Salvage surgery for recurrent larynx cancer
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01.11.2019 |
Mimica X.
Hanson M.
Patel S.
McGill M.
McBride S.
Lee N.
Dunn L.
Cracchiolo J.
Shah J.
Wong R.
Ganly I.
Cohen M.
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Head and Neck |
10.1002/hed.25925 |
1 |
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© 2019 Wiley Periodicals, Inc. Background: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%. Methods: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed. Results: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage. Conclusions: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS.
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Significance and management of incidentally diagnosed metastatic papillary thyroid carcinoma in cervical lymph nodes in neck dissection specimens
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01.11.2019 |
Mandapathil M.
Lennon P.
Ganly I.
Patel S.
Shah J.
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Head and Neck |
10.1002/hed.25905 |
0 |
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© 2019 Wiley Periodicals, Inc. Background: The management of patients with incidentally discovered metastatic thyroid cancer in cervical lymph nodes in neck dissection specimens for other pathologies is unclear. Methods: Retrospective review of neck dissection specimens for nonthyroid malignancy during a 30-year period was undertaken to identify incidental metastatic papillary thyroid cancer (PTC). Results: Twenty-six patients had an incidental finding of PTC in lymph node(s) in neck dissection specimens. Subsequent ultrasound of the thyroid showed nodules in 20 patients. Eleven (42%) underwent total thyroidectomy, 1 (4%) had a lobectomy, and 14 (54%) were kept under active surveillance only. At a median follow-up of 48 months (range 10-189 months), all patients who had undergone surgery and those under surveillance were free of PTC recurrence. Conclusion: Evaluation for detection of a primary thyroid tumor is essential in all patients with incidentally discovered metastatic PTC. Decision regarding surgery or surveillance is dependent on clinical and radiological tumor features and patient factors.
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Numerical modeling of continuous-flow left ventricular assist device performance
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01.11.2019 |
Telyshev D.
Petukhov D.
Selishchev S.
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International Journal of Artificial Organs |
10.1177/0391398819852365 |
0 |
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© The Author(s) 2019. Responses of five rotary blood pumps, namely HeartAssist 5, HeartMate II, HeartWare, Sputnik 1, and Sputnik 2, were extensively assessed in six test cases using a mathematical model of the cardiovascular system. Data for the rotary pumps were derived from pressure–flow curves reported in the literature. The test cases were chosen to attempt to cover most common clinical conditions, such as partial or full support or transitions between different levels of ventricular support. The investigated parameters are collected in a table and presented in figures, such as pressure–volume loops, H-Q curves, pump flow, and aortic pressure waveforms. HeartAssist, Sputnik 1, and Sputnik 2 pumps provide comparable level of aortic pressure, pump flow pulsatility PI(QP), and aortic pressure pulsatility PI(AoP) due to the similarity of pressure–flow characteristic curves of these pumps. HeartMate II provides a minimal backflow among other investigated rotary blood pumps due to the maximum pressure head at zero flow. HeartWare provides minimal pulsation of flow, which is confirmed by a flow range from −2 to 7 L/min in case 1. At the same time, the greatest degree of unloading was demonstrated by the HeartWare due to the flatness of the pressure–flow curve shape. The conclusions were made based on the obtained results, including the influence of pressure–flow curve shape on the pump performance and occurrences of adverse events, such as backflow or suction. For example, the increase of the pressure head at zero flow decreases the likelihood of backflow through the pump, and with it, increasing the flow under minimal pressure head increases the likelihood of suction.
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Modeling arterial pulse waves in healthy aging: a database for in silico evaluation of hemodynamics and pulse wave indexes
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01.11.2019 |
Charlton P.
Mariscal Harana J.
Vennin S.
Li Y.
Chowienczyk P.
Alastruey J.
