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Evaluation of the physiological state of cattle is crucial in creating healthy, high-performing dairy cattle herds. Technological stress is one of the most critical factors determining the biological potential of higher-yielding cows. This work aimed to assess the effect of technological stress on various oxidative parameters and mitochondrial states in dairy cows' blood, milk yield and milk composition. The study was conducted on the black-and-white breed of healthy herds. Regrouping, changing service personnel, and carrying out veterinary and sanitary manipulations were considered technological stress factors. The concentration of cortisol in the blood serum was studied by the immunological method. The concentrations of malonic dialdehyde (MDA), diene conjugates (D.C.), Schiff bases (S.B.), reduced glutathione and catalase activity were measured spectrophotometrically. The mitochondrial state was estimated by laser interference microscopy. While the milk yield, protein and lipid composition of cow milk were studied using an ultrasound analyzer. The researched indicators were analyzed before and for 30 days after the effect of technological stress. Results of the study suggested that technological stress caused an increase in oxidative processes, along with a reduction of antioxidant activity of blood and milk at the initial stages of registration (1-7 days). The concentration of glutathione remained reduced for 30 days after technological stress. A decrease in mitochondrial refractoriness and disintegration accompanied these processes. The milk yield indicator decreased was not restored to the values of intact animals by 30 days after technological stress. Further, the protein and lipid composition also reduced. Thus, a decrease in the quantity and quality of milk under technological stress may be mediated by the development of oxidative stress, which the refractoriness and disintegration of mitochondria might trigger.

The purpose of the study was to substantiate strategic directions to overcome the asymmetry of regional development. The methodological basis involved a systemic approach that allowed, in turn, a holistic approach to clarify the linkages and patterns of regional development asymmetry and justify strategic measures to overcome it. In the results, it was found that the region's development strategy is a set of interrelated measures aimed at ensuring the principles of sustainable development, improving the quality of life, creating conditions for economic growth, ensuring the efficient use of resources, improving regional self-sufficiency, economic security and competitiveness of the region. It is argued that the region's development strategies should be based on: a) associative approach to the formation of goals and tools to achieve them; b) efficiency in the use of resources; c) participation of a wide range of stakeholders in the substantiation of strategic development directions; d) overall coordination of planning and control processes for the achievement of the set objectives. It is concluded that it is proven that the strategic directions of overcoming the asymmetry of regional development must be led by strategic thinking.

The purpose of the article is to substantiate the directions of state regulation of the processes of information and digital development, which will contribute to the reduction of the processes of differentiation of the development of regional economic systems. The study used an institutional approach that allows with a high degree of subordination, logic and consistency to study the diverse phenomena and processes associated with innovation and digital development, to take into account not only changes in formal and informal institutions, but also changes in global economic processes. self-identification of regions. The tools of state regulation of innovation and digital development of the regions should be singled out. The role and importance of informal institutions of innovation and digital development of regions are outlined. Direct and indirect methods of supporting scientific, technical and innovative activities are identified. The necessity of formation of strategic directions of innovation and digital development of regions is proved.

In the past decade, advances in both separations and mass spectrometry (MS) technologies have enabled new, streamlined, and data-rich approaches to monitor product quality attributes and their relationship with process parameters throughout the lifecycle of therapeutic proteins. As we enter a new decade of technology and method development, MS-based approaches utilized in the biopharmaceutical industry are evolving further. In this mini-review, we explore key developments that could inspire and improve the future of therapeutic protein development.

The article examines some aspects of the musical and educational activities carried out at the turn of the XIX-XX centuries. provincial church-singing communities of various Christian denominations. As an example, the cities of Saratov, Samara, Simbirsk and Syzran are covered - the largest economic and cultural centers of the Middle and Lower Volga regions. The authors analyze the concert activity of the represented provinces in several directions: concerts of pra-glorious liturgical chants, spiritual concerts with mixed programs, concerts of sacred music in Catholic and Protestant churches, and also separately highlight examples of the premiere performance of author's spiritual works in provincial temples. Thus, the work highlights the educational concert and educational work of the professor of the Saratov Conservatory I.V. Lipaev, the Saratov Bishops' Choir under the direction of N.M. Dmitriev, Simbirsk Bishop's Choir (choir director S.P. Yagodinsky). The authors provide examples of touring performances by leading choral groups of the Russian Empire in the Volga cities, in particular, the Moscow Synodal Choir (conducted by N.N. Tolstyakov) in Saratov and the choir of the St. Samara. In addition, the article touches on the problem of interaction between Orthodox and co-religion communities, the performance of joint services by them (possible within the framework of the same-faith Liturgical practice), as well as the preservation of the Volga region of a living tradition of using the znamenny chant. As a result of the research carried out, the article traces the idea of the continuity of the ideas of the New direction in Russian sacred music by the Volga choir directors, as well as the active inclusion of the latter in the general process of development of Russian church singing art.

