7 research outputs found

    International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

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    Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

    Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?

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    Understanding the interaction of fluorescent dyes with monolayer-protected gold nanoparticles (AuNPs) is of fundamental importance in designing new fluorescent nanomaterials. Among a variety of molecular sensors and reporters, fluorescent probes based on a 3-hydroxychromone (3HC) skeleton appear to be very promising. They exhibit the phenomenon of dual band emission, resulting from excited-state intramolecular proton transfer (ESIPT), known to be highly sensitive to a nature of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected gold nanoparticles were synthesized, and, owing to the transmission electron micrograph imaging, their average diameter was found to be ∌1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with AuNPs in toluene solutions demonstrate significant changes in the intensity ratio of their normal and tautomeric emission bands, suggesting that the probe molecules become noncovalently bound to a dodecanethiol layer of AuNPs. Despite expected fluorescence quenching induced by close proximity to the metal surface, no fluorescence lifetime decrease was observed, indicating that a bound-fluorophore is shielded from a nanoparticle core. Further spectral analysis revealed that the ratiometric fluorescence changes could be interpreted as a consequence of intermolecular hydrogen bonding between a probe and residual ethanol molecules, trapped into the dodecanethiol shell of AuNPs during the synthesis. Evidences for residual traces of ethanol in the ligand shell of the nanoparticles were also observed in NMR spectra, suggesting that alkylthiol-coated gold nanoparticles may not be as hydrophobic as one could expect. To elucidate structural features of dodecanethiol-stabilized gold nanoparticles at the supramolecular level, a molecular dynamics (MD) model of AuNP was developed. The model was based on the all-atom CHARMM27 force field parameters and parametrized according to available experimental data of the synthesized AuNPs. Our MD simulations show that in bulk toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol monolayer, so that a fluorophore favors residence in an outer shell of AuNP. In addition, MD simulations of transfer of AuNP from bulk ethanol to toluene demonstrate that a small population of ethanol molecules are able to penetrate deeply into the dodecanethiol layer and may indeed be trapped into the ligand shell of alkylthiol-functionalized gold nanoparticles. The results of our fluorescence experiments and molecular dynamics simulation suggest that 3-hydroxychromones can be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized noble metal nanoparticles

    Fluorescence Probing of Thiol-Functionalized Gold Nanoparticles: Is Alkylthiol Coating of a Nanoparticle as Hydrophobic as Expected?

    No full text
    Understanding the interaction of fluorescent dyes with monolayer-protected gold nanoparticles (AuNPs) is of fundamental importance in designing new fluorescent nanomaterials. Among a variety of molecular sensors and reporters, fluorescent probes based on a 3-hydroxychromone (3HC) skeleton appear to be very promising. They exhibit the phenomenon of dual band emission, resulting from excited-state intramolecular proton transfer (ESIPT), known to be highly sensitive to a nature of microenvironment surrounding a fluorophore. In this study, dodecanethiol-protected gold nanoparticles were synthesized, and, owing to the transmission electron micrograph imaging, their average diameter was found to be ∌1.4 nm. Fluorescence titrations of the 3HC ESIPT probes with AuNPs in toluene solutions demonstrate significant changes in the intensity ratio of their normal and tautomeric emission bands, suggesting that the probe molecules become noncovalently bound to a dodecanethiol layer of AuNPs. Despite expected fluorescence quenching induced by close proximity to the metal surface, no fluorescence lifetime decrease was observed, indicating that a bound-fluorophore is shielded from a nanoparticle core. Further spectral analysis revealed that the ratiometric fluorescence changes could be interpreted as a consequence of intermolecular hydrogen bonding between a probe and residual ethanol molecules, trapped into the dodecanethiol shell of AuNPs during the synthesis. Evidences for residual traces of ethanol in the ligand shell of the nanoparticles were also observed in NMR spectra, suggesting that alkylthiol-coated gold nanoparticles may not be as hydrophobic as one could expect. To elucidate structural features of dodecanethiol-stabilized gold nanoparticles at the supramolecular level, a molecular dynamics (MD) model of AuNP was developed. The model was based on the all-atom CHARMM27 force field parameters and parametrized according to available experimental data of the synthesized AuNPs. Our MD simulations show that in bulk toluene the 3HC probe molecule becomes weakly bound to a dodecanethiol monolayer, so that a fluorophore favors residence in an outer shell of AuNP. In addition, MD simulations of transfer of AuNP from bulk ethanol to toluene demonstrate that a small population of ethanol molecules are able to penetrate deeply into the dodecanethiol layer and may indeed be trapped into the ligand shell of alkylthiol-functionalized gold nanoparticles. The results of our fluorescence experiments and molecular dynamics simulation suggest that 3-hydroxychromones can be used as a noncovalent fluorescent labeling agent for alkylthiol-stabilized noble metal nanoparticles

    Thermodynamic Properties and Ideal-Gas Enthalpies of Formation for Methyl Benzoate, Ethyl Benzoate, ( R

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