Репозиторий Университета

© 2018 The implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.

© 2018 Walter de Gruyter GmbH, Berlin/Boston. The focus of the study is to determine the prevalence of CYP2C19 alleles, associated with the risk of changes in the pharmacological response to clopidogrel and proton pump inhibitors in patients with acute coronary syndrome (ACS) and gastric ulcer from Russian and Yakut ethnic groups. The research included 411 patients with ACS (143 Russians and 268 Yakuts) and 204 patients with histologically confirmed gastric ulcer (63 Russians and 141 Yakuts). Genotyping of 681G>A and 636G>A polymorphisms was performed by using polymerase real-time chain reaction. In both ethnic groups, Hardy-Weinberg equilibrium was followed in a distribution of alleles and genotypes in the population (p>0.05). The 681A allele frequency in the Yakut ethnic group was higher than in the Russian group: 17.53% vs. 8.39% (p=0.001). No statistically significant difference was found in the frequency of 636A in Yakuts and Russians with ACS: 3.92% vs. 3.50% (p=0.840). While comparing the frequency distribution of alleles 681A (13.49% vs. 14.54%, p=0.878) and 636A (7.94% vs. 7.80%, p=1) in patients with a gastric ulcer from Russian and Yakut ethnic groups, no significant difference was found in carrier frequency. The results of the present study may be helpful for developing guidelines for CYPC19 genotype-directed antiplatelet therapy for Yakut and Russian patients.

© Am J Case Rep, 2018.  Objective: Unusual setting of medical care Background: Noninvasive assessment of the fractional flow reserve (FFR) in patients with coronary artery disease plays an important role in determining the need for revascularization. It is particularly relevant for patients with a borderline stenoses and painless myocardial ischemia. Our article describes the first clinical experience in the Russian Federation of using an automated method of noninvasive assessment of the fractional flow reserve (FFR ct ) with a one-dimensional (1-D) mathematical model in a patient with painless myocardial ischemia. Case Report: A 58-year-old male patient who underwent stent implantation in the left circumflex coronary artery (LCX) due to an acute non-ST-elevation posterior myocardial infarction had borderline stenoses of the left anterior descending artery (LAD). After stent implantation, there were no relapse angina symptoms on drug treatment, and according to our examination guideline for patients with borderline stenoses, a treadmill test was performed. The test was positive; therefore, FFR assessment was recommended, with coronary multi-slice CT being performed. The following results were obtained: FFR ct LAD – 0.57; FFR ct LCX – 0.88. An invasive assessment of FFR was also performed as a reference standard and revealed: FFR LAD – 0.6; FFR LCX – 0.88, and simultaneously a LAD percutaneous coronary intervention (PCI) was performed. Three months later, the patient underwent a stress test, which revealed no evidence of induced ischemia. Conclusions: Our method of noninvasive assessment of FFR has shown encouraging results, but we believe that larger-scale studies are needed to establish it as common clinical practice.

© 2018 Denisenko et al. Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation. Purpose: The aim of the study was to find if CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole. Patients and methods: Forty-eight gastric or duodenal ulcer patients (15 men, 33 women; mean age 55.0±15.3 years, age range 18–91 years) from Moscow region of Russia were enrolled. Peripheral venous blood was collected for DNA extraction, and real-time polymerase chain reaction was performed for CYP3A5*3A6986G (rs776746), CYP3A4*22 C>T in intron 6 (rs35599367), CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893), and CYP2C19*17C-806T (rs12248560) polymorphism analyses. Urine samples of patients were collected in the morning between 6 and 9 am before food or drug intake. Urine cortisol and 6β-hydroxycortisol concentrations (for CYP3A activity) and omeprazole and 5-hydroxyomeprazole concentrations (for CYP2C19 activity) were measured using high-performance liquid chromatography/mass spectroscopy. Results: We found a connection between CYP2C19 genotypes and CYP3A activity. Median metabolic ratios 6β-hydroxycortisol/cortisol (25%–75% percentiles) were 2.84 (1.99–4.39) for CYP2C19 extensive metabolizers (EMs), 2.51 (1.86–4.73) for CYP2C19 ultra-rapid metabolizers (UMs), and 1.45 (1.12–2.16) for CYP2C19 intermediate metabolizers (IMs) + poor metabolizers (PMs). A statistically significant difference in CYP3A activity (Mann–Whitney test) was found between CYP2C19 EMs vs CYP2C19 IMs+PMs (p=0.006), between CYP2C19 UMs vs CYP2C19 IMs+PMs (p=0.018), and in multiple comparison Kruskal–Wallis test (p=0.014). Conclusion: In CYP2C19 IMs+PMs, CYP3A activity was significantly lower than in CYP2C19 EMs and UMs.

