Репозиторий Университета

© 2019, Pleiades Publishing, Inc. Abstract: Angiomyolipoma (AML) is one of the most frequent and, at the same time, AML molecular genetics is one of the least studied among benign tumors. We performed deep sequencing of 409 genes involved in oncogenesis in tumor samples and peripheral blood of patients with sporadic AML of the kidney. We recorded mutations in the TSC2 gene in 65% of samples, which is consistent with international results. As a result of our work, we uncovered mutations in the SETD2, PDGFRA, STK36, SYNE1, PIK3CD, NF1, TOP1, and ITGB3 genes in sporadic renal AML for the first time. In two samples, we were able to clarify the clinical and morphological diagnosis by finding mutations in the genes in tumors lacking TSC2 gene lesions. Mutations in MET and CDC73 are also causative for other types of renal tumors: papillary renal cell carcinoma and CDC73-related disorders, respectively. The latter disease is accompanied by kidney cysts and hamartomas. The obtained results demonstrate a promising potential of mutational profiling of sporadic renal angiomyolipoma (sAML). Genotyping of sAML is particularly important for clarification of the clinical diagnosis in ambiguous cases, as well as for a more in-depth understanding of AML molecular genetics and etiopathogenesis, and for the identification of new molecular targets for personalized AML therapies.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. We studied the sensitivity of domestic proprietary human and animal cell lines from the collection of M. P. Chumakov Federal Scientific Center for Research and Development of Immuneand-Biological Products to infection with different enterovirus 71 strains. A cell system based on domestic proprietary permanent cell line 4647 was for the first time used for reproduction of four enterovirus 71 strains (BrCr, 42266, 42934, and 43374). It was shown that strain 4647 is the optimal cell substrate for enterovirus 71 reproduction. The titers of enterovirus 71 for all four strains considerably (by 2 lgTCID50/ml and more) increased during sequential passages in permanent cell line 4647. The prospects of using permanent cell line 4647 for creation of diagnostic and preventive preparations against 71 was demonstrated.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. We studied the effect of LPS on the state of stress-marker organs in rats at various periods after a single exposure to long-term stress on the model of 24-h immobilization. The animals were intraperitoneally injected with LPS in a dose of 100 μg/kg immediately after the negative emotiogenic exposure. Changes in physiological parameters were evaluated 3 h, 1 day, and 8 days after immune stimulation. Acute stress was accompanied by a decrease in the weight of the thymus during all stages of the post-stress period. An increase in the relative weight of theadrenal glands in animals under these conditions was observed only on day 8 after restraint stress. The induction of immune reactions due to systemic treatment with LPS was shown to prevent involution of the spleen in the late stage after a single exposure to long-term stress (day 8). Hypertrophy of the adrenal glands, which serves as one of the typical reactions of mammals to negative emotiogenic factors, was not revealed during the post-stress period after antigenic stimulation. These data hold much promise for the development of new approaches to the use of immunoactive substances to prevent or reduce the severity of physiological changes after emotiogenic loads.

© 2019, Pediatria Ltd. All rights reserved. The question of the methodology for assessing the physical development (PD) of the child population remains debatable. An analytical, prospective, cohort study (8300 children) was performed. A comparative evaluation of 4 methods of PD assessment based on informativity criterion is presented. The ratio of methods and content of regulatory documents of the Ministry of Health of the Russian Federation is shown. Advantages of the complex technique were revealed, which is important for pediatricians, since the stated deviation in child's PD allows to determine the amount of diagnostic, preventive, and health-improving measures and recommendations for a healthy lifestyle. Within the confines of Decade of Childhood, it is necessary to eliminate the existing contradictions in normative base of the Ministry of Health of the Russian Federation, medical statistics, and medical personnel training.

