Basketball players possess a higher bone mineral density than matched non-athletes, swimming, soccer, and volleyball athletes: a systematic review and meta-analysis
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01.12.2020 |
Stojanović E.
Radovanović D.
Dalbo V.J.
Jakovljević V.
Ponorac N.
Agostinete R.R.
Svoboda Z.
Scanlan A.T.
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Archives of Osteoporosis |
10.1007/s11657-020-00803-7 |
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© 2020, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: Basketball athletes possess a higher bone mineral density (BMD) than matched non-athletes and swimming, soccer, and volleyball athletes. Differences appear to be exacerbated with continued training and competition beyond adolescence. The greater BMD in basketball athletes compared to non-athletes, swimming, and soccer athletes is more pronounced in males than females. Purpose: The aim of this study was to examine differences in total and regional bone mineral density (BMD) between basketball athletes, non-athletes, and athletes competing in swimming, soccer, and volleyball, considering age and sex. Methods: PubMed, MEDLINE, ERIC, Google Scholar, and Science Direct were searched. Included studies consisted of basketball players and at least one group of non-athletes, swimming, soccer, or volleyball athletes. BMD data were meta-analyzed. Cohen’s d effect sizes [95% confidence intervals (CI)] were interpreted as: trivial ≤ 0.20, small = 0.20–0.59, moderate = 0.60–1.19, large = 1.20–1.99, and very large ≥ 2.00. Results: Basketball athletes exhibited significantly (p < 0.05) higher BMD compared to non-athletes (small-moderate effect in total-body: d = 1.06, CI 0.55, 1.56; spine: d = 0.67, CI 0.40, 0.93; lumbar spine: d = 0.96, CI 0.57, 1.35; upper limbs: d = 0.70, CI 0.29, 1.10; lower limbs: d = 1.14, CI 0.60, 1.68; pelvis: d = 1.16, CI 0.05, 2.26; trunk: d = 1.00, CI 0.65, 1.35; and femoral neck: d = 0.57, CI 0.16, 0.99), swimming athletes (moderate-very large effect in total-body: d = 1.33, CI 0.59, 2.08; spine: d = 1.04, CI 0.60, 1.48; upper limbs: d = 1.19, CI 0.16, 2.22; lower limbs: d = 2.76, CI 1.45, 4.06; pelvis d = 1.72, CI 0.63, 2.81; and trunk: d = 1.61, CI 1.19, 2.04), soccer athletes (small effect in total-body: d = 0.58, CI 0.18, 0.97), and volleyball athletes (small effect in total-body: d = 0.32, CI 0.00, 0.65; and pelvis: d = 0.48, CI 0.07, 0.88). Differences in total and regional BMD between groups increased with age and appeared greater in males than in females. Conclusion: Basketball athletes exhibit a greater BMD compared to non-athletes, as well as athletes involved in swimming, soccer, and volleyball.
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Probing temperature and capsaicin-induced activation of TRPV1 channel via computationally guided point mutations in its pore and TRP domains
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01.09.2020 |
Lubova K.I.
Chugunov A.O.
Volynsky P.E.
Trofimov Y.A.
Korolkova Y.V.
Mosharova I.V.
Kozlov S.A.
Andreev Y.A.
Efremov R.G.
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International Journal of Biological Macromolecules |
10.1016/j.ijbiomac.2020.04.239 |
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© 2020 Elsevier B.V. In a recent computational study, we revealed some mechanistic aspects of TRPV1 (transient receptor potential channel 1) thermal activation and gating and proposed a set of probable functionally important residues — “hot spots” that have not been characterized experimentally yet. In this work, we analyzed TRPV1 point mutants G643A, I679A + A680G, and K688G/P combining molecular modeling, biochemistry, and electrophysiology. The substitution G643A reduced maximal conductivity that resulted in a normal response to moderate stimuli, but a relatively weak response to more intensive activation. I679A + A680G channel was severely toxic for oocytes most probably due to abnormally increased basal activity of the channel (“always open” gates). The replacement K688G presumably facilitated movements of TRP domain and disturbed its coupling to the pore, thus leading to spontaneous activation and enhanced desensitization of the channel. Finally, mutation K688P was suggested to impair TRP domain directed movement, and the mutated channel showed ~100-fold less sensitivity to the capsaicin, enhanced desensitization and weaker activation by the heat. Our results provide a better understanding of TRPV1 thermal and capsaicin-induced activation and gating. These observations provide a structural basis for understanding some aspects of TRPV1 channel functioning and depict potentially pathogenic mutations.