© 2018 IEEE. The work is focused on the research of urea elimination possibilities out of the waste dialysis solution by its electro-oxidation on the surface of platinum group metals and carbon materials. The work includes findings of experimental tests of various electrode materials for the specific urea elimination rate in a model solution.

© 2018 IEEE. A hybrid mock circulatory loop (MCL) intended for training and study of engineers and physicians involved into ventricular assist devices design and development is described in this paper. Represented hybrid MCL allow to simulate different cardiovascular conditions including normal and heart failure states.

© 2018 IEEE. The paper presents an algorithm of system identification for implantable rotary blood pumps. The algorithm allows to build mathematical models in accordance with the quality metric introduced to assess the effectiveness of identification. The quality metric was set as an error of pump flow estimation. In the result the mathematical models were identified using experimental dataset for two different rotary blood pumps Sputnik. The identified model of Sputnik 1 characterizes by the mean error about 0.12 L on the control set, the identified model of updated pump-Sputnik 2-mean error about 0.14 L. The identified models intended for control of pump flow during in vitro trials.

© 2018 IEEE. The possibility of noninvasive detection of magnetic particles in biological objects has been investigated. It has been found that magnetic particles, including magnetite, hematite, and catalytic iron particles in carbon nanotubes, can be detected by ultrasensitive magnetic field sensors with resolutions of 10-8-10-14 T. This research direction is shown to be promising for noninvasive monitoring of organs, implants, prosthesis, and other elements of biological systems.

© 2018 IEEE. In accordance with the results of the analysis of the current status of the medical industry in Russia, the methodical approach to the assessment of the feasibility of medical device creation project has been developed based on the calculation of the potential socio-economic impact of the implementation of medical devices by the cost of illness method, which includes the model and evaluation methodology and allows to make formalized quantitative assessment of the positive effect of the implementation of medical devices, to compare the potential impacts of the implementation of different medical devices being developed with the costs of the creation of medical device, as well as to prioritize medical device creation projects in the portfolio.

© 2018 IOP Publishing Ltd. The integration of energy harvesting and energy storage in a single device both enables the conversion of ambient energy into electricity and provides a sustainable power source for various electronic devices and systems. On the other hand, mechanical flexibility, coupled with optical transparency of the energy storage devices, is required for many applications, ranging from self-powered rolled-up displays to wearable optoelectronic devices. We integrate a piezoelectric poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)) film into a flexible supercapacitor system to harvest and store the energy. The asymmetric output characteristics of the piezoelectric P(VDF-TrFE) film under mechanical impacts results in effective charging of the supercapacitors. The integrated piezo-supercapacitor exhibits a specific capacitance of 50 F g-1. The open-circuit voltage of the flexible and transparent supercapacitor reached 500 mV within 20 s during the mechanical action. Our hybridized energy harvesting and storage device can be further extended to provide a sustainable power source for various types of sensors integrated into wearable units.

