Pathologic response and surgical outcomes in patients undergoing nephrectomy following receipt of immune checkpoint inhibitors for renal cell carcinoma
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01.12.2019 |
Singla N.
Elias R.
Ghandour R.
Freifeld Y.
Bowman I.
Rapoport L.
Enikeev M.
Lohrey J.
Woldu S.
Gahan J.
Bagrodia A.
Brugarolas J.
Hammers H.
Margulis V.
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Urologic Oncology: Seminars and Original Investigations |
10.1016/j.urolonc.2019.08.012 |
0 |
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© 2019 Elsevier Inc. Objective: To evaluate the pathologic response, safety, and feasibility of nephrectomy following receipt of immune checkpoint inhibition (ICI) for renal cell carcinoma (RCC). Methods: Patients who underwent nephrectomy for RCC after exposure to nivolumab monotherapy or combination ipilimumab/nivolumab were reviewed. Primary surgical outcomes included operative time (OT), estimated blood loss (EBL), length of stay (LOS), readmission rates, and complication rates. Pathologic response in the primary and metastatic sites constituted secondary outcomes. Results: Eleven nephrectomies (10 radical, 1 partial) were performed in 10 patients after ICI with median postoperative follow-up 180 days. Six patients received 1 to 4 cycles of ipilimumab/nivolumab, while 5 received 2 to 12 infusions of nivolumab preoperatively. Five surgeries were performed laparoscopically, and 4 patients underwent concomitant thrombectomy. One patient exhibited complete response (pT0) to ICI, and 3/4 patients who underwent metastasectomy for hepatic, pulmonary, or adrenal lesions exhibited no detectable malignancy in any of the metastases resected. No patients experienced any major intraoperative complications, and all surgical margins were negative. Median OT, EBL, and LOS were 180 minutes, 100 ml, and 4 days, respectively. Four patients experienced a complication, including 3 that were addressed with interventional radiology procedures. One patient died of progressive disease >3 months after surgery, and 1 patient succumbed to pulmonary embolism complicated by sepsis. No complications or readmissions were noted in 6 patients. Conclusion: Nephrectomy following ICI for RCC is safe and technically feasible with favorable surgical outcomes and pathologic response. Timing of the nephrectomy relative to checkpoint dosing did not seem to impact outcome. Biopsies of lesions responding radiographically to ICI may warrant attention prior to surgical excision.
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A novel guided surgery system with a sleeveless open frame structure: a retrospective clinical study on 38 partially edentulous patients with 1 year of follow-up
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21.11.2019 |
Mouhyi J.
Salama M.
Mangano F.
Mangano C.
Margiani B.
Admakin O.
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BMC oral health |
10.1186/s12903-019-0940-0 |
0 |
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BACKGROUND: This retrospective clinical study aims to present results of experience with a novel guided surgery system with a sleeveless, open-frame structure, in which the surgical handpiece (not the drills used for preparation) is guided. METHODS: This study was based on an evaluation of the records of partially edentulous patients who had been treated with a sleeveless open-frame guided surgery system (TWIN-Guide®, 2Ingis, Brussels, Belgium), between January 2015 and December 2017. Inclusion criteria were patients with good systemic/oral health and a minimum follow-up of 1 year. Exclusion criteria were patients who had been treated without a guide, or with a guide with sleeves, patients with systemic/oral diseases and who did not have a follow-up of 1 year. The main outcomes were surgical (fit and stability of the surgical guide, duration of the intervention, implant stability, and any intra-operative or immediate post-operative complication), biologic, and prosthetic. RESULTS: Thirty-eight patients (24 males, 14 females; mean age 56.5 ± 14.0 years) were included in the study. These patients had been treated with 110 implants inserted by means of 40 sleeveless, open-frame guides. With regard to fit and stability, 34 guides were excellent, 4 acceptable, and 2 inadequate for use. The mean duration of the intervention was 23.7 (± 6.7) minutes. Immediately after placement, 2 fixtures were not stable and had to be removed. Two patients experienced pain/swelling after surgery. The 108 surviving implants were restored with 36 single crowns and 32 fixed partial prostheses (24 two-unit and 8 three-unit bridges); these restorations survived until the 1-year follow-up, with a low incidence of biologic and prosthetic complications. CONCLUSIONS: Within the limits of this study, this novel guided surgery system with sleeveless, open frame-structure guides seems to be clinically reliable; further studies on a larger sample of patients are needed to confirm these outcomes.