The problem of comorbidity becomes especially relevant in the conditions of demographic aging of the population. In recent years the number of studies devoted to diagnostic and treatment features of comorbidities, especially in elderly and senile patients, has increased. In spite of this fact, until now there are no clear recommendations for the management of comorbidities in the therapeutic practice.The article is devoted to the presentation and discussion of a clinical case of a comorbid patient with arterial hypertension. The stages of the performed diagnostic search with verification of the clinical diagnosis and the tactics of the prescribed pharmacotherapy are presented. On the basis of the presented data it is shown that exacerbation of one of the chronic diseases of the patient’s general comorbid background may significantly increase the severity of the general pathology and in its turn will determine the prognosis and influence the treatment tactics. The complexity of this case is that the patient has chronic single kidney disease in the stage of chronic renal failure. In analysing this case, it is also important to note the difficulties in the choice of drug therapy, as this situation poses significant limitations in the use of many drugs. This is a challenge that every clinician faces on a daily basis, regardless of clinical experience and medical knowledge. Only a multilevel approach will enable comprehensive medical and social care to be organised for patients with co-morbidities with chronic diseases, provide follow-up not only during exacerbations but also during remissions, contribute to the prevention of exacerbations and complications, which will consequently improve prognosis and quality of life.

The decline in the forecast indicators of the economy and production activity, the structural transformation of international production and consumer preferences, the reduction in income from bonds and world tourism, the massive layoffs of workers that led to an increase in unemployment and a decrease in household income, deferred investments and the reorientation of investment flows, both in economic sectors and in the regional context, are all the result of the impact of another challenge called COVID-19. The COVID-19 pandemic has changed and continues to change many characteristics of the economy and society. Together with the onset of the Fourth Industrial Revolution and the transition to the digital era, as well as taking into account completely new realities of the development of future generations, which are regulated by the concept of sustainable development, the formation of investment attractiveness is also taking place in a fundamentally different way. In this regard, the article substantiates the need to introduce the category sustainable investment attractiveness into everyday use. The author’s vision of the interpretation of this concept is presented. A procedure for forming a stable investment attractiveness of regions in the conditions of COVID-19 has been developed.

The article discusses the organism`s adaptive capabilities of different age groups in the population with the use of cardiointervalography and hemodynamic parameters. There was a decrease in the total power of the heart rate variability spectrum and the power of all spectral parameters with an increasing age. In age groups 1 and 2, LF, % and VLF, % were more pronounced, there was a significant predominance of VLF, % in group 2, which reflected an increase in the level of the sympathetic link regulation activity. A more significant increase in the power of very low frequency oscillations indicates an increase in the influence of the central circuit of regulation along with an increase in the cerebral ergotropic influences. Assessment of oxidative metabolism by fluorescence spectroscopy showed an increase in the indicator in group 2, with a tendency to decrease in group 3 as compared to the values of group 1. The performed analysis of the frequency-amplitude spectrum revealed changes in the reactivity of the structures of the microvasculature depending on age. An increase in the volume of blood entering the microcirculation system was recorded, but the regulatory effect on microcirculation was different: group 2 was dominated by central mechanisms of regulation, in group 3 there was a predominance of local regulatory mechanisms. Thus, with age, there is a decrease in the adaptive reserves of the body with a tension in the regulatory vegetative homeostasis and a transition from nervous mechanisms of regulation to a lower level of humoral mechanism.

