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Background. The shortage of healthcare human resources is currently one of the most discussed topics in both Russian and global discourse. Along with the study of such important problems in the healthcare system, as its unevenness, a lack of access to health services among the most vulnerable groups, a low quality of the care provided, etc., much attention is currently paid to the professional competence, adaptation, and retention of mid-level specialists in medical organizations. One possible solution to the above problems is seen in the institute of mentorship.Objectives. To analyze the main approaches to defining the concept of “nursing mentorship” in the foreign and Russian research literature.Methods. A comparative analysis of literature sources by foreign and Russian authors addressing the definition, content, and implementation of nursing mentorship was conducted using the PubMed and eLibrary.ru databases.Results. Three main approaches — “dyadic”, “triadic,” and “integrated” (mixed) — to defining the concept of nurse mentorship were identified. The dyadic approach focuses on the analysis of interpersonal interactions between mentor and mentee. Such interactions arise during a specifically planned and goal-oriented activity aimed at a dynamic psychosocial intervention in the mentee’s professional life to bridge gaps in his/her knowledge and skills and to increase self-confidence. Dyadic mentoring can be of individual, group, distance, peer, cascade, and reverse types. The triadic approach implies interaction not only between mentor and mentee, but also involvement of the medical organization as a party. The administrators are interested in personnel stability, improved professional skills of the staff, increased loyalty and commitment to the organization. The main focus here is on the functionality, formalization, and comprehensiveness of mentoring programs, allowing the goals of the medical organization to be achieved. Within the integrated (mixed) approach, the negative experience of mentoring and the possibilities of forming a culture of mentorship are analyzed. The mentorship culture, while reflecting the interests of the medical organization, bolsters “authentic friendship” within the nursing team. Mentorship is considered as a set of activities that influence mentors, mentees, and the medical organization as a whole, passing through various development phases and stages in the interests of the three interacting parties. The contribution of Russian authors to the development of mentorship consists in the elucidation of issues related to the professional development and sociocultural adaptation of young specialists in the healthcare system, as well as in modeling mentorship relations. Mentorship is considered not only in terms of the specifics of interpersonal professional relations that arise in the mentor and mentee interaction, but also as an instrument in labor management. Mentorship programs can increase the personnel’s commitment to their profession and the results achieved.Conclusion. In the current scientific literature, different approaches to defining the concept of mid-level medical personnel mentorship are presented. The existing experience in organizing mentorship programs may significantly improve their qualitative level, thereby contributing to professional self-realization of both mentors and young nursing specialists.

Abstract The microstrip of modulated width is a realization of a one-dimensional photonic crystal operating in the microwave regime. Like any photonic crystal, the periodic microstrip is characterised by the presence of frequency bands and band gaps that enable and prohibit wave propagation, respectively. The frequency bands for microstrip of the symmetric unit cell can be distinguished by 0 or $$\pi$$ π Zak phase. The sum of these topological parameters for all bands below a given frequency gap determines the value of the surface impedance at the end of the microstrip. We demonstrate that edge modes are absent in a finite microstrip terminated at both ends in the centres of unit cells, but they can be induced by adding the defected cells. Edge modes present at both ends of the microstrip enable microwave tunneling with high transitivity in the frequency gap with or without a change in phase. This has been demonstrated experimentally and developed in detail using numerical simulations and model calculations. The investigated system, with a doublet of edge modes in the frequency gap, can be considered as a narrow passband filter of high selectivity and characterised by a significant group delay.

The aim of this study was to study the effect of metformin (Met) on the formation of the conditional passive avoidance skills, markers of neurogenesis and oxidative stress in the brain of rats with acute intracerebral hemorrhage (ICH) in the setting of streptozotocin-nicotinamide-induced diabetes. Type 2 diabetes mellitus (T2DM) was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH – by microinjection of bacterial collagenase into the striatum. Rats were randomly divided into four groups: 1 – intact animals (n=8), 2 – T2DM (n=9); 3 – T2DM+ICH (n=7); 4 – T2DM+ICH+Met (n=7). The passive avoidance test was used to evaluate behavioural activity. Advanced oxidation protein products (AOPP) and lactate were measured by spectrophotometry, advanced glycation end products (AGEs) by quantitative fluorescence, level of 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed by enzyme-linked immunosorbent assay (ELISA). Histopathological examination was performed using general histological staining techniques and immunohistochemical methods for assessment of expression of endothelial NO-synthase (eNOS), Growth Associated Protein 43 (GAP43), Hypoxia-inducible factor 1-alpha (HIF-1α), neural cadherine (N-cadherine) and vascular endothelial cadherine (VE-cadherine). In this study, metformin had nootropic (anti-amnestic) activity and decreased oxidative stress markers (AGEs, AOPPs and 8-OHdG) levels by 29.1% (p

Abstract When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Abstract Background Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

