745 research outputs found

    Retinoid X Receptor and Peroxisome Proliferator-Activated Receptor-Gamma Agonists Cooperate to Inhibit Matrix Metalloproteinase Gene Expression

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    We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-β)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARγ), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1--induced expression of MMP-1andMMP-13 by combinatorial treatment with RXR and PPAR ligands and to investigate the molecular mechanisms of this inhibition

    Evaluating outcomes from an integrated health service for older patients

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    Background: Hospital-associated disability is the loss of the ability to complete one activity of daily living (ADL), with this decline occurring between the onset of acute illness and discharge from the hospital. Approximately 30% of patients who are >70 years old and admitted to hospitals are discharged with an ADL disability. Comprehensive geriatric assessment (CGA) models use a multidimensional, interdisciplinary process of diagnosis and treatment with the goal of improving outcomes and decreasing lengths of stay. Methods: A retrospective clinical audit of Ipswich Hospital’s medical records included patients for random selection who were >75 years of age and had an acute admission to the Older Person Evaluation Review and Assessment (OPERA) or general medicine (GM) service from July 2012 to December 2012. Data were collected for the entire admission period on length of stay, comorbidities, allied health visits, functional ability, and delirium and dementia at admission. Results: Of the 267 patients evaluated, 133 were admitted to the OPERA service, and 134 were admitted to the GM service. Patients admitted to the OPERA service were significantly more ill than patients admitted to the GM service as measured by the Charlson Comorbidity Index scores (6.53 - 1.83 vs 6.02 - 1.96, respectively, P¼0.02), Katz Index of Independence in ADL scores (3.77 - 2.22 vs 4.72 - 2.00, respectively,

    Educating pharmacists on the risks of strong opioids with descriptive and simulated experience risk formats: A randomized controlled trial

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    Objectives. High opioid prescription rates in the United States and Europe suggest miscalibrated risk perceptions among those who prescribe, dispense, and take opioids. Findings from cognitive decision science suggest that risk perceptions and behaviors can differ depending on whether people learn about risks by experience or description. This study investigated effects of a descriptive versus an experience-based risk education format on pharmacists’ risk perceptions and counseling behavior in the long-term administration of strong opioids to patients with chronic noncancer pain. Methods. In an exploratory, randomized controlled online trial, 300 German pharmacists were randomly assigned to either a descriptive format (fact box) or a simulated experience format (interactive simulation). Primary Outcome Measures. 1) Objective risk perception, 2) subjective risk perception, and 3) intended and 4) actual counseling behavior. Results. Both risk formats significantly improved pharmacists’ objective risk perception, but pharmacists exposed to the fact box estimated the benefit-harm ratio more accurately than those exposed to the simulation. Both formats proved equally effective in adjusting pharmacists’ subjective risk perception toward a better recognition of opioids’ harms; however, pharmacists receiving the simulation showed a greater change in their actual counseling behavior and higher consistency between their intended and actual counseling than pharmacists receiving the fact box. Conclusion. The simulated experience format was less effective than the descriptive format in improving pharmacists’ objective risk perception, equally effective in motivating pharmacists to counsel patients on less risky treatment alternatives and more effective in changing the reported actual counseling behavior. Implications. These exploratory findings provide important insights into the relevance of the description-experience gap for drug safety and raise questions for future research regarding the specific mechanisms at work

    Suppression of mid-infrared plasma resonance due to quantum confinement in delta-doped silicon

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    The classical Drude model provides an accurate description of the plasma resonance of three-dimensional materials, but only partially explains two-dimensional systems where quantum mechanical effects dominate such as P:δ\delta-layers - atomically thin sheets of phosphorus dopants in silicon that induce novel electronic properties beyond traditional doping. Previously it was shown that P:δ\delta-layers produce a distinct Drude tail feature in ellipsometry measurements. However, the ellipsometric spectra could not be properly fit by modeling the δ\delta-layer as discrete layer of classical Drude metal. In particular, even for large broadening corresponding to extremely short relaxation times, a plasma resonance feature was anticipated but not evident in the experimental data. In this work, we develop a physically accurate description of this system, which reveals a general approach to designing thin films with intentionally suppressed plasma resonances. Our model takes into account the strong charge density confinement and resulting quantum mechanical description of a P:δ\delta-layer. We show that the absence of a plasma resonance feature results from a combination of two factors: i), the sharply varying charge density profile due to strong confinement in the direction of growth; and ii), the effective mass and relaxation time anisotropy due to valley degeneracy. The plasma resonance reappears when the atoms composing the δ\delta-layer are allowed to diffuse out from the plane of the layer, destroying its well-confined two-dimensional character that is critical to its novel electronic properties
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