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Probing temperature and capsaicin-induced activation of TRPV1 channel via computationally guided point mutations in its pore and TRP domains
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01.09.2020 |
Lubova K.I.
Chugunov A.O.
Volynsky P.E.
Trofimov Y.A.
Korolkova Y.V.
Mosharova I.V.
Kozlov S.A.
Andreev Y.A.
Efremov R.G.
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International Journal of Biological Macromolecules |
10.1016/j.ijbiomac.2020.04.239 |
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Ссылка
© 2020 Elsevier B.V. In a recent computational study, we revealed some mechanistic aspects of TRPV1 (transient receptor potential channel 1) thermal activation and gating and proposed a set of probable functionally important residues — “hot spots” that have not been characterized experimentally yet. In this work, we analyzed TRPV1 point mutants G643A, I679A + A680G, and K688G/P combining molecular modeling, biochemistry, and electrophysiology. The substitution G643A reduced maximal conductivity that resulted in a normal response to moderate stimuli, but a relatively weak response to more intensive activation. I679A + A680G channel was severely toxic for oocytes most probably due to abnormally increased basal activity of the channel (“always open” gates). The replacement K688G presumably facilitated movements of TRP domain and disturbed its coupling to the pore, thus leading to spontaneous activation and enhanced desensitization of the channel. Finally, mutation K688P was suggested to impair TRP domain directed movement, and the mutated channel showed ~100-fold less sensitivity to the capsaicin, enhanced desensitization and weaker activation by the heat. Our results provide a better understanding of TRPV1 thermal and capsaicin-induced activation and gating. These observations provide a structural basis for understanding some aspects of TRPV1 channel functioning and depict potentially pathogenic mutations.
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Greenhouse gas-producing soil biological activity in burned and unburned forests along a transect in European Russia
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01.04.2020 |
Goncharov A.
Gongalsky K.
Yazrikova T.
Kostina N.
Korobushkin D.
Makarov M.
Zaitsev A.
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Applied Soil Ecology |
10.1016/j.apsoil.2019.103491 |
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© 2020 Elsevier B.V. It is not clear which mechanisms are responsible for changing soil biological activity following a fire. To address this knowledge gap, we measured such parameters of soil biological activity as flux rates of CH4, and CO2 and identified key environmental parameters that can influence soil biological activity. Soil samples were collected in burned and adjacent unburned control forests, along a 3000 km-long north-south transect in European Russia. A raw biological activity of tested soil samples varied significantly between forest types, but not between burned and control forest stands. Linear mixed effect modeling demonstrated a striking contrast in the importance of different drivers in sustaining a soil biological activity in the burned and control forests. The optimal model of basal soil respiration consisted of: “Soil moisture” (26%), “Fire treatment × Soil moisture × Labile soil N:P ratio” (21%), and “Fire treatment × Labile soil C × Labile soil N:P ratio” (13%). The model for CH4 in turn was defined by interactions of bulk and labile soil C with soil moisture and other factors. Our study clearly demonstrated that forest fires affect soil biological activity rather indirectly through modifying soil properties. The results enable forecasting post-fire effects on soil functioning in a changing climate under varied fire regimes.
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Lung epithelium damage in COPD – An unstoppable pathological event?
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01.04.2020 |
Hadzic S.
Wu C.
Avdeev S.
Weissmann N.
Schermuly R.
Kosanovic D.
