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Septicemia caused by gram-negative bacteria is characterized by high death rate due to the endotoxin release. Since the septicemia depends not only on biochemical aspects of interactions in the system bloodstream, the study of mechanical interactions is also important. Using a model of experimental septicemia caused by E. coli, a hyperproduction of integrins CD11a and CD11b by neutrophils was shown, but this did not lead to the establishment of strong adhesion contacts between endothelial cells and neutrophils. On the contrary, adhesion force and work, as assessed by FS spectroscopy, were statistically significantly reduced in the presence of bacteria. It has also been shown that exposure to the pathogenic strain E. coli 321 increases the stiffness of the membrane-cytoskeleton complex of endothelial cells and bacteria significantly change their morphology on long-term observation. At the same time, we observed the death of neutrophils by apoptosis. Thus, it was shown that besides lipopolysaccharide release there are other pathogenic factors of E. coli: decrease in the interaction between neutrophil and endothelial cell caused by an increase of the endothelial cell rigidity and apoptotic death of neutrophils probably as a result of adhesins and exotoxin effects. Obtained results should be taken in mind during the therapy of septicemia.

Інститут страхування історично був сформо­ваний ще за часів античності та на даний момент є одним із ключових економічних та інвестицій­нихінститутів європейських країн. Правове ре­гулюваннядіяльності страховиків в Україні пе­ребуває на етапі динамічного розвитку з ураху­ванням європейських інтеграційних процесів та актуальних соціальних, економічних та воєнних факторів. Повномасштабне вторгнення Росій­ської Федерації на територію України вплинуло на всі інститути права, в тому числі на інститут страхування. Діяльність страховиків є особливо актуальною під час дії правового режиму воєн­ного стану, оскільки фізичні та юридичні особи прагнуть до належного стану захищеності своїх активів. Правове регулювання страховиків в Україні має відображати актуальний стан економіки та наслідки воєнного стану. Наразі відбувається адаптація українського законодавства до євро­пейськихстандартів, що в умовах дії воєнного стану є особливо складним, колізійним та довго­тривалим процесом. Левова частка страховиків в Україні залишила страховий ринок за власним бажанням, або була виведена регулятором за різних підстав, що безперечно потребує уваги зі сторони законодавця, держави та суспільства в цілому. У статті досліджуються проблеми становлен­ня та розвитку правового регулювання діяль­ності страховиків в Україні. Висвітлено етапи становлення правового регулювання діяльності страховиків незалежної України, проаналізовані особливості цих етапів. Акцентовано увагу на тому, що правове ре­гулюванняпід час дії воєнного стану в Україні є новим історичним етапом розвитку цього інсти­туту та цей період потребує детального дослі­дження. Проведено аналіз правового регулювання ді­яльності страховиків в Україні під час воєнного стану та висвітлено проблеми розвитку правового регулювання діяльності страховиків в цей період. Автором запропоновано шляхи вирішення та подолання проблем сучасного правового регу­лювання діяльності страховиків під час особли­вого періоду в Україні. Сформовано авторську періодизацію становлення та розвитку діяльно­сті страховиків в Україні з урахуванням історич­них, соціальних та економічних аспектів розвит­ку інституту страхування незалежної України.