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A Multicenter Study Evaluating Natural Orifice Specimen Extraction Surgery for Rectal Cancer
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01.11.2019 |
Liu Z.
Efetov S.
Guan X.
Zhou H.
Tulina I.
Wang G.
Tsarkov P.
Wang X.
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Journal of Surgical Research |
10.1016/j.jss.2019.05.034 |
0 |
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© 2019 Elsevier Inc. Background: Low anterior resections are increasingly performed laparoscopically for rectal cancer. Recently, natural orifice specimen extraction surgery (NOSES) has been reported as an alternative approach without additional incisions or extensions. In this study, we aimed to evaluate the safety and feasibility of NOSES by comparing the short-term outcomes with those of conventional laparoscopic resection (CLR) in a multicenter retrospective study from China and Russia. Methods: The retrospective multicenter study was conducted at three centers between January 2015 and December 2017. Relevant collected data included patient demographics, operative parameters, and postoperative complications. All procedures were performed using either a NOSES or a CLR approach. Results: The data of a total of 768 consecutive patients with rectal cancer were retrospectively analyzed, including 412 CLR and 356 NOSES cases. The two groups were comparable for all demographics and characteristics except for the median tumor size (P = 0.038). No difference was found in the operative time and number of retrieved lymph nodes. Intraoperative complications and positive resection margins were nil in both groups. No difference was found in the time to first flatus (P = 0.150), time to first defecation (P = 0.084), length of postoperative hospital stay (P = 0.152), anastomotic leakage (P = 0.377), and intra-abdominal abscess (P = NA). The CLR group but not the NOSES group had incisional hernia or wound infection events, although the difference between groups was not significant (P = 0.253). Conclusions: The NOSES procedure is a well-established strategy and may be considered as an alternative procedure to CLR for rectal cancer. However, the long-term benefits of this approach require further evaluation.
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Polymorphism of 3-(5-phenyl-1,3,4-oxadiazol-2-yl)- And 3-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]-2H-chromen-2-ones
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01.11.2019 |
Shishkina S.
Konovalova I.
Trostianko P.
Geleverya A.
Kovalenko S.
Bunyatyan N.
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Acta Crystallographica Section C: Structural Chemistry |
10.1107/S2053229619014256 |
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© 2019 International Union of Crystallography. This study of 3-(5-phenyl-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one, C17H10N2O3, 1, and 3-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]-2H-chromen-2-one, C16H9ON3O3, 2, was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the 'head-to-head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar-layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.
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Cationic penetrating antioxidants switch off Mn cluster of photosystem II in situ
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01.11.2019 |
Ptushenko V.
Solovchenko A.
Bychkov A.
Chivkunova O.
Golovin A.
Gorelova O.
Ismagulova T.
Kulik L.
Lobakova E.
Lukyanov A.
Samoilova R.
Scherbakov P.
Selyakh I.
Semenova L.
Vasilieva S.
Baulina O.
Skulachev M.
Kirpichnikov M.
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Photosynthesis Research |
10.1007/s11120-019-00657-2 |
0 |
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© 2019, Springer Nature B.V. Mitochondria-targeted antioxidants (also known as ‘Skulachev Ions’ electrophoretically accumulated by mitochondria) exert anti-ageing and ROS-protecting effects well documented in animal and human cells. However, their effects on chloroplast in photosynthetic cells and corresponding mechanisms are scarcely known. For the first time, we describe a dramatic quenching effect of (10-(6-plastoquinonyl)decyl triphenylphosphonium (SkQ1) on chlorophyll fluorescence, apparently mediated by redox interaction of SkQ1 with Mn cluster in Photosystem II (PSII) of chlorophyte microalga Chlorella vulgaris and disabling the oxygen-evolving complex (OEC). Microalgal cells displayed a vigorous uptake of SkQ1 which internal concentration built up to a very high level. Using optical and EPR spectroscopy, as well as electron donors and in silico molecular simulation techniques, we found that SkQ1 molecule can interact with Mn atoms of the OEC in PSII. This stops water splitting giving rise to potent quencher(s), e.g. oxidized reaction centre of PSII. Other components of the photosynthetic apparatus proved to be mostly intact. This effect of the Skulachev ions might help to develop in vivo models of photosynthetic cells with impaired OEC function but essentially intact otherwise. The observed phenomenon suggests that SkQ1 can be applied to study stress-induced damages to OEC in photosynthetic organisms.