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Cellular Signalling |
10.1016/j.cellsig.2020.109540 |
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© 2020 Elsevier Inc. Chronic obstructive pulmonary disease (COPD) is a common term for alveolar septal wall destruction resulting in emphysema, and chronic bronchitis accompanied by conductive airway remodelling. In general, this disease is characterized by a disbalance of proteolytic/anti-proteolytic activity, augmented inflammatory response, increased oxidative/nitrosative stress, rise in number of apoptotic cells and decreased proliferation. As the first responder to the various environmental stimuli, epithelium occupies an important position in different lung pathologies, including COPD. Epithelium sequentially transitions from the upper airways in the direction of the gas exchange surface in the alveoli, and every cell type possesses a distinct role in the maintenance of the homeostasis. Basically, a thick ciliated structure of the airway epithelium has a major function in mucus secretion, whereas, alveolar epithelium which forms a thin barrier covered by surfactant has a function in gas exchange. Following this line, we will try to reveal whether or not the chronic bronchitis and emphysema, being two pathological phenotypes in COPD, could originate in two different types of epithelium. In addition, this review focuses on the role of lung epithelium in COPD pathology, and summarises underlying mechanisms and potential therapeutics.
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In silico simulation of reversible and irreversible swelling of mitochondria: The role of membrane rigidity
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01.01.2020 |
Makarov V.
Khmelinskii I.
Khuchua Z.
Javadov S.
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Mitochondrion |
10.1016/j.mito.2019.09.006 |
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© 2019 Elsevier B.V. and Mitochondria Research Society Mitochondria have been widely accepted as the main source of ATP in the cell. The inner mitochondrial membrane (IMM) is important for the maintenance of ATP production and other functions of mitochondria. The electron transport chain (ETC) generates an electrochemical gradient of protons known as the proton-motive force across the IMM and thus produces the mitochondrial membrane potential that is critical to ATP synthesis. One of the main factors regulating the structural and functional integrity of the IMM is the changes in the matrix volume. Mild (reversible) swelling regulates mitochondrial metabolism and function; however, excessive (irreversible) swelling causes mitochondrial dysfunction and cell death. The central mechanism of mitochondrial swelling includes the opening of non-selective channels known as permeability transition pores (PTPs) in the IMM by high mitochondrial Ca2+ and reactive oxygen species (ROS). The mechanisms of reversible and irreversible mitochondrial swelling and transition between these two states are still unknown. The present study elucidates an upgraded biophysical model of reversible and irreversible mitochondrial swelling dynamics. The model provides a description of the PTP regulation dynamics using an additional differential equation. The rigidity tensor was used in numerical simulations of the mitochondrial parameter dynamics with different initial conditions defined by Ca2+ concentration in the sarco/endoplasmic reticulum. We were able to estimate the values of the IMM rigidity tensor components by fitting the model to the previously reported experimental data. Overall, the model provides a better description of the reversible and irreversible mitochondrial swelling dynamics.
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Industrial Cyber-Physical Systems: Risks Assessment and Attacks Modeling
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01.01.2020 |
Kravets A.
Salnikova N.
Dmitrenko K.
Lempert M.
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Studies in Systems, Decision and Control |
10.1007/978-3-030-32648-7_16 |
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© 2020, Springer Nature Switzerland AG. The chapter is devoted to the attacks modeling for Cyber-Physical systems of industrial enterprises with regard to risk assessment. In this chapter the analysis of corporate systems of industrial is held; systems’ attacks and risk assessment techniques were studied; software for attacks modeling are compared. Information models of corporate networks and attacks are developed; describes the design and basic functions of the module for assessing the risks of attacks in the corporate system. Corporate networks of more than 70% of industrial enterprises are potentially vulnerable to hacker attacks. Today, according to research by Positive Technologies analysts, hackers can cross the perimeter and get into the corporate network of 73% of the companies in the industrial segment. In 82% of companies, penetration from the corporate network to the technological one is possible. One of the main opportunities for obtaining unauthorized access to the enterprise network turned out to be administrative control channels. Solving the problem of ensuring the information security of Cyber-Physical systems is an urgent task today.