The article is devoted to the opportunities and key contradictions of the Russian state healthcare system digitalization project implementation. The authors analyze various aspects of the system digitalization algorithms in light of the federal project “Creation of the Single Digital Circuit in Healthcare based on the Unified State Health Information System”. The aim of the article was to identify problems within goal-setting, documentation development, and practical implementation of the healthcare system digitalization project, as well as to come up with proposals for eliminating these issues. The analysis showed the inefficiency of the expensive healthcare system digitalization project, which has both objective and subjective reasons for its low effectiveness. The authors come to the conclusion that it is necessary to eliminate a number of contradictions and barriers in the framework of the project implementation in order to increase the efficiency of both the healthcare system itself and the high budget federal project of the economy digitalization as a whole. The practical significance of the article consists in the applicability of proposed approach to making the necessary amendments to the current federal project documentation, which will ensure a focus on real needs within the framework of the initiative implementation. The work may be of interest to civil servants, initiators of projects on the healthcare system digital transformation, governmental bodies, healthcare organizations managers, students, and practitioners.

The article is devoted to the study of theoretical and methodological aspects of the analysis of exports of goods and services in the context of regional development. The structural and logical scheme of the analysis of export of goods and services is of-fered. Export of the Kharkiv region was assessed by geographical structure, by goods and by countries. In general, the geograph-ical structure of export Kharkiv region shows a reorientation of commodities to EU countries. The export of services of the Kharkiv region by geographical structure and by types of economic activity is analyzed. Kharkiv region has a developed and diversified economy. There are large enterprises of mechanical engineering, agricultural and food industries, energy, developed oil and gas complex in the region. The geopolitical situation, as well as the crisis caused by the COVID­19 pandemic, have significantly con-tributed to changes in the directions and instruments of the region's foreign policy. Based on this, it is possible to determine the objectives of the study, which is to analyze and evaluate the exports of the Kharkiv region in order to determine priorities to ensure its competitiveness. It is determined that the export of services of the Kharkiv region is dominated by services and computer services. To ensure the efficiency of exports of services, it is necessary to pursue a policy of increasing their volume by expand-ing the volume of other activities, such as education, tourism and others. A SWOT­analysis of exports of the Kharkiv region was conducted. The risks of slowing down export flows and strategic directions for improving the export activity of the Kharkiv region have been identified.Kharkiv region has enough competitive advantages in the development of export of commodities: natural resource potential, high quality and competitiveness of food industry and mechanical engineering, diversification of export flows by country, adaptation to European standards and quality requirements. Foreign economic entities are the most efficient part of business, and therefore deregulation and tax leverages are an important incentive to ensure favorable conditions for export flows. Given the high intellectual capital of the region, it is important to support the development of innovation through attracting investment in research and development, the introduction of public funding. Innovative products and services will help improve he position of the region and the country at the global level and ensure the growth of exports. The imperfection of the institutional framework in the innovation sphere also affects Ukraine's ratings in the internationally competitive environment. Regulatory policy in the context of the region's exports should be comprehensive and balanced using determined instruments.Keywords: export, regional development, Kharkiv region, export of goods, export of services, SWOT­analysis, export potential. Статтю присвячено дослідженню теоретико­методичних аспектів аналізу експорту товарів і послуг у контексті регіонального розвитку. Запропоновано структурно­логічну схему аналізу експорту товарів і послуг. Проведено аналіз експорту Харківського регіону за географічною структурою, за товарами та за країнами. У цілому географічна структура експорту України показує переорієнтацію поставок до країн ЄС. Проаналізовано експорт послуг Харківської області за географічною структурою та за видами економічної діяльності. Визначено, що в експорті послуг Харківської області домінують консалтингові та комп'ютерні послуги. Для забезпечення ефективності експорту послуг необхідно проводити політику щодо збільшення їхніх обсягів шляхом розширення обсягів за іншими видами діяльності, такими як освітні, туристичні та ін. Проведено SWOT­аналіз експортного потенціалу Харківського регіону. Визначено ризики гальмування експортних потоків та стратегічні напрями поліпшення експортної діяльності в Харківській області. Ключові слова: експорт, регіональний розвиток, Харківська область, експорт товарів, експорт послуг, SWOT­аналіз, експортний потенціал.