Abstract Security Information and Event Management (SIEM) technologies play an important role in the architecture of modern cyber protection tools. One of the main scenarios for the use of SIEM is the detection of attacks on protected information infrastructure. Consorting that ISO 27001, NIST SP 800-61, and NIST SP 800-83 standards objectively do not keep up with the evolution of cyber threats, research aimed at forecasting the development of cyber epidemics is relevant. The article proposes a stochastic concept of describing variable small data on the Shannon entropy basis. The core of the concept is the description of small data by linear differential equations with stochastic characteristic parameters. The practical value of the proposed concept is embodied in the method of forecasting the development of a cyber epidemic at an early stage (in conditions of a lack of empirical information). In the context of the research object, the stochastic characteristic parameters of the model are the generation rate, the death rate, and the independent coefficient of variability of the measurement of the initial parameter of the research object. Analytical expressions for estimating the probability distribution densities of these characteristic parameters are proposed. It is assumed that these stochastic parameters of the model are imposed on the intervals, which allows for manipulation of the nature and type of the corresponding functions of the probability distribution densities. The task of finding optimal functions of the probability distribution densities of the characteristic parameters of the model with maximum entropy is formulated. The proposed method allows for generating sets of trajectories of values of characteristic parameters with optimal functions of the probability distribution densities. The example demonstrates both the flexibility and reliability of the proposed concept and method in comparison with the concepts of forecasting numerical series implemented in the base of Matlab functions.

Introduction. One of the main factors affecting postoperative outcomes in patients with advanced ovarian cancer is the cardiopulmonary status. Several studies have reported that preoperative multifactorial rehabilitation and physical fitness can lead to reduced postoperative morbidity, mortality, shorter length of stay, and improved quality of life in cancer patients. The issue of adaptability to physical activity of overweight and obese patients who undergoing debulking surgery is insufficiently studied. The study of compensatory changes that occur in physically inactive obese patients remains relevant, especially against the background of neoadjuvant chemotherapy, in the conditions of preoperative preparation with ERAS-recommended physical activity. The aim of the study is to determine the differences between women with advanced ovarian cancer and obesity compared to women with normal weight in terms of heart rate variability during exercise. To assess the adaptive capabilities to physical activity of patients with advanced ovarian cancer and obesity at the stage of preoperative preparation, who undergoing debulking surgery. Result. Achieved METs, peak HR, CI, and HR recovery were higher in nonobese women, whereas training had no significant effect in obese women. Women who had already received neoadjuvant CT achieved a lower level of MET (6.8 ± 3.2 vs. 8.9 ± 4.1; P < 0.001). Also, peak HR and CI were lower in women after neoadjuvant CT (126±27 vs. 138±20; P = 0.001 and 0.65±0.22 vs. 0.71±0.22; P = 0.001, respectively). BMI was a significant predictor of exercise capacity only in the obese subgroup, whereas age, peak HR, and prior adjuvant HT were always significantly associated with METs achieved. Conclusions. No significant difference was found between trained and untrained women with comorbid obesity in HR behavior or physical capacity. Different heart rate behavior in patients of this group is thus explained by obesity as such, regardless of the degree of physical training.

Explaining the complex structure and dynamics of sleep, which consist of alternating and physiologically distinct nonREM and REM sleep episodes, has posed a significant challenge. In this study, we demonstrate that a single wave model concept captures the distinctly different overnight dynamics of the four primary sleep measures—the duration and intensity of nonREM and REM sleep episodes—with high quantitative precision for both regular and extended sleep. The model also accurately predicts how these polysomnographic measures respond to sleep deprivation or abundance. Furthermore, the model passes the ultimate test, as its prediction leads to a novel experimental finding—an invariant relationship between the duration of nonREM episodes and the intensity of REM episodes, the product of which remains constant over consecutive sleep cycles. These results suggest a functional unity between nonREM and REM sleep, establishing a comprehensive and quantitative framework for understanding normal sleep and sleep disorders.

This comparative research is aimed to study the effect of perindopril and metformin on the levels of biochemical markers of endothelial dysfunction in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage. The study was carried out on 30 white male Wistar rats. T2DM was simulated by a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum on the 60th day of the experiment. Animals were randomized into 5 groups: A – negative control (intact, n=6); B – positive control 1 (NA/STZ, n=6); C – positive control 2 (NA/STZ+ICH, n=6); D – perindopril (“Prestarium”, 2 mg/kg+NA/STZ+ICH, n=6); E – metformin (“Siofor”, 250 mg/kg+NA/STZ+ICH, n=6). The studied drugs were administered intragastrically for 20 days, starting from the 50th day after the induction of T2DM. Endothelial function was assessed by the content of homocysteine (Hcy), advanced glycation end products (AGEs), endothelin-1 (ET-1), and von Willebrand factor (vWF) in blood serum. It was found that long-term separate T2DM is accompanied by hyperhomocysteinemia, as well as an increase in AGEs, ET-1, and vWF levels, indicating dysregulation of the hemostasis system and vascular tone. It should be noted that brain hemorrhage in T2DM can enhance these manifestations, although the obtained differences were characterized only by a persistent trend. At the same time, the effect of perindopril was limited only by a significant decrease in AGEs levels by 31.2% (p

Purpose of the study. Motivations of healthy lifestyle for modern teenage students are studying. Materials and methods. The questionnaire method was used, which included self-assessment of the motivational components of the formation of a healthy lifestyle. Results. Among the life goals and values in both groups, the most important were the categories that determine life values. For the group of 13–15 years, they found themselves in health (70,5%) happy, close family (63,0%), friends (48,8%), health of loved ones (28,9%), love (15,3%). For the 16–18 age group, choices included family value (74,8%), health (68,4%), and good education (45,4%). In the block of the questionnaire related to the factors that stimulate movement to HL, the results for the two groups were almost identical. Leading 9th and 11th graders were caring for their health (92,8% and 90,2%, respectively), caring for their future (75,8% and 83,4%), the example of parents and other relatives (65,5 and 58,8%), as well as caring for their future children (45,2 and 55,8%). For the 9th graders more important than for the 11th graders, there were also such incentives as the example of friends and teachers (24,2% and 18,0% respectively). The stimulating impact of advertising and examples of «stars» noted only 4 teenagers of the older group. Conclusion. Health among the positive motivations of the surveyed students is one of the first places, being a stable dominant in the age range of 13–18 years. Real motivation for healthy lifestyles coincides with promising ones, and conscious choices coincide with goals, testifying to the formation of an individual capable of taking responsibility for one's health.