© Yu.I. OSMANOV1, Zh.A. GAIBOV, E.A. KOGAN, S.G. RADENSKA-LOPOVOK, Kh.Z. TURSUNOV. The molecular subtypes of urothelial carcinoma in each classification scheme have characteristic immunohistochemical features. At the same time, the results of conducted studies often demonstrate a discrepancy between the genomic profile of urothelial carcinoma and its immunophenotype, which complicates the immunohistochemical verification of the molecular subtypes of these tumors. Objective - to compare the morphological and immunophenotypic characteristics of the molecular subtypes of urothelial carcinoma. Material and methods. Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin-embedded sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CK17, Rb1 (Dako), CK14, CK18, CK20, Cyclin D1, Cyclin E1, Cyclin A, Cyclin B, Chromogranin, E-Cadherin, P-Cadherin, p16, Uroplakin II, TUBB2B, Vimentin, ZEB-2 («Novocastra»), CD44, GATA-3, and Uroplakin III («Cell Marque») were used. Results. Out of 68 (35%) superficial papillary urothelial carcinomas, 24 (12%) tumors constituted Molecular Class I and 12 (6%) and 32 (16%) ones did Molecular Classes II and III, respectively. Of the 128 (65%) muscle-invasive urothelial carcinomas, 57 (29%) tumors were referred to as the luminal-papillary molecular subtype, and 24 (12%) and 14 (7%) were as the luminal-infiltrated and luminal molecular subtypes, respectively. The basal squamous molecular subtype was verified in 31 (16%) neoplasms and the neuronal phenotype was detected in 2 (1%) cases. Conclusion. Most pT1 tissues correspond to Molecular Class II. In the muscle-invasive urothelial carcinoma group, the neoplasms with a luminal phenotype predominate over the tumors with basal and neuronal phenotypes.

© 2019 The authors. Estrogens may affect bone growth locally or systemically via the known estrogen receptors ESR1, ESR2 and G protein-coupled estrogen receptor 1 (GPER1). Mouse and human growth plate chondrocytes have been demonstrated to express GPER1 and ablation of this receptor increased bone length in mice. Therefore, GPER1 is an attractive target for therapeutic modulation of bone growth, which has never been explored. To investigate the effects of activated GPER1 on the growth plate, we locally exposed mouse metatarsal bones to different concentrations of the selective GPER1 agonist G1 for 14 days ex vivo. The results showed that none of the concentrations of G1 had any direct effect on metatarsal bone growth when compared to control. To evaluate if GPER1 stimulation may systemically modulate bone growth, ovariectomized C57BL/6 mice were treated with G1 or β-estradiol (E2). Similarly, G1 did not influence tibia and femur growth in treated mice. As expected, E2 treatment suppressed bone growth in vivo. We conclude that ligand stimulation of GPER1 does not influence bone growth in mice.

© 2019, Advanced Scientific Research. All rights reserved. A topical problem in traumatology is the choice of treatment methods for ankle fractures. The consideration of the anatomical and functional features of the ankle, condition of soft tissues in the area of fractures and the degree of edema in the ankle region is of great importance when choosing a particular treatment method. Therefore, reducing the degree of surgical aggression during surgical treatment of these injuries is an important task.. The aim of this study was to examine the possibilities of improving the results of surgical treatment of patients with ankle fractures with minimally invasive osteosynthesis technologies. This study presents the experience of treating 62 patients with fractures of the ankle joint. Two statistically homogeneous groups of patients with ankle fractures were identified. In one group, osteosynthesis with minimally invasive osteosynthesis techniques was used in 34 patients; in the other, osteosynthesis was performed in a conventional manner in 28 patients. A comparative analysis of the immediate and long-term results of treatment of patients in the study groups was carried out. The advantage of closed technology of osteosynthesis was proved. The preservation of the blood supply to the surrounding soft tissues with closed osteosynthesis provides a greater likelihood of fracture fusion, therefore the only condition in such cases is to eliminate the interposition of soft tissues in the area of lateral and medial ankle fractures.. The analysis of the obtained immediate and remote results of osteosynthesis in the two groups showed the best efficiency when using minimally invasive closed metal implantationtechnologies, especially when there are skin problems in the area of the injured ankle joint.