Radiation and polychemotherapy significantly affect the immune system of a cancer patient, unabling to adequately respond to infectious agents and provide effective antitumor protection. Rehabilitation of immune disorders is an urgent task, the solution of which will contribute to the generalization of experience when suing the immune modulators in cancer patients. To summarize the existing data on the use of concomitant immune therapy in antitumor treatment, the reports published within 30 years in Pubmed, Cochrane Library, ScienceDirect and the Vernadsky National Library of Ukraine were analyzed. It is expedient to use immune correction at different stages of antitumor treatment in the case of compliance with certain criteria for the prescribing the immune modulatory drugs. Their use is most justified after the primary tumor removal, even in the presence of metastases, because the increase in antitumor resistance is achieved in the absence of tumor cells in the patient's body or their presence in minimal quantities. Possibilities and goals of concomitant immune therapy in cancer patients should be considered taking into account the stage of treatment. Immune modulators with additional properties (detoxification, antioxidant) can serve as universal drugs. In the early post−surgery period, it is advisable to use the drugs, affecting the cells of the mononuclear phagocyte system for the prevention of postoperative infectious complications. During radiation and chemotherapy, preference should be given to the drugs with antitoxic effects and capable of preventing the leukopenia development. Thus, the prescribing of concomitant immune therapy in the combined treatment of cancer patients is an important task, demanding a balanced approach. Key words: immune therapy, immune modulators, quality of life, cancer patients.

The article studies the indicators of renal tests in patients with diabetes mellitus (DM) type 2 associated with nonalcoholic fatty liver disease (NAFLD). It is found that NAFLD in patients with DM type 2 potentiates the development of diabetic nephropathy. Patients with DM type 2 and NAFLD have enhancement of tubular reabsorption, resulting from the violations in vasoconstriction/vasodilatation ratio. Urine creatinine can be considered a stable indicator of liver function test parameters and an early marker for progression of diabetic nephropathy in patients with type 2 DM and NAFLD.

Currently, COVID-19 has spread widely around the world, affecting more than eighty countries. The active mutation of the virus and the emergence of new strains, the shortage of highly effective antiviral (including immunobiological) drugs, and non-pharmacological methods of treatment, the economic burden of infection and some social factors contribute to an increase in the number of adverse clinical outcomes. At the same time, it is extremely important to determine the risk factors for mortality from COVID-19, which would allow clinicians to choose more aggressive therapeutic strategies for patients with a high risk of death, as well as optimally plan the resources of medical organizations that care for patients with coronavirus disease. All this served as the basis for this study. We conducted a retrospective analysis of 1377 medical records of patients with COVID-19 who were on inpatient treatment in the period from April 2020 to March 2021, as well as data from a telephone survey of 450 patients from this group at the rehabilitation stage. The average age of patients was 55.0 (95% CI [36.0–78.0]) years, men-58% (800 people), women-42% (577 people). Thus, the results of this study allowed us to identify a number of modifiable factors related to the organization of medical care that affect the prognosis of patients with COVID-19.

Solving communication problems in the digital environment is becoming increasingly difficult for both teachers and students. The formation of communicative skills of future teachers in the learning process is also important from the standpoint of increasing relevance in the development of emotional intelligence of the personality. The purpose of the academic paper was to develop and test a model of formation of communicative skills of future teachers in the process of studying at higher educational institutions (HEI). The research methodology is qualitative and quantitative; it is based on a quantitative assessment of the formation success of communication skills in the process of teaching the course “Psychology” for 120 students of the Faculty of Philology in Ukraine. Qualitative analysis of the effectiveness of the developed formation model of future teachers’ communicative skills involved observing the teachers’ and students’ behavior of control and experimental groups of the course. The results demonstrate the effectiveness of the proposed formation model of future teachers’ communicative skills in the process of studying at HEI. A liberal approach to teaching ensures the participation of students in discussions, confidence, lack of fear of making mistakes. As a result, the expression of false opinion does not reduce the level of participation in the communication process in the group. The teacher’s behavior forms his image and attitude to the course as a whole, the level of interest and ease of perception of information by students, regardless of the complexity level of the material. Feedback in the form of teacher – student – teacher is extremely effective in the formation of communication skills. The student-centered approach provided a better level of communication skills in the experimental group. In the control group, the traditional approach based on classical teaching methods reduced the level of communication, both in lectures and seminars. The practical value of the research results lies in the possibility of integration of certain strategies and methods as components of the developed formation model of communicative skills of future teachers in the process of teaching specialized courses at HEI.

