Understanding how consumers with food allergies make decisions based on precautionary labelling
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01.11.2019 |
DunnGalvin A.
Roberts G.
Regent L.
Austin M.
Kenna F.
Schnadt S.
Sanchez-Sanz A.
Hernandez P.
Hjorth B.
Fernandez-Rivas M.
Taylor S.
Baumert J.
Sheikh A.
Astley S.
Crevel R.
Mills C.
|
Clinical and Experimental Allergy |
10.1111/cea.13479 |
3 |
Ссылка
© 2019 John Wiley & Sons Ltd Background: Understanding consumer perceptions is crucial if effective food safety policy and risk communication are to be developed and implemented. We sought to understand how those living with food allergy assess risk with precautionary allergen labelling (PAL) and their preference in how risks are communicated within a quantitative risk assessment (QRA) framework. Methods: The Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) labelling online survey was developed for adults and parents of children with food allergy and distributed across Germany, Ireland, Netherlands, Spain and UK via patient support groups. Results: There were 1560 complete responses. ‘This product is not suitable for’ was selected as first choice for PAL by 46% overall and ‘May contain’ was selected as the first choice by 44%. Seventy-three percent reported that it would improve their trust in a product if a QRA process had been used to make a decision about whether to include ‘may contain’. Overall, 66% reported that a ‘statement + symbol’ on the label indicating a QRA, would help them to understand the risk assessment process that had been used by the food manufacturer. Conclusions: Consumers want to know what process has actually taken place for the placing of a PAL and/or risk assessment statement on a particular food product. Our findings provide a basis for the development of more informative communication around food allergen risk and safety and support evidence-based policy-making in the context of the legislative requirements of the European Union's Food Information for Consumers Regulation.
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European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update
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01.11.2019 |
Babjuk M.
Burger M.
Compérat E.
Gontero P.
Mostafid A.
Palou J.
van Rhijn B.
Rouprêt M.
Shariat S.
Sylvester R.
Zigeuner R.
Capoun O.
Cohen D.
Escrig J.
Hernández V.
Peyronnet B.
Seisen T.
Soukup V.
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European Urology |
10.1016/j.eururo.2019.08.016 |
2 |
Ссылка
© 2019 Context: This overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). Objective: To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2–6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1–3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Non–muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.
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Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study
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01.11.2019 |
Valentini G.
Huscher D.
Riccardi A.
Fasano S.
Irace R.
Messiniti V.
Matucci-Cerinic M.
Guiducci S.
Distler O.
Maurer B.
Avouac J.
Tarner I.
Frerix M.
Riemekasten G.
Siegert E.
Czirják L.
Lóránd V.
Denton C.
Nihtyanova S.
Walker U.
Jaeger V.
Del Galdo F.
Abignano G.
Ananieva L.
Gherghe A.
Mihai C.
Henes J.
Schmeiser T.
Vacca A.
Moiseev S.
Foeldvari I.
Gabrielli A.
Krummel-Lorenz B.
Rednic S.
Allanore Y.
Müeller-Ladner U.
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Annals of the Rheumatic Diseases |
10.1136/annrheumdis-2019-215486 |
3 |
Ссылка
© Author(s) (or their employer(s)) 2019. Objectives To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). Methods 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. Results During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). Conclusions The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.
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Update of Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS)): Part B
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01.11.2019 |
Bittner R.
Bain K.
Bansal V.
Berrevoet F.
Bingener-Casey J.
Chen D.
Chen J.
Chowbey P.
Dietz U.
de Beaux A.
Ferzli G.
Fortelny R.
Hoffmann H.
Iskander M.
Ji Z.
Jorgensen L.
Khullar R.
Kirchhoff P.
Köckerling F.
Kukleta J.
LeBlanc K.
Li J.
Lomanto D.
Mayer F.
Meytes V.
Misra M.
Morales-Conde S.
Niebuhr H.
Radvinsky D.
Ramshaw B.
Ranev D.
Reinpold W.
Sharma A.
Schrittwieser R.
Stechemesser B.
Sutedja B.
Tang J.
Warren J.
Weyhe D.
Wiegering A.
Woeste G.
Yao Q.
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Surgical Endoscopy |
10.1007/s00464-019-06908-6 |
0 |
Ссылка
© 2019, The Author(s). Abstract: In 2014 the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias”. Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based-Medicine. For the present update all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne) the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite still insufficient evidence with respect to these new techniques it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initially guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.
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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 |
Ссылка
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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Synthesis, in vivo and in silico anticonvulsant activity studies of new derivatives of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)acetamide
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15.10.2019 |
El Kayal W.
Shtrygol S.