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Molecular Characterization of Leishmania RNA virus 2 in Leishmaniamajor from Uzbekistan
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21.10.2019 |
Kleschenko Y.
Grybchuk D.
Matveeva N.
Macedo D.
Ponirovsky E.
Lukashev A.
Yurchenko V.
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Genes |
10.3390/genes10100830 |
0 |
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Here we report sequence and phylogenetic analysis of two new isolates of Leishmania RNA virus 2 (LRV2) found in Leishmania major isolated from human patients with cutaneous leishmaniasis in south Uzbekistan. These new virus-infected flagellates were isolated in the same region of Uzbekistan and the viral sequences differed by only nineteen SNPs, all except one being silent mutations. Therefore, we concluded that they belong to a single LRV2 species. New viruses are closely related to the LRV2-Lmj-ASKH documented in Turkmenistan in 1995, which is congruent with their shared host (L. major) and common geographical origin.
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Assessment of Gender Effects and Reference Values of Mane Hair Trace Element Content in English Thoroughbred Horses (North Caucasus, Russia) Using ICP-DRC-MS
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15.10.2019 |
Kalashnikov V.
Zajcev A.
Atroshchenko M.
Miroshnikov S.
Zavyalov O.
Frolov A.
Skalny A.
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Biological Trace Element Research |
10.1007/s12011-019-1634-9 |
0 |
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was assessment of gender differences in hair trace element content in English Thoroughbred horses (North Caucasus, Russia) using ICP-DRC-MS and calculation of the reference values. Trace element content in mane hair of 190 stallions and 94 mares (3–7 years old) bred in North Caucasus (Russia) was assessed using inductively coupled plasma mass spectrometry. Mane hair Co, Cr, Mn, Li, Si, and Sr levels in mares exceeded those in stallions by 77%, 63%, 64%, 42%, 39%, and 64%, respectively. Hair Fe and Si content was nearly twofold higher in female horses as compared to the males. Only hair Zn content was 5% higher in stallions as compared to mares. In addition, mares were characterized by 63%, 65%, 29%, and 40% higher levels of As, Pb, Sn, and Ni levels in hair as compared to the respective values in stallions. In turn, hair Al and Hg were more than twofold higher in mares than in stallions. The reference intervals of mane hair content (μg/g) for Co (0.006–0.143), Cr (0.028–0.551), Cu (4.17–6.84), Fe (10.11–442.2), I (0.026–3.69), Mn (0.551–12.55), Se (0.108–0.714), Zn (97.43–167), Li (0.011–0.709), Ni (0.060–0.589), Si (0.665–29.12), V (0.006–0.584), Al (1.98–168.5), As (0.006–0.127), Cd (0.002–0.033), B (0.494–16.13), Pb (0.018–0.436), Sn (0.002–0.144), Sr (1.0–9.46), and Hg (0.0018–0.017) in the total cohort of horses were estimated using the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines. The reference intervals were also estimated for stallions and mares bred in North Caucasus (Russia) and may be used for interpretation of the results of hair trace element analysis in horses.
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Structural Transition States Explored With Minimalist Coarse Grained Models: Applications to Calmodulin
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15.10.2019 |
Delfino F.
Porozov Y.
Stepanov E.
Tamazian G.
Tozzini V.
