Abstract-Insulin-like growth factor-I (IGF-I) plays an important role in regulating vascular smooth muscle cell (VSMC) proliferation and directed migration. The mitogenic and chemotactic actions of IGF-I are mediated through the IGF-I receptor, but how the activation of the IGF-I receptor leads to these biological responses is poorly understood. In this study, we examined the role of phosphatidylinositol 3-kinase (PI3 kinase) in mediating the mitogenic and chemotactic signals of IGF-I. IGF-I treatment resulted in a significant increase in phosphotyrosine-associated PI3 kinase activity in cultured primary VSMCs. To determine whether insulin receptor substrate (IRS)-1, -2, or both are involved in IGF-I signaling in VSMCs, cell lysates were immunoprecipitated with either an anti-IRS-1 or an anti-IRS-2 antibody, and the associated PI3 kinase activity was determined. IGF-I stimulation resulted in a significant increase in IRS-1-but not IRS-2-associated PI3 kinase activity, suggesting that IGF-I primarily utilizes IRS-1 to transmit its signal in VSMCs. The IGF-I-induced increase in IRS-I-associated PI3 kinase activity was concentration dependent. At the maximum concentration (50 ng/mL), IGF-I induced a 60-fold increase. This activation occurred within 5 minutes and was sustained at high levels for at least 6 hours. IGF-I also caused a concentration-dependent and long-lasting activation of protein kinase B (PKB/Akt). Inhibition of PI3 kinase activation by LY294002 or wortmannin abolished IGF-Istimulated VSMC proliferation and reduced IGF-I-directed VSMC migration by Ϸ60%. These results indicate that activation of PI3 kinase is required for both IGF-I-induced VSMC proliferation and migration. (Circ Res. 2000;86:15-23.)

OBJECTIVE: To identify and quantify risk factors for atonic postpartum hemorrhage. DATA SOURCES: PubMed, CINAHL, EMBASE, Web of Science, and and ClinicalTrials.gov databases were searched for English language studies with no restrictions on date or location. Studies included randomized trials, prospective or retrospective cohort studies, and case–control studies of pregnant patients who developed atonic postpartum hemorrhage and reported at least one risk factor. METHODS OF STUDY SELECTION: Title, abstract, and full-text screening were performed using the Raayan web application. Of 1,239 records screened, 27 studies were included in this review. Adjusted or unadjusted odds ratios (ORs), relative risks, or rate ratios were recorded or calculated. For each risk factor, a qualitative synthesis of low and moderate risk of bias studies classifies the risk factor as definite, likely, unclear, or not a risk factor. For risk factors with sufficiently homogeneous definitions and reference ranges, a quantitative meta-analysis of low and moderate risk of bias studies was implemented to estimate a combined OR. TABULATION, INTEGRATION, AND RESULTS: Forty-seven potential risk factors for atonic postpartum hemorrhage were identified in this review, of which 15 were judged definite or likely risk factors. The remaining 32 assessed risk factors showed no association with atonic postpartum hemorrhage or had conflicting or unclear evidence. CONCLUSION: A substantial proportion of postpartum hemorrhage occurs in the absence of recognized risk factors. Many risk factors for atonic hemorrhage included in current risk-assessment tools were confirmed, with the greatest risk conferred by prior postpartum hemorrhage of any etiology, placenta previa, placental abruption, uterine rupture, and multiple gestation. Novel risk factors not currently included in risk-assessment tools included hypertension, diabetes, and ethnicity. Obesity and magnesium were not associated with atonic postpartum hemorrhage in this review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020157521.

Patient-centered care (PCC) is increasingly being highlighted as an important model to improve quality of health care having been linked to improved patient satisfaction, better health outcomes, and cost-effective care (

Event-specific, simulation-based training resulted in superior performance in scenarios compared with traditional training and simulation-based training in an alternate event.

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