One of the most severe complications of metastatic lesion of the skeleton is the development of a pathological fracture, which not only affects the quality of life, makes it difficult to carry out adequate systemic treatment, but also has a negative effect on survival. In case of a pathological fracture, the main method of treatment is a surgical method. The main goal of the correction is to achieve stability and reduce metastatic pain in the area of damage or fracture. Today, the most popular organ-preserving operations for metastatic lesions of the femur in combination with pathological fractures are endoprosthesis and intramedullary osteosynthesis. In this paper, a comparative analysis of the results of their use is carried out, the advantages and disadvantages of each of the methods are described.

The aim of this study was to determine the general patterns of pathogenetic changes in the blood coagulation system and in non-specific proteinases and their inhibitors during the development of experimental ischemiareperfusion injury.Materials and methods. The study was conducted on 48 male Wistar rats (180–200 g). We used a model of ischemia-reperfusion injury achieved by applying rubber tourniquets to both hind limbs at the inguinal fold level for 6 hours. Revascularization was performed for 6, 12, or 24 hours following the application of tourniquets, after which we examined the state of the internal and external blood coagulation pathways and the activity of nonspecific proteinases and their inhibitors.Results. Indicators of blood coagulation system change show the development of blood hypocoagulation changes as the reperfusion time increases. By the 6th hour of reperfusion, the prothrombin time (PT) was lengthened by 112.0% (p = 0.0142) and the activated partial thromboplastin time (APTT) by 170.0% (p = 0.0147) compared with values in the control group. By the 12th reperfusion hour, the PT was lengthened by 174.2% (p = 0.0389), and the APTT increased 4.9-fold (p = 0.0002). When the reperfusion period was increased to 24 hours, it was characterized by lengthened PT and APTT, accompanied by an increase in antithrombin III by 11.5% (p = 0.0371) and a decrease in protein C by 71.4% (p = 0.0071). Changes in the non-specific proteinases and their inhibitors were characterized by a 2.8-fold increase in the trypsin-like proteinase activity (p < 0.001) relative to the control, as well as a 2.2-fold decrease in antitrypsin activity and acid-stable inhibitors (p < 0.001), which reached a maximum after 24 hours of reperfusion. A direct correlation was found between indicators characterizing the deficiency of coagulation system factors and a decrease in antiproteinase potential.Conclusion. Hemostatic system disorders are characterized by the development of hypocoagulation during ischemia-reperfusion injury as the result of an increase in the trypsin-like proteinase activity and a decrease in the levels of inhibitors. The established changes may be associated with the deficiency of coagulation factors and proteinase inhibitors and share common pathogenic mechanisms.

COVID-19 pandemic is recognized as a present day major public health burden. Risk factors for developing a more severe course of COVID-19 include increased levels of C-reactive protein and D-dimer. Pulmonary embolism (PE) is challenging in patients with COVID-19. The purpose: to analyze clinical and paraclinical manifestations of PE in patients with COVID-19 in order to develop a system for its early diagnosis, prediction of complications, prevention and treatment. 52 patients aged 28 - 81 y.o. with a diagnosis "Acute respiratory disease COVID-19" have been examined during 2020-2021. (98.08±1.9)% of PE patients had a history of one or more comorbidities, including obesity (80.77%), coronary heart disease (96.15%), hypertension (98.08%), peripheral arteries (92.3%), type 2 diabetes mellitus (48.08%). Evaluation of laboratory parameters revealed increasing lymphocytopenia, leukocytosis, neutrophilia, thrombocytopenia (p

The work involved a molecular biological technique (ISSR-PCR) using ISSR-primer S-2, with structure (AGC) 6G. Changes in the gastric mucosa in chronic duodenal ulcer disease against the background of severe chronic atrophic gastritis have been analyzed. Noteworthy is the fact that there is a strong correlation between the degree of dysplasia of the epithelium of the gastric mucosa and the mitotic index, the Pearson's correlation coefficient rxy was 0.853, respectively. A strong and very strong correlation relationship between the indicators of the degree of dysplasia of the epithelium of the gastric mucosa by phenotypic characteristics and indicators of DNA typing of samples of the gastric mucosa, the Pearson's correlation coefficient rxy was 0.863, respectively. DNA profiles of the gastric mucosa of patients with duodenal ulcer according to the results of typing by the ISSR-PCR method ranging from 520 to 620 bp. had the character of microsatellite expansions and differed from the profile of the norm, which is evidence of precancerous changes.