© 2019 Walter de Gruyter GmbH, Berlin/Boston. Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI). The study population was divided in two groups according to the presence of cardiac remodelling, defined as LVSI <5th centile. The following outcomes were explored: Gestational age at birth, birthweight, caesarean section (CS) for fetal distress, umbilical artery (UA) pH and neonatal admission to special care unit. The differences between the 2 groups in UA pulsatility index (PI), middle cerebral artery (MCA) PI, uterine artery PI, cerebroplacental ratio (CPR) and umbilical vein (UV) flow corrected for fetal abdominal circumference (UVBF/AC) were tested. In total, 212 pregnancies with late FGR were enrolled in the study. An abnormal LV SI was detected in 119 fetuses (56.1%). Late FGR fetuses with cardiac remodeling had a lower birthweight (2390 g vs. 2490; P = 0.04) and umbilical artery pH (7.21 vs. 7.24; P = 0.04) and were more likely to have emergency CS (42.8% vs. 26.9%; P = 0.023) and admission to special care unit (13.4% vs. 4.3%; P = 0.03) compared to those with normal LVSI. No difference in either UA PI (p = 0.904), MCA PI (P = 0.575), CPR (P = 0.607) and mean uterine artery PI (P = 0.756) were present between fetuses with or without an abnormal LV SI. Conversely, UVBF/AC z-score was lower (-1.84 vs.-0.99; P ≤ 0.001) in fetuses with cardiac remodeling and correlated with LV (P ≤ 0.01) and RV SI (P ≤ 0.02). Fetal cardiac remodelling occurs in a significant proportion of pregnancies complicated by late FGR and is affected by a high burden of short-term perinatal compromise. The occurrence of LV SI is independent from fetal arterial Dopplers while it is positively associated with umbilical vein blood flow.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Photobiomodulation (PBM) is a non-plant-cell manipulation through a transfer of energy by means of light sources at the non-ablative or thermal intensity. Authors showed that cytochrome-c-oxidase (complex IV) is the specific chromophore's target of PBM at the red (600-700 nm) and NIR (760-900 nm) wavelength regions. Recently, it was suggested that the infrared region of the spectrum could influence other chromospheres, despite the interaction by wavelengths higher than 900 nm with mitochondrial chromophores was not clearly demonstrated. We characterized the interaction between mitochondria respiratory chain, malate dehydrogenase, a key enzyme of Krebs cycle, and 3-hydroxyacyl-CoA dehydrogenase, an enzyme involved in the β-oxidation (two mitochondrial matrix enzymes) with the 1064 nm Nd:YAG (100mps and 10 Hz frequency mode) irradiated at the average power density of 0.50, 0.75, 1.00, 1.25 and 1.50 W/cm2 to generate the respective fluences of 30, 45, 60, 75 and 90 J/cm2. Our results show the effect of laser light on the transmembrane mitochondrial complexes I, III, IV and V (adenosine triphosphate synthase) (window effects), but not on the extrinsic mitochondrial membrane complex II and mitochondria matrix enzymes. The effect is not due to macroscopical thermal change. An interaction of this wavelength with the Fe-S proteins and Cu-centers of respiratory complexes and with the water molecules could be supposed.

© 2019 Elsevier Ltd The widespread application of laser devices requires development of new protections against light pulses of high intensity. This problem is relevant because of the danger of hitting the civil aviation pilots with bright and powerful radiation originating from the laser sources which are widely used in the everyday life. Therefore, this work is devoted to continuing our research on a new class of macroheterocyclic compounds – thermally and chemically stable J-type phthalocyanine dimers as potential nonlinear absorbers for optical limiting technology. The dimeric complexes of magnesium (1a) and zinc (1b) were covalently bonded to single-walled carbon nanotubes (SWCNTs) to improve the overall characteristics of the potential optical limiters 2a,b as compared to the previously studied corresponding dyes in solutions. The conjugates obtained were investigated using atomic force microscopy (AFM), as well as Raman and IR spectroscopy to confirm formation of the covalent binding of phthalocyanine macrocycles with the carbon surface. Open-aperture Z-scan and a fixed limiter location experiments have demonstrated low values of the limiting threshold and high degree of attenuation of the input laser radiation with the pulses duration located in the nanosecond range.