The study highlights the development of the genre of church carols in the work of Ukrainian priests as a component of the spiritual song culture of the 17th – 19th centuries with a possible specification of their authors. A review of the scientific works of Ukrainian and foreign scientists was carried out, in which the question of the existence of church carols at various stages of their development was investigated. The works of Ivan Franko, Mykhailo Wozniak, Hans Rohte, Larysa Hnatiuk, Lidia Korniy, Larysa Kostiukovets, Yuriy Medvedyk and others were analysed. In the process of research, it was found out that the first sources where the use of church carols was noticed were: school drama, live and puppet verteps (nativity scenes). The authors of the first Christmas dramas that have survived to this day were Pamvo Berynda, Dmytro Tuptalo (Rostovskyi), Yepifanii Dovgalevskyi and a number of authors unknown to modern science. They were probably the authors of church carols used in dramas. The result of the creation of church carols was the first printed collection of Ukrainian spiritual songs “Bogoglasnyk”, published in Pochaiv in 1773, later a more complete edition, an anthology collection of Ukrainian spiritual songs “Bogoglasnyk”, was made, and published in Pochaiv in 1790-1791. There were published 24 Ukrainian and 5 Polish carols in it among 240 spiritual songs. The probable names of the authors of several Ukrainian carols are mentioned. The research indicates that the process of creating church carols intensified in the 19th century. Their authors were Greek-Catholic priests Viktor Matiuk, Maksym Kopko, Ostap Nyzhankivskyi, Yosyp Kyshakevych and others. In addition to pastoral activities, they were also engaged in composing, were the authors of Holy Liturgies, spiritual songs, including church carols. The most famous carols were “Na Nebi Yasna Zirka Zasiala” (“A Bright Star Shone in the Sky”) by Viktor Matiuk, “Vselennaya Veselysia” (“Rejoice the Universe”), “Na Rozhdestvo Khrysta” (“On the Birth of Christ”), “Vistku Holosyt’ Svitu Zirnytsia” (“A Starling Announces the News to the World”) by Maksym Kopko, “U Vyfleyemi Nyni Novyna” (“News in Bethlehem Today”) by O. Nyzhankivskyi, “Nad Vyfleyemom Zablysla Zoria” (“A Star Twinkled Over Bethlehem”, “Slava Vo Vyshnykh Bogu” (“The Highest Glory to God”), “Spy, Isuse, Spy” (“Sleep, Jesus, Sleep”) by Yosyp Kyshakevych. The periodization of the development of the genre of church carols in the works of Ukrainian priests of the 17th-19th centuries was carried out. The first period is called the “manuscript” one (the end of the 16th century – 1773), and is associated with the first recording of Christmas songs without specifying the names of the songs and their authors. The second period is the “edition period” (1773 – the beginning of the 19th century) is associated with the appearance of the first collection of Ukrainian spiritual songs, published in Pochaiv in 1773, the beginning of the tradition of printing collections of spiritual songs, including carols, with the specified titles and partly the names of the authors. The third period, which is called the “author’s” (the middle of the 19th – the end of the 19th century) was initiated and developed by composers and priests such as Ivan Bilykovskyi, Viktor Matiuk, Maksym Kopko, Ostap Nyzhankivskyi, Yosyp Kyshakevych. During this period, a church carol undergoes stylistic changes. It loses the features of church hymnography (solemn, extended character, literary strophic structure, solemn melody, refined and solemn performance style). Instead, it acquires the features of folk song creativity, both in strophic and melodic structures.

Objective: to assess the impact of various wartime stresses on the condition of patients with mental illnesses, followed by the development of preventive measures. Materials and methods: a questionnaire and a survey of 510 patients with mental and behavioral disorders were conducted on voluntary terms. Then the subjects were divided into 2 groups: 1 group — those who were in the zone of direct combat operations; 2 group — those who were in safer zones. The calculation of the proportion of persons depending on the appropriate answers to questions, a comparison of the levels of anxiety and anxiety in connection with the military situation in patients of groups 1 and 2, as well as an analysis of the corresponding 510 outpatient charts studied in order to assess the impact of wartime stress on the nature of the course of mental illness. Results: the negative impact of wartime stress on the course of mental disorders was established in the form of a worsening of the clinical picture of diseases, an increase in the number of exacerbations and resistance to therapy. Conclusion: according to the results of the study, preventive measures are recommended.

The main goal of this work is to highlight the connection between nanomotion and the metabolic activity of living cells. We therefore monitored the nanomotion of four different clinical strains of bacteria (prokaryotes) and the bacterial phagocytosis by neutrophil granulocytes (eukaryotes). All clinical strains of bacteria, regardless of their biochemical profile, showed pronounced fluctuations. Importantly, the nature of their nanomotions was different for the different strains. Flagellated bacteria (Escherichia coli, Proteus mirabilis) showed more pronounced movements than the non-flagellated forms (Staphylococcus aureus, Klebsiella pneumoniae). The unprimed neutrophil did not cause any difference in cantilever oscillations with control. However, in the process of phagocytosis of S. aureus (metabolically active state), a significant activation of neutrophil granulocytes was observed and cell nanomotions were maintained at a high level for up to 30 min of observation. These preliminary results indicate that nanomotion seems to be specific to different bacterial species and could be used to monitor, in a label free manner, basic cellular processes.