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Hemodynamic factors associated with fetal cardiac remodeling in late fetal growth restriction: A prospective study
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01.09.2019 |
Rizzo G.
Mattioli C.
Mappa I.
Bitsadze V.
Khizroeva J.
Słodki M.
Makatsarya A.
D'Antonio F.
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Journal of Perinatal Medicine |
10.1515/jpm-2019-0217 |
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© 2019 Walter de Gruyter GmbH, Berlin/Boston. Altered cardiac geometry affects a proportion of fetuses with growth restriction (FGR). The aim of this study was to explore the hemodynamic factors associated with cardiac remodeling in late FGR. This was a prospective study of singleton pregnancies complicated by late-onset FGR undergoing assessment of left (LV) and right (RV) ventricular sphericity-index (SI). The study population was divided in two groups according to the presence of cardiac remodelling, defined as LVSI <5th centile. The following outcomes were explored: Gestational age at birth, birthweight, caesarean section (CS) for fetal distress, umbilical artery (UA) pH and neonatal admission to special care unit. The differences between the 2 groups in UA pulsatility index (PI), middle cerebral artery (MCA) PI, uterine artery PI, cerebroplacental ratio (CPR) and umbilical vein (UV) flow corrected for fetal abdominal circumference (UVBF/AC) were tested. In total, 212 pregnancies with late FGR were enrolled in the study. An abnormal LV SI was detected in 119 fetuses (56.1%). Late FGR fetuses with cardiac remodeling had a lower birthweight (2390 g vs. 2490; P = 0.04) and umbilical artery pH (7.21 vs. 7.24; P = 0.04) and were more likely to have emergency CS (42.8% vs. 26.9%; P = 0.023) and admission to special care unit (13.4% vs. 4.3%; P = 0.03) compared to those with normal LVSI. No difference in either UA PI (p = 0.904), MCA PI (P = 0.575), CPR (P = 0.607) and mean uterine artery PI (P = 0.756) were present between fetuses with or without an abnormal LV SI. Conversely, UVBF/AC z-score was lower (-1.84 vs.-0.99; P ≤ 0.001) in fetuses with cardiac remodeling and correlated with LV (P ≤ 0.01) and RV SI (P ≤ 0.02). Fetal cardiac remodelling occurs in a significant proportion of pregnancies complicated by late FGR and is affected by a high burden of short-term perinatal compromise. The occurrence of LV SI is independent from fetal arterial Dopplers while it is positively associated with umbilical vein blood flow.
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Investigation of the Size Distribution for Diffusion-Controlled Drug Release From Drug Delivery Systems of Various Geometries
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01.08.2019 |
Spiridonova T.
Tverdokhlebov S.
Anissimov Y.
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Journal of Pharmaceutical Sciences |
10.1016/j.xphs.2019.03.036 |
2 |
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© 2019 American Pharmacists Association® Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.
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Genetic re-engineering of polyunsaturated phospholipid profile of Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the effects of cardiolipin peroxidation
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01.10.2018 |
Lou W.
Ting H.
Reynolds C.
Tyurina Y.
Tyurin V.
Li Y.
Ji J.
Yu W.
Liang Z.
Stoyanovsky D.
Anthonymuthu T.
Frasso M.
Wipf P.
Greenberger J.
Bayır H.
Kagan V.
Greenberg M.