Zalevskyi S.
Shark A.
Tsyvunin V.
Kovalenko S.
Bunyatyan N.
Perekhoda L.
Severina H.
Georgiyants V.
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European Journal of Medicinal Chemistry |
10.1016/j.ejmech.2019.06.085 |
0 |
Ссылка
© 2019 Elsevier Masson SAS In order to expand the arsenal of biologically active substances of anticonvulsive action by the interaction of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)acetic acid with the corresponding amines in the presence of N,N′-carbonyldiimidazole in the dioxane medium, a systematic series of 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-R-acetamides was obtained. A novel approach to synthesis of the key intermediate - 2-(2,4-dioxo-1,4-dihydro-quinazolin-3(2H)-yl)acetic acid was developed. The structure and purity of the resulting substances was confirmed by elemental analysis, 1H NMR, 13C NMR spectroscopy and LC/MS. Based on the results of docking studies using SCIGRESS software, selected compounds with the best affinity for anticonvulsant protein biomes (PDB codes: 4COF, 3F8E and 1 EOU) are promising for experimental studies of anticonvulsant activity. A comparative analysis of the results of molecular docking and in vivo results suggests that there is a positive correlation between scoring protein inhibition and experimental data. Pharmacological studies have revealed the leader compound 2-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)-N-[(2,4-dichlorophenyl)methyl]acet-amide, which improved all the experimental convulsive syndrome rates in mice without motor coordination impairment and may be recommended for further research. The lowest values of the scoring function of the ligand-peptide interaction are obtained for the synthesized compound and сarbonic anhydrase II (gene name CA2) (PDB code 1 EOU), so its inhibition is proposed by us as the most probable mechanism of the anticonvulsive effect of the leader compound.
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Finite volume method for coupled subsurface flow problems, I: Darcy problem
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15.10.2019 |
Terekhov K.
Vassilevski Y.
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Journal of Computational Physics |
10.1016/j.jcp.2019.06.009 |
0 |
Ссылка
© 2019 Elsevier Inc. The article introduces a finite-volume method for the Darcy problem in heterogeneous anisotropic media. The method is based on the mixed formulation for the pressure and its gradient. The method is stable despite collocation of both pressure and its gradient at cell centers and demonstrates the first order convergence on numerous benchmarks as well as good monotonicity property. The method produces quasi-definite matrix, which is numerically shown to have good asymptotics of the condition number. Our flux discretization method is a realization of our more general concept of stable flux discretization for saddle-point systems with vector of several unknowns. In this paper this vector is composed of pressure and its gradient and the saddle-point system is the mixed formulation of the Darcy problem.
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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 |
Ссылка
© 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 |
0 |
Ссылка
© 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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Update of Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias (International Endohernia Society (IEHS))—Part A
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15.10.2019 |
Bittner R.
Bain K.
Bansal V.
Berrevoet F.
Bingener-Casey J.
Chen D.
Chen J.
Chowbey P.
Dietz U.
de Beaux A.
Ferzli G.
Fortelny R.
Hoffmann H.
Iskander M.
Ji Z.
Jorgensen L.
Khullar R.
Kirchhoff P.
Köckerling F.
Kukleta J.
LeBlanc K.
Li J.
Lomanto D.
Mayer F.
Meytes V.
Misra M.
Morales-Conde S.
Niebuhr H.
Radvinsky D.
Ramshaw B.
Ranev D.
Reinpold W.
Sharma A.
Schrittwieser R.
Stechemesser B.
Sutedja B.
Tang J.
Warren J.
Weyhe D.
Wiegering A.
Woeste G.
Yao Q.
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Surgical Endoscopy |
10.1007/s00464-019-06907-7 |
2 |
Ссылка
© 2019, The Author(s). Abstract: In 2014, the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias.” Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.
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The influence of taurine and L-carnitine on 6 β-hydroxycortisol/cortisol ratio in human urine of healthy volunteers
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11.10.2019 |
Makhova A.
Shikh E.
Bulko T.
Sizova Z.
Shumyantseva V.