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Frontiers in Molecular Biosciences |
10.3389/fmolb.2019.00104 |
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© Copyright © 2019 Delfino, Porozov, Stepanov, Tamazian and Tozzini. Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems whose complexity is already high in the stable states. Here we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to Calmodulin, based on an empirical force field with a partial structural bias, to explore the transition paths between the apo-closed state and the Ca-bound open state of the protein. We then select representative structures along the trajectory based on a structural clustering algorithm and build a cleaned-up trajectory with them. We finally compare this trajectory with that produced by the online tool MinActionPath, by minimizing the action integral using a harmonic network model, and with that obtained by the PROMPT morphing method, based on an optimal mass transportation-type approach including physical constraints. The comparison is performed both on the structural and energetic level, using the coarse-grained and the atomistic force fields upon reconstruction. Our analysis indicates that this method returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multi-stable proteins transition pathways.
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Microfluidics for Porous Systems: Fabrication, Microscopy and Applications
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01.10.2019 |
Gerami A.
Alzahid Y.
Mostaghimi P.
Kashaninejad N.
Kazemifar F.
Amirian T.
Mosavat N.
Ebrahimi Warkiani M.
Armstrong R.
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Transport in Porous Media |
10.1007/s11242-018-1202-3 |
2 |
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© 2018, Springer Nature B.V. No matter how sophisticated the structures are and on what length scale the pore sizes are, fluid displacement in porous media can be visualized, captured, mimicked and optimized using microfluidics. Visualizing transport processes is fundamental to our understanding of complex hydrogeological systems, petroleum production, medical science applications and other engineering applications. Microfluidics is an ideal tool for visual observation of flow at high temporal and spatial resolution. Experiments are typically fast, as sample volume is substantially low with the use of miniaturized devices. This review first discusses the fabrication techniques for generating microfluidics devices, experimental setups and new advances in microfluidic fabrication using three-dimensional printing, geomaterials and biomaterials. We then address multiphase transport in subsurface porous media, with an emphasis on hydrology and petroleum engineering applications in the past few decades. We also cover the application of microfluidics to study membrane systems in biomedical science and particle sorting. Lastly, we explore how synergies across different disciplines can lead to innovations in this field. A number of problems that have been resolved, topics that are under investigation and cutting-edge applications that are emerging are highlighted.
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Pancreatic calcifications associate with diverse aetiological risk factors in patients with chronic pancreatitis: A multicentre study of 1500 cases
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01.10.2019 |
Olesen S.
Lisitskaya M.
Drewes A.
Novovic S.
Nøjgaard C.
Kalaitzakis E.
Jensen N.
Engjom T.
Erchinger F.
Waage A.
Hauge T.
Haas S.
Vujasinovic M.
Lindkvist B.
Zviniene K.
Pukitis A.
Ozola-Zālīte I.
Okhlobystin A.
Parhiala M.
Laukkarinen J.
Frøkjær J.
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Pancreatology |
10.1016/j.pan.2019.08.009 |
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© 2019 IAP and EPC Background: Pancreatic calcifications is a common finding in patients with chronic pancreatitis (CP), but the underlying pathophysiology is incompletely understood. Past studies for risk factors of calcifications have generally been focused on single parameters or limited by small sample sizes. The aim of this study was to explore several patient and disease characteristics and their associations with pancreatic calcifications in a large cohort of CP patients with diverse aetiological risk factors. Methods: This was a multicentre, cross-sectional study including 1509 patients with CP. Patient and disease characteristics were compared for patients with calcifications (n = 912) vs. without calcifications (n = 597). Multivariable logistic regression was performed to assess the parameters independently associated with calcifications. Results: The mean age of patients was 53.9 ± 14.5 years and 1006 (67%) were men. The prevalence of calcifications was 60.4% in the overall patient cohort, but highly variable between patients with different aetiological risk factors (range: 2–69%). On multivariate analysis, alcoholic aetiology (OR 1.76 [95% CI, 1.39–2.24]; p < 0.001) and smoking aetiology (OR 1.77 [95% CI, 1.39–2.26], p < 0.001) were positively associated with the presence of calcifications, while an autoimmune aetiology was negatively associated with calcifications (OR 0.15 [95% CI, 0.08–0.27], p < 0.001). Patients with pancreatic calcifications were more likely to have undergone pancreatic duct stenting (OR 1.59 [95%CI, 1.16–2.19], p = 0.004). Conclusion: The presence of pancreatic calcifications is associated with diverse aetiological risk factors in patients with CP. This observation attest to the understanding of CP as a complex disease and may have implications for disease classification.