Changes in the distribution and abundance of ixodid ticks Ixodes persulcatus and I. ricinus in St. Petersburg and Leningrad Province over the period of 1970–2018 are analyzed. As compared with the data of the 1970s, the abundance of ticks has decreased by 6–9 times in the city parks and suburbs and by 1.5–10 times in Leningrad Province. With the increasing anthropogenic impact caused by the population growth and seasonal migration of people in the territories of Leningrad Province bordering the city, contacts of people with ixodid ticks have become more frequent, increasing the number of tick bites and complicating the epidemic situation of tick-borne infections.

The phase of the cell cycle determines numerous aspects of cancer cell behaviour including invasiveness, ability to migrate and responsiveness to cytotoxic drugs. To non-invasively monitor progression of cell cycle in vivo, a family of genetically encoded fluorescent indicators, FUCCI (fluorescent ubiquitination-based cell cycle indicator), has been developed. Existing versions of FUCCI are based on fluorescent proteins of two or more different colors fused to cell-cycle-dependent degradation motifs. Thus, FUCCI-expressing cells emit light of different colors in different phases providing a robust way to monitor cell cycle progression by fluorescence microscopy and flow cytometry but limiting the possibility to simultaneously visualize other markers. To overcome this limitation, we developed a single-color variant of FUCCI, called FUCCI-Red, which utilizes two red fluorescent proteins with distinct fluorescence lifetimes, mCherry and mKate2. Similarly to FUCCI, these proteins carry cell cycle-dependent degradation motifs to resolve G1 and S/G2/M phases. We showed utility of FUCCI-Red by visualizing cell cycle progression of cancer cells in 2D and 3D cultures and monitoring development of tumors in vivo by confocal and fluorescence lifetime imaging microscopy (FLIM). Single-channel registration and red-shifted spectra make FUCCI-Red sensor a promising instrument for multiparameter in vivo imaging applications, which was demonstrated by simultaneous detection of cellular metabolic state using endogenous fluorescence in the blue range.

Acute intermittent porphyria is a rare autosomal dominant disorder characterized by excessive accumulation and excretion of porphyrins and their precursors, repeated attacks of neurological and mental symptoms. Due to the rarity of this pathology and the atypical course in the onset, certain difficulties often arise during the initial diagnosis. The main pathogenetic drug is gemin (Normosang), which allows obtaining a stable clinical response and preventing the development of severe changes in the nervous system. This article presents an analysis of a clinical case of acute intermittent porphyria among blood relatives and discusses the effectiveness of targeted therapy.

Introduction. Arterial hypertension (AH) is a widespread disease in the population of the world. It also acts as one of the constituent components of metabolic syndrome (MS), which is a global “epidemic” of our time. Target organs in such patients are affected much earlier and their changes are more pronounced than in hypertensive patients without metabolic disorders. It is important to study the contribution of risk factors to the progression of cardiac dysfunction in this category of patients.Purpose of the study. To study the influence of risk factors on heart remodeling in patients with hypertension, burdened and not burdened by metabolic disorders, selected for clinical analysis from the cardiology department of the Republican Clinical Hospital № 4, Saransk in 2016-2019.Materials and methods. For clinical analysis, 139 patients were selected from the cardiology department of the Republican Clinical Hospital No. 4, Saransk. Depending on the presence of metabolic disorders, the following groups were identified: Group I (n = 72) – patients with MS and AH; Group II (n = 67) – AH patients without metabolic disorders. The study evaluated the morphological and functional state of the myocardium and risk factors in the analyzed groups.Results. In the group of patients with hypertension, aggravated by metabolic disorders, more pronounced processes of cardiac remodeling were revealed. It has been shown that patients with MS develop both eccentric and concentric models of left ventricular hypertrophy. The influence of the level of blood pressure and body mass index is differently reflected on the type of restructuring of the geometry of the myocardium. Patients with hypertension combined with metabolic disorders have a wider prevalence of risk factors. The burden of risk factors is higher in patients with concentric left ventricular hypertrophy and MS.Conclusions. The role of metabolic disorders in the mechanism of cardiac remodeling development in patients with hypertension in combination with MS was determined.