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Drug metabolism and personalized therapy |
10.1515/dmpt-2019-0013 |
0 |
Ссылка
Background Cytochrome P450s (CYPs, EC 1.14.14.1) are the main enzymes of drug metabolism. The functional significance of CYPs also includes the metabolism of foreign chemicals and endogenic biologically active compounds. The CYP3A4 isoform contributes to the metabolism of about half of all marketed medicinal preparations. The aim of this study was to investigate the effects of two biologically active compounds: 2-aminoethane-sulfonic acid (taurine) and 3-hydroxy-4-trimethylaminobutyrate (L-carnitine) on urinary 6β-hydroxycortisol/cortisol (6β-OHC/cortisol) metabolic ratio as a biomarker of the CYP3A4 activity of healthy volunteers. Taurine is used for the treatment of chronic heart failure and liver disease. Cardiologists, nephrologists, neurologists, gerontologists in addition to the main etiopathogenetic therapies, use L-carnitine. The quantification of the 6β-OHC/cortisol metabolic ratio as a biomarker of CYP3A4 activity in human urine was used for the assessment of CYP3A4 catalytic activity as a non-invasive test. Methods The study included 18 healthy male volunteers (aged from 18 to 35 years old). The volunteers took taurine in a dose of 500 mg twice a day or L-carnitine in a dose of 2.5 mL 3 times a day for 14 consecutive days. The test drug was given 20 min before meals. The collection of urine samples was performed before and after 3, 7, 10, and 14 days after taurine intake. The metabolic ratio of 6β-OHC/cortisol in morning spot urine samples was studied by the liquid chromatography/mass spectroscopy (LC/MS) method. Results The ratio of 6-6β-OHC/cortisol was used as a biomarker to study the taurine and L-carnitine influence on CYP3A4 metabolism of cortisol. The ratio of urinary 6β-OCH/cortisol in the morning urine samples of volunteers before the beginning of taurine therapy (baseline ratio) was 2.71 ± 0.2. Seven days after the administration of taurine in a dose of 500 mg twice a day, the 6β-OCH/cortisol ratio was 3.3 ± 0.2, which indicated the increased catalytic activity of CYP3A4 towards cortisol. As for the L-carnitine supplementation, analysis of the 6β-OCH/cortisol ratio in the urine for 14 days did not show any significant changes in this baseline ratio, indicating the lack of L-carnitine influence on the catalytic activity of CYP3A4 to cortisol. Conclusions The results obtained demonstrated the influence of taurine on 6β-OCH/cortisol metabolic ratio as a biomarker of CYP3A4 catalytic activity to cortisol. L-carnitine did not affect the activity of CYP3A4. The lack of a clinically meaningful effect of L-carnitine was established.
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Comparative genomics of Leishmania (Mundinia)
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11.10.2019 |
Butenko A.
Kostygov A.
Sádlová J.
Kleschenko Y.
Bečvář T.
Podešvová L.
MacEdo D.
Žihala D.
Lukeš J.
Bates P.
Volf P.
Opperdoes F.
Yurchenko V.
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BMC Genomics |
10.1186/s12864-019-6126-y |
0 |
Ссылка
© 2019 The Author(s). Background: Trypanosomatids of the genus Leishmania are parasites of mammals or reptiles transmitted by bloodsucking dipterans. Many species of these flagellates cause important human diseases with clinical symptoms ranging from skin sores to life-threatening damage of visceral organs. The genus Leishmania contains four subgenera: Leishmania, Sauroleishmania, Viannia, and Mundinia. The last subgenus has been established recently and remains understudied, although Mundinia contains human-infecting species. In addition, it is interesting from the evolutionary viewpoint, representing the earliest branch within the genus and possibly with a different type of vector. Here we analyzed the genomes of L. (M.) martiniquensis, L. (M.) enriettii and L. (M.) macropodum to better understand the biology and evolution of these parasites. Results: All three genomes analyzed were approximately of the same size (~ 30 Mb) and similar to that of L. (Sauroleishmania) tarentolae, but smaller than those of the members of subgenera Leishmania and Viannia, or the genus Endotrypanum (~ 32 Mb). This difference was explained by domination of gene losses over gains and contractions over expansions at the Mundinia node, although only a few of these genes could be identified. The analysis predicts significant changes in the Mundinia cell surface architecture, with the most important ones relating to losses of LPG-modifying side chain galactosyltransferases and arabinosyltransferases, as well as β-amastins. Among other important changes were gene family contractions for the oxygen-sensing adenylate cyclases and FYVE zinc finger-containing proteins. Conclusions: We suggest that adaptation of Mundinia to different vectors and hosts has led to alternative host-parasite relationships and, thereby, made some proteins redundant. Thus, the evolution of genomes in the genus Leishmania and, in particular, in the subgenus Mundinia was mainly shaped by host (or vector) switches.
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Physiologically based mathematical modelling of solute transport within the epidermis and dermis
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05.10.2019 |
Calcutt J.
Anissimov Y.