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Evolution of crystal structure of Ba and Ti co-doped BiFeO<inf>3</inf> ceramics at the morphotropic phase boundary
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30.09.2019 |
Karpinsky D.
Silibin M.
Trukhanov A.
Zhaludkevich A.
Latushka S.
Zhaludkevich D.
Sikolenko V.
Khomchenko V.
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Journal of Alloys and Compounds |
10.1016/j.jallcom.2019.06.145 |
0 |
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© 2019 Elsevier B.V. Crystal structure of the Bi1-xBaxFe1-xTixO3 ceramics across the phase boundary region between the polar rhombohedral and pseudo-cubic phases has been investigated by means of X-ray and neutron diffraction, scanning electron microscopy and differential scanning calorimetry techniques. The structural measurements have revealed a decrease in the rhombohedral distortions upon increase in the dopant content followed by the stabilization of the pseudo-cubic phase at x ≥ 0.20. While temperature increase gives rise to the similar pattern of structural changes for the lightly-doped samples, an unpredictable temperature-driven strengthening of the rhombohedral distortions has been found for the compounds belonging to the phase boundary region. The study specifies the peculiarities of the temperature-driven evolution of the crystal structure depending on the structural state of the compounds at room temperature.
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Lysine-specific post-translational modifications of proteins in the life cycle of viruses
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02.09.2019 |
Loboda A.
Soond S.
Piacentini M.
Barlev N.
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Cell Cycle |
10.1080/15384101.2019.1639305 |
0 |
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© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. The process of protein post-translational modifications (PTM) is one of the critical mechanisms of regulation of many cellular processes, which makes it an attractive target for various viruses. Since viruses cannot replicate on their own, they have developed unique abilities to alter metabolic and signaling cell pathways, including protein PTMs, to ensure faithful replication of their genomes. This review describes several ways of how lysine-specific PTMs are used by various viruses to ensure its successful invasion and replication. Covalent modifications like acetylation, ubiquitination, and methylation form a complex system of reversible and often competing modifications, which adds an additional level of complexity to the system of regulation of the activity of host proteins involved in viral replication and propagation. In furthering these, we also describe the manner in which PTM pathways can also be accosted by various types of viruses to neutralize the host’s cellular mechanisms for anti-viral protection and highlight key areas for future therapeutic targeting and design.
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Medical aspects of domestic violence against women and girls (review)
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01.09.2019 |
Kekelidze Z.
Kachayeva M.
Kharitonova N.
Vasianina V.
Shishkina O.
Skibina N.
Nazarova L.
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Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny |
10.32687/0869-866X-2019-27-5-936-939 |
0 |
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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.
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Osteosynthesis of ankle fractures: Problems and solutions
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01.09.2019 |
Akraa M.
Malt E.
Zagorodniy N.
Abdulkhabirov M.
Hasanbasic D.
Akraa M.
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International Journal of Pharmaceutical Research |
10.31838/ijpr/2019.11.03.066 |
0 |
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© 2019, Advanced Scientific Research. All rights reserved. A topical problem in traumatology is the choice of treatment methods for ankle fractures. The consideration of the anatomical and functional features of the ankle, condition of soft tissues in the area of fractures and the degree of edema in the ankle region is of great importance when choosing a particular treatment method. Therefore, reducing the degree of surgical aggression during surgical treatment of these injuries is an important task.. The aim of this study was to examine the possibilities of improving the results of surgical treatment of patients with ankle fractures with minimally invasive osteosynthesis technologies. This study presents the experience of treating 62 patients with fractures of the ankle joint. Two statistically homogeneous groups of patients with ankle fractures were identified. In one group, osteosynthesis with minimally invasive osteosynthesis techniques was used in 34 patients; in the other, osteosynthesis was performed in a conventional manner in 28 patients. A comparative analysis of the immediate and long-term results of treatment of patients in the study groups was carried out. The advantage of closed technology of osteosynthesis was proved. The preservation of the blood supply to the surrounding soft tissues with closed osteosynthesis provides a greater likelihood of fracture fusion, therefore the only condition in such cases is to eliminate the interposition of soft tissues in the area of lateral and medial ankle fractures.. The analysis of the obtained immediate and remote results of osteosynthesis in the two groups showed the best efficiency when using minimally invasive closed metal implantationtechnologies, especially when there are skin problems in the area of the injured ankle joint.
