95 research outputs found

    A Potent and Selective Inhibitor of Cdc42 GTPase

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    Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family

    Quality of care for hypertension in the United States

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    BACKGROUND: Despite heavy recent emphasis on blood pressure (BP) control, many patients fail to meet widely accepted goals. While access and adherence to therapy certainly play a role, another potential explanation is poor quality of essential care processes (QC). Yet little is known about the relationship between QC and BP control. METHODS: We assessed QC in 12 U.S. communities by reviewing the medical records of a randomly selected group of patients for the two years preceding our study. We included patients with either a diagnosis of hypertension or two visits with BPs of ≥140/90 in their medical records. We used 28 process indicators based on explicit evidence to assess QC. The indicators covered a broad spectrum of care and were developed through a modified Delphi method. We considered patients who received all indicated care to have optimal QC. We defined control of hypertension as BP < 140/90 in the most recent reading. RESULTS: Of 1,953 hypertensive patients, only 57% received optimal care and 42% had controlled hypertension. Patients who had received optimal care were more likely to have their BP under control at the end of the study (45% vs. 35%, p = .0006). Patients were more likely to receive optimal care if they were over age 50 (76% vs. 63%, p < .0001), had diabetes (77% vs. 71%, p = .0038), coronary artery disease (87% vs. 69%, p < .0001), or hyperlipidemia (80% vs. 68%, p < .0001), and did not smoke (73% vs. 66%, p = .0005). CONCLUSIONS: Higher QC for hypertensive patients is associated with better BP control. Younger patients without cardiac risk factors are at greatest risk for poor care. Quality measurement systems like the one presented in this study can guide future quality improvement efforts

    'An Ingenious Man Enabled by Contract': Entrepreneurship and the Rise of Contract

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    Toward Transatlantic Convergence in Financial Regulation

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    Secondhand Smoke Is an Important Modifiable Risk Factor in Sickle Cell Disease: A Review of the Current Literature and Areas for Future Research

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    Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy that causes significant morbidity and mortality related to chronic hemolytic anemia, vaso-occlusion, and resultant end-organ damage. Tobacco smoke exposure (TSE) through secondhand smoke exposure in people with SCD of all ages and through primary smoking in adolescents and adults is associated with significantly increased morbidity, with increased rates of emergency department visits and hospitalizations for painful vaso-occlusive crises and acute chest syndrome (ACS). Secondhand smoke is also associated with pulmonary function abnormalities in children with SCD who are already at risk for pulmonary function abnormalities on the basis of SCD. TSE is emerging as one of the few modifiable risk factors of SCD. This review discusses the current state of the evidence with respect to TSE and SCD morbidity, discusses potential mechanisms, and highlights current gaps in the evidence and future research directions
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