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International Journal of Pharmaceutics |
10.1016/j.ijpharm.2019.118547 |
0 |
Ссылка
© 2019 Elsevier B.V. The stratum corneum is the main barrier to transdermal drug delivery which has previously resulted in mathematical modelling of solute transport in the skin being primarily directed at this skin layer. However, for topical treatment and skin toxicity studies, the concentration in the epidermis and dermis is important and needs to be modelled mathematically. Hitherto, mathematical models for viable skin layers typically simplified the clearance of solute by blood, either assuming sink condition at the top of the skin capillary loops or assuming a distributed clearance in the dermis. This paper is an attempt to develop a physiologically based mathematical model of drug transport in the viable skin. It incorporates explicit modelling of the capillary loops within the dermis and employs COMSOL Multiphysics® software to model the transport in three dimensions. Previously derived simplified models were compared to the results from this new numerical model. The results of this comparison showed that the simplified model reasonably described the average concentration in the viable skin layers when parameters of the models were chosen appropriately. When the recruitment of the capillary loops in the dermis was full and the top of capillary loops was at a depth of 100μm, the effective depth to place a sink condition in the simpler models was found to be at 150μm. However, when there was only partial recruitment of the capillaries, the effective depth increased to 180μm. The presented modelling is also essential for determining a transdermal flux when the stratum corneum barrier is compromised by such methods as microporation, application of chemical enhancers or microneedles.
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Effect of CYP3A4, CYP3A5, ABCB1 Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Undergoing Total Hip and Knee Replacement Surgery
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01.10.2019 |
Sychev D.
Minnigulov R.
Bochkov P.
Ryzhikova K.
Yudina I.
Lychagin A.
Morozova T.
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High Blood Pressure and Cardiovascular Prevention |
10.1007/s40292-019-00342-4 |
0 |
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© 2019, Italian Society of Hypertension. Introduction: Population ageing in developed countries will inevitably increase the need for knee and hip replacement surgery. Over the years, direct oral anticoagulants, such as rivaroxaban, have been widely used for thromboprophylaxis in patients undergoing knee and hip replacement surgery. The study of pharmacogenetic characteristics of rivaroxaban is important for enhancing the effectiveness and safety of rivaroxaban thromboprophylaxis. Aim: Evaluation of CYP3A4, CYP3A5 and ABCB1 gene polymorphisms influence on rivaroxaban pharmacokinetics and prothrombin time dynamics in patients undergoing total hip and knee replacement surgery. Methods: The study included 78 patients undergoing total hip and knee replacement surgery. The patients received 10 mg of rivaroxaban once a day. Genotyping of polymorphisms ABCB1 rs1045642, ABCB1 rs4148738, CYP3A4 rs35599367 and CYP3A5 rs776746 was performed. Peak steady-state and trough steady-state rivaroxaban concentrations were determined. Prothrombin time was also evaluated. Results: The study revealed the following haplotypes: (1) ABCB1 rs1045642—CYP3A4 rs35599367 and (2) ABCB1 rs4148738—CYP3A4 rs35599367. The analysis of the peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes revealed no significant differences. However, there was a statistically significant average correlation between peak steady-state rivaroxaban concentration and prothrombin time (r = 0.421; r2 = 0.178; p < 0.001). Conclusion: No significant difference was identified in peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes. The revealed statistically significant average correlation between the prothrombin time and peak steady-state rivaroxaban concentration is important in clinical practice for assessing the anticoagulant activity of rivaroxaban.
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Emergence of intronless evolutionary forms of stress response genes: Possible relation to terrestrial adaptation of green plants
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01.10.2019 |
Morozov S.
Solovyev A.
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Frontiers in Plant Science |
10.3389/fpls.2019.00083 |
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Protein-polymer matrices with embedded carbon nanotubes for tissue engineering: Regularities of formation and features of interaction with cell membranes
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01.10.2019 |
Slepchenkov M.
Gerasimenko A.
Telyshev D.
Glukhova O.
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Materials |
10.3390/ma12193083 |
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© 2019 by the authors. This paper reveals the mechanism of nanowelding a branched network of single-walled carbon nanotubes (SWCNTs) used as a framework for the formation of protein-polymer matrices with albumin, collagen, and chitosan. It is shown that the introduction of certain point defects into the structure of SWCNTs (single vacancy, double vacancy, Stone-Wales defect, and a mixed defect) allows us to obtain strong heating in defective regions as compared to ideal SWCNTs. The wavelengths at which absorption reaches 50% are determined. Non-uniform absorption of laser radiation along with inefficient heat removal in defective regions determines the formation of hot spots, in which nanowelding of SWCNTs is observed even at 0.36 nm between contacting surfaces. The regularities of formation of layered protein-polymer matrices and the features of their interaction with cell membrane are revealed. All studies are carried out in silico using high-precision quantum approaches.
