Репозиторий Университета

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. A growing number of studies are focusing on the associations between human milk (HM) immunological composition and allergic diseases. This scoping review aims to identify statistical methods applied in the field and highlight pitfalls and unmet needs. A comprehensive literature search in MEDLINE and Embase retrieved 13,607 unique records. Following title/abstract screening, 29 studies met the selection criteria and were included in this review. We found that definitions of colostrum and mature milk varied across the studies. A total of 17 out of 29 (59%) studies collected samples longitudinally, but only 12% of these used serial (longitudinal) analyses. Multivariable analysis was used in 45% of the studies, but statistical approaches to modelling varied largely across the studies. Types of variables included as potential confounding factors differed considerably between models. Discrimination analysis was absent from all studies and only a single study reported classification measures. Outcomes of this scoping review highlight lack of standardization, both in data collection and handling, which remains one of the main challenges in the field. Improved standardization could be obtained by a consensus group of researchers and clinicians that could recommend appropriate methods to be applied in future prospective studies, as well as already existing datasets.

© 2019 John Wiley  &  Sons, Ltd. Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

© 2019 Elsevier Ltd Schizophrenia is a severely debilitating, lifelong psychiatric disorder affecting approximately 1% of global population. The pathobiology of schizophrenia remains poorly understood, necessitating further translational research in this field. Experimental (animal) models are becoming indispensable for studying schizophrenia-related phenotypes and pro/antipsychotic drugs. Mounting evidence suggests the zebrafish (Danio rerio) as a useful tool to model various phenotypes relevant to schizophrenia. In addition to their complex robust behaviors, zebrafish possess high genetic and physiological homology to humans, and are also sensitive to drugs known to reduce or promote schizophrenia clinically. Here, we summarize findings on zebrafish application to modeling schizophrenia, as well as discuss recent progress and remaining challenges in this field. We also emphasize the need in further development and wider use of zebrafish models for schizophrenia to better understand its pathogenesis and enhance the search for new effective antipsychotics.

© 2019 by author(s). The purpose of the study was to analyze the medical representatives' activities aimed on information support for promoted medications. The assessment of the medical representatives' activity by doctors, pharmacists, and chemists was used to do so. The following methods of the study were used: Comparative, structural and system analysis, as well as sociological methods of research (survey and interview). As a result of the study, it has been found that the activity of medical representatives is one of the main ways to obtain information about medications by medical or pharmaceutical workers, but the objectivity and completeness of the information received largely depends on the contact frequency and trust in the information materials provided. Following the results of the study, recommendations have been developed for improving the activities of medical representatives and their interaction with pharmaceutical organizations and doctors.

© 2019 Elsevier B.V. SERS substrate containing SERS-active array of Ag, Au and Ag50Au50 nanoparticles with normal size distribution, a mirror layer and a separating SiO2 layer was optimized. A layer of amorphous carbon was used as the object of study. It is shown that such a structure enhances the Raman signal both due to the localized surface plasmon resonance and due to interference. The average size of nanoparticles, the reflection coefficient of mirror layer, and the thickness of SiO2 layer influence the amplification of the Raman signal. To provide amplification the thickness of SiO2 layer should be calculated for the appropriate wavelength in order to get constructive interference. It is revealed that additional amplification of the Raman signal occurs if the mirror layer as well as the array of particles is made of plasmon metal and thickness of separating SiO2 layer is quite small (up to 30 nm).

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Neurovirulent enterovirus 71 (EV-A71) caused a massive epidemic in China in 2008-2011. While subgenotype C4 was the major causative agent, a few isolates were almost identical to the prototype EV-A71 strain and belonged to genotype A. This variant was allegedly extinct since 1970, and its identification in this epidemic suggests reintroduction of the archive virus. Regression analysis of genetic distances (TempEst software) was of moderate utility due to the low resolution of classical phylogenetic methods. Bayesian phylogenetic analysis (BEAST software) suggested artificial introduction event based on highly aberrant phylogenetic tree branch rates that differed by over three standard deviations from the mean substitution rate for EV71. Manual nucleotide-level analysis was used to further explore the virus spread pattern after introduction into circulation. Upon reintroduction, the virus accumulated up to seven substitutions in VP1, most of them non-synonymous and located within the capsid's canyon or at its rims, compatible with readaptation of a lab strain to natural circulation.

© Copyright © 2019 Krasil’nikova, Surin, Sorokina, Fisenko, Boyarkin, Balyasin, Demchenko, Pomytkin and Pinelis. Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.

© 2019 Elsevier Ltd Sandpiles are ubiquitous in nature and engineering applications but still not fully understood due to the complexity of structures and materials properties. This work presents a systematic study on the piles of Platonic solids using the discrete element method (DEM), mainly focusing on the effect of particle shape on the repose angles and bottom pressure distributions of the piles. Five Platonic particles (tetrahedron, cube, octahedron, dodecahedron, and icosahedron) were discharged to form wedge-shaped piles. It was found that the repose angle did not increase with the decrease of particle sphericity. The pile formed by the cubes had the maximum repose angle and its bottom stress dip phenomena were more significant in terms of dip width and depth than that of other particle piles. The pressure distributions at different heights of the piles were quite similar to those of the whole piles, while the shear stress distributions near the boundaries exhibited different characteristics for the cube piles. The analyses of packing structures in terms of coordination number, radial distribution function, as well as contact types inside the piles were discussed to understand the change of pressure dips. The influence of static friction on the repose angle was more significant and it enhanced the stress dip phenomenon.