The dynamics of neutrophil transendothelial migration was investigated in a model of experimental septicopyemia. Scanning ion-conductance microscopy allowed us to determine changes in morphometric characteristics of endothelial cells during this process. In the presence of a pyogenic lesion simulated by Staphylococcus aureus, such migration was accompanied by both compensatory reactions and alteration of both neutrophils and endothelial cells. Neutrophils demonstrated crawling along the contact sites between endothelial cells, swarming phenomenon, as well as anergy and formation of neutrophil extracellular traps (NETs) as a normergic state. Neutrophil swarming was accompanied by an increase in the intercellular spaces between endothelial cells. Endothelial cells decreased the area of adhesion to the substrate, which was determined by a decrease in the cell projection area, and the cell membrane was smoothed. However, endothelial cell rigidity was paradoxically unchanged compared to the control. Over time, neutrophil migration led to a more significant alteration of endothelial cells: first, shallow perforations in the membrane were formed, which were repaired rather quickly, then stress fibrils were formed, and finally, endothelial cells died and multiple perforations were formed on their membrane.

The reactive oxygen species (ROS) production by a single neutrophil after stimulation with S. aureus and E. coli was estimated by an electrochemical amperometric method with a high time resolution. This showed significant variability in the response of a single neutrophil to bacterial stimulation, from a “silent cell” to a pronounced response manifested by a series of chronoamperometric spikes. The amount of ROS produced by a single neutrophil under the influence of S. aureus was 5.5-fold greater than that produced under the influence of E. coli. The response of a neutrophil granulocyte population to bacterial stimulation was analyzed using luminol-dependent biochemiluminescence (BCL). The stimulation of neutrophils with S. aureus, as compared to stimulation with E. coli, caused a total response in terms of ROS production that was seven-fold greater in terms of the integral value of the light sum and 13-fold greater in terms of the maximum peak value. The method of ROS detection at the level of a single cell indicated the functional heterogeneity of the neutrophil population, but the specificity of the cellular response to different pathogens was the same at the cellular and population levels.

Despite significant advances in genetic predisposition to type 2 diabetes mellitus (T2DM), which have been confirmed by large-scale genomic and clinical studies, most of the genetic factors that cause the development of T2DM remain unclear. The aim of the study – to determine the association of IRS1 gene polymorphism (rs2943640) with carbohydrate metabolism in patients with type 2 diabetes mellitus in combination with obesity and chronic pancreatitis. Materials and Methods. The study included 33 patients with T2DM (patients with T2DM, T2DM + obesity, T2DM + obesity + chronic pancreatitis) and 10 healthy individuals. The level of glycated hemoglobin (HbA1c) was determined using an automatic biochemical analyzer COBAS 6000 (Roche Hitachi, Germany). The level of insulin in the blood was determined on an enzyme-linked immunosorbent assay from Thermo Scientific Multiskan FC, and the glucose concentration was determined using standard kits on an automatic biochemical analyzer from COBAS INTEGRA® 400 (Roche Diagnostics). Polymorphism of the IRS1 gene (rs2943640) C> A was genotyped by real-time PCR TaqMan method (Applied Biosystems, Foster City, CA, USA). Results. Carriers of the C allele of the IRS1 gene (rs2943640), patients with combined type 2 diabetes, obesity and chronic pancreatitis have the highest levels of insulin and HOMA-IR, which are probably higher than in patients with type 2 diabetes (329.75 %, respectively) and 65.13 %) and in patients with combined type 2 diabetes and obesity (314.53 % and 69.23 %, respectively). Patients with type 2 diabetes mellitus, regardless of the presence/absence of comorbid obesity and chronic pancreatitis, carriers of the C/C genotype of the IRS1 gene (rs2943640) have the highest carbohydrate metabolism, relative to the data of carriers of the C/A genotype. Conclusions. In patients with combined course of type 2 diabetes, obesity and chronic pancreatitis, the nature of carbohydrate metabolism disorders is influenced by polymorphism of the IRS1 gene (rs2943640)

