Репозиторий Университета

© 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.

© 2019, International League of Associations for Rheumatology (ILAR). Abstract: Streptococcus is well associated with a myriad of inflammatory diseases. Among others, this bacterium is linked to the triggering of psoriasis and to post-streptococcal reactive arthritis (PSRA), an arthritis which is typically confined to peripheral joints. Three patients who developed acute psoriatic spondyloarthritis (SpA) following a recent streptococcal infection are described in this article. We searched the existing literature for cases of axial involvement in PSRA and reviewed the association between streptococcal infection and psoriasis or psoriatic arthritis )PsA). In all patients, psoriatic SpA occurred within 7–10 days of a confirmed streptococcal infection. The main presenting syndrome was inflammatory back pain with evidence of acute axial spondyloarthritis on magnetic resonance imaging. One patient had guttate psoriasis, the second patient developed pustular psoriasis, and the third patient had exacerbation of pustular palmoplantar psoriasis. Two patients required treatment with tumor necrosis factor alpha (TNF-α) blockers. Axial involvement in PSRA is very rare. A potential association of streptococcal infection and development of PsA has been explored in several articles. However, to the best of our knowledge, acute psoriatic SpA as a manifestation of PSRA has yet to be described. Acute psoriatic SpA should be considered in the differential diagnosis of new-onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection. Key Points: • Our case series describes three cases of acute psoriatic spondyloarthritis that occurred within 7–-10 days of a confirmed streptococcal infection and progressed to full blown chronic disease. • Acute psoriatic spondyloarthritis as a manifestation of post streptococcal reactive arthritis should be considered in the differential diagnosis of new onset inflammatory back pain followed by psoriasis in young adults who had a recent throat infection.

© 2019 Society for Vascular Surgery Objective: This study aimed to evaluate the impact of gravity, reservoir size, and competence of the ostial valve on venous reflux in different body positions. Methods: Our study included 61 lower limbs with primary incompetence of the great saphenous vein (GSV). The diameter of the GSV and its cross-sectional area, time-averaged mean velocity (TAMEAN), and reflux time (RT) were measured with duplex ultrasound with pulsed wave Doppler. Reflux volume (RV) and reflux volume flow rate (Q) were calculated. The measurements were carried out in three body positions: horizontal, A; seated upright with stretched legs, B; and vertical, C. Distal automatic cuff compression-decompression (120 mm Hg) was used as a provocation maneuver. Results: There was 100% occurrence of reflux in the patient positions B and C. Reflux was observed in 91.8% of cases in position A. All reflux parameters (TAMEAN, RT, Q, RV) and the size of the vein were significantly different in the three studied positions. The patient's height did not influence the magnitude of change in reflux parameters. All reflux parameters increased more significantly when the position changed from A to B than from B to C (TAMEAN, +103% and +37%; GSV diameter, +33% and +5%; RV, +408% and +65%, respectively). Conclusions: Observed positional changes in reflux parameters suggest that gravitational forces are not a sole explanation for reflux flow in incompetent GSV. It is likely that the gravitational effect on venous flow is mediated by the changes in vein diameter and the total volume of the venous reservoir of the leg.

© 2019 Elsevier Ltd Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC. CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies. APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture. Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor. The data suggest that APC should be further investigated as a possible effective treatment for CNV.

© 2019 Elsevier B.V. To date, laser-induced forward transfer (LIFT) is one of the most developing areas in bioprinting. It is based on a precise nozzle-free laser-assisted hydrogel microdroplet transfer. Although this technique was first mentioned in the 1980s, it started to gain popularity in biomedicine only a decade ago. While the interest in LIFT bioprinting is constantly growing, it is essential to provide a framework of its possibilities and limitations. This review aims to facilitate the search for a common language between physicists and biologists and thus become a short guide to using LIFT technology for biomedicine. Here, we compared various points such as lasers, bioinks components, collector substrate, post-treatment, and printing processes that are crucial for LIFT bioprinting and applied in published studies on it. The core of this review is the discussion of biological and physical aspects to fabricate tissues and organs and the not-known difficulties that can be encountered during the laser printing process and were not given sufficient attention earlier.

