3,561 research outputs found

    Osteopontin ablation ameliorates muscular dystrophy by shifting macrophages to a pro-regenerative phenotype.

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    In the degenerative disease Duchenne muscular dystrophy, inflammatory cells enter muscles in response to repetitive muscle damage. Immune factors are required for muscle regeneration, but chronic inflammation creates a profibrotic milieu that exacerbates disease progression. Osteopontin (OPN) is an immunomodulator highly expressed in dystrophic muscles. Ablation of OPN correlates with reduced fibrosis and improved muscle strength as well as reduced natural killer T (NKT) cell counts. Here, we demonstrate that the improved dystrophic phenotype observed with OPN ablation does not result from reductions in NKT cells. OPN ablation skews macrophage polarization toward a pro-regenerative phenotype by reducing M1 and M2a and increasing M2c subsets. These changes are associated with increased expression of pro-regenerative factors insulin-like growth factor 1, leukemia inhibitory factor, and urokinase-type plasminogen activator. Furthermore, altered macrophage polarization correlated with increases in muscle weight and muscle fiber diameter, resulting in long-term improvements in muscle strength and function in mdx mice. These findings suggest that OPN ablation promotes muscle repair via macrophage secretion of pro-myogenic growth factors

    Health Information Technology in the United States: On the Cusp of Change, 2009

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    In this report we use the data collected for ONCHIT to focus on EHR adoption in the inpatient setting. We report on several important policy issues. These include the rate of adoption of EHRs among U.S. hospitals generally and among safety-net hospitals, changes in both state and federal policy, and the potential of EHRs to change the quality measurement enterprise

    A Systems Approach to Improving Tdap Immunization Within 5 Community-Based Family Practice Settings: Working Differently (and Better) by Transforming the Structure and Process of Care.

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    OBJECTIVES: We examined how family medicine clinic physicians and staff worked in collaborative teams to implement an automated clinical reminder to improve tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine administration and documentation. METHODS: A clinical reminder was developed at 5 University of Michigan family medicine clinics to identify patients 11 to 64 years old who were in need of the Tdap booster vaccine. Quality improvement cycles were used to improve clinic care processes. Immunization rates from 2008 to 2011 were compared with rates at 4 primary care control clinics. RESULTS: Vaccination rates among eligible patients increased from 15.5% to 47.3% within the family medicine clinics and from 14.1% to 30.2% within the control clinics. After adjustment for covariates, family medicine patients had a higher probability of vaccination than control patients during each measurement period (0.17 vs 0.15 at baseline, 0.53 vs 0.22 during year 1, and 0.50 vs 0.30 during year 2). CONCLUSIONS: Automated clinical reminders, when designed and implemented via a consensus-based framework that addresses the process of care, can dramatically improve provision of preventive health care

    Synthesis of 2,6-disubstituted dihydropyrans via an efficient BiBr3-initiated three component, one-pot cascade

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    The rapid synthesis of cis-2,6-disubstituted dihydropyrans is achieved in a three-component, one-pot cascade reaction. BiBr3-mediated addition of ketene silyl acetals or silyl enol ethers to beta,gamma-unsaturated cis-4-trimethylsilyl-3-butenal provides a Mukaiyama aldol adduct containing a vinylsilane moiety tethered to a silyl ether. Addition of a second aldehyde initiates a domino sequence involving intermolecular addition followed by an intramolecular silyl-modified Sakurai (ISMS) reaction. Isolated yields of this one-pot reaction vary from 44 to 80% and all compounds were isolated as the cis-diastereomers (10 examples). (C) 2009 Elsevier Ltd. All rights reserved
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