To study immobilization properties of oxide borosilicate systems, we have assessed the effect of molybdenum on the structure, phase composition, and thermal properties of glass-ceramic materials prepared via rapid cooling of high-alkali melts in the Li2O–(Na2O–K2O)–B2O3–SiO2 system. The results demonstrate that the molybdenum-free materials consist of homogeneous borosilicate glass, which partially crystallizes during heat treatment (annealing). The only exception is a glass sample of the K2O–B2O3–SiO2 system, which has high thermal stability. The addition of molybdenum oxide to these materials in the high-temperature synthesis step initiates crystallization processes, which are most pronounced after heat treatment (annealing). In the materials containing one alkali metal cation in their composition, all of the added molybdenum oxide enters into the composition of the alkali metal molybdates embedded in a homogeneous amorphous highly polymerized borosilicate matrix. In the samples containing cations of two alkali metals in their composition, crystallization processes lead to the formation of a highly inhomogeneous crystalline material. The good homogeneity of the glass-ceramic materials prepared via rapid cooling of high-alkali molybdenum-containing melts of the Li2O–(Na2O–K2O)–B2O3–SiO2 system with one type of alkali metal cation in their composition allows them to be recommended for temporary immobilization of molybdenum oxide-rich radioactive waste.

Our study was aimed at assessing a relationship between immune system alterations, hypoxia and inflammation in arterial hypertension (AH) coupled to metabolic disturbances. A total of 117 patients were enrolled into clinical study, having been randomized into groups in accordance with study protocol, aged 30 to 62 years. They sought care in outpatient setting or underwent periodic health examination at the Republican Clinical Hospital №5, Saransk, Mordovia, Russia. A control group contained 25 apparently healthy subjects lacking signs of metabolic syndrome (MS) and elevated arterial pressure. A comparison group contained 47 patients with AH grade I-II featured with damaged target organs, but lacking associated relevant clinical manifestations, as based on the assay data. The main group contained 45 patients receiving antihypertensive therapy with overt AH grade I-II verified upon medical consultation coupled to damaged target organs and MS signs with its randomly combined components, but lacking associated clinical manifestations. The patients from main and comparison groups received antihypertensive therapy in accordance with approved guidelines and clinical recommendations for management of AH patients consisting of one of renin-angiotensin-aldosterone system blockers, diuretic and/or dihydropyridine calcium channel blocker. Cytokine profile, level of hypoxia and non-specific inflammation were measured in blood serum. The data obtained demonstrated that AH patients with/without metabolic syndrome were noted to display cytokine profile shifted towards elevated proand anti-inflammatory immune arm pointing at imbalanced immune regulation. Hypoxic changes were also found in blood serum that was confirmed by elevated level of lactic and pyruvic acid in these groups. Moreover, development of such pathology was coupled to hypoxia which served as a modulator of immune-related and non-specific inflammation. Rise of non-specific low-grade inflammation correlates developing irreversible AH-associated changes in organs, progression of atherosclerosis and accelerated cardio-metabolic continuum. Altogether, such alterations underlie pathogenetic mechanisms of tissue damage emerging upon AH and MS being mutually aggravating factor along with activated renin-angiotensin-aldosterone system.

Amyloidosis is a group of diseases characterized by the deposition of a protein having a fibrillar structure in the organs and tissues of the body. The main difference between amyloid is a high ordering of the structure, which manifests itself in the ability to birefringence in combination with dichroism, i.e. a change in the red colour of amyloid deposits to apple green in polarized light. Today, the disease has stopped to be a rare one, but the similarity of clinical data with well-known diseases increases the timing of diagnosis, affects the prognosis and survival of patients. Rare forms of amyloidosis, the description of which is reflected in this article, deserve special attention.

Processes of the multi-stage decomposition of maleic acid and Li, Na, and Cd maleates in an inert atmosphere are studied via thermal analysis with synchronous analysis of the composition of the released gases. Reaction mechanisms are proposed according to the data on the mass loss stages determined via thermal analysis, gaseous products, and the final solid decomposition products. It is shown that when heated to 700°C, Li and Na carbonates incorporated into the porous carbon matrix are the final products. Above 350°C, cadmium is reduced from oxide to metal and evaporates to form a porous carbon residue as the only product of thermolysis. All carbon products are X-ray amorphous. Maleic acid decomposes completely into gaseous products in the range of 133–239°C. The maleate ion is more stable in the structure of lithium maleate than in free maleic acid, and Na and Cd cations reduce its stability.