© 2019, European Society of Radiology. Objectives: Invasive treatment of tumors adjacent to large hepatic vessels is a continuous clinical challenge. The primary aim of this study was to examine the feasibility of ablating liver tissue adjacent to large hepatic and portal veins with magnetic resonance imaging–guided high-intensity focused ultrasound (MRgHIFU). The secondary aim was to compare sonication data for ablations performed adjacent to hepatic veins (HV) versus portal veins (PV). Materials and methods: MRgHIFU ablations were performed in six male land swine under general anesthesia. Ablation cells of either 4 or 8 mm diameter were planned in clusters (two/animal) adjacent either to HV (n = 6) or to PV (n = 6), with diameter ≥ 5 mm. Ablations were made using 200 W and 1.2 MHz. Post-procedure evaluation was made on contrast-enhanced MRI (T1w CE-MRI), histopathology, and ablation data from the HIFU system. Results: A total of 153 ablations in 81 cells and 12 clusters were performed. There were visible lesions with non-perfused volumes in all animals on T1w CE-MRI images. Histopathology showed hemorrhage and necrosis in all 12 clusters, with a median shortest distance to vessel wall of 0.4 mm (range 0–2.7 mm). Edema and endothelial swelling were observed without vessel wall rupture. In 8-mm ablations (n = 125), heat sink was detected more often for HV (43%) than for PV (19%; p = 0.04). Conclusions: Ablations yielding coagulative necrosis of liver tissue can be performed adjacent to large hepatic vessels while keeping the vessel walls intact. This indicates that perivascular tumor ablation in the liver is feasible using MRgHIFU. Key Points: • High-intensity focused ultrasound ablation is a non-invasive treatment modality that can be used for treatment of liver tumors. • This study shows that ablations of liver tissue can be performed adjacent to large hepatic vessels in an experimental setting. • Liver tumors close to large vessels can potentially be treated using this modality.

© 2019 by author(s) and VsI Entrepreneurship and Sustainability Center. Corruption in various sectors causes serious damage not only to individual economies, countries, and regions but also to humanity as a whole. This paper analyzes the state of corruption in the Republic of Tatarstan, the manifestations of which restrain the development of the Republic, and presents the results of a pilot sociological study that demonstrate changes in the perception of problems of corruption in society. The sustainable development of a region is influenced by various economic and social factors. The results of this research show that one of these factors is corruption, which is often used as a tool for managing territories at various levels. It is a serious obstacle to the achievement of continuous sustainable development of a region, as it impedes the building of harmonious relations between state, government, society, and business. Sustainable development of a region can be described as a system and as a process. In this study, “sustainable development” refers to the process in which various stakeholder interactions take place that influence the established order of relations in the region. The findings suggest that when assessing the effectiveness of a region’s sustainable development, the level of corruption should be considered as an indicator of its stability. Some measures were proposed to improve the organization of anti-corruption work in the Republic of Tatarstan for leveling social tensions in society.

PURPOSE OF REVIEW: The human body is the host of trillions of different prokaryotic microorganisms that colonize the skin and the mucosae. The interaction between human cells and these organisms is mediated by the immune system, sustaining a very complex and fragile balance. The immune cells need to prevent uncontrolled growth of pathogenic microbes and promote tolerance toward the existence of the beneficial ones. Growing evidence associates the disruption of this symbiotic relationship with the development of autoimmune diseases. RECENT FINDINGS: Human studies led to the identification of gut dysbiosis patterns in patients with rheumatoid arthritis, lupus and multiple sclerosis. Interestingly, the inoculation of pathogenic bacteria in animal models was associated with the development of these autoimmune diseases. SUMMARY: A better understanding of the microbiota-human interaction will enable the development of novel treatment choices. Currently, new molecules using helminth compounds are under investigation and have already revealed promising results.

© 2019 Elsevier B.V. Lassa fever is a severe viral hemorrhagic illness caused by Lassa virus. Based on estimates, the number of LASV infections ranges from 300,000 to 500,000 cases in endemic areas with a fatality rate of 1%. Development of fast and sensitive tools for the control and prevention of Lassa virus infection as well as for clinical diagnostics of Lassa fever are crucial. Here we reported development and evaluation of a one-step quantitative RT-qPCR assay for the Lassa virus detection – LASV-Fl. This assay is suitable for the detection of lineages I-IV of Lassa virus. The limit of detection of the assay ranged from 103 copies/ml to 105 copies/ml and has 96.4% diagnostic sensitivity, whereas analytical and diagnostic specificities both were 100%. Serum, whole blood and tissue are suitable for use with the assay. The assay contains all the necessary components to perform the analysis, including an armored positive control (ARC+) and an armored internal control (IC). The study was done during the mission of specialized anti-epidemic team of the Russian Federation (SAET) in the Republic of Guinea in 2015-2018. Based on sequencing data, LASV-specific assay was developed using synthetic MS2-phage-based armored RNA particles, RNA from Lassa virus strain Josiah, and further, evaluated in field conditions using samples from patients and Mastomys natalensis rodents.