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Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids |
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0 |
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© 2018 Elsevier B.V. Cardiolipin (CL) is a unique phospholipid localized almost exclusively within the mitochondrial membranes where it is synthesized. Newly synthesized CL undergoes acyl remodeling to produce CL species enriched with unsaturated acyl groups. Cld1 is the only identified CL-specific phospholipase in yeast and is required to initiate the CL remodeling pathway. In higher eukaryotes, peroxidation of CL, yielding CLOX, has been implicated in the cellular signaling events that initiate apoptosis. CLOX can undergo enzymatic hydrolysis, resulting in the release of lipid mediators with signaling properties. Our previous findings suggested that CLD1 expression is upregulated in response to oxidative stress, and that one of the physiological roles of CL remodeling is to remove peroxidized CL. To exploit the powerful yeast model to study functions of CLD1 in CL peroxidation, we expressed the H. brasiliensis Δ12-desaturase gene in yeast, which then synthesized poly unsaturated fatty acids(PUFAs) that are incorporated into CL species. Using LC-MS based redox phospholipidomics, we identified and quantified the molecular species of CL and other phospholipids in cld1Δ vs. WT cells. Loss of CLD1 led to a dramatic decrease in chronological lifespan, mitochondrial membrane potential, and respiratory capacity; it also resulted in increased levels of mono-hydroperoxy-CLs, particularly among the highly unsaturated CL species, including tetralinoleoyl-CL. In addition, purified Cld1 exhibited a higher affinity for CLOX, and treatment of cells with H2O2 increased CLD1 expression in the logarithmic growth phase. These data suggest that CLD1 expression is required to mitigate oxidative stress. The findings from this study contribute to our overall understanding of CL remodeling and its role in mitigating oxidative stress.
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Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds
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21.08.2018 |
Litvinov R.
Kononova O.
Zhmurov A.
Marx K.
Barsegov V.
Thirumalai D.
Weisel J.
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Proceedings of the National Academy of Sciences of the United States of America |
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2 |
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© 2018 National Academy of Sciences. All Rights Reserved. Fibrin formation and mechanical stability are essential in thrombosis and hemostasis. To reveal how mechanical load impacts fibrin, we carried out optical trap-based single-molecule forced unbinding experiments. The strength of noncovalent A:a knob-hole bond stabilizing fibrin polymers first increases with tensile force (catch bonds) and then decreases with force when the force exceeds a critical value (slip bonds). To provide the structural basis of catch–slip-bond behavior, we analyzed crystal structures and performed molecular modeling of A:a knob-hole complex. The movable flap (residues γ295 to γ305) containing the weak calcium-binding site γ2 serves as a tension sensor. Flap dissociation from the B domain in the γ-nodule and translocation to knob ‘A’ triggers hole ‘a’ closure, resulting in the increase of binding affinity and prolonged bond lifetimes. The discovery of biphasic kinetics of knob-hole bond rupture is quantitatively explained by using a theory, formulated in terms of structural transitions in the binding pocket between the low-affinity (slip) and high-affinity (catch) states. We provide a general framework to understand the mechanical response of protein pairs capable of tension-induced remodeling of their association interface. Strengthening of the A:a knob-hole bonds at 30- to 40-pN forces might favor formation of nascent fibrin clots subject to hydrodynamic shear in vivo.
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Which cytochrome P450 metabolizes phenazepam? Step by step in silico, in vitro, and in vivo studies
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27.06.2018 |
Ivashchenko D.
Rudik A.
Poloznikov A.
Nikulin S.
Smirnov V.
Tonevitsky A.
Bryun E.
Sychev D.
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Drug Metabolism and Personalized Therapy |
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2 |
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© 2018 Walter de Gruyter GmbH, Berlin/Boston. Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features. To determine phenazepam's metabolic pathways, the study was divided into three stages: In silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes. The in vitro study was performed using a hepatocytes' cell culture, cultivated in a microbioreactor to produce cytochrome P450 isoenzymes. The culture medium contained specific cytochrome P450 isoforms inhibitors and substrates (for CYP2C9, CYP3A4, CYP2C19, and CYP2B6) to determine the cytochrome that was responsible for phenazepam's metabolism. We also measured CYP3A activity using the 6-betahydroxycortisol/cortisol ratio in patients. According to in silico and in vitro analysis results, the most probable metabolizer of phenazepam is CYP3A4. By the in vivo study results, CYP3A activity decreased sufficiently (from 3.8 [95% CI: 2.94-4.65] to 2.79 [95% CI: 2.02-3.55], p=0.017) between the start and finish of treatment in patients who were prescribed just phenazepam. Experimental in silico and in vivo studies confirmed that the original Russian benzodiazepine phenazepam was the substrate of CYP3A4 isoenzyme.