Conducting of clinical trials is closely associated with the ethical justification, with ensuring the rights and safety of the subjects participating in them. Only through trials, it becomes possible to obtain reliable data for the inclusion of new drugs in practice, which are designed to save millions of lives. In the constantly developing field of clinical research, science does not stand still and it becomes necessary to conduct more and more new research: pediatric, geriatric, biomedical products and research involving acute social problems, and of course they all involve certain risks during their implementation. The question of the ethics of conducting research in the context of the COVID-19 pandemic is very relevant at the moment, when it is necessary to make quick decisions in the interests of all mankind, assessing all possible risks that they may entail.

Improving the quality of drugs is the main task of the pharmaceutical industry as a whole. Getting safe and eff ective medications is directly related to minimizing the risks of conducting clinical trials. Maintaining the quality of clinical research based on risk management is a continuous, constant and dynamic process ensuring the success of the study, which in turn leads to the integrity of the data collected, the safety of subjects and compliance with legal requirements, as well as to the financial cost savings of pharmaceutical companies. The cost of research is growing inexorably, and the quality of their research is rapidly declining, so it is important to use a risk-based approach when developing the upcoming clinical trial project.

Mortality from diseases of the circulatory system is a challenge for the modern health care. Arterial hypertension (AH) mostly contributes to development of cardiovascular complications. It often proceeds against the background of metabolic disorders. Pathogenesis of hypertension is currently being considered a multifactorial disease. Pathogenesis of hypertension certainly has distinct features in presence of metabolic disorders,. Therefore, it is relevant to summarize current literature on the role of immunological disorders, endothelial dysfunction and hemostatic disorders in AH genesis during metabolic syndrome (MS). Most authors agree with existence of several mechanisms that determine relationships between AH and insulin resistance. Development of hypertension in MS patients with is a consequence of immunometabolic processes. Abdominal obesity is an important component of MS. It is associated with chronic inflammation of visceral adipose tissue, its excessive infiltration by immune cells, and increased production of adipokines and cytokines (TNFα, IL-6) with hypertension. AH is associated with a significant increase in T cells, that mediate endothelial dysfunction (ED) and provide a link between hypertension and subsequent atherosclerosis. T lymphocytes trigger a cascade of reactions. IL-17 is the end product of these events It is involved not only in increasing blood pressure, but also contributes to the development of vascular wall stiffness in АН patients. Thus, the relationship between several types of immune cells leads to inflammatory reactions, including those of vascular wall, initiating endothelial dysfunction. Chronic non-specific inflammation in MS, supported by the cytokine system, is a triggering mechanism for ED progression. Excessive production of endothelin-1 and inhibition of nitric oxide production are the classic markers of ED. Immune damage leads to imbalance in the production of vasoconstrictor and vasodilating substances, proliferative and antiproliferative factors in endothelium. It was shown that ED is an integral aspect of the insulin resistance syndrome in pathogenesis of arterial hypertension associated with metabolic disorders, and contributes to its worsening, increased vascular reactivity and further AH development. According to modern studies, it has been shown that excessive synthesis of pro-inflammatory cytokines introduces disturbances in the system of vascular hemostasis. When studying the effects of metabolic disorders upon hemostatic system, we may conclude that activation of fibrinolytic and plasma chains occurs in the same way for both men and women, with small gender characteristics of individual components. The rheological properties of the blood are also changed with developing MS. Systematization of the available literature data on the issue under study can serve as a basis for determining prognostic criteria of hypertension progression and risk of thrombotic complications.

Study objectives: To investigate the quality and in-use stability of diluted ABP 980 (a trastuzumab biosimilar) versus reference trastuzumab to mimic dosing in intravenous (IV) bags, transportation and extended storage prior to infusion. Methods: Low dose (70 mg; 0.3 mg/mL) and high dose (1,200 mg; 3.8 mg/mL) ABP 980 and reference trastuzumab solutions were prepared, light-protected and subjected to transportation simulation and storage (2°C–8°C or 30°C for 5 weeks, followed by 48 hours at 30°C). Stability was assessed pre- and post-transport; at Weeks 1, 2, 4, and 5; at Week 5 after 48 hours at 30°C; and pre- and post-infusion using an infusion pump. Results: Across doses and temperatures, there was little change in high molecular weight species and no detectable loss in purity. Following storage, visible particles (> 125 µm) were intermittently observed for both products, with increased subvisible particles detected with low doses. Extended storage at 2°C–8°C did not lead to any significant loss in the active molecule, with consistent biological potency across doses and temperatures for both products. Higher-dose dilutions maintained pH closer to the initial formulation specifications. Discussion: This study examined the impact of dilution, transport and extended storage at different temperatures on the stability of ABP 980 and reference trastuzumab. No major differences between the two products were observed. Conclusion: Across storage temperatures, multiple stability-indicating assays demonstrated no clinically meaningful impact to product quality and stability for both ABP 980 and reference trastuzumab, which provides assurance that ABP 980 retains stability and activity over extended storage periods.