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American journal of physiology. Heart and circulatory physiology |
10.1152/ajpheart.00218.2019 |
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The arterial pulse wave (PW) is a rich source of information on cardiovascular (CV) health. It is widely measured by both consumer and clinical devices. However, the physical determinants of the PW are not yet fully understood, and the development of PW analysis algorithms is limited by a lack of PW data sets containing reference CV measurements. Our aim was to create a database of PWs simulated by a computer to span a range of CV conditions, representative of a sample of healthy adults. The typical CV properties of 25-75 yr olds were identified through a literature review. These were used as inputs to a computational model to simulate PWs for subjects of each age decade. Pressure, flow velocity, luminal area, and photoplethysmographic PWs were simulated at common measurement sites, and PW indexes were extracted. The database, containing PWs from 4,374 virtual subjects, was verified by comparing the simulated PWs and derived indexes with corresponding in vivo data. Good agreement was observed, with well-reproduced age-related changes in hemodynamic parameters and PW morphology. The utility of the database was demonstrated through case studies providing novel hemodynamic insights, in silico assessment of PW algorithms, and pilot data to inform the design of clinical PW algorithm assessments. In conclusion, the publicly available PW database is a valuable resource for understanding CV determinants of PWs and for the development and preclinical assessment of PW analysis algorithms. It is particularly useful because the exact CV properties that generated each PW are known.NEW & NOTEWORTHY First, a comprehensive literature review of changes in cardiovascular properties with age was performed. Second, an approach for simulating pulse waves (PWs) at different ages was designed and verified against in vivo data. Third, a PW database was created, and its utility was illustrated through three case studies investigating the determinants of PW indexes. Fourth, the database and tools for creating the database, analyzing PWs, and replicating the case studies are freely available.
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An improved extraction protocol for therapeutic dabigatran monitoring using HPLC-MS/MS
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01.11.2019 |
Kozlov A.
Ramenskaya G.
Sychev D.
Vlasov A.
Makarenkova L.
Stepanova E.
Gegechkori V.
Agatonovic-Kustrin S.
Chistyakov V.
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Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences |
10.1016/j.jchromb.2019.121808 |
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© 2019 Elsevier B.V. A new sample extraction protocol was developed for pharmacokinetic studies of dabigatran with high-performance liquid chromatography separation - electrospray ionization time-of-flight mass spectrometry analysis. After protein precipitation with acetonitrile, free dabigatran and its metabolites are separated into water phase by water-dichloromethane liquid-liquid extraction to purify the sample from proteins and endogenous lipophilic compounds. Chromatographic separation was achieved on an Agilent Zorbax SB-CN column (150 × 4.6 mm, 5 µm)) using 0.1% aqueous solution of formic acid and acetonitrile (80:20) as the mobile phase. Agilent Zorbax SB-CN column was selected to improve sample resolution and to avoided early elution of dabigatran previously seen when using a C18 column. The extended calibration curve was constructed from 5 to 1000 ng/L while precision and accuracy were assessed at four levels across the linear dynamic ranges. Within-run precision was <5.6% and the between-run precision was <3.9%. The method accuracy ranged from 89.8% to 104.4%. The developed method was successfully applied to 30 patient samples to evaluate antithrombotic efficacy and anticoagulant activity of dabigatran following knee endoprosthesis surgery.
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Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
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01.11.2019 |
Gaetani M.
Sabatier P.
Saei A.
Beusch C.
Yang Z.
Lundström S.
Zubarev R.
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Journal of Proteome Research |
10.1021/acs.jproteome.9b00500 |
0 |
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© 2019 American Chemical Society. Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.
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Cell cycle-dependent flagellar disassembly in a firebug trypanosomatid leptomonas pyrrhocoris
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01.11.2019 |
He C.
Singh A.
Yurchenko V.