© 2019 Inter-Research. Sponges are considered promising sources of biomolecules for both pharmaceutical and cosmetic interests as well as for the production of biomaterials suitable for tissue engineering and regenerative medicine. Accordingly, the ability to grow sponges in captivity and in healthy conditions to increase their biomass is a required goal for the development of sponge aquaculture systems. To date, little information is available about the pathogenicity of fungi associated with sponges. In our study, we identified an infection in freshly collected specimens of Chondrosia reniformis (Porifera, Demospongiae) and determined that the fungus Aspergillus tubingensis was the pathogen responsible. This is the first description of a natural infection of C. reniformis by A. tubingensis. Despite raising an inflammatory response by means of an increase in tumour necrosis factor (TNF) mRNA, the infected C. reniformis specimens were not able to control the fungal infection, leading to rotting in 15 d. Characterization of this infection shows that a widely distributed fungus can represent a potential hazard to sponge aquaculture industries and how, especially in stressed or compromised marine environments, this fungus could represent a fatal opportunistic pathogen.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Objectives. To study the expression of various neurotransmitter transporters (glutamate, aspartate, lactate, choline) in cultures of astrocytes from different part of the brain (cortex, hippocampus, and brainstem) in rats aged three and 11 days. Materials and methods. An experimental study was performed using 24 Rattus norvegicus rats aged three (n = 12) and 11 days (n = 12). High-throughput sequencing results were analyzed. Results. Expression of the glutamate and aspartate transporters in the brainstem in three-day-old rats was greater than in other areas, though the reverse pattern was seen in rats aged 11 days. Expression of the lactate transporter with age was identical to that in the cortex. Conclusions. The data obtained here demonstrated the nature of neuroastrocyte relationships and the role of astrocytes in the process of signal transmission. The results of the study, carried out using original methods of investigating neurotransmitter transporters, allow them to be recommended for monitoring the processes of neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.

© 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.

© 2018, © 2018 Japan College of Rheumatology. Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3–6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3–9) months (p =.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p =.045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.

The article presents technique of calculation of the planned volume of outpatient care consumed by population of the subject of the Russian Federation considering demographic structure and level of morbidity. The formulas are presented developed for calculating financial costs of outpatient care and treatment in day hospital to be included into of mandatory health insurance program.

© 2019, Pediatria Ltd. All rights reserved. Acute kidney damage (AKD) is characterized by rapidly progressing organ dysfunction, which often results in development of chronic kidney disease. There are difficulties in diagnosing initial stages of kidney damage, which are usually reversible. Molecular diagnostics is a sensitive method that can detect early nephron changes that are not detectable by conventional methods (by assessing serum creatinine and urinary albumin in urine, diuresis) before renal filtration function decrease. The review examines markers of AKD development key stages: Ischemia (Kidney Injury Molecule-1 (KIM-1), Clusterin), hypoxia (Vascular Endothelial Growth Factor), Hypoxia Inducible Factor (HIF)), inflammation (Monocyte Chemoattractact Protein-1 (MCP-1), Interleukin 18 (IL18)), kidney tubule damage proximal (Beta-2-Microglobulin (B2M), Cystatin C, Neutrophil gelatinase associated lipocalin (NGAL)), distal (NGAL, Calbindin, Osteopontin). The study of these biomarkers in children's urine can be recommended for non-invasive screening, diagnosis and monitoring of AKD.

© 2019, Pediatria Ltd. All rights reserved. Attention deficit hyperactivity disorder (ADHD) is an urgent problem due to the high incidence rate, reaching 3–5% in the child population. The article discusses diagnostic criteria for ADHD and manifestation peculiarities in different age periods. It also duscusses etiopathogenesis of ADHD as a multifactorial developmental disorder; reviews main groups of drugs used for the pharmacological correction of the disease, among which nootropics, in particular aminophenylbutyric acid («Anvifen»), occupy a special place. Author discusses and justifies the need for an integrated approach to ADHD treatment, which should combine pharmacotherapy, neuropsychological correction and psychotherapy with a child, parents and teachers.

© 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.

© 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, Pediatria Ltd. All rights reserved. Urinary tract infection (UTI) is one of the most common diseases of the urinary system faced by pediatricians. Objective of the research: To study and analyze outpatient records of patients in their first year of life, sent to a nephrologist for a consultation due to microbial inflammatory changes in urine general analysis. Materials and methods: Outpatient records of 160 children aged from 1 month to 1 year, who were sent in 2017 for a consultation with a nephrologist in consultative diagnostic clinic of G.N. Speransky City Children's Hospital № 9 with directing diagnosis UTI. Results: Authors performed an assessment of guiding diagnoses, age and gender composition of patients, an assessment of life anamnesis and disease clinical symptoms dynamics before referring patients for consultation with a nephrologist. The article discusses mistakes and issues of diagnosing UTI in young children. Conclusion: Authors substantiates pediatrician’s tactics for timely UTI diagnosis in young children and correct tactics of managing these patients.

© 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.