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Atomic Structural Models of Fibrin Oligomers
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05.06.2018 |
Zhmurov A.
Protopopova A.
Litvinov R.
Zhukov P.
Weisel J.
Barsegov V.
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Structure |
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2 |
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© 2018 Elsevier Ltd The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically converted to fibrin, which self-assembles to form double-stranded protofibrils. When reaching a critical length, these intermediate species aggregate laterally to transform into fibers arranged into branched fibrin network. We combined multiscale modeling in silico with atomic force microscopy (AFM) imaging to reconstruct complete atomic models of double-stranded fibrin protofibrils with γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions—all important structural determinants not resolved crystallographically. Structures of fibrin oligomers and protofibrils containing up to 19 monomers were successfully validated by quantitative comparison with high-resolution AFM images. We characterized the protofibril twisting, bending, kinking, and reversibility of A:a knob-hole bonds, and calculated hydrodynamic parameters of fibrin oligomers. Atomic structures of protofibrils provide a basis to understand mechanisms of early stages of fibrin polymerization. Zhmurov et al. used 27 relevant crystal structures to computationally reconstruct the full-atomic models of fibrin oligomers and protofibrils, which correlate with high-resolution atomic force microscopy images. The structures contain much valuable information for understanding the early stages of fibrin polymerization.
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Parameters of vancomycin pharmacokinetics in postoperative patients with renal dysfunction: Comparing the results of a pharmacokinetic study and mathematical modeling
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01.01.2018 |
Ramenskaya G.
Shokhin I.
Lukina M.
Andrushchishina T.
Chukina M.
Tsarev I.
Vartanova O.
Morozova T.
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Bulletin of Russian State Medical University |
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0 |
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© 2018 Pirogov Russian National Research Medical University. All rights reserved. Mathematical modeling of pharmacokinetic (PK) and pharmacodynamic (PD) parameters essential for establishing correct dosing regimens is an alternative to pharmacokinetic studies (PKS) adopted in the clinical setting. The aim of this work was to compare the values of PK parameters for vancomycin obtained in an actual PKS and through MM in postoperative patients with kidney injury. Our prospective study included 61 patients (47 males and 14 females aged 60.59 ± 12.23 years). During PKS, drug concentrations at steady state Сtrough and Cpeak were measured by high-performance liquid chromatography followed by the calculation of the area under the plasma concentration-time curve AUC24. For mathematical modeling, a single-compartment model was employed; PK parameters were estimated using R 3.4.0. The values of Ctrough measured 48 h after the onset of antibiotic therapy during PKS were significantly lower than those predicted by MM (р = 0.004). In a group of patients with acute kidney injury (AKI), AUC24 measured at the end of treatment was significantly higher than its value predicted by MM (р = 0.011). The probability of achieving the target AUC24 to MIC ratio of over 400 µg•h /ml is higher in the group of patients with Ctrough = 10–15 µg /ml. Our findings confirm that the use of MM in postoperative patients with renal dysfunction is limited and therapeutic drug monitoring should be used instead.
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Matrix metalloproteinases: Role in cardiac remodeling in patients with connective tissue dysplasia
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01.01.2018 |
Djazaeva M.
Gladkikh N.
Reshetnikov V.
Yagoda A.