Vaccinia H1-related phosphatase (VHR) is a dual-specific phosphatase that is a promising potential target for the treatment of many human diseases. In this work, we have proposed a series of 6-(4-chlorophenyl)-N-aryl-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amines as potential VHR inhibitors. The SuperPred online server predicts VHR inhibition for the studied compounds with a probability of 88.88–98.51%. To establish the efficiency of binding of 4H-1,3,5-oxadiazine derivatives to the active site of VHR (PDB ID: 3F81) in the AutoDock Vina program, we have carried out molecular docking studies. According to the results, the studied compounds effectively interact with the hydrophobic region of the VHR active site due to aromatic rings and the trichloromethyl group, but the polar catalytic cavity is not involved, and therefore inhibition cannot be effective. In this regard, we have built a number of model compounds containing a sulfate group and its derivatives (methyl ester and amide) in the para-position of the arylamine fragment. According to the results of molecular docking, these compounds effectively bind to the polar catalytic cavity of the enzyme due to hydrogen bonds, but due to the relative rigidity of their molecules, hydrophobic interactions are not fully realized. Therefore, in these model compounds between the arylamine fragment and the sulfo group, we introduced a spacer with a length of one to three methylene groups. Hit compounds have been selected—2-(4-((6-(4-chlorophenyl)-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-yl)amino)phenyl)ethane-1-sulfonic acid and its amide.

Objectives to develop the main strategies of emergency medical care improvement for patients with acute coronary syndrome, in order to reduce the morbidity and mortality in the population of a large industrial region. Material and methods.The study was conducted on the basis of the Moscow regional ambulance station. We used the content analysis, logical, system analysis, the method of mathematical statistics. Results.In the period 20172018, in the region's population, there is a tendency for decrease in the number of calls for ambulance teams caused by acute coronary syndrome. During the analyzed period, we noticed the reduction of the number of cases of pre-hospital thrombolytic therapy (by 17.5%). The response time to the patient's call not more than 20minutes was observed in 92.9% of cases, the number of lethal outcomes in presence of the ambulance team decreased by 4.6%. The results can be explained by the dynamic development of the infrastructure of cities and districts of the Moscow Region, by the improvement of road networks, by the complete renewal of the service's motor vehicle fleet, and by the opening of a number of new specialized medical institutions. A set of medical and organizational measures has been developed and put into practice in the ambulance service of the region, aimed at further improvement of the system of ambulance care for patients with acute coronary syndrome at the prehospital stage. Conclusion.The mortality reduction, preservation and improvement of public health can be achieved only through the comprehensive sustainable development of the regions infrastructure, improvement of the organizational structure of the emergency medical service, mandatory use of algorithms and standards for the provision of medical care to patients at all stages.

Aim. To evaluate impact of different clinical features on prognosis in Diffuse Large B-cell lymphoma (DLBCL) patients and to determine potential correlation between IHC markers (double-expression of c-myc, bcl-2 and p53) on unfavorable clinical characteristics in DLBCL patients.Methods. We analyzed 215 patients with DLBCL who received treatment from 2008 to 2016. We assess impact of different clinical features, such as B-symptoms, extranodal involvement, advanced stages and refractory course on PFS. In this study we also access potentially unfavorable impact of double expression of c-myc and bcl-2 and p 53 by immunohistochemical analysis.Results. In both uni- and multivariant analysis B-symptoms, advanced stages and primary-refractory course were identified as negative prognostic factors for PFS rates. We found tendency to correlation between double expression of c-myc and bcl-2 and high International prognostic index as well as expression of p53 and advanced stages (87,5% vs 56,4% respectively, р = 0,095). Сonclusion. Patients with DLBCL aggressive course of the disease (B-symptoms, advanced stages and primary-refractory disease) have lower rates of PFS. Double-expression of c-myc and bcl-2 and p53 can be potentially associated with aggressive course of the disease.

Background. Dental health in patients with diabetes mellitus type 2 and methods of its correction is an important part in the complex of medical and preventive care of the pathology. Objective. The objective of the research is to study the efficiency of medications with probiotic potency in the process of prosthodontic treatment with whole piece permanent structures of dental prostheses of patients with diabetes mellitus type 2. Material and мethods. Qualitative and quantitative characteristics of oral fluid microbiocenosis of patients with diabetes mellitus type 2 have been studied in the process of the combination treatment including denture treatment with whole piece permanent structures with the use of «Bifidumbacterinum». Bacterial inoculation for oral fluid was done using Gould serial delution method. Results. Progressive reduction in the quantification which marks the content of pathogenic and liable to be pathogenic organisms in patients with diabetes mellitus type 2 stoma was noted after the combination treatment had been done. Herewith, the significance of stabilizing flora agents increased. Conclusions. The results of the microbiological research presented prove applicability of bacterial medication along with a package of measures during oral rehabilitation of patients with diabetes mallitus type 2 .