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Brain–lung–thyroid syndrome: Literature review and series of clinical observations
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01.09.2019 |
Zhestkova M.
Ovsyannikov D.
Vasilieva T.
Donin I.
Klyukhina Y.
Kolmykova A.
Kryuchko D.
Kustova O.
Migali A.
Migali A.
Nikitina M.
Orlov A.
Petruk N.
Petryaykina E.
Samsonovich I.
Fisenko A.
Кhaldeev S.
Khaldeeva M.
Chernyaev A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
10.24110/0031-403X-2019-98-5-85-93 |
0 |
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© 2019, Pediatria Ltd. All rights reserved. Brain–lung–thyroid syndrome (BLTS) is a rare genetic disease associated with mutations in the NKX2.1 gene encoding thyroid transcription factor 1. The most common manifestations of this syndrome are benign hereditary chorea, hypothyroidism and respiratory distress syndrome, however, mutations in the NKX2.1 gene can also cause other pathologies of nervous, respiratory systems and thyroid gland. The article describes 4 patients with mutations in the NKX2.1 gene observed by authors. Based on the analysis of the observations of 168 patients with BLTS presented in the world literature from 1998 to 2019, current information on the genetics, pathogenesis, clinical X-ray manifestations, outcomes and treatment of the syndrome are summarized.
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Holter Monitoring (24-Hour ECG) Parameter Dynamics in Patients with Ischemic Heart Disease and Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia
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01.08.2019 |
Fiev D.
Vinarov A.
Tsarichenko D.
Kopylov P.
Demidko Y.
Syrkin A.
Rapoport L.
Alyaev Y.
Glybochko P.
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Advances in Therapy |
10.1007/s12325-019-00977-8 |
0 |
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© 2019, The Author(s). Introduction: This study examined the dynamics of 24-h electrocardiogram (ECG) monitoring parameters (Holter monitoring) in patients with ischemic heart disease (IHD) before and after conservative or surgical treatment of patients with voiding and storage lower urinary tract symptoms (LTS) due to benign prostatic hyperplasia (BPH). Methods: A total of eighty-three 57 to 81-year-old (mean age 70.4 ± 5.75 years) patients with LUTS/BPH and accompanying IHD were examined and treated at the Institute of Urology and Human Reproductive Health and Clinic of Cardiology of Sechenov University. All patients received recommended cardiac therapy at least 6 months before inclusion in the study. Results: Our study demonstrated that there is correlation between voiding and storage LUTS/BPH and Holter-detected cardiac impairments in patients with IHD/BPH. These data make it possible to consider LUTS/BPH (voiding and storage) as a factor in the additional functional and psychological load on the activity of patients with ischemic heart disease. Improvement of voiding and storage LUTS due to BPH and objective parameters of urination (Qmax) in patients treated with alpha-1 adrenoceptor blocker tamsulosin correlated with improvement of 24-h ECG monitoring parameters (Holter monitoring) in 72% of patients. Improvement of 24-h ECG monitoring parameters (Holter monitoring) 1 month after transurethral resection of the prostate (TURP) in IHD/BPH patients and indications for surgical treatment was observed in 65.7%. Negative dynamics of the Holter-based ECG was not registered in patients who were operated on. Conclusion: Holter monitoring helps to identify groups of patients in whom urinary impairments caused by prostatic hyperplasia negatively affect the course of IHD. Restored urination (either conservatively or operatively) in patients with BPH in 72% of cases decreased the number of fits of angina, thus influencing favourably the course of IHD. Trial Registration: ClinicalTrials.gov Identifier: NCT03856242.