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Medical News of North Caucasus |
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0 |
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© 2018 Stavropol State Medical University. All Rights Reserved. 57 men and 43 women, aged 22.0±4.2 years were examined to determine the clinical and prognostic value of matrix metalloproteinases in heart remodeling in CTD. Serum concentrations of MMP-1, MMP-9, TIMP-1 were determined by ELI-SA («Cloud-Clone Corp.», China). Imbalance of MMP-1, MMP-9 and their inhibitor - TIMP-1 was revealed in patients with CTD. Significant increase in MMP-1 level was registered in cases of MVP with myxomatous degeneration and mitral regurgitation of II degree. Risk of cardiac remodeling progression at three-year follow-up increases in cases of elevated of MMP-1/TIMP-1 coefficient. Identified changes in the MMPs system in patients with CTD may be used as additional criteria of severity and determination of probability of progression of heart connective tissue structures remodeling.
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Evaluation of the potential efficiency of primary prevention of drug addiction using a mathematical modeling technique
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01.01.2018 |
Korshunov V.
Gerasimov A.
Mindlina A.
Vyazovichenko Y.
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Profilakticheskaya Meditsina |
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0 |
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© 2018 Media Sphera Publishing Group. All rights reserved. The relevance of the investigation is due to the need to optimize the system for the primary prevention of drug addiction and use because of its insufficient efficiency in the Russian Federation. This problem is manifested in the low awareness of the population, primarily young people, about the negative consequences of the use of narcotic drugs and psychotropic substances and about the high associated risk of their involvement in the use of narcotics, including new types of psychotropic substances (synthetic narcotics). In this connection, the aim of our investigation was to develop a method for determining the potential efficiency of measures for the primary prevention of drug addiction and use, by applying mathematical modeling. The Kermak - McKendrick epidemic model of the susceptible infected removed (SIR) - like type was used as a basis to build a drug use spread model that represented as transition of groups of individuals from one state to another in relation to drug use. This gave rise to a simulation model estimating the magnitude of a drug use reduction in the risk group in relation to the initial one if varying effective preventive measures were implemented. The drug abuse scenario in case of effective measures was analyzed. Enhancing the effectiveness of measures for primary prevention of drug addiction was shown to lead to a stronger rather than linear decline in the size of a group at risk for drug and in the number of drug users. This model may be used to prepare programs, strategies for the primary prevention of drug addiction to evaluate their potential effectiveness.
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Effects of fixed combination of indacaterol/glycopyrronium in chronic obstructive pulmonary disease: State-of-the art review
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01.01.2018 |
Avdeev S.
Trushenko N.
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Pulmonologiya |
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1 |
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© 2018 Medical Education. All rights reserved. Long-acting bronchodilators (long-acting β 2 -agonists (LABA), long-acting anticholinergics (LAMA) and their combinations) are the basic drugs for treatment of stable chronic obstructive pulmonary disease (COPD). Indacaterol/glycopyrronium (IND/GLY) is the first fixed LABA/LAMA combination acquired significant evidence of its efficacy for improvement lung function, symptoms, and quality of life, and decrease in the rate of acute exacerbations of COPD. The aim of this review was to reassess clinical efficacy of IND/GLY in treatment of COPD with regard to recent data and to outline the further role of this combination in therapy of COPD.
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Modern methods of mathematical modeling of blood flow using reduced order methods
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01.01.2018 |
Simakov S.
