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Вступление. Единственным радикальным методом лечения перихилярной холангиокарциномы является хирургический, позволяющий улучшить отдаленные результаты и показатели выживаемости пациентов. Особую сложность представляют ситуации с инвазией опухоли в воротную вену. Цель. Изучение результатов хирургического лечения пациентов по поводу перихилярной холангиокарциномы с инвазией воротную в вену (ВВ). Материалы и методы. С 2003 по 2017 г. в клинике обширная и расширенная резекция печени по поводу перихилярной холангиокарциномы произведена 153 больным. Результаты. Для оценки характера поражения билиарного дерева использовали анатомическую классификацию перихилярной холангиокарциномы Bismuth-Corlette. У 66 (43%) больных резекция печени дополнена резекция ВВ с ее последующей реконструкцией. Показатели 1, 3- и 5-летней выживаемости после резекции ВВ составили соответственно 81,8, 40,9 и 31,8%. Выводы. Агрессивная тактика хирургического лечения перихилярной холангиокарциномы обеспечивает максимальную радикальность, позволяет увеличить резектабельность при инвазии опухоли в ВВ с приемлемой летальностью и отдаленными показателями выживаемости.

Production systems in the structure of economic systems occupy the most fundamental place and act as both initial and basic subsystem of any economic development. There is a tendency to change the forms of production and the study of these process systems poses a wider aspect of their dynamics analysis. The article tries to prove both theoretically and practically that global production networks are one of the most important factors in the innovative transformation of countries and regions. It is concluded due to global production networks, being the channel for the transfer of global knowledge and technical know-how to regional structures, regions of the former periphery have quickly become developed, innovative regions with a specialization in the sector of highly qualified services, production of high-tech products, and generation of scientific knowledge. For transnational companies global production networks reduce their costs and financial risks by sharing with other companies, as well as global division of labor, an important part of global production.

The objective is to assess the economic efficiency of the current practice of complicated IAI (intra-abdominal infections) treatment with antibiotics compared to the strategy of the therapy with carbapenem without antipseudomonal activity (Ertapanem).Materials and methods. We analyzed the economic efficiency of the current practice of IAI treatment compared to alternative therapy.Results. In current practice the cost of treatment of 1 case of complicated IAI is 82771.85 rub compared to 91471.55 rub for alternative strategy. Analysis of the impact on the Russian budget, out of the expected number of IAI cases in the Russian Federation, revealed that the current practice of antibacterial therapy allows saving up to 544166014 rubles. The proceeds allows to treat additionally 6574 patients with IAI.Conclusions. In real practice the use of antibiotics in complicated IAI treatment was assessed as more beneficial. Nevertheless, there is a lack of necessary data regarding the bacterial resistance in dynamic that could provide more information about the real economic consequences of «collateral damage» due to the current practice of using the antibiotic therapy.

The article is devoted one of issues of the day of modern theoretical research – to national economic security. An author chosen the іnstituciоnal way of development of problem, here attracting attention on the institute of аmbivalance. Ambivalence is certain an author, as an inadequate, ambiguous conduct of subjects of market economy: from power to the citizens. To to presently ambivalence was probed in sociology and medicine. An author lays out own vision of reasons of economic security breach, accenting attention not on the earlier the expounded factors, but above all things on socially psychological factors in a that number on аmbivalance. The article reveals the essence of the paternalistic potential, which should be understood as the resourceprovided ability to provide social support and protection to certain groups of people for the realization of the goals of economic and social development. The dependence of the potential of paternalism from the interaction of the goals of economic and social development, which the state sets itself, as well as socio-economic institutions have been analyzed. The notion of the potential of paternalism, which means the correspondence between the possibility of providing assistance and the socially justified need for it, has been introduced into scientific circulation.