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Changes of the Heart Valves in the Long Term after Chemoradiotherapy According to Different Protocols for Hodgkin's Lymphoma in Children and Adolescents
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01.08.2019 |
Parkhomenko R.
Shcherbenko O.
Rybakova M.
Zelinskaya N.
Kharchenko N.
Kunda M.
Zapirov G.
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Journal of Adolescent and Young Adult Oncology |
10.1089/jayao.2018.0142 |
0 |
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© 2019, Mary Ann Liebert, Inc., publishers 2019. The purpose of our work was to study late cardiac complications after treatment for Hodgkin's lymphoma (HL) in children and adolescents. Methods: Sixty-seven patients were examined in the long term (>5 years) after chemoradiotherapy for HL according to two different programs of treatment (groups I and II). Mean total doses of radiotherapy (RT) to the mediastinum were 37.2 and 28.9 Gy, respectively. The status of the heart was assessed at the mean age of 22.7 years with electrocardiography (ECG) and echocardiography (EchoCG). Mean terms of follow-up were 16.4 and 9.5 years for group I and group II, respectively. Results: Incidence of ECG changes was equal between the groups (88% and 90%). The prevalence of signs of valvular calcifications and fibrosis was 70.9% after mediastinal doses ≥30 Gy, and 16.6% after lower doses (p = 0.002). Those changes led to considerable valvular dysfunction in four patients. EchoCG signs of pulmonary hypertension were seen in 33.3% patients of group I versus 4.8% in group II (p = 0.047). Pericardial effusion was observed in 7.4% and 5.1%, respectively (p = 1.0). Left ventricular ejection fraction decreased slightly only in two patients (one in each group). Conclusions: The RT mediastinal dose level is the important risk factor of late heart complications. Nevertheless, the differences in the rate and severity of those complications between the groups should be viewed with caution because of differences in the age at baseline and in follow-up terms. The survivors of HL should undergo life-long regular examinations of the heart status.
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Neurological, sensorimotor and cardiorespiratory alterations induced by methoxetamine, ketamine and phencyclidine in mice
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01.10.2018 |
Ossato A.
Bilel S.
Gregori A.
Talarico A.
Trapella C.
Gaudio R.
De-Giorgio F.
Tagliaro F.
Neri M.
Fattore L.
Marti M.
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Neuropharmacology |
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5 |
Ссылка
© 2018 Elsevier Ltd Novel psychoactive substances are intoxicating compounds developed to mimic the effects of well-established drugs of abuse. They are not controlled by the United Nations drug convention and pose serious health concerns worldwide. Among them, the dissociative drug methoxetamine (MXE) is structurally similar to ketamine (KET) and phencyclidine (PCP) and was created to purposely mimic the psychotropic effects of its “parent” compounds. Recent animal studies show that MXE is able to stimulate the mesolimbic dopaminergic transmission and to induce KET-like discriminative and rewarding effects. In light of the renewed interest in KET and PCP analogs, we decided to deepen the investigation of MXE-induced effects by a battery of behavioral tests widely used in studies of “safety-pharmacology” for the preclinical characterization of new molecules. To this purpose, the acute effects of MXE on neurological and sensorimotor functions in mice, including visual, acoustic and tactile responses, thermal and mechanical pain, motor activity and acoustic startle reactivity were evaluated in comparisons with KET and PCP to better appreciate its specificity of action. Cardiorespiratory parameters and blood pressure were also monitored in awake and freely moving animals. Acute systemic administrations of MXE, KET and PCP (0.01–30 mg/kg i.p.) differentially alter neurological and sensorimotor functions in mice depending in a dose-dependent manner specific for each parameter examined. MXE and KET (1 and 30 mg/kg i.p.) and PCP (1 and 10 mg/kg i.p.) also affect significantly cardiorespiratory parameters, systolic and diastolic blood pressure in mice.
