Репозиторий Университета

© 2019, Indian Association of Surgical Oncology. The role of surgery in the management of metastatic gastric cancer (MGC) remains unclear. The aim of this study was to investigate the surgical and oncologic outcomes of gastrectomy in patients with MGC. The study included prospectively collected data of patients with MGC operated at four medical centers in Yerevan, Armenia, between 2000 and 2014. Armenian National Center of Oncology Registry and hospital records were used to obtain survival data. Factors associated with performing gastrectomy in patients with MGC were analyzed by using the logistic regression model. The Kaplan-Meier method was applied for survival analysis, and the Cox regression model with backward selection was used for multivariate analysis. A total number of 733 patients were operated for gastric cancer including 112 (15.3%) with MGC. Of those, 70 underwent gastrectomy, while 42 had exploratory laparotomy or bypass. Morbidity and mortality were similar after gastrectomy and exploratory laparotomy/bypass (18.6 vs 21.4%, p = 0.71 and 2.9 vs 7.1% p = 0.36, respectively). Female gender, involvement of N1 and/or N2 lymph node stations, and differentiated adenocarcinoma were associated with opting for gastrectomy. Gastrectomy with synchronous resection of distant metastases resulted in postoperative outcomes similar to those following gastrectomy without synchronous organ resection. Median follow-up was 6 months. Eighteen (16.1%) patients received chemotherapy. Median survival following gastrectomy and exploratory laparotomy/bypass were 7 and 4 months (p = 0.015), respectively. The use of chemotherapy following gastrectomy significantly improved survival compared with gastrectomy only (14 vs 6 months, p = 0.01). In the multivariable analysis, chemotherapy and nodal stage correlated with survival after gastrectomy. Gastrectomy for MGC is associated with satisfactory surgical outcomes and can be combined with synchronous resection of distant metastases in selected patients. Gastrectomy results in longer survival compared with exploratory laparotomy/bypass, especially when followed by chemotherapy.

© 2019 The Author(s). Background: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. Material and methods: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. Results: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. Conclusion: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.

© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.

In recent years scientists actively study the influence of domestic violence on psychological status and occurrence of mental disorders in women and girls. Psychological, physical, sexual and other types of violence are distinguished, the consequences of which are studied in many countries under the auspices of WHO. In international studies the serious consequences of domestic violence for women are investigated. It was found out that women develop stressful disorders, depression and dependence on psychoactive substances. Negative influence of domestic violence at girls is expressed in formation of behavioral disorders, violations of sexual development, suicidal trends. At analysis of consequences of domestic violence by WHO was developed the concept of "cycle of violence" and cruelty inside family when in process of long influence of psychological traumatic factors at women and girls aggressive actions occurred so that victim and aggressor changed places. The objective of the study was to analyze the current state of the problem on the basis of the literature data, to study the data on the consequences of domestic violence and cruelty against women and girls, to identify gender-specific violations.

One demographic indicator is the structure of mortality by cause. Analysis of the causes of death allows you to define the fight against the disease, efforts should be focused to reduce mortality and on the effectiveness of measures against those or other diseases. The basis of information about the causes of death is a medical certificate of death, filling it depends on the correct diagnosis, the choice of the original cause of death, coding, as well as on policy documents aimed at reducing mortality from a particular cause. In the Russian Federation, in contrast to the countries of the European region, there is a fairly high proportion of inaccurately marked conditions, which account for 6.9% of all causes (in 2010 - 5%), the main reason for this is «old age», which ranks 4th among the leading causes of death (5% of all causes, in 2010 - 2.8%), as well as damage with uncertain intentions, which are on the 7th rank place of the leading causes of death (2.3% of all causes, in 2010 - 2%).