The purpose of this research was to study the effect of L-type voltage-gated calcium channels (L-VGCC) blocking on mRNA content and intensity of protein synthesis in cells of the metanephros. Materials and Methods: The study was performed on 27 outbred Wistar rats weighing 250-270 g from 5 to 7 months of age. Pregnant females were divided into 3 groups of 9 individuals each. Group1 (the control group) included intact pregnant females treated with distilled water; Group 2 (the first experimental group) included animals receiving a therapeutic dose of nifedipine; Group 3 (the second experimental group) included animals receiving a toxic dose of nifedipine. The dihydropyridine nifedipine (Sigma-Aldrich, Gillingham, UK) was used as a Ca2+ channel blocker. Nifedipine was dissolved in distilled water. The dose of nifedipine was calculated based on therapeutic and toxic doses for humans. The therapeutic dose for rats was 127 mg/kg, toxic dose – 762 mg/kg. In each group, when rats reached Day 14, 15, 16 and consistently up to 22 of gestation, they were removed from the experiment by decapitation under ether anesthesia. The embryos and fetuses were removed, subjected to external examination and quickly fixed with 10% neutral formalin entirely up to the age of 15 days. At an older age, both metanephros were removed from the fetuses by preparation and fixed with 10% neutral formalin. The intensity of protein synthesis was estimated by the content of mRNA in the cytoplasm. Results: The development of the metanephros in rats of the control group was accompanied by a gradual decrease in the content of mRNA, indicating the activity of protein synthesis in the cell cytoplasm of epithelial and mesenchymal buds of the metanephros. In the fetuses of rats whose mothers received therapeutic and toxic doses of nifedipine, statistically significant changes in the content of mRNA in the cytoplasm of the metanephric cells were observed. These changes were most significant in the metanephric cells after administration of the toxic dose. On ED 17, an L-VGCC blockade with a therapeutic dose of nifedipine led to a paradoxical reaction of cells with an increase in protein synthesis, compared with the control group. Conclusion: Both doses of nifedipine have a greater effect on the content of mRNA in the cytoplasm of epithelial cells, compared to mesenchymal buds.

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less nuclear magnetic resonance spectroscopy, and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the exact modus operandi for H-NS-mediated environmental sensing and suggested that this sensing mechanism resulted from the exaptation of an ancestral protein feature.

Early endosomes, regarded as the main sorting station on endocytic pathway, are characterized by high frequency of homotypic fusions mediated by tethering protein EEA1. Despite intensive investigations, biogenesis of endosomes, boundaries between early and late endosomes, and process of cargo transition though them remain obscure. Here, using EGF/EGFR endocytosis as a model and confocal microscopy of fixed and live cells, we provide evidence favoring EEA1-vesicles being pre-existed vesicular compartment, that maintains its resident proteins' level and is sensitive to biosynthetic, but not endocytic pathway disturbance. EEA1-vesicles directly fuse with incoming EGF/EGFR-vesicles into hybrid endosomes with separated EEA1- and EGFR-domains, thus providing a platform for rapid achievement of an excess of surface-derived membrane that is used to form intraluminal vesicles (ILVs). Thus, multivesicular structures colocalized with EEA1 are still early endosomes. "EEA1-cycle" ends by exclusion of EGFR-containing domains with ILVs inside that turns into MVE and restoration of initial EEA1-vesicles population.

The presence of additional fully formed accessory breast (polymastia), accessory nipples (polythelia) or other options ectopically positioned breast tissue is fairly rare developmental anomalies. Its occurrence frequency is approximately 1% of the general population. This article describes a rare case of localization of additional mammary glands and their surgical correction.

There are many measures for the effective functioning of the system of health protection of women and children in the Samara region: organizational, improving the system of legal norms, aimed at the optimization of medical aid to mother and child, strengthening the material-technical base of medical institutions, mastering modern methods of diagnosis and treatment, training of medical personnel at a high level. Plan of measures of structural transformation health care delivery system on women and children included the adoption of the regional target program “Health of the Samara region children” for 2013-2015. Within the framework of its implementing are used new prevention technologies affecting on indicators morbidity and mortality of the child population.

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 Significant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell’s transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.

Phylloid (leaf-shaped) breast tumors are a rare disease and constitute 0.3–0.5% of all breast tumors. Due to the rare frequency of occurrence, as well as the small number of randomized studies that have been conducted on this pathology, there is currently no standardized approach to the diagnosis and treatment of phylloid tumors. The reports about these rare cases appearing in the literature are, as a rule, descriptive, which only emphasizes the difficulty of differential diagnosis, the development of the correct tactics for treating such patients. In connection with the rarity, it is very difficult to diagnose correctly this pathology, which requires a highly qualified doctor as a diagnostician in the initial contact with such a patient, and a pathologist doctor who establishes the final morphological diagnosis. Often, leaf-shaped tumors are mistaken for mammary fibroadenomas. Such difficulties in correct diagnosis in the preoperative period can lead to errors in the planning of treatment. Also, the recommendations for the treatment of patients with this diagnosis are not fully understood, since up to now there are no accepted treatment standards in both Russian and foreign recommendations. Due to the fact that this pathology of mammary glands is rare, the principles of treatment are based on small retrospective studies and clinical observations. In this review, we will discuss the results of major retrospective studies, including data on epidemiology, etiology, diagnostic approach, strategies and results of treatment of this complex group of breast pathologies.

The study included 108 patients with B-cell lymphoma which had complication with invasive aspergillosis, 57 patients with Hodgkin lymphoma (HL) and 51 patients with non-Hodgkin lymphoma (NHL). All patients in both groups received chemotherapy before the development of invasive aspergillosis, 73% of patients with HL and 67% patients with NHL received chemotherapy for induction and consolidation of remission. The main predictive factors for IA in patients with HL and NHL were: prolonged lymphocytopenia (70% vs 48%), agranulocytosis (64% vs 71%), use of glucocorticosteroids as part of treatment protocol (61% vs 85%), presence of B – symptoms (63% vs 48%), respectively. In most cases nosocomial invasive aspergillosis was diagnosed in both groups: 65% vs 83% respectively. We identified etiological agents in Hodgkin and non-Hodgkin lymphoma patients: A. fumigatus (50% vs 39%), A. niger (43% vs 33%) and A. flavus (7% vs 8%). The lungs were involved in 100% cases, in group with NHL patients 6% had combined lesions in lungs and other organs and different types of tissues. Clinical manifestation of IA was nonspecific in both groups: fever – 83% vs 76%, cough – 75% vs 59%, respiratory insufficiency – 50% vs 40%, respectively. CT-signs of IA were also nonspecific in both groups: infiltrative (75% vs 66%), focal changes (61% vs 63%), and «ground-glass opacity» (28% vs 31%), respectively. In most cases patients were treated with voriconazole in both patients (88% vs 98%). Overall 12-weeks survival in patients with Hodgkin lymphoma and invasive aspergillosis was 84%, in patients with non-Hodgkin lymphoma and invasive aspergillosis – 81%.