OBJECTIVE. The authors developed a low invasive method of bimammary coronary artery bypass grafting (CABG) of minimum two arteries through left-sided thoracotomy. MATERIAL AND METHODS. The left internal thoracic artery was used for bypass grafting of anterior interventricular artery according to V.I. Kolesov method. Anastomosis of the right interventricular artery with conduit (from autoartery or autovein) was performed by using extrapleural way in the second intercostal space from the right of the breast. Conduit was lengthened behind the sternum to pericardium cavity in order to create the second distal anastomosis with branch of coronary artery. RESULTS. The operations (10 cases) were conducted at the period from October 2015 to December 2016. The second distal anastomosis between conduit and coronary artery was performed with diagonal artery in 1 case, with branch of blunt edge in 5 cases and with posterior interventricular branch in 4 cases. Tolerance of operation and early postoperative period were satisfactory. CONCLUSIONS. New method of bimammary coronary artery bypass allowed doctors to perform revascularization minimum of two coronary vessels on working heart by avoiding manipulations on aorta and the sternum.

In the present study, we investigated whether calcium content modulation in D-domains of fibrin(ogen) was involved in fibrinolytic process activation. To investigate the effect of Ca2+-dependent changes in D-domains two types of fibrinogen fragments D and cross-linked fibrin fragments DD were obtained from plasmin hydrolysate of human fibrin(ogen): chelator-treated and without chelating agents. The study of plasminogen activation by tissue-type plasminogen activator on D- and DD-fragments had shown the intensification of plasmin formation in case of EDTA pretreatment of fragments. The proenzyme activation rate on DD also increased in the presence of EGTA in concentration-dependent manner. Potentiating effect of EGTA-pretreated DD-fragment on plasminogen activation by tPA was decreased in the presence of Ca2+. Activation rate reduction was observed according to the increase of CaCl2 concentration in the reaction medium. The intensification of plasminogen activation potentiation by chelator-treated fibrin(ogen) D-domain containing fragments and subsequent potentiation decrease in the presence of Ca2+ indicated the requirement of Ca2+-dependent changes in D-domains for plasminogen activation sites exposure and initiation of fibrinolysis.

Abstract Implantation of reporter-labeled tumor cells in an immunocompetent host involves a risk of their immune elimination. We have studied this effect in a mouse model of breast cancer after the orthotopic implantation of mammary gland adenocarcinoma 4T1 cells genetically labelled with luciferase (Luc). Mice were implanted with 4T1 cells and two derivative Luc-expressing clones 4T1luc2 and 4T1luc2D6 exhibiting equal in vitro growth rates. In vivo, the daughter 4T1luc2 clone exhibited nearly the same, and 4T1luc2D6, a lower growth rate than the parental cells. The metastatic potential of 4T1 variants was assessed by magnetic resonance, bioluminescent imaging, micro-computed tomography, and densitometry which detected 100-μm metastases in multiple organs and bones at the early stage of their development. After 3–4 weeks, 4T1 generated 11.4 ± 2.1, 4T1luc2D6, 4.5 ± 0.6; and 4T1luc2,

Abstract A quantum critical point (QCP) is currently being conjectured for the BaFe2(As1−x P x )2 system at the critical value x c ≈ 0.3. In the proximity of a QCP, all thermodynamic and transport properties are expected to scale with a single characteristic energy, given by the quantum fluctuations. Such a universal behavior has not, however, been found in the superconducting upper critical field H c2. Here we report H c2 data for epitaxial thin films extracted from the electrical resistance measured in very high magnetic fields up to 67 Tesla. Using a multi-band analysis we find that H c2 is sensitive to the QCP, implying a significant charge carrier effective mass enhancement at the doping-induced QCP that is essentially band-dependent. Our results point to two qualitatively different groups of electrons in BaFe2(As1−x P x )2. The first one (possibly associated to hot spots or whole Fermi sheets) has a strong mass enhancement at the QCP, and the second one is insensitive to the QCP. The observed duality could also be present in many other quantum critical systems.

