Endothelial alpha3beta1-integrin represses pathological angiogenesis and sustains endothelial-VEGF.

Integrin alpha3beta1 is a major receptor for laminin. The expression levels of laminins-8 and -10 in the basement membrane surrounding blood vessels are known to change during tumor angiogenesis. Although some studies have suggested that certain ligands of alpha3beta1 can affect angiogenesis either positively or negatively, either a direct in vivo role for alpha3beta1 in this process or its mechanism of action in endothelial cells during angiogenesis is still unknown. Because the global genetic ablation of alpha3-integrin results in an early lethal phenotype, we have generated conditional-knockout mice where alpha3 is deleted specifically in endothelial cells (ec-alpha3-/-). Here we show that ec-alpha3-/- mice are viable, fertile, and display enhanced tumor growth, elevated tumor angiogenesis, augmented hypoxia-induced retinal angiogenesis, and increased vascular endothelial growth factor (VEGF)-mediated neovascularization ex vivo and in vivo. Furthermore, our data provide a novel method by which an integrin may regulate angiogenesis. We show that alpha3beta1 is a positive regulator of endothelial-VEGF and that, surprisingly, the VEGF produced by endothelial cells can actually repress VEGF-receptor 2 (Flk-1) expression. These data, therefore, identify directly that endothelial alpha3beta1 negatively regulates pathological angiogenesis and implicate an unexpected role for low levels of endothelial-VEGF as an activator of neovascularization.

Understanding the association between employee satisfaction and family perceptions of the quality of care in hospice service delivery.

Families often draw their conclusions about the quality of care received by a family member during the last months of life from their interactions with professional caregivers. A more comprehensive understanding of how these relationships influence the care experience should include an investigation of the association between employee job satisfaction and family perception of the quality of care. This cross-sectional study investigated the association at a