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Levels of nitric oxide metabolites, adiponectin and endothelin are associated with SNPs of the adiponectin and endothelin genes
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01.10.2019 |
Gumanova N.
Klimushina M.
Smetnev S.
Kiseleva A.
Skirko O.
Meshkov A.
Shanoyan A.
Kots A.
Metelskaya V.
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Biomedical Reports |
10.3892/br.2019.1238 |
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© 2019, Spandidos Publications. All rights reserved. Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbal-ance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin (ADIPOQ) gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin-1 (EDN1) gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the ADIPOQ gene and rs2070699 and rs1800543 of the EDN1 gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the ADIPOQ gene were associated with adiponectin levels, whereas rs17366743 of the ADIPOQ gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender-specific manner and contribute to the development of clinical manifestations of atherosclerosis.
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Development and validation of spectrophotometric procedure for quantitative determination of flavonoid content used to control the quality of mixture herbal product
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01.10.2019 |
Smyslova O.
Bokov D.
Potanina O.
Litvinova T.
Samylina I.
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Journal of Advanced Pharmaceutical Technology and Research |
10.4103/japtr.JAPTR_61_19 |
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© 2019 Journal of Advanced Pharmaceutical Technology & Research Published by Wolters Kluwer - Medknow. Species, known as mixture herbal products, are compositions of several types of crushed, sometimes whole, medicinal plant materials with additives; they are a widely used dosage form in the Russian Federation. A large range of species are produced at the pharmaceutical companies. In pharmacopoeial analysis, the most popular and widely used method for the determination of flavonoids, suitable for the standardization of species, is the method of differential spectrophotometry, based on the complexation of flavonoids with aluminum chloride. In accordance with modern requirements for the drugs production, the validation of analytical methods is a prerequisite for the creation of pharmacopoeial monographs projects regulating the quality of pharmaceutical substances of plant origin. Therefore, it is necessary to validate analytical methods for their intended use in evaluating the drug quality. This article discusses/presents the main stages of development and validation (by parameters: accuracy, precision, specificity, linearity) of the methodology for determining total flavonoid content using original species 'Fitourol' as a model.
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Surgically-oriented anatomical study of mandibular premolars: A CBCT study
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01.10.2019 |
Corbella S.
Baruffaldi M.
Perondi I.
Taschieri S.
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Journal of Clinical and Experimental Dentistry |
10.4317/jced.55848 |
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© Medicina Oral S. L. C.I.F. Background: The knowledge of root canal anatomy and of the anatomical relationship should be considered mandatory when planning surgical endodontics. The aim of the study was to investigate the anatomical features of mandibular premolars, evaluating their relationship with mental nerve. Material and Methods: CBCT scans were evaluated recording the number of roots, root canal configuration and the relationship with mental nerve of 100 mandibular premolars. After simulating a resection of 3 mm of the root, the shape and the number of canals, and the distance to the buccal and lingual bone plate and to the mental foramen was evaluated. Results: The one root - one canal configuration was the most common configuration. The mental foramen was located at the level of MSPs in 40% cases, and it was between MSP and MFP in 46% of cases. The distance between the apex and the vestibular plate was lower than the distance to the lingual one. Conclusions: We found a significant heterogeneity in the anatomy of mandibular premolars. CBCT could be considered important when planning surgical endodontics in this region.
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Anaphylaxis in adolescents
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01.10.2019 |
Comberiati P.
Spahn J.
Peroni D.
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Current Opinion in Allergy and Clinical Immunology |
10.1097/ACI.0000000000000572 |
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© 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose of reviewThe frequency of hospitalization for anaphylaxis has increased over the last 20 years across Europe, Australia, and North America, particularly, for food and medication triggers. Adolescents show the highest risk for morbidity and fatality from food-induced anaphylaxis, yet there is little high-quality evidence addressing the reasons for this disproportionate vulnerability.Recent findingsRecent data seem to suggest a possible increasing burden of food-induced anaphylaxis among adolescents. Trends in anaphylaxis mortality are stable in North America and the United Kingdom, but not in Australia where the incidence of fatal anaphylaxis has recently doubled. The age distribution of fatal anaphylaxis varies according to the nature of the culprit trigger, with data suggesting an age-related predisposition to fatal food anaphylaxis in adolescents and young adults. Adolescence represents a critical phase of transition when rapid and substantial physical, emotional, and social changes occur. Therefore, adolescents show challenges in self-management that are different from other age groups, contributing to a higher risk of poor anaphylaxis outcomes.SummaryThe purpose of this review is to summarize recent data on epidemiology and elicitors of anaphylaxis in adolescents and to address currently known barriers and potential facilitators to self-management of anaphylaxis in this vulnerable age group.
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