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mBio |
10.1128/mBio.02424-19 |
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© 2019 He et al. Current understanding of flagellum/cilium length regulation focuses on a few model organisms with flagella of uniform length. Leptomonas pyrrhocoris is a monoxenous trypanosomatid parasite of firebugs. When cultivated in vitro, L. pyrrhocoris duplicates every 4.2 ± 0.2 h, representing the shortest doubling time reported for trypanosomatids so far. Each L. pyrrhocoris cell starts its cell cycle with a single flagellum. A new flagellum is assembled de novo, while the old flagellum persists throughout the cell cycle. The flagella in an asynchronous L. pyrrhocoris population exhibited a vast length variation of ∼3 to 24 μm, casting doubt on the presence of a length regulation mechanism based on a single balance point between the assembly and disassembly rate in these cells. Through imaging of live L. pyrrhocoris cells, a rapid, partial disassembly of the existing, old flagellum is observed upon, if not prior to, the initial assembly of a new flagellum. Mathematical modeling demonstrated an inverse correlation between the flagellar growth rate and flagellar length and inferred the presence of distinct, cell cycle-dependent disassembly mechanisms with different rates. On the basis of these observations, we proposed a min-max model that could account for the vast flagellar length range observed for asynchronous L. pyrrhocoris. This model may also apply to other flagellated organisms with flagellar length variation. IMPORTANCE Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme stability and lack of ciliary disassembly/absorption during the cell cycle. This is different from cilia in Chlamydomonas and mammalian cells, which undergo complete absorption prior to cell cycle initiation. In this study, we examined flagellum duplication during the cell cycle of Leptomonas pyrrhocoris. With the shortest duplication time documented for all Trypanosomatidae and its amenability to culture on agarose gel with limited mobility, we were able to image these cells through the cell cycle. Rapid, cell cycle-specific flagellum disassembly different from turnover was observed for the first time in trypanosomatids. Given the observed length-dependent growth rate and the presence of different disassembly mechanisms, we proposed a min-max model that can account for the flagellar length variation observed in L. pyrrhocoris.
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Effects of different dietary regimes alone or in combination with standardized Aronia melanocarpa extract supplementation on lipid and fatty acids profiles in rats
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01.11.2019 |
Milic P.
Jeremic J.
Zivkovic V.
Srejovic I.
Jeremic N.
Bradic J.
Nikolic Turnic T.
Milosavljevic I.
Bolevich S.
Bolevich S.
Labudovic Borovic M.
Arsic A.
Mitrovic M.
Jakovljevic V.
Vucic V.
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Molecular and Cellular Biochemistry |
10.1007/s11010-019-03597-6 |
0 |
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© 2019, Springer Science+Business Media, LLC, part of Springer Nature. This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12–14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.
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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 |
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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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Polyisobutylene-based thermoplastic elastomers for manufacturing polymeric heart valve leaflets: In vitro and in vivo results
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01.11.2019 |
Ovcharenko E.
Rezvova M.
Nikishau P.
Kostjuk S.
Glushkova T.
Antonova L.
Trebushat D.
Akentieva T.
Shishkova D.
Krivikina E.
Klyshnikov K.
Kudryavtseva Y.
Barbarash L.
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Applied Sciences (Switzerland) |
10.3390/app9224773 |
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© 2019 by the authors. Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials' hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.
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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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Highly hydrophilic 1,3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure
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01.11.2019 |
Kalinin S.
Valtari A.
Ruponen M.
Toropainen E.
Kovalenko A.
Nocentini A.
Gureev M.
Dar'in D.
Urtti A.
Supuran C.
Krasavin M.
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Bioorganic and Medicinal Chemistry |
10.1016/j.bmc.2019.115086 |
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© 2019 Elsevier Ltd Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.
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Assessment of hemostatic disturbances in women with established rheumatoid arthritis
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01.11.2019 |
Vranic A.
Pruner I.
Veselinovic M.
Soutari N.
Petkovic A.
Jakovljevic V.
Antovic A.
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Clinical Rheumatology |
10.1007/s10067-019-04629-8 |
0 |
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© 2019, The Author(s). Objectives: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. Method: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. Results: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. Conclusions: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting.Key Points• Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis.• Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause.• Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis.• Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.
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Dysregulated iron metabolism-associated dietary pattern predicts an altered body composition and metabolic syndrome
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01.11.2019 |
Cempaka A.
Tseng S.
