvalumab and chemotherapy (gemcitabine plus cisplatin) as the first immunotherapy regimen for patients with locally advanced or metastatic BTC. In July 2022, durvalumab plus chemotherapy (gemcitabine plus cisplatin) was added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a preferred regimen category 1 in first-line therapy for Unresectable or metastatic BTC based on the data from TOPAZ-1. In addition, the durvalumab plus gemcitabine and cisplatin was recently added to the practical recommendations of the Russian Society of Clinical Oncology (RUSSCO) for the treatment of hepatobiliary cancers as an alternative to standard first-line treatment of BTC.

The subject of the study is human hair. The authors consider the issues of hair research for biological and forensic chemical research. Currently, despite the large number of studies conducted by forensic medical experts and clinicians, there is no complete, targeted program for the study of hair for elemental composition, psychoactive and toxic substances, enzyme system, in which methods of hair research would be announced not only for forensic, but also for clinical, environmental practice. Forensic doctors have developed methods and techniques for conducting such studies. However, there are no such developments for clinicians, toxicologists. Removal and examination of hair to study the morphological structure is carried out without following the rules (length, description of the structure, indication of magnification of the microscope, characteristics of inclusions and others). The novelty of the study lies in the fact that the lack of widely available data on the characteristics of hair; by determining the content of foreign substances introduced into the body, gives rise to contradictory and even erroneous data. A special contribution of the authors to the study of hair is the proposed algorithm for morphological examination of their elements, which includes such sections as hair removal, macroscopic examination and microscopic examination. The described lesions in the form of inclusions of "black color", "flask-like formations" and "thickening of the core" are characteristic of normal hair and are not signs of exposure to any toxicant. The morphological shape of some hair indicates the effect on the hair of a toxic agent that affected their structure, as a result of which their loss occurred. The damaging factor acts on the desmosomes of the cuticle of the rod and the vaginal membranes of the hair and is exfoliated from its own hair bed. It was determined that the hair carries information about the entry of an intoxicant into the body in the phase of active growth – anagen.