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Frederik Flenner, Nicole Arlt, Mahtab Nasib, Sophie Schobesberger, Thea Koch, Ursula Ravens, Felix Friedrich, Viacheslav Nikolaev, Torsten Christ, Sebastian N Stehr
BACKGROUND: Systemic toxicity of local anesthetics is predominantly complicated by their myocardial toxicity. Especially long-acting local anesthetics exert a negative inotropic effect that has been described at lower concentrations than defined for blockade of myocardial ion channels. We evaluated the negative inotropic effect of bupivacaine at a concentration described for clinical toxicity testing the hypothesis that negative inotropy is a result of reduced Ca sensitivity rather than blockade of ion channels...
March 16, 2018: Anesthesiology
Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
March 15, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Angela Contreras, Magdalena Ribbeck, Guillermo D Gutiérrez, Pablo M Cañon, Sebastián N Mendoza, Eduardo Agosin
The effect of ethanol on the metabolism of Oenococcus oeni , the bacterium responsible for the malolactic fermentation (MLF) of wine, is still scarcely understood. Here, we characterized the global metabolic response in O. oeni PSU-1 to increasing ethanol contents, ranging from 0 to 12% (v/v). We first optimized a wine-like, defined culture medium, MaxOeno, to allow sufficient bacterial growth to be able to quantitate different metabolites in batch cultures of O. oeni . Then, taking advantage of the recently reconstructed genome-scale metabolic model iSM454 for O...
2018: Frontiers in Microbiology
Jeroen Frank, Sebastian Lücker, Rolf H A M Vossen, Mike S M Jetten, Richard J Hall, Huub J M Op den Camp, Seyed Yahya Anvar
Anaerobic ammonium-oxidizing (anammox) bacteria are a group of strictly anaerobic chemolithoautotrophic microorganisms. They are capable of oxidizing ammonium to nitrogen gas using nitrite as a terminal electron acceptor, thereby facilitating the release of fixed nitrogen into the atmosphere. The anammox process is thought to exert a profound impact on the global nitrogen cycle and has been harnessed as an environment-friendly method for nitrogen removal from wastewater. In this study, we present the first closed genome sequence of an anammox bacterium, Kuenenia stuttgartiensis MBR1...
March 15, 2018: Scientific Reports
Tina C Roeske, Damian Kelty-Stephen, Sebastian Wallot
Music is thought to engage its listeners by driving feelings of surprise, tension, and relief through a dynamic mixture of predictable and unpredictable patterns, a property summarized here as "expressiveness". Birdsong shares with music the goal to attract its listeners' attention and might use similar strategies to achieve this. We here tested a thrush nightingale's (Luscinia luscinia) rhythm, as represented by song amplitude envelope (containing information on note timing, duration, and intensity), for evidence of expressiveness...
March 15, 2018: Scientific Reports
William Pao, Chia-Huey Ooi, Fabian Birzele, Astrid Ruefli-Brasse, Michael A Cannarile, Bernhard Reis, Sebastian H Scharf, David A Schubert, Klas Hatje, Nadege Pelletier, Olivia Spleiss, John C Reed
Checkpoint inhibitor therapy has been a breakthrough in cancer research, but only some patients with cancer derive substantial benefit. Although mechanisms underlying sensitivity and resistance to checkpoint inhibitors are being elucidated, the importance of organ-specific regulation of immunity is currently underappreciated. Here, we call for a greater understanding of tissue-specific immunoregulation, namely, "tissue-specific immunostats," to make advances in treatments for cancer. A better understanding of how individual organs at baseline regulate the immune system could enable an improved precision medicine approach to cancer immunotherapy...
March 15, 2018: Cancer Discovery
Hetal Patel, Manikandan Periyasamy, Georgina P Sava, Alexander Bondke, Brian W Slafer, Sebastian H B Kroll, Marion Barbazanges, Richard Starkey, Silvia Ottaviani, Alison Harrod, Eric O Aboagye, Laki Buluwela, Matthew J Fuchter, Anthony G M Barrett, Charles Coombes, Simak Ali
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942...
March 15, 2018: Molecular Cancer Therapeutics
Tobias Koppara, Tomohisa Tada, Erion Xhepa, Sebastian Kufner, Robert A Byrne, Tareq Ibrahim, Karl-Ludwig Laugwitz, Adnan Kastrati, Michael Joner
BACKGROUND: Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. METHODS: We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months...
May 1, 2018: International Journal of Cardiology
Sebastian Hiller, Björn M Burmann
Living cells contain molecular chaperones that are organized in intricate networks to surveil protein homeostasis by avoiding polypeptide misfolding, aggregation, and the generation of toxic species. In addition, cellular chaperones also fulfill a multitude of alternative functionalities: transport of clients towards a target location, help them fold, unfold misfolded species, resolve aggregates, or deliver clients towards proteolysis machineries. Until recently, the only available source of atomic resolution information for virtually all chaperones were crystal structures of their client-free, apo-forms...
April 2018: Journal of Magnetic Resonance
Michael A Samaan, Stacie I Ringleb, Sebastian Y Bawab, Eric K Greska, Joshua T Weinhandl
The effects of ACL-reconstruction on lower extremity joint mechanics during performance of the Star Excursion Balance Test (SEBT) and Single Leg Hop (SLH) are limited. The purpose of this study was to determine if altered lower extremity mechanics occur during the SEBT and SLH after ACL-reconstruction. One female Division I collegiate athlete performed the SEBT and SLH tasks, bilaterally, both before ACL injury and 27 months after ACL-reconstruction. Maximal reach, hop distances, lower extremity joint kinematics and moments were compared between both time points...