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Modern antimicrobial preservatives authorized for use in dosage form technology are reviewed. The nomenclature and various classifications of preservatives according to chemical nature, mechanism and spectrum of antimicrobial action, optimum effective concentrations for antimicrobial activity, and separate factors affecting the activity of antimicrobial preservatives in various dosage forms, e.g., optimum solution pH values and specific adsorbents reducing preservative activity, are presented. Antimicrobial preservatives used widely in pharmaceutical technology, i.e., parabens, sorbic acid and its salts, benzoic acid and its salts, and benzalkonium chloride, are discussed in detail. Ascience-based approach to selecting antimicrobial preservatives is shown to produce the most stable and safest medicines.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. There is a pressing clinical need for advanced colon-specific local drug delivery systems that can provide major advantages in treating diseases associated with the colon, such as inflammatory bowel disease (IBD) and colon cancer. A precise colon targeted drug delivery platform is expected to reduce drug side effects and increase the therapeutic response at the intended disease site locally. In this study, we report the fabrication of hyaluronan (HA) functionalized polymeric hybrid nanoparticulate system (Cur-HA NPs) by using curcumin as a model fluorescent drug. The Cur-HA NPs were about 200–300 nm in size, −51.3 mV overall surface charge after HA functionalization, with 56.0% drug released after 72 h in simulated gastrointestinal fluids. The Cur-HA NPs did not exhibit any cytotoxicity by AlamarBlue, PicoGreen and Live/Dead assays. Following the Cur-HA NPs use on HT-29 monolayer cell cultures demonstrating, the efficacy of HA functionalization increases cellular interaction, uptake when compared to uncoated nanoparticulate system. These findings indicate that HA functionalized nano-hybrid particles are effective in delivering drugs orally to the lower gastrointestinal tract (GIT) in order to treat local colonic diseases.

© 2019, Pediatria Ltd. All rights reserved. Objective of the research: To study the effect of different temperature conditions and shelf life of expressed mother and donor breast milk (BM) on its microbiological safety. Materials and methods: N open prospective study was performed, which included 120 lactating women. BM samples were microbiologically evaluated under various storage conditions. Seeding of biological material was performed by a semi-quantitative method. Species identification of the obtained microorganisms was performed using a MALDI-TOF-MS Biotyper MicroFlex mass spectrometer and a VITEK bacteriological analyzer. Results: In 66% of women, samples of expressed BM showed an increase (103–105 CFU/ml) of conditionally pathogenic bacteria (CPB) with a predominance of S. epidermidis (55%). None of the samples of the expressed BM stored for 3 hours at room temperature (t° + 23°C) during the day in the refrigerator (t° + 4–6°C) and for 1 month in the freezer (t ° –18°C), the growth of CPB was not recorded. However, a decrease in the growth of bacteria total number was revealed, including S. epidermidis, when storing expressed milk for 24 hours at t° + 4–6°С and for 1 month at t° –18°С. It was found that BM pasteurization leads to a significant decrease in the number of CPB. The study revealed no increase in the total number of bacteria during storage of donor milk at t° –18°C for both 1 and 3 months.

© 2019 Institution of Chemical Engineers Enabling technologies have led to the design of new extraction protocols for naturally occurring compounds that are fast, sustainable and have low energy demands. Ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) have been used, in this study, for the recovery of valuable nutraceuticals and primary metabolites from pumpkin seeds (Curcubita sp.) and have been compared with conventional methods. In order to optimise extraction parameters and conditions, we have compared yields, total phenolic content, antioxidant activity, as well as fatty-acid and lipid profiles. The best yield, in both lipophilic and hydrophilic compounds, was achieved under UAE with a ternary solvent mixture (hexane/ethanol/water - 30:49:21). However, the highest phenolic content and antioxidant capacity were obtained using MAE under subcritical conditions with good extraction yields. The oil composition, as obtained using GC-FID analyses, showed a prevalence for unsaturated fatty acids; mainly linoleic and oleic acids. The use of UAE with ternary mixtures presented the highest lipid content and a slightly higher percentage of unsaturated compounds. Preliminary tests to verify the scalability of UAE with a ternary mixture showed that the extraction performance was maintained when using larger volumes (factor 10). This study will pave the road for the potential exploitation of UAE as a fast and efficient procedure for the simultaneous recovery of lipophilic and hydrophilic compounds from pumpkin seeds.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Acid-sensing ion channel (ASIC) channels belong to the family of ligand-gated ion channels known as acid-sensing (proton-gated) ion channels. Only a few activators of ASICs are known. These are exogenous and endogenous molecules that cause a persistent, slowly desensitized current, different from an acid-induced current. Here we describe a novel endogenous agonist of ASICs-peptide nocistatin produced by neuronal cells and neutrophils as a part of prepronociceptin precursor protein. The rat nocistatin evoked currents in X. laevis oocytes expressing rat ASIC1a, ASIC1b, ASIC2a, and ASIC3 that were very similar in kinetic parameters to the proton-gated response. Detailed characterization of nocistatin action on rASIC1a revealed a proton-like dose-dependence of activation, which was accompanied by a dose-dependent decrease in the sensitivity of the channel to the protons. The toxin mambalgin-2, antagonist of ASIC1a, inhibited nocistatin-induced current, therefore the close similarity of mechanisms for ASIC1a activation by peptide and protons could be suggested. Thus, nocistatin is the first endogenous direct agonist of ASICs. This data could give a key to understanding ASICs activation regulation in the nervous system and also could be used to develop new drugs to treat pathological processes associated with ASICs activation, such as neurodegeneration, inflammation, and pain.