The clinic-rentgenological differential diagnosis is difficult especially in case of localized mediastinal disease. Just detailed histological diagnosis allows making a right tactic decision and choosing effective therapy. Furthermore, some indolent B-cell lymphomas and T-cell lymphomas can arise in mediastinum. Mediastinal tumors are frequent in young adults, and most of these neoplasms are lymphoproliferative disorders. The spectrum of mediastinal lymphoma is broad. The most often of them are large B-cell lymphomas: classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, diffuse large B-cell lymphoma and mediastinal grey zone lymphoma.

Antibiotic resistance of microorganisms is one of the most acute problems of modern obstetrics. The paper analyzes current antibiotic resistance. It considers the mechanisms of its formation and ways to overcome the resistance.

“The cost of illness” is a detailed index for assessing the socio-economic losses caused by illness and related disability and death in money terms. The indicator is used in a variety of tasks, including the prediction of the positive effect of the medical devices introduction planning of the complex of medical-diagnostic and preventive measures in the healthcare system. The authors discussed in detail the structure of containing cost of illness losses (costs) - direct, indirect and intangible, briefly describes the key techniques for assessing cost of illness. SWOT-analysis carried out in the paper proved that “strongs” and “opportunities” despite possible negative impact of the internal and external factors contribute to the successful use of the “cost of illness” indicator in a wide range of different applications. In an aspect of the problem the key indicators of the road transport situation in Russia are described and the comparison of some key performance indicators of road transport situation in the country and in the world was carried out. Using specific examples in the field of traffic injuries the expedieny of the effect of the cost of illness-consequence on the structure of the cost of illness-cause was shown. Based on the foregoing, the modification of the structure of “cost of illness” proposed, taking into account an additional element, which we called “additive” losses, determining the contribution of a disease or condition in the cost of the other, which is the root cause of it. In view of these results it was concluded that the economic “assessment of the cost” of various diseases in the context of their relationship is of interest both from a theoretical and applied perspectives, and deserves further detailed study.

The aim of the present study was to investigate biological properties of the novel nitrobenzoxadiazole derivative 7-(1-methyl-3-pyrrolyl-)-4,6-dinitrobenzofuroxan. Materials and Methods: We used a bioluminescent test based on a set of lux-biosensors, which are genetically modified E.coli strains able to react on different types of factors that can induce an SOS-response with light emission. The spontaneous and induced mutation frequencies of antibiotic resistance in E. coli were determined by methods of classical genetics of microorganisms. Results: 7-(1-methyl-3-pyrrolyl-)-4,6-dinitrobenzofuroxan demonstrated inhibition of SOS-response in a biosensor model system and significantly reduced the frequency of spontaneous mutations and mutations induced by ciprofloxacin of antibiotic resistance. Conclusion: Based on our data, we can recommend using compound-1 as a starting point for the development of drugs that block mutagenesis associated with the emergence of antibiotic-resistant bacteria.

Summary. Objective: to investigate the effectiveness and factors that can influence on surgical treatment of isolated recurrent ovarian cancer involving the liver. Materials and methods: A retrospective analysis of medical documentation of ovarian cancer patients, who underwent surgical removal of the recurrent tumors localized in the liver, performed in State Establishment «Zaitsev V.T. Institute of General and Emergency Surgery of the Academy of Medical Sciences of Ukraine» from January 2001 to December 2010 (n = 29). Results. Overall survival increased significantly while disease-free interval (DFI) increase (after primary cytoreduction) and optimal secondary cytoreduction is achieved. Median overall survival for DFI 24 months – 61 months (p

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.

Until 2030 theulcermortalitywillhaveagrowingtrendasestimatedbytheWorldHealthOrganization. Detectionofcountriesandpopulationgroupswithhighrisksfortheulcermortalityispossibleusingforecast method. The authors madeaforecastofmortalityratefromcomplicatedulcerdiseaseinmalesandfemalesandtheiragegroups (15-24, 25-34, 35-54, 55-74, over 75, 15 - over 75) in our country. ThestudyincludeddataoftheWorldHealthOrganizationDatabase from 1991 to 2012. The work analyzed absolute all-Ukrainian numbers of persons of both genders died from the ulcer causes (К25-К27 coded by the 10th International Diseases Classification). The relative mortality per 100 000 of alive persons of the same age was calculated denovo. Theanalysisofdistributionlawsandtheirestimationpresentsatrendofgrowthoftherelativemortality. Aremarkableincreaseofdeathsfromtheulcerdiseaseisobservedinmalesandfemalesoftheageafter 55 years old. After the age of 75 years this trend is more expressed.