Despite advances in early detection and treatment, breast cancer remains the deadliest oncopathology for women worldwide. Today there is an urgent need for new approaches to this disease treatment. Recently, immune therapy, especially inhibitors of immune checkpoints, has taken the lead when fighting against cancer. Blocking immune checkpoints is an effective approach to enhance the effector T cell function. Immune checkpoint blockers, namely inhibitors of cytotoxic T−lymphocyte−associated antigen 4 (CTLA−4), programmed cell death protein 1 (PD−1) and ligand 1 of programmed cell death protein 1 (PD−L1) are approved by the US Food and Drug Association (FDA) to be used in various solid tumors, refractory cancers with microsatellite instability, classical Hodgkin's lymphoma. In March 2019, the first inhibitor for the treatment of breast cancer was approved, i.e. atezolizumab (anti−PD−L1) in combination with nab−paclitaxel in the patients with metastatic triple−negative breast cancer, which aroused the interest of experts in the study of immunotherapeutic agents for the treatment of these patients. The review presents the results of using the inhibitors of immune control points in monotherapy and in combination with standard methods of antitumor treatment (chemotherapy and radiotherapy, targeted therapy) in patients with breast cancer. Information on potential biomarkers of response to immunotherapy in breast cancer is presented. Key words: breast cancer, checkpoint inhibitors, biomarkers of response.

The widespread prevalence of comorbid pathology determines the relevance of this problem. Comorbid pathology due to the interaction of diseases, drug pathomorphism, age characteristics of the patient, significantly changes clinical picture and course of the main nosology, affects severity of complications and their nature, significantly affects quality of life and prognosis of patients. Diagnosis and treatment of many diseases is complicated in the conditions of comorbidity. The article presents a clinical case of a comorbid patient with arterial hypertension from the moment of exposure to risk factors and ending with the formation of many concomitant diseases, as an example of trans-nosological comorbidity.

Factors that have a negative impact on the economy of the country were identified: geopolitical and financial and economic instability, inflationary fluctuations, migration processes, decline in financial stability of enterprises and their bankruptcy, etc. This necessitates the development of monitoring mechanisms, theoretical and methodological approaches and their practical implementation, aimed at the objective analysis and assessment of Ukraine's rating positions in the context of ensuring its economic security. This is an important methodological toolkit during the recovery and adaptation phase of the country's economy in the postwar period. The threats posed by hybrid warfare encompass all areas of the country's socio-economic development and negatively affect the level of its economic security. That is why the analysis of Ukraine's international rating positions should be comprehensive and aimed at identifying negative factors in order to develop appropriate programs and measures to minimize their impact and maintain the level of economic security of the state. The purpose of the study is to analyze the international ratings of Ukraine in the context of economic security. To analyze the rating positions of Ukraine in the context of economic security, a research panel containing general and specific international ratings and indices is used. The matrix of correspondence of international ratings and indices to the functional components of the economic security of Ukraine is constructed. A retrospective analysis of Ukraine's positioning in international rankings (ICT Development Index, Global Cybersecurity Index, Speedtest Global Index, ND-GAIN Country Index, International Property Rights Index, Fragile States Index, PowerIndex) was conducted. The methodological support for the calculation of these indices is considered. The results of the analysis show that most of the considered specific indices of independent rating agencies have a positive trend. The dynamics of the integral index of economic security of Ukraine for 2010-2022 is presented.

The objective of this article is to expose basic concepts of risks and encourage managers and members of high-tech companies with private capital to know more about this topic. Risk Management is taking up space in the many organizations through internal control standards. However, little mention is made of academia and risk management standards, causing organizations executives to know little about the concepts of risk and treatment. This situation makes risk plans have obvious conceptual problems that impair risk management and prevention in organizations. In addition, the article exposes actual methodologies and risk management strategies that minimize them in the environment of digital economy and innovation and also is the process of development of business structures in the conditions of risks affecting them.