© 2019 Background: The aim of this meta-analysis was to determine whether transanal total mesorectal excision (taTME) improves histopathology metrics and/or complication rates when compared to robotic total mesorectal excision (R-TME) of resectable rectal cancer. Methods: MEDLINE, Pubmed, Cochrane Library, and Scopus were systematically searched by two independent researchers. Six observational studies totaling 1,572 patients (811 taTME; 761 R-TME) were included after screening 14 potentially eligible records. Mantel-Haenszel method using odds ratios with 95% confidence intervals (OR (95%CI)) and inverse variance with mean difference with 95% confidence intervals (MD (95%CI)) as an effect measure for dichotomous and continuous variables, respectively, was employed for meta-analysis. Statistical heterogeneity among effect estimates was evaluated using I2 and Tau2. Results: Circumferential resection margin (CRM) involvement rates (3.8% taTME; 5.3% R-TME) did not differ [OR (95%CI) = 0.86 (0.35, 2.15); p = 0.75] with low among-study heterogeneity (I2 = 21%). Complication rates (35.4% taTME; 32.3% R-TME) did not differ [OR (95%CI) = 0.92 (0.64, 1.32); p = 0.65], although with moderate among-study heterogeneity (I2 = 40%). CRM involvement [OR (95%CI) = 0.76 (0.40, 1.43); p = 0.40] and complication rates [OR (95%CI) = 0.84 (0.59, 1.21); p = 0.35] did not significantly differ in subgroup meta-analysis including mid- and low rectal cancer. Distal resection margin (mm) did not significantly differ between the interventions [MD (95%CI) = −0.41 (−1.29, 0.47); p = 0.37]. Conclusions: This meta-analysis found that taTME of rectal cancer does not improve histopathology metrics and complication rates when compared to R-TME.

The acute stroke is one of leading causes of mortality and disability both in Russia Federation and worldwide. The specialized vascular centers and units proved to be effective in improving diagnostics, treatment and functional outcome inpatients in various countries. The purpose of article is to evaluate efficacy of regional vascular center (RVC) in Tyumen. The functioning of RVC in 2011-2017 was assessed using purposefully developed and implemented score card of medical care quality assessment in vascular centers. The epidemiological data for 2007-2017 was obtained from statistical materials of the Department of Health of Tyumen oblast. The epidemiological parameters were calculated both in absolute units by simple summing up of cases of illness and in relative units per number of population. It was established that all diagnostic and treatment procedures in RVC were implemented according actual medical standards. The significant increase of the percentage of patients hospitalized during first three hours after the onset of stroke symptoms was established. The patients receiving thrombolytic therapy was observed, with an improvement of functional status of patients upon discharge. The significant improvement of early diagnosis of cerebrovascular diseases (CVD) in the service area of RVC was demonstrated. The development and implementation of the plan of a regional vascular center placement and stroke patient routing enabled optimization of medical care accessibility to this group of patients and increased identification of CVD.

© 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, 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.

© 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, 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 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 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.