© 2018 Contemporary Clinical Dentistry | Published by Wolters Kluwer - Medknow. Background: The success of endodontic treatment depends on the knowledge of root canal system. The root canals have complex morphology and wide individual variations. The aim of this study was to evaluate the root canal morphology of the maxillary first molars among residents of the Moscow region using cone-beam computed tomography (CBCT) scanning. Materials and Methods: Three hundred CBCT images of patients aged 20-70 years old were analyzed to study the root canal system (the number of canals and the configuration according to Vertucci's classification) of the maxillary first molars. The prevalence of a second mesiobuccal (MB2) in the mesiobuccal root (MB) was recorded in each age group. Results: three separated roots of the maxillary first molar were observed in 100% of cases. MB2 canals were found in 59.8% of cases. A second distobuccal canal was observed in 0.5% of cases. The canal morphology in the MB root was 40.2% in Type I, 22.4% in Type II, and 37.3% in Type IV. Conclusion: The prevalence of MB2 canals was 59.8%, and the most common canal morphology was Vertucci's Type I. Using CBCT scanning is a useful technique to evaluate and analyze the root canal system.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (Cmax) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The levels of pollution by heavy metals and arsenic in top soil layers and medicinal plant raw materials in Voronezh Region were studied using Urtica dioica and Plantago major leaves as examples. The analyses were carried out using atomic absorption spectrometry on a graphite-furnace MGA-915MD spectrometer. Samples were collected from districts with different anthropogenic impacts across the whole region. Leaves of P. major characteristically had the highest coefficients of accumulation from the soil for Cd, As, and Ni. Leaves of U. dioica typically had high accumulation coefficients for Ni.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective: The article studies state-of-the art physical therapeutic techniques as a high degree of relevance to minimize invalidation and improve quality of life for patients with dental osteosarcoma. Materials and Methods: A randomized controlled clinical trial was conducted in 21 patients with osteogenic sarcoma of mandible (C41.1). There were 10 patients in the experimental group and 11 patients in the control group. Results: A comprehensive treatment and rehabilitation program for patients with osteosarcoma of mandible was developed. The first part of the program comprised 3 basic phases: preop chemotherapy, surgery, and postop rehabilitation. The surgical treatment further included resection of an affected part of the mandible and primary repair of the defect with jaw fragments and an autoimplant joined together with the help of positioning devices. The postop rehabilitation included postop chemotherapy and mesodiencephalic modulation (MDM). The second part of the program comprised preop examination, modeling, using stereolytic 3-dimensional models of the mandible, corrective surgeries, including implantation into the auto-implantda fragment of patient’s fibula, and building of a removable titanium alloy–based denture. MDM sessions were administered after each invasive intervention. Conclusions: Higher psychological and physical well-being was observed in the experimental group as compared with the control group (P, 0.01) in 2 weeks after the first surgery and 2 months after scheduled corrective surgeries, which finished in denture installation.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the biochemical composition of the tear film is a critical risk factor for the development of chronic perioperative dry eye syndrome, because increasing the duration of general anesthesia did not affect the dynamics of tear secretion recovery, but slowed down normalization of its structure and antioxidant activity in the post-anesthetic period.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the frequency characteristics of EEG alpha rhythm in during falling asleep were studied in three healthy individuals under conditions of long-term isolation (MARS-500 project). Falling asleep was preceded by enhanced alpha rhythm frequency. An inverse correlation between the duration of falling asleep and prevailing alpha rhythm frequency during active and relaxed wakefulness was revealed in the left hemisphere. These results demonstrate the principal possibility of predicting the duration of falling asleep by using alpha rhythm spectral analysis. It is assumed that the frequency of the alpha range spectral peak can be a marker of drowsiness and reflect the current need for sleep.

© 2018 by the authors. Composite fibers and films based on cellulose and betulin were spun for the first time from solutions in N-methylmorpholine-N-oxide using the dry-wet jet method. The rheological properties of the composite solutions did not reveal any fundamental difference from those of the cellulose solutions. Introduction of betulin into the cellulose matrix (up to 10%) led to a decrease in the mechanical properties of the obtained fibers. The structure of the composite fibers was analyzed using SEM and X-ray diffraction methods. It was shown that the introduction of an additive into the cellulose matrix led to a decrease in the structural ordering of the cellulose. Comparative studies of the antibacterial activity of the composite films on Escherichia coli (E. coli) were carried out. The antifungal activity of the composite films was estimated using the strain of the O-97 Trichoderma viride Pers ex Fr (Gause Institute of New Antibiotics, Moscow, Russia).