Yuan K.
Bai C.
Tinkov A.
Skalny A.
Chang J.
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Nutrients |
10.3390/nu11112733 |
0 |
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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Diet plays an important role in the development of obesity and may contribute to dysregulated iron metabolism (DIM). A cross-sectional survey of 208 adults was conducted in Taipei Medical University Hospital (Taipei, Taiwan). A reduced-rank regression from 31 food groups was used for a dietary pattern analysis. DIM was defined as at least four of the following criteria: serum hepcidin (men >200 ng/mL and women >140 ng/mL), hyperferritinemia (serum ferritin of >300 ng/mL in men and >200 ng/mL in women), central obesity, non-alcoholic fatty liver disease, and two or more abnormal metabolic profiles. Compared to non-DIM patients, DIM patients were associated with an altered body composition and had a 4.52-fold (95% confidence interval (CI): (1.95–10.49); p < 0.001) greater risk of metabolic syndrome (MetS) after adjusting for covariates. A DIM-associated dietary pattern (high intake of deep-fried food, processed meats, chicken, pork, eating out, coffee, and animal fat/skin but low intake of steamed/boiled/raw foods and dairy products) independently predicted central obesity (odds ratio (OR): 1.57; 95% CI: 1.05–2.34; p < 0.05) and MetS (OR: 1.89; 95% CI: 1.07–3.35; p < 0.05). Individuals with the highest DIM pattern scores (tertile 3) had a higher visceral fat mass (%) (β = 0.232; 95% CI: 0.011–0.453; p < 0.05) but lower skeletal muscle mass (%) (β = −1.208; 95% CI: −2.177–−0.239; p < 0.05) compared to those with the lowest DIM pattern scores (tertile 1). In conclusion, a high score for the identified DIM-associated dietary pattern was associated with an unhealthier body composition and a higher risk of MetS.
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The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats
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01.11.2019 |
Djuric M.
Nikolic Turnic T.
Kostic S.
Stankovic S.
Radonjic K.
Djuric D.
Zivkovic V.
Jakovljevic V.
Stevanovic P.
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Canadian journal of physiology and pharmacology |
10.1139/cjpp-2019-0029 |
0 |
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This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.
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Mortality of patients with rheumatoid arthritis requiring intensive care: a single-center retrospective study
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01.11.2019 |
Haviv-Yadid Y.
Segal Y.
Dagan A.
Sharif K.
Bragazzi N.
Watad A.
Amital H.
Shoenfeld Y.
Shovman O.
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Clinical Rheumatology |
10.1007/s10067-019-04651-w |
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© 2019, International League of Associations for Rheumatology (ILAR). Background: Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU. Methods: This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002–2018. The main outcome was 30-day mortality. Using Student’s t test, χ2, and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant. Results: Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respectively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032). Conclusions: Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly.Key Points• The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%.• The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients.• Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly.
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Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate
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01.11.2019 |
Ivachtchenko A.
Mitkin O.
Kravchenko D.
Kovalenko S.
Shishkina S.
Bunyatyan N.
Konovalova I.
Dmitrieva I.
Ivanov V.
Langer T.
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Heliyon |
10.1016/j.heliyon.2019.e02738 |
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© 2019 The Author(s) A method of 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate synthesis has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single crystal X-ray analysis has revealed that it exists in a monoclinic P21/c space group, with one molecule in the asymmetric part of the unit cell. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking study evaluates the investigated compound as a new potential inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance demonstrates in vitro nanomolar inhibitory activity against HBV. Organic chemistry; Theoretical chemistry; Pharmaceutical chemistry, Hepatitis B; HBV; Pharmaceutical crystals; 4-Fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate; Benzothiophene; Hydrogen bond; Hirshfeld surface analysis; Molecular docking study
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Harmful alcohol use among acutely ill hospitalized medical patients in Oslo and Moscow: A cross-sectional study
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01.11.2019 |
Kabashi S.
Vindenes V.
Bryun E.
Koshkina E.
Nadezhdin A.