Until 2030 the ulcer mortality will have a growing trend as estimated by the World Health Organization. Detection of countries and population groups with high risks for the ulcer mortality is possible using forecast method. The authors made a forecast of mortality rate from complicated ulcer disease in males and females and their age groups (15-24, 25-34, 35-54, 55-74, over 75, 15 - over 75) in our country. The study included data of the World Health Organization Database from 1991 to 2012. The work analyzed absolute all-Ukrainian numbers of persons of both genders died from the ulcer causes (К25-К27 coded by the 10th International Diseases Classification). The relative mortality per 100 000 of alive persons of the same age was calculated de novo. The analysis of distribution laws and their estimation presents a trend of growth of the relative mortality. A remarkable increase of deaths from the ulcer disease is observed in males and females of the age after 55 years old. After the age of 75 years this trend is more expressed.

The article presents the results of analysis of the relevant publications and research works over the last 20 years, devoted to the value of radiation therapy in the treatment of low-grade gliomas. This literature review reflects the role and place of radiation therapy in the treatment of such patients according to the latest research data and modern standards of treatment developed by the most authoritative scientific institutes and international research groups.

The paper highlights the topical problems of nosocomial infection in the practice of obstetrics and perinatology. It systematizes procedures for controlling the occurrence of nosocomial infection and preventing its spread, such as identification of risk groups and risk factors and prerequisites for complications of epidemiological surveillance, as well as specific diagnosis in pregnant women. Group B streptococcus, one of the major pathogens of nosocomial infection, is described.

The paper considers the role of the immune system, endoplasmic network stress, metabolic dysregulation, and epigenetic mechanisms in the pathogenesis of essential hypertension, as well as the limited possibilities of therapy with existing antihypertensive agents.

The article is devoted to problem of pancreatic intra- and extrasecretory function impairment in patients with pancreatic cancer after a astropancreatoduodenal resection. New technical aspects of pancreatoenteroanastomosis were suggested to prevent its insufficiency.

The objective of the research was to estimate early and long-term results of secondary cytoreductive surgery performed for recurrent ovarian cancer with involvement of urinary organs. Materials and methods. The study included 62 patients with recurrent ovarian cancer treated in the Institute of General and Emergency Surgery named after V.T. Zaitsev of the Academy of Medical Sciences of Ukraine during January 2009 – September 2015. Selection criteria for secondary cytoreductive surgery were the following: recurrent ovarian cancer with involvement of the bladder and/or the ureter, no urologic surgery during primary cytoreductive surgery, the ECOG performance status of 0-2. Urological surgery that had been a subject to the analysis was the following: cystoscopy with or without intraoperative urethral stenting, bladder resection, ureterectomy, ureteral reimplantation, cystectomy with further reconstruction. Evaluation criteria included the presence and the level of surgical and postoperative urological complications within 30 days after surgery, relaparatomy rates, postoperative mortality, type of cytoreduction. Long-term results were evaluated through recurrence rates after secondary cytoreductive surgery, median survival, disease-free survival and overall survival. Results. Volumes of performed surgery (excluding urological one) were the following: lymphadenectomy (n=29; 46.7%), bowel resection (n=17; 27.4%), vascular resection (n=4; 6.5%) and others. Minimally invasive urological surgery included urethral stenting (n=6; 9.7%) and cystoscopy (n=13; 20.9%). Bladder resection was performed in 26 (41.9%) cases, cystectomy – in 17 (27.4%) cases. R0 resections were performed in all the cases. Postoperative non-urological complications were observed in 7 (11.2%) patients. Urological complications were found in 9 (14.5%) patients. Postoperative mortality was 3.2%. Recurrence was documented in 7 (11.3%) cases. Median survival was 24 months. Follow-up mortality was 30% (n=18). Conclusions. The results of combined secondary cytoreductive surgery performed for recurrent ovarian cancer with involvement of urinary organs indicate the possibility of en bloc resection of tumor and surrounding organs at acceptable rates of postoperative complications and mortality. Extended combined surgery and even pelvic exenteration are effective in treatment of patients with recurrent ovarian cancer.

Heavy metals have a negative effect on the contractility of uterine smooth muscles (myometrium), these effects can lead to various pathologies of a women reproductive system. To overcome these effects the methods for correcting the myometrium contractile activity are to be developed. Catalyzed by myosin ATPase ATP hydrolysis is the most important reaction in the molecular mechanism of myo­metrium contraction. We have found an inhibitory effect of 0.03-0.3 mM Ni2+, Pb2+ and Cd2+ on enzymatic hydrolysis of ATP by myosin subfragment-1 obtained from swine uterine smooth muscles. We have demonstrated that 100 µM thiacalix[4]arene-tetrasulphonate (C-798) recovered to the control level of ATPase activity of myosin subfragment-1 in the presence of heavy metal cations. One of the most probable mechanisms of C-798 corrective activity is based on its ability to chelate heavy metals, thus cations Pb, Cd and Ni can be removed from the incubation medium. Computer simulation has demonstrated that the protective effect of C-798 may also be the result of weakening the interaction of heavy metal ions with amino acid residues of the myosin molecule near the active site of ATP hydrolase. The obtained results can be used for further research aimed at assessing the prospects of thiacalix[4]arene-tetrasulfonate as pharmacological compounds.