March 15, 2018: Computer Methods in Biomechanics and Biomedical Engineering
Sebastian Trippel, Joss Wiese, Terry Mullins, Jochen Küpper
Strong quasi-adiabatic laser alignment of the indole-water-dimer clusters, an amino-acid chromophore bound to a single water molecule through a hydrogen bond, was experimentally realized. The alignment was visualized through ion and electron imaging following strong-field ionization. Molecular-frame photoelectron angular distributions showed a clear suppression of the electron yield in the plane of the ionizing laser's polarization, which was analyzed as strong alignment of the molecular cluster with ⟨cos2 θ2D ⟩ ≥ 0...
March 14, 2018: Journal of Chemical Physics
Bruno Sommacal, Miodrag Savic, Andreas Filippi, Sebastian Kühl, Florian M Thieringer
PURPOSE: To compare the suitability of a fused filament fabrication (FFF) consumer 3D printer with a professional digital light processing (DLP) printer for the production of surgical templates for guided oral implant surgery. MATERIALS AND METHODS: Eight virtual templates were printed with two different 3D printers. These were optically scanned and the incongruences between virtual and printed templates were determined after alignment of the surface scans and the virtual data...
March 15, 2018: International Journal of Oral & Maxillofacial Implants
Sebastian Wallis, Lorcan O'Toole, Laszlo Karsai, Jose Jemy
Cancer of the unknown primary (CUP) makes up 2-4% of new head and neck squamous cell carcinoma (SCC) diagnoses. This scenario is recognised as a diagnostic challenge for head and neck surgeons. For all patients with proven cervical lymph node metastatic SCC without a clinically apparent primary site, the current UK guidelines recommends PET-CT, panendoscopy with directed biopsies and bilateral tonsillectomy as a standard of care. This article is protected by copyright. All rights reserved.
March 15, 2018: Clinical Otolaryngology
Zornitza Stark, Sebastian Lunke, Gemma R Brett, Natalie B Tan, Rachel Stapleton, Smitha Kumble, Alison Yeung, Dean G Phelan, Belinda Chong, Miriam Fanjul-Fernandez, Justine E Marum, Matthew Hunter, Anna Jarmolowicz, Yael Prawer, Jessica R Riseley, Matthew Regan, Justine Elliott, Melissa Martyn, Stephanie Best, Tiong Y Tan, Clara L Gaff, Susan M White
PurposeThe purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers.MethodsRapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed.ResultsOf 40 enrolled patients, 21 (52...
March 15, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Mehrshad Vafaie, Matthias Hochadel, Thomas Münzel, Birgit Hailer, Burghard Schumacher, Gerd Heusch, Thomas Voigtländer, Harald Mudra, Michael Haude, Sebastian Barth, Claus Schmitt, Harald Darius, Lars S Maier, Hugo A Katus, Jochen Senges, Evangelos Giannitsis
BACKGROUND: Since 2008, the German Cardiac Society certified 256 Chest Pain Units (CPUs). Little is known about adherence to recommended performance measures in patients with suspected acute coronary syndrome (ACS) presenting to CPUs. We investigated guideline-adherence regarding critical time intervals and selected performance measures in German Chest Pain Units. METHODS: From 2008 to 2014, 23,804 consecutive patients with suspected ACS were prospectively enrolled in the Chest Pain Unit registry of the German Cardiac Society...
March 1, 2018: European Heart Journal. Acute Cardiovascular Care
Alexander Buchholz, Laura Ueberham, Kaja Gorczynska, Borislav Dinov, Sebastian Hilbert, Nikolaos Dagres, Daniela Husser, Gerhard Hindricks, Andreas Bollmann
BACKGROUND: Apixaban is a non-vitamin K oral anticoagulant and has been approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). Current labelling recommends dose reduction based on patients age, weight and renal function. OBJECTIVES: The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and to identify factors associated with inappropriate dose reduction...
March 15, 2018: Clinical Cardiology
Sergej Friesen, Sebastian Krickl, Magdalena Luger, Andreas Nazet, Glenn Hefter, Richard Buchner
Aqueous solutions of five lanthanide salts: LaCl3 , La(NO3 )3 , La2 (SO4 )3 , Eu(NO3 )3 and Eu2 (SO4 )3 have been studied at 25 °C by dielectric relaxation spectroscopy over the frequency range 0.05 ≤ ν/GHz ≤ 89. Detailed analysis of the solvent-related modes located at higher frequencies showed that both La3+ and Eu3+ are strongly hydrated, even including partial formation of a third hydration shell similar to that of Al3+ (aq). Up to two solute-related modes could be detected at lower frequencies, due to the formation of various types of 1 : 1 ion pairs (IPs)...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Muhmmad Omar-Hmeadi, Nikhil Gandasi, Sebastian Barg
Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution TIRF imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules...
March 14, 2018: Traffic
María E Errasti, Claudia L Natalucci, Néstor O Caffini, Alejandra E Rotelli, Adriana Brullo, Bruno Maras, Sebastián A Trejo, Laura M I López
The primary structure of macrodontain I, a peptidase from Pseudananas macrodontes fruits, was determined using Edman's degradation. The enzyme is a non-glycosylated peptidase composed by 213 amino acids with a calculated molecular weight of 23,486.18 Da, pI value 6.99, and a molar extinction coefficient at 280 nm of 61,685 M-1  cm-1 . The alignment of the sequence of macrodontain I with those cysteine peptidases from species belonging to the family Bromeliaceae showed the highest identity degree (87.74%) against fruit bromelain...
March 15, 2018: Applied Biochemistry and Biotechnology
Nikunjkumar Patel, Oliver Hatley, Alexander Berg, Klaus Romero, Barbara Wisniowska, Debra Hanna, David Hermann, Sebastian Polak
Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis...
March 14, 2018: AAPS Journal
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