The characteristic feature of molecular medicine as medicine based on molecular structure of human genome data, is its individual character. It is focused on correcting pathological process in specific individual considering unique characteristics of its genome. The other most important feature is its expressed preventive direction. The complete genome information can be obtained well before the onset of disease. The appropriate preventive measures can completely eliminate or significantly prevent development of severe disease. The establishment of gene network of every multi-factorial disease, identification of central genes and genes-modifiers in it, analysis of association of their alleles with disease, development on this basis of set of preventive measures for specific patient constitute conceptual and methodological basis of predictive medicine. As a result of the examination, information can be obtained concerning particular risk of disease development. The physician, considering the results of molecular genetic analysis, elaborates tactics of pathogenetically justified preventive therapy, i.e. corrects congenital metabolic defect.

The article analyzes the indicators of population reproduction on the example of the Kostroma region, presents the dynamics of the main medical and demographic indicators of the region: age structure of the population, mortality, fertility, migration, marriage and divorce rates, as well as the starting positions for overcoming reproductive and demographic disadvantages.

© 2019, Advanced Scientific Research. All rights reserved. The failure of the pelvic floor (NTD) is a common syndrome in the modern female population, in which there is a combined or isolated prolapse of the pelvic floor and pelvic organs. In the study, tissues of the vaginal walls of 20 patients were studied by pelvic floor failure using light microscopy, PCR diagnostics, and immunohistochemistry before and after treatment with contact diathermy method. The results of the study of the material obtained after a course of diathermic treatment indicate compensation of chronic oxidative stress at the molecular level by leveling the imbalance of collagen and elastin and restoring the architectonics of the vaginal wall.

© 2019, Pleiades Publishing, Ltd. Abstract: Histone-like protein HU is a dimeric nucleoid-associated protein (NAP). HU is the most conserved NAP. It binds nonspecifically to duplex DNA with a preference for targeting nicked and bent DNA. HU limits the architecture of the bacterial nucleoid and its deletion is lethal for Bacillus subtilis and Mycoplasma genitalium which do not contain other NAPs. E. coli lacking HU is viable but has numerous growth defects. The effects of the HU protein on gene expression is known from microarray analysis and HU regulons were identified. In HU-deficient E. coli, absence of this DNA architectural protein causes a disorder in gene regulation; on the other hand, E. coli growth under standard conditions is almost unaltered in the absence of HU. To understand how the bacterium confronts the chromosomal disorder, we performed proteome analysis to compare protein abundances in cells containing the HU protein or not. Comparison of the proteomic profile of wild-type and HU-deficient E. coli shows how the altered gene expression influences the protein content. We show that proteome profile changes are very similar to the gene expression profile changes in HU-deficient E. coli. Several exceptions show that proteome studies are very important.

© 2019 The Authors Eighty years after the last published record of human leishmaniasis from Dagestan, Russian Federation, we report two recent cases which were most probably acquired locally: one case of visceral leishmaniasis in a 2-year old child, and one cutaneous leishmaniasis case in a 39-year-old man co-infected with HIV, both resident in Dagestan.

© 2019 by the authors. Developing bone scaffolds can greatly improve the patient's quality of life by accelerating the rehabilitation process. In this paper, we studied the process of composite polycaprolactone supercritical foaming for tissue engineering. The influence of graphene oxide and reduced graphene oxide on the foaming parameters was studied. The structural and mechanical properties were studied. The scaffolds demonstrated mechanical flexibility and endurance. The co-culturing and live/dead tests demonstrated that the obtained scaffolds are biocompatible. Different composite scaffolds induced various surface cell behaviors. The experimental data demonstrate that composite foams are promising candidates for in vivo medical trials.