The objective of research was to study the state of prooxidant and antioxidant systems in the tissues of the lungs, kidneys, pancreas and salivary glands at burn disease. The intensity of the free radical processes was evaluated on the basis of the content of malondialdehyde (MDA) and antioxidant system – based on the indexes of its enzymatic chain: superoxide dismutase and catalase in homogenates of the studied organs. It has been found that changes in experimental burn disease depend on the studied organs and the stage of burn disease. The activation of free radical processes observed in all investigated organs (lungs, kidneys, pancreas and salivary glands). Reactive oxygen species induce lipid peroxidation, which is a universal marker of tissue damage. MDA appears in the body during degradation of polyunsaturated fatty acids and it’s a marker of lipid peroxidation and oxidative stress. It was found the increasing of MDA in all organs, especially in the lungs and kidneys at stage of burn shock. Under these conditions it was observed the decrease of superoxide dismutase and catalase in all investigated organs. At burn disease there is development of disbalance between the action of prooxidant and antioxidant systems due to the activation of free radical processes.

In normal cell apoptosis and proliferation are strictly controlled by intra- and extracell mechanisms. These signals interfere with cell pathways through cell receptors, estrogen, progesterone, HER2/neu receptors in the case of breast cancer. Expression of apoptotic and proliferative genes is different in breast cancer depending on hormonal status. Besides correlation analysis shows different role of cell receptors in proliferation control in normal and breast tissue.

Early breast cancer (BC) diagnosis is a basis for overall and relapse-free survival improvement. But methods of X-ray and morphological examination sometimes are failed in BC diagnosis. New molecular markers may give more information about BC progression. One of these markers is mammaglobin. We studied 114 tissue samples: 57 I—IV stages BC samples and 57 samples of morphologically normal breast tissue (MNBT). mRNA mammaglobin expression was assessed by qPCR with reverse transcription. mRAN mammaglobin expression was significantly higher in BC samples as compared to MNBT (p = 0,0019), besides expression level decreased during BC progression: minimal level in T3 (p = 0,0338), grade 3 (p = 0,037) and stage IV (p = 0,035) tumors. hMAM expression correlated with steroid receptors (estrogen receptor, progesterone receptpor) in MNBT (p < 0.05), but not in BC tissue. hMAM mRNA expression decreased during BC progression and correlated with steroid receptors in MNBT. hMAM expression profiling may be used as a marker in BC diagnosis.

This review considers the classification of cardiorenal syndromes (CRS), the pathogenesis of heart failure, and a search for therapeutic targets for its treatment, biomarkers for heart and kidney failure, difficulties in therapy and reversion of the pathogenetic continuum of CRS, and promises for the use of some new technologies to treat this condition.

The review considers the results of studies of the psychosomatic aspects of rheumatoid arthritis (RA), which have been published in the past 5 years. In particular, there is evidence for the impact of chronic pain on the psychological status of patients with RA, for that of the disease on quality of life in the patients, their sociopsychological and interpersonal relationships; trials of the efficiency of additional treatment options for RA are given.

Retroperitoneal tumours arre rare and compose 0,01-0,3% of all tumours types. The basic method of retroperitoneal tumour treatment is surgical resection which is carried out in 43-95% of patients. In this study we present analysis of surgical treatment of 104 patients with retroperitoneal tumours. Complited resection was made in 87 patients (83,7%); partial surgical resection - in 7 patients (6,7%), explorative laparotomyes have been executed in 8 patients (7,7%), symptomatic operations - 2 patients (1,9%). Operability percentage - 88,1%. Resectobility - 90,3%. Level of an intraoperation and postoperation complications was 29,8% and hospital lethality - 4,2%. Analysis of surgical treatment direct resultstestifies to high indicators of operability of patients with retroperitoneal tumours resectobility. Surgical treatment of retroperitoneal tumours isn't accompanied with high frequency of postoperative complications and lethality.

Recent experiments reveal both passive subdiffusion of various nanoparticles and anomalous active transport of such particles by molecular motors in the molecularly crowded environment of living biological cells. Passive and active microrheology reveals that the origin of this anomalous dynamics is due to the viscoelasticity of the intracellular fluid. How do molecular motors perform in such a highly viscous, dissipative environment? Can we explain the observed co-existence of the anomalous transport of relatively large particles of 100 to 500 nm in size by kinesin motors with the normal transport of smaller particles by the same molecular motors? What is the efficiency of molecular motors in the anomalous transport regime? Here we answer these seemingly conflicting questions and consistently explain experimental findings in a generalization of the well-known continuous diffusion model for molecular motors with two conformational states in which viscoelastic effects are included.

The article is concerned with the substantive nature of late capitalism, which determines all spheres of social existence. It is clarified that neoliberal ideology forms a special type of socio-cultural relations, in which the politics' technocratic nature disregards humanitarian and cultural aspects and doubts the very existence of the social. Under the circumstances of IT intensified development and real crisis of capitalism, the fundamental process of human-human interaction is ignored, consequently resulting in the loss of the human's fundamental feature, that is, his sociality. Socio-philosophical research in modern realities is assigned to actualize the issues of spiritual production related to preservation of the social as the ontological essence of society existence in the future. Therefore, our paper aims to analyze the socio-productive function of education and medicine in the formation of a humanitarian and anthropological model of preserving social partnership and tolerance in modern society as opposed to the disappointing and disturbing experience of chronic social pathologies, medicalization and formation of the "remission society" model within the framework of capitalism. The formation of a humanitarian and anthropological model of preserving the social consists in actualizing the evolutionary mechanisms for social humanism, which is the basic characteristic of the post-capitalist reality. [ABSTRACT FROM AUTHOR]