The article deals with a current trend of the global energy market, which is characterized by rising tension in relations between the performers of the energy market regulation mechanisms, and it leads to the emergence of alternative energy sources. The article is called to identify the causes of renewable energy markets nascence, to make comparative description of Ukrainian and European Renewable Energy Markets attractiveness, and to characterize the state policy change in a renewable energy market. Different interpretation of nature and classification of the field of renewable energy in foreign and Ukrainian approaches shows the problem of legal criteria of renewable energy markets regulation. It is proved the existence of double barrier penetration of the European market for renewable energy for Ukrainian companies, which includes compliance with the accepted EU Directives and compliance with the Rules of each member individually. The presence of clearly defined standards and certificates of quality for the European market allows producers to show the competitiveness of Ukrainian products in the international market and stimulate Ukrainian manufacturers. The presence of clearly formulated laws, stable and balanced political and legal environment of the EU allows Ukrainian producers of renewable energy to develop such a strategy that considers the time factor, as the primary parameter of competitiveness in international business. The market of solid biofuels in EU is under formation, its development timeframe and uncertainty of environmental risks becoming is especially important for Ukrainian producers.

The metal-free reaction of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles with arenes in neat triflic acid (TfOH, CF3SO3H), both under thermal and microwave conditions, leads to 5-(2,2-diarylethyl)-3-aryl-1,2,4-oxadiazoles. The products are formed through the regioselective hydroarylation of the side chain carbon–carbon double bond of the starting oxadiazoles in yields up to 97%. According to NMR data and DFT calculations, N4,C-diprotonated forms of oxadiazoles are the electrophilic intermediates in this reaction.

The purpose of the present study was to examine the plasminogen localization and to detect levels of its fragments (angiostatins) in various regions of rat brain as well as to establish whether rat brain astrocytes could be involved in angiostatin production. It was shown immunohistochemically that plasminogen is distributed broadly in the various brain regions, with predominant expression in meningeal layer and IV, V, and VI layers or cerebral cortex, dentate gyrus, meningeal and Purkinje cells, molecular and granular layers of cerebellum, as well as vessel walls. Angiostatin polypeptides were detected by Western blot analysis mostly in the cerebral cortex and were represented by 50 and 40-30 kDa polypeptides. In the whole cell lysates from primary cultures of rat astrocytes, immunoreactive polypeptides with Mm ~ 92, 84, 65-60, 50, 40, 38-30 kDa, correspon­ding to native plasminogen and a variety of its truncated products, including angiostatin polypeptides, were revealed. Incubation of astrocytes with exogenous plasminogen resulted in gradual increasing levels of some plasminogen fragments, particularly 30 kDa protein. Moreover, this polypeptide appeared to be the single angiostatin released by astrocytes in vitro. We report here for the first time that astrocytes are one of the cell types in CNS that could be responsible for angiostatin formation and releasing.

Plasminogen/plasmin system is known for its ability to support hemostatic balance of blood. However, plasminogen may be considered as an adhesive ligand and in this way could affect the functioning of blood cells. We showed that exogenous Lys-plasminogen, but not its Glu-form, inhibited platelet aggregation and suppressed platelet α-granule secretion. The aim of this work was to investigate the influence of Glu- and Lys-form of plasminogen on the formation of platelet procoagulant surface using phosphatidylserine exposure as a marker. Human platelets were obtained from human platelet-rich plasma (donors were healthy volunteers, men aged 30-40 years) by gel-filtration on Sepharose 2B. Phosphatidylserine exposure on the platelet surface was evaluated by flow cytometry with FITC-conjugated annexin A5. Glu- and Lys-plasminogen have different impact on the platelet functioning. Exogenous Lys-plasminogen has no significant effect on phosphatidylserine exposure, while Glu-plasminogen increases phosphatidylserine exposure on the surface of thrombin- and collagen-activated human platelets. Glu-plasminogen can be considered as a co-stimulator of agonist-induced platelet secretion and procoagulant surface formation. Meanwhile effects of Lys-plasminogen are probably directed at platelet-platelet interactions and not related to agonist-stimulated pro-apoptotic changes. The observed different effects of Glu- and Lys-plasminogen on phosphatidylserine exposure can be explained by their structural peculiarities.