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Oncobox bioinformatical platform for selecting potentially effective combinations of target cancer drugs using high-throughput gene expression data
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01.10.2018 |
Sorokin M.
Kholodenko R.
Suntsova M.
Malakhova G.
Garazha A.
Kholodenko I.
Poddubskaya E.
Lantsov D.
Stilidi I.
Arhiri P.
Osipov A.
Buzdin A.
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Cancers |
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5 |
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© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Sequential courses of anticancer target therapy lead to selection of drug-resistant cells, which results in continuous decrease of clinical response. Here we present a new approach for predicting effective combinations of target drugs, which act in a synergistic manner. Synergistic combinations of drugs may prevent or postpone acquired resistance, thus increasing treatment efficiency. We cultured human ovarian carcinoma SKOV-3 and neuroblastoma NGP-127 cancer cell lines in the presence of Tyrosine Kinase Inhibitors (Pazopanib, Sorafenib, and Sunitinib) and Rapalogues (Temsirolimus and Everolimus) for four months and obtained cell lines demonstrating increased drug resistance. We investigated gene expression profiles of intact and resistant cells by microarrays and analyzed alterations in 378 cancer-related signaling pathways using the bioinformatical platform Oncobox. This revealed numerous pathways linked with development of drug resistant phenotypes. Our approach is based on targeting proteins involved in as many as possible signaling pathways upregulated in resistant cells. We tested 13 combinations of drugs and/or selective inhibitors predicted by Oncobox and 10 random combinations. Synergy scores for Oncobox predictions were significantly higher than for randomly selected drug combinations. Thus, the proposed approach significantly outperforms random selection of drugs and can be adopted to enhance discovery of new synergistic combinations of anticancer target drugs.
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Clinical features of different orbital manifestations of granulomatosis with polyangiitis
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01.09.2018 |
Ismailova D.
Abramova J.
Novikov P.
Grusha Y.
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Graefe's Archive for Clinical and Experimental Ophthalmology |
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2 |
Ссылка
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: The aim of this study was to distinguish different forms of orbital involvement in granulomatosis with polyangiitis (GPA) and to compare their clinical course and outcomes. Methods: Two hundred twenty-six consecutive patients with GPA were retrospectively studied. All patients fulfilled the classification criteria of American College of Rheumatology; diagnosis of localized GPA was established according to Chapel Hill Consensus. Of those, 74 patients with orbital disease were enrolled into further investigation of different forms of orbital disease. Results: Overall ocular involvement was diagnosed in 50% (113/226) of patients; in 5.3% (12/226), inflammatory eye disease resulted in permanent visual loss. Most common ophthalmic manifestations were orbital masses, episcleritis/conjunctivitis, and scleritis (74/226, 32/226, and 12/226, respectively). Seventy-four patients with orbital involvement were divided into three groups: those with orbital mass without primary lacrimal gland involvement (1st group, 45 patients), those with lacrimal gland involvement (2nd group, 26 patients), and those with extraocular myositis (3rd group, 3 patients). Symptoms such as orbital pain, decreased vision, double vision, red eye, scleritis, orbital wall destruction, primary gaze strabismus, and ocular motility restriction were significantly more common in the 1st group. Peripheral ulcerative keratitis (PUK) was present in the 1st group only. Patients of the 1st group suffered from visual loss, double vision, primary gaze strabismus, and ocular motility restriction significantly more often. Eleven of them developed visual loss; 5 of them underwent enucleation, whereas in the group of patients with dacryoadenitis, only 1 patient had BCVA less than 0.3. Conclusions: Three types of orbital disease in GPA were proposed: orbital mass without primary lacrimal gland involvement, dacryoadenitis, and extraocular myositis. Patients with orbital mass without lacrimal gland involvement are characterized with a higher rate of systemic disease, severe clinical course not uncommonly associated with other ophthalmic manifestations (necrotizing scleritis, PUK, orbital walls destruction), relatively unfavorable outcome with high level of morbidity (optic nerve atrophy, anophthalmos, strabismus), and higher rate of recurrences. Dacryoadenitis in GPA showed to be not severe manifestation with favorable prognosis.
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