© 2018  Extensive scar tissue formation often occurs after severe burn injury, trauma, or as one of complications after surgical intervention. Despite significant therapeutic advances, it is still a significant challenge to manage massive scar tissue formation while also promoting normal wound healing. The goal of this study was to investigate the therapeutic effect of bone mesenchymal stem cells (BMSCs) that were genetically modified to overexpress transforming growth factor-beta 3 (TGF-β 3 ), an inhibitor of myofibroblast proliferation and collagen type I deposition, on full-thickness cutaneous wound healing in a rabbit model. Twenty-four rabbits with surgically-induced full-thickness cutaneous wounds created on the external ear (1.5 × 1.5 cm, two wounds/ear) were randomized into four groups: (G1), wounds with no special treatment but common serum-free culture medium as negative controls; (G2), topically-applied recombinant adenovirus, expressing TGF-β 3 /GFP; (G3), topically-applied BMSCs alone; (G4), topically-applied BMSCs transfected with Ad-TGF-β 3 /GFP (BMSCs TGF-β3 ); and (G5), an additional normal control (n = 2) with neither wound nor treatment on the external ear skin. The sizes of wounds on the ear tissues were grossly examined, and the scar depth and density of wounds were histologically evaluated 21, 45, and 90 days after surgical wound creation. Our results demonstrated that G4 significantly reduced the wound scar depth and density, compared to G1~3. Numbers of cells expressing GFP significantly increased in G4, compared to G2. The protein expression of TGF-β 3 and type III collagen in G4 significantly increased, while the ratio of type I to type III collagen was also significantly reduced, which is similar to the tissue architecture found in G5, as compared the other treatment groups. In conclusion, transplantation of BMSCs TGF-β3 remarkably improves wound healing and reduces skin scar tissue formation in an animal model, which may potentially provide an alternative in the treatment of extensive scar tissue formation after soft tissue injury.

© 2017 Elsevier B.V. Background: Hospitalization is an opportunity to optimize heart failure (HF) therapy. As optimal treatment for hospitalized HF patients in sinus rhythm with heart rate ≥ 70 bpm is unclear, we investigated the impact of combined beta-blocker (BB) and ivabradine versus BBs alone on short and longer term mortality and rehospitalization. Methods and results: A retrospective analysis was performed on 370 hospitalized HF patients with heart rate ≥ 70 bpm (150 BB + ivabradine, 220 BB alone) in the Optimize Heart Failure Care Program in Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Russia, Ukraine, and Uzbekistan, from October 2015 to April 2016. Results: At 1 month, 3 months, 6 months and 12 months, there were fewer deaths, HF hospitalizations and overall hospitalizations in patients on BB + ivabradine vs BBs alone. At 12 months, all-cause mortality or HF hospitalization was significantly lower with BB + ivabradine than BBs (adjusted hazard ratio [HR] 0.45 (95% confidence interval [CI] 0.32–0.64, P < 0.0001). Significantly greater improvement was seen in quality of life (QOL) from admission to 12 months with BB + ivabradine vs BBs alone (P = 0.0001). With BB + ivabradine, significantly more patients achieved ≥ 50% target doses of BBs at 12 months than on admission (82.0% vs 66.6%, P = 0.0001), but the effect was non-significant with BBs alone. Conclusions: Heart rate lowering therapy with BB + ivabradine started in hospitalized HF patients (heart rate ≥ 70 bpm) is associated with reduced overall mortality and re-hospitalization over the subsequent 12 months. A prospective randomized trial is needed to confirm the advantages of this strategy.

© 2018 National Academy of Sciences. All rights reserved. Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.