In addition to representing a significant part of the natural background radiation exposure, α-particles are thought to be a powerful tool for targeted radiotherapy treatments. Understanding the molecular mechanisms of recognition, signaling, and repair of α-particle-induced DNA damage is not only important in assessing the risk associated with human exposure, but can also potentially help in identifying ways of improving the efficacy of radiation treatment. α-particles (He2+ ions), as well as other types of ionizing radiation, and can cause a wide variety of DNA lesions, including DNA double-strand breaks (DSBs). In mammalian cells, DNA DSBs can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). Here, we investigated their dynamics in mouse NIH-3T3 cells through the recruitment of key proteins, such as the KU heterodimer for NHEJ and RAD51 for HR upon localized α-particle irradiation. To deliver α-particles, we used the MIRCOM microbeam, which allows targeting of subnuclear structures with submicron accuracy. Using mouse NIH-3T3 cells, we found that the KU heterodimer is recruited much earlier at DNA damage sites marked by H2AX phosphorylation than RAD51. We also observed that the difference in the response of the KU complex and RAD51 is not only in terms of time, but also in function of the chromatin nature. The use of a microbeam such as MIRCOM, represents a powerful tool to study more precisely the cellular response to ionizing irradiation in a spatiotemporal fashion at the molecular level.

Staphylococcus aureus induces the expression of VCAM-1, P- and E-selectins on the endothelial cells of the EA.hy926 cell line but, at the same time, causes the significant suppression of the force and work of adhesion between these receptors of endotheliocytes and the receptors of neutrophils in an experimental septicemia model. Adhesion contacts between the receptors of neutrophils and endotheliocytes are statistically significantly suppressed under non-opsonized and opsonized S. aureus treatment, which disrupts the initial stage of transendothelial migration of neutrophils—adhesion. Thus, S. aureus causes the arrest of neutrophils in the bloodstream in an experimental septicemia model.

The article presents literature data and therapeutic experience on the use of oral provocation tests. They are considered to be the golden standard for the diagnosis of food allergy and provide an opportunity not only to confirm the pre­sence of the condition, but also to determine the level of to­lerance to the product and to monitor the effectiveness of food desensitization. The risks and indications for oral provocation tests are presented. Difficulties in the results interpretation have also been evaluated. In particular, information about the fact that the mild, subjective, or atypical symptoms of food allergy are most complicated in the evaluation, as they can not only indicate the beginning of the development of serious reactions, but also be the result of the influence of emotional factors. The individual approach to choosing the dose of the food allergen and the interval between its administration during oral provocation tests was described. Our therapeutic experience confirms that symptoms during oral provocation tests predominantly occur after the administration of the allergen in higher doses. And, accordingly, at higher doses, as a rule, there were more severe symptoms of food allergy. A short time interval between the administration of an allergen (less than 30 minutes) can complicate the interpretation of the results and compromise the test. The article presents a clinical case of the oral provocation test in a 7-month-old child, which confirmed the presence of allergy to cow’s milk proteins. This case allows us to trace the peculiarities of the diagnostic investigation and the method of conducting the test at an early age using infant formulas (standard adapted milk and formula with complete protein hydrolysis).

The adsorption and substitution of transition metal atoms (Fe and Co) on Au-supported planar silicene have been studied by means of first-principles density functional theory calculations. The structural, energetic and magnetic properties have been analyzed. Both dopants favor the same atomic configurations with rather strong binding energies and noticeable charge transfer. The adsorption of Fe and Co atoms do not alter the magnetic properties of Au-supported planar silicene, unless a full layer of adsorbate is completed. In the case of substituted system only Fe is able to produce magnetic ground state. The Fe-doped Au-supported planar silicene is a ferromagnetic structure with local antiferromagnetic ordering. The present study is the very first and promising attempt towards ferromagnetic epitaxial planar silicene and points to the importance of the substrate in structural and magnetic properties of silicene.

Modern data about the causes, course peculiarities, principles of diagnosis and symptomatic treatment of Wolf-Hirshhorn syndrome are given in the article. The description of own clinical case is presented. In most cases, there are multiple developmental abnormalities, in particular heart and kidney defects. External symptoms include: the unusual structure of the skull (“ancient warrior’s helmet”), straight bridge of the nose, moderately severe microcephaly, hypertelorism, small mouth with drooping corners, abnormal auricle’s forms, also cleft lip and cleft palate, eyeballs anomalies, hypospadias, feet deformity. Hemangiomas of the skin are often presented, they are usually flat, small and located on the face. Muscle hypotonia, significantly reduced reaction to external stimuli are revealed during the examination. The diagnosis is based on clinical changes and is confirmed by the DNA research. Deletion of the short arm of chromosome 4 is detected in approximately 80 % of probands. The description of own clinical observation of a child with Wolf-Hirshhorn syndrome, confirmed at the age of 3 months, is presented. Despite the early detection of the syndrome and prescribed appropriate therapy, the disease has a poor prognosis.