Tetenova E.
Kolgashkin A.
Petukhov A.
Perekhodov S.
Davydova E.
Gamboa D.
Hilberg T.
Lerdal A.
Nordby G.
Zhang C.
Bogstrand S.
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Drug and Alcohol Dependence |
10.1016/j.drugalcdep.2019.107588 |
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© 2019 The Authors Background: The aim was to estimate the prevalence of harmful alcohol use in relation to socio-demographic characteristics among acutely ill medical patients, and examine identification measures of alcohol use, including the alcohol biomarker phosphatidylethanol 16:0/18:1 (PEth). Methods: A cross-sectional study, lasting one year at one hospital in Oslo, Norway and one in Moscow, Russia recruiting acute medically ill patients (≥ 18 years), able to give informed consent. Self-reported data on socio-demographics, mental distress (Symptom Check List-5), alcohol use (Alcohol Use Disorder Identification Test-4 (AUDIT-4) and alcohol consumption past 24 h were collected. PEth and alcohol concentration were measured in whole blood. Results: Of 5883 participating patients, 19.2% in Moscow and 21.1% in Oslo were harmful alcohol users, measured by AUDIT-4, while the prevalence of PEth-positive patients was lower: 11.4% in Oslo, 14.3% in Moscow. Men in Moscow were more likely to be harmful users by AUDIT-4 and PEth compared to men in Oslo, except of those being ≥ 71 years. Women in Oslo were more likely to be harmful users compared to those in Moscow by AUDIT-4, but not by PEth for those aged < 61 years. Conclusions: The prevalence of harmful alcohol use was high at both study sites. The prevalence of harmful alcohol use was lower when assessed by PEth compared to AUDIT-4. Thus, self-reporting was the most sensitive measure in revealing harmful alcohol use among all groups except for women in Moscow. Hence, screening and identification with objective biomarkers and self-reporting might be a method for early intervention.
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Outcome of isolated fetal talipes: A systematic review and meta-analysis
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01.11.2019 |
Di Mascio D.
Buca D.
Khalil A.
Rizzo G.
Makatsariya A.
Sileo F.
Liberati M.
Benedetti Panici P.
Acharya G.
D'Antonio F.
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Acta Obstetricia et Gynecologica Scandinavica |
10.1111/aogs.13637 |
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© 2019 Nordic Federation of Societies of Obstetrics and Gynecology Introduction: The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes. Material and methods: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data. Results: Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up. Conclusions: Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.
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A-site ordered state in manganites with perovskite-like structure based on optimally doped compounds Ln<inf>0.70</inf>Ba<inf>0.30</inf>MnO<inf>3</inf> (Ln = Pr, Nd)
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01.11.2019 |
Trukhanov S.
Khomchenko V.
Karpinsky D.
Silibin M.
Trukhanov A.
Lobanovsky L.
Szymczak H.
Botez C.
Troyanchuk I.
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Journal of Rare Earths |
10.1016/j.jre.2018.12.010 |
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© 2019 Chinese Society of Rare Earths In this paper, we report on the crystal structure and magnetic properties of the nanostructured Ba-ordered phases of rare-earth manganites obtained from the optimally doped solid solutions Ln0.70Ba0.30MnO3 (Ln = Pr, Nd). The materials were studied by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy and SQUID-magnetometry techniques. It is found that states with different degrees of cation ordering in the A-sublattice of the ABO3 perovskite can be obtained by employing special conditions of chemical treatment. In particular, reduction of the parent compounds results in the formation of a nanocomposite containing ferrimagnetic anion-deficient ordered phase LnBaMn2O5. Oxidation of the composite does not change an average size of the nanocrystallites, but drastically alters their phase composition to stabilize ferromagnetic stoichiometric ordered phase LnBaMn2O6 and ferromagnetic superstoichiometric disordered phase Ln0.90Ba0.10MnO3+δ. It is shown that the magnetic properties of the materials are determined by the joint action of chemical (cation ordering) and external (surface tension) pressures.
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