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Computer Research and Modeling |
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4 |
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© 2018 Sergey S. Simakov. The study of the physiological and pathophysiological processes in the cardiovascular system is one of the important contemporary issues, which is addressed in many works. In this work, several approaches to the mathematical modelling of the blood flow are considered. They are based on the spatial order reduction and/or use a steady-state approach. Attention is paid to the discussion of the assumptions and suggestions, which are limiting the scope of such models. Some typical mathematical formulations are considered together with the brief review of their numerical implementation. In the first part, we discuss the models, which are based on the full spatial order reduction and/or use a steady-state approach. One of the most popular approaches exploits the analogy between the flow of the viscous fluid in the elastic tubes and the current in the electrical circuit. Such models can be used as an individual tool. They also used for the formulation of the boundary conditions in the models using one dimensional (1D) and three dimensional (3D) spatial coordinates. The use of the dynamical compartment models allows describing haemodynamics over an extended period (by order of tens of cardiac cycles and more). Then, the steady-state models are considered. They may use either total spatial reduction or two dimensional (2D) spatial coordinates. This approach is used for simulation the blood flow in the region of microcirculation. In the second part, we discuss the models, which are based on the spatial order reduction to the 1D coordinate. The models of this type require relatively small computational power relative to the 3D models. Within the scope of this approach, it is also possible to include all large vessels of the organism. The 1D models allow simulation of the haemodynamic parameters in every vessel, which is included in the model network. The structure and the parameters of such a network can be set according to the literature data. It also exists methods of medical data segmentation. The 1D models may be derived from the 3D Navier - Stokes equations either by asymptotic analysis or by integrating them over a volume. The major assumptions are symmetric flow and constant shape of the velocity profile over a cross-section. These assumptions are somewhat restrictive and arguable. Some of the current works paying attention to the 1D model's validation, to the comparing different 1D models and the comparing 1D models with clinical data. The obtained results reveal acceptable accuracy. It allows concluding, that the 1D approach can be used in medical applications. 1D models allow describing several dynamical processes, such as pulse wave propagation, Korotkov's tones. Some physiological conditions may be included in the 1D models: gravity force, muscles contraction force, regulation and autoregulation.
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The effects of angiotensin-converting enzyme inhibitors in heart recipients: A single center experience
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01.01.2018 |
Shevchenko A.
Faradzhov R.
Izotov D.
Koloskova N.
Nikitina E.
Gichkun O.
Orlov V.
Tunyaeva I.
Mironkov B.
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Vestnik Transplantologii i Iskusstvennykh Organov |
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0 |
Ссылка
© 2018 Russian Transplant Society. All Rights Reserved. Aim. To study the effect of ACE inhibitors (ACEI) in heart recipients on the prognosis and myocardial remodeling. Materials and methods. Three hundred and eighty-six patients who received orthotopic heart transplantation (HT) were consequently enrolled to the study from February 2009 to November 2016. Results. Thirty days after the HT, ACEIs were assigned to 141 recipients. Arterial hypertension was diagnosed in all cardiac recipients who received ACEI and among 48 patients (19.5%) from non-ACEI group. Patients receiving ACEI had significantly better event-free survival than control group (p = 0.045) during the follow-up for 1361,6 ± 36,9 days. Left ventricle (LV) end-diastolic dimension did not change over the time in both groups, whereas LV posterior wall thickness in non-ACEI group significantly increased from 1.35 ± 0.03 cm to 1,23 ± 0.05 cm (p < 0.05). Conclusion. Cardiac recipients who received ACE inhibitors had better survival and less transplant left ventricle progression, that could reflect beneficial effects of renin-aldosterone-angiotensin system inhibition after heart transplantation.
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тезис
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Noninvasive assessment of fractional flow reserve using mathematical modeling of coronary flow
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01.01.2018 |
Gognieva D.
Syrkin A.
Vassilevski Y.
Simakov S.
Melerzanov A.
Liang F.
Lomonosova A.
Bykova A.
El Manaa H.
Kopylov P.
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Kardiologiya |
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2 |
Ссылка
© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Nowadays an invasive evaluation of fractional flow reserve (FFR) is one of the main methods used for detecting lesions that cause ischemia. Invasively obtained FFR <0.75 has the specificity of 100%, and FFR >0.80 has the sensitivity >90%. Recent achievements in computational fluid dynamics and computer simulations allow noninvasive assessment of FFR using data obtained by CT angiography performed according to standard protocol at rest without additional radiation, modification of image acquisition protocols, or added medications for vasodilatation. The present review covers the results of the DISCOVER, the NXT, the DEFACTO and the PLATFORM randomized multicenter studies as well as the prospects of using a noninvasive method for measuring FFR developed by specialists of the Institute of Numerical Mathematics in collaboration with specialists of the I. M. Sechenov First Moscow State Medical University.
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