© 2019 by author(s) and VsI Entrepreneurship and Sustainability Center. The effective use of resource potential is a prerequisite for implementing all the functions of the territory and thus, can be considered fundamental for sustainable territorial development. Within the context of the current crisis in the economic sphere, regional affiliation generally occupies a special place in the structure of socio-economic development. Therefore, finding ways to ensure the effective use of resource potential is a crucial task, combining territorial specifics with the interests of the state. Modern approaches to the organization and management of the resource potential of the territory in the direction of its sustainable strategic development are analyzed. The authors substantiate the conditions and factors of formation of the resource potential of the region. On the basis of a detailed study of the problem, the mechanism developed by the authors to implement the strategy of effective use of resource potential at the regional level is presented. The proposed mechanism can be implemented in the socio-economic management of the territory focused on sustainable development.

© 2019 Wiley-Blackwell. All rights reserved. Laccases are enzymes that catalyze the oxidation of a wide range of organic and inorganic substrates accompanied by the reduction of molecular oxygen to water. Here, a subatomic resolution X-ray crystallographic study of the mechanism of inhibition of the laccase from the basidiomycete fungus Steccherinum murashkinskyi by chloride and fluoride ions is presented. Three series of X-ray diffraction data sets were collected with increasing doses of absorbed X-ray radiation from a native S. murashkinskyi laccase crystal and from crystals of complexes of the laccase with chloride and fluoride ions. The data for the native laccase crystal confirmed the previously deduced enzymatic mechanism of molecular oxygen reduction. The structures of the complexes allowed the localization of chloride and fluoride ions in the channel near the T2 copper ion. These ions replace the oxygen ligand of the T2 copper ion in this channel and can play the role of this ligand in the enzymatic reaction. As follows from analysis of the structures from the increasing dose series, the inhibition of laccases by chloride and fluoride anions can be explained by the fact that the binding of these negatively charged ions at the position of the oxygen ligand of the T2 copper ion impedes the reduction of the T2 copper ion.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This study examined the differences in health spending within the World Health Organization (WHO) Europe region by comparing the EU15, the EU post-2004, CIS, EU Candidate and CARINFONET countries. The WHO European Region (53 countries) has been divided into the following sub-groups: EU15, EU post-2004, CIS, EU Candidate countries and CARINFONET countries. The study period, based on the availability of WHO Global Health expenditure data, was 1995 to 2014. EU15 countries have exhibited the strongest growth in total health spending both in nominal and purchasing power parity terms. The dynamics of CIS members’ private sector expenditure growth as a percentage of GDP change has exceeded that of other groups. Private sector expenditure on health as a percentage of total government expenditure, has steadily the highest percentage point share among CARINFONET countries. Furthermore, private households’ out-of-pocket payments on health as a percentage of total health expenditure, has been dominated by Central Asian republics for most of the period, although, for the period 2010 to 2014, the latter have tended to converge with those of CIS countries. Western EU15 nations have shown a serious growth of health expenditure far exceeding their pace of real economic growth in the long run. There is concerning growth of private health spending among the CIS and CARINFONET nations. It reflects growing citizen vulnerability in terms of questionable affordability of healthcare. Health care investment capability has grown most substantially in the Russian Federation, Turkey and Poland being the classical examples of emerging markets.

© 2019 Special Care Dentistry Association and Wiley Periodicals, Inc. Aims: This study aimed to investigate the morphology of the palate, palatal rugae pattern, and dental arch form in patients with schizophrenia. Methods and results: An observational case-control study was designed following the STROBE statement and checklist. The sample consisted of 132 patients (39 diagnosed with schizophrenia and 93 controls). Dental casts of the patients were classified based on the pattern of their palatal rugae, their dental arch form, and the area of their palate. The palatal rugae in patients with schizophrenia had a more random distribution and shape compared to the control group (P =.027). Oval dental arches were the most prevalent in both groups (P =.473). The palate area was slightly larger in the control group (3.2318 ± 0.549 mm2) compared with the group of patients with schizophrenia (3.060 ± 0.470 mm2) (P =.090). Conclusion: Palatal rugae pattern may feature as a potential minor physical anomaly for schizophrenia. Additional studies with alternative sampling and classification systems are necessary to understand this finding and its applications in practice.