The ability to efficiently control charge and spin in the cuprate high-temperature superconductors is crucial for fundamental research and underpins technological development. Here, we explore the tunability of magnetism, superconductivity, and crystal structure in the stripe phase of the cuprate La2-xBaxCuO4, with x = 0.115 and 0.135, by employing temperature-dependent (down to 400 mK) muon-spin rotation and AC susceptibility, as well as X-ray scattering experiments under compressive uniaxial stress in the CuO2 plane. A sixfold increase of the three-dimensional (3D) superconducting critical temperature Tc and a full recovery of the 3D phase coherence is observed in both samples with the application of extremely low uniaxial stress of ~0.1 GPa. This finding demonstrates the removal of the well-known 1/8-anomaly of cuprates by uniaxial stress. On the other hand, the spin-stripe order temperature as well as the magnetic fraction at 400 mK show only a modest decrease under stress. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. However, strain produces an inhomogeneous suppression of the spin-stripe order at elevated temperatures. Namely, a substantial decrease of the magnetic volume fraction and a full suppression of the low-temperature tetragonal structure is found under stress, which is a necessary condition for the development of the 3D superconducting phase with optimal Tc. Our results evidence a remarkable cooperation between the long-range static spin-stripe order and the underlying crystalline order with the three-dimensional fully coherent superconductivity. Overall, these results suggest that the stripe- and the SC order may have a common physical mechanism. [ABSTRACT FROM AUTHOR]

Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.

Fibrin clot lysis by plasminogen/plasmin system results in fibrin degradation products formation with subsequent release into bloodstream. The fragments contain specific binding sites for fibrinolytic system components and can interact with them. In this study, we investigated the way in which fibrin fragments effect fibrinolytic process. We have shown that high molecular weight products of fibrin degradation and fibrin fragments of DDE-complex and DD, but not end product Е3, stimulate plasmin formation. Additionally, components of DDE-complex mixture of fragments Е1 and Е2 have potentiation ability. The intermediate fibrin fragments hmFDPs and DDE attenuate clot lysis by plasmin and hmFDPs protect plasmin from α2-antiplasmin inhibition but under further fragmentation to endpoint fibrin fragments loose this ability. The plasma inhibitors reduce fibrinolytic system activity generated by the degradation products. Thus, fibrin fragments formed during the clot lysis can bind and move out fibrinolytic system components from clot volume and in this way result in clot resistance to hydrolysis.

Hematopoietic stem cells (HSCs) remain mostly quiescent under steady-state conditions but switch to a proliferative state following hematopoietic stress, e.g., bone marrow (BM) injury, transplantation, or systemic infection and inflammation. The homeostatic balance between quiescence, self-renewal, and differentiation of HSCs is strongly dependent on their interactions with cells that constitute a specialized microanatomical environment in the BM known as the HSC niche. Here, we identified the secreted extracellular matrix protein Del-1 as a component and regulator of the HSC niche. Specifically, we found that Del-1 was expressed by several cellular components of the HSC niche, including arteriolar endothelial cells, CXCL12-abundant reticular (CAR) cells, and cells of the osteoblastic lineage. Del-1 promoted critical functions of the HSC niche, as it regulated long-term HSC (LT-HSC) proliferation and differentiation toward the myeloid lineage. Del-1 deficiency in mice resulted in reduced LT-HSC proliferation and infringed preferentially upon myelopoiesis under both steady-state and stressful conditions, such as hematopoietic cell transplantation and G-CSF- or inflammation-induced stress myelopoiesis. Del-1-induced HSC proliferation and myeloid lineage commitment were mediated by [beta] integrin on hematopoietic progenitors. This hitherto unknown Del-1 function in the HSC niche represents a juxtacrine homeostatic adaptation of the hematopoietic system in stress myelopoiesis., Introduction Hematopoietic stem cells (HSC) lie at the core of the hematopoietic and immune systems and have a unique capacity for self-renewal and differentiation to multipotent and lineage-committed hematopoietic progenitors, [...]