© 2019, Pediatria Ltd. All rights reserved. The article presents main pathogenetic factors of enuresis formation in children without malformations and diseases of the spine and spinal cord. 48 children were treated with cognitive and behavioral methods, based on formation of an age-related physiological regimen of fluid intake and urination. The drug of choice for drug therapy was desmopressin (Antikva Rapid) 120 mcg, efficacy was evaluated after 6 weeks of treatment by the number of night bedwetting per week. If its number was reduced by 50% or more from the original, then the drug dose remained the same. For children, whose proportion of night bedwetting was more than 50%, the desmopressin dose was increased by 60 mcg/ day. The total treatment course was 3 months. Treatment efficacy at the end of the course was evaluated by the “dry” period duration. If it was less than 14 days, a similar repeat course was planned. A correlation was found between the volume of nocturnal diuresis (ND) and the number of enuresis episodes per week, a decrease of these indicators by 32% at the stage of 1,5-month treatment and by 67% at the end of 3-month treatment was noted. DD showed a statistically significant increase, and ND a statistically significant decrease following the results of 1,5 and 3 months of treatment. After a 3-month course, a dry period of 14 days was observed in 16 children (33%). 2/3 of patients (67%) required a second course of treatment.

© 2019 Here we report that trypanosomatid flagellates of the genus Blastocrithidia possess catalase. This enzyme is not phylogenetically related to the previously characterized catalases in other monoxenous trypanosomatids, suggesting that their genes have been acquired independently. Surprisingly, Blastocrithidia catalase is less enzymatically active, compared to its counterpart from Leptomonas pyrrhocoris, posing an intriguing biological question why this gene has been retained in the evolution of trypanosomatids.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Ovarian cancer is fifth in the rankings of cancer deaths among women, and accounts for more deaths than any other gynecological malignancy. Despite some improvement in overall-(OS) and progression-free survival (PFS) following surgery and first-line chemotherapy, there is a need for development of novel and more effective therapeutic strategies. In this mini review, we provide a summary of the current landscape of the clinical use of tyrosine kinase inhibitors (TKIs) and mechanistic target of rapamycin (mTOR) inhibitors in ovarian cancer. Emerging data from phase I and II trials reveals that a combinatorial treatment that includes TKIs and chemotherapy agents seems promising in terms of PFS despite some adverse effects recorded; whereas the use of mTOR inhibitors seems less effective. There is a need for further research into the inhibition of multiple signaling pathways in ovarian cancer and progression to phase III trials for drugs that seem most promising.

© 2019 by the authors. Background: Vitamin D insuffciency is prevalent among athletes, and it can negatively affect physical performance. At the same time, most of the available data were obtained from untrained individuals of various ages, and published studies performed in athletes led to contradictory conclusions. Methods: This cohort prospective study examined the serum concentration of 25-hydroxycalciferol (25(OH)D) and its association with running speed and muscle power in 131 young football players (mean age 15.6 ± 2.4 years). Results: 25(OH)D levels were below reference in 42.8% (serum 25(OH)D <30 ng/mL) and above reference in 30.5% of the participants (serum 25(OH)D 61-130 ng/mL). A comparison of the results of 5, 15, and 30 m sprint tests and the standing long jump test found no statistically significant differences between the two groups. Athletes from the 25(OH)D-insuffcient group were treated with 5000 IU cholecalciferol supplement daily for 60 days. After the treatment, the 25(OH)D concentration increased by 79.2% and was within reference in 84% of the treated athletes (serum 25(OH)D 30-60 ng/mL). Testing was repeated after the end of treatment, and a statistically significant increase in the results of the 5, 15, and 30 m sprint tests was observed (Cohen’s d was 0.46, 0.33, and 0.34, respectively), while the results of the standing long jump test remained unchanged. Body height, body weight, and lean body mass of the football players also increased. Conclusions: These findings indicate that there is likely no correlation between serum levels of 25(OH)D, muscle power, and running speed in young professional football players, and the changes observed post-treatment might have been caused by changes in the anthropometric parameters. During the study, all the anthropometric parameters changed, but the amount of lean body mass only correlated with the results of the 5 m sprint.

© 2019, Pediatria Ltd. All rights reserved. Brain–lung–thyroid syndrome (BLTS) is a rare genetic disease associated with mutations in the NKX2.1 gene encoding thyroid transcription factor 1. The most common manifestations of this syndrome are benign hereditary chorea, hypothyroidism and respiratory distress syndrome, however, mutations in the NKX2.1 gene can also cause other pathologies of nervous, respiratory systems and thyroid gland. The article describes 4 patients with mutations in the NKX2.1 gene observed by authors. Based on the analysis of the observations of 168 patients with BLTS presented in the world literature from 1998 to 2019, current information on the genetics, pathogenesis, clinical X-ray manifestations, outcomes and treatment of the syndrome are summarized.

© 2019 European Association of Urology In this review, we investigated the treatment options for primary urethral cancer. While organ-confined disease can be managed with local resection, growth beyond the organ calls for a combination of different treatment modalities, such as surgery, chemotherapy, and radiotherapy, to improve the survival of patients.

© 2019 John Wiley  &  Sons Ltd Background: Human milk (HM) transforming growth factor beta (TGF-β) is critical for inflammation regulation and oral tolerance promotion. Previous reports suggested that variations in HM TGF-β levels are associated with allergic outcomes. Objective: We undertook a systematic review (PROSPERO 2017 CRD42017069920) to reassess the evidence on the relationships between HM TGF-β and allergic outcomes in children. Methods: Electronic bibliographic databases (MEDLINE, EMBASE and Cochrane Library) were systematically searched. Two independent reviewers screened reference lists, extracted the data and assessed risk of bias using the National Institute for Clinical Excellence methodological checklist. Results: A total of 21 studies were identified. Sixteen studies assessed relationships between HM TGF-β and risk of eczema; 14, allergic sensitization; nine, wheezing/asthma; six, food allergy; three, allergic rhinitis/conjunctivitis. Five cohorts (5/18, 28%) reported a protective effect of TGF-β1, while 3 (3/10, 30%) suggested increased risk of allergic outcomes development and 1 (1/10, 10%), a protective effect of TGF-β2 on eczema. Meta-analysis was not possible due to significant heterogeneity in methodology, age of outcome assessment and differing statistical approaches. 71% (15/21) of studies carried a high risk of bias. Conclusion and clinical relevance: In contrast with previous findings, we did not find strong evidence of associations between HM TGF-β and allergic outcomes. Differences in studies' methodology and outcomes do not allow unconditional rejection or acceptance of the hypothesis that HM TGF-β influences the risk of allergy development. Future studies on diverse populations employing standardized methods, accurate phenotyping of outcomes and evaluation of the effect of TGF-β in combination with other HM immune markers, microbiome and oligosaccharides are required.

© 2019 Elsevier GmbH Background: The objective of the study was to assess hair trace element and mineral content in children undergoing WFP UN and the governmental programs of school nutrition in Tajikistan. Methods: WFP program included provision or wheat flour fortified with micronutrients including Fe and Zn, and iodized salt, whereas within the governmental program hot meals were provided. A total of 202 children studying in schools that were not (Type 1, n = 100) or were involved in dietary intervention programs (Type 2, n = 102). Food and hair trace element content was assessed using ICP-MS. Results: Daily intake of Fe, I, Zn, B, Co, Mg, Si, and Sr in Type 2 schools was more than 2.5, 12, 4, 2.9, 2.6, 2, 3, and 2-fold higher than that in Type 1 schools. Correspondingly, anthropometric parameters in children from Type 2 schools exceeded the control values. Surprisingly, no significant difference in hair iodine levels was detected. Hair analysis demonstrated a significant increase in hair Ca, Mg, Na, Co, Cr, Cu, Fe, Li, Mn, Se, V, Zn content. Certain toxic elements including Al, As, and Be were also characterized by an increase in Type 2 schools. At the same time, nutritional intervention was associated with a significant decrease in hair B, Hg, and Sn levels. Conclusions: Nutritional intervention within WFP and the governmental program was effective in increasing essential trace element supply in Tajik schoolchildren. However, further studies including a detailed assessment of nutritional and health status with a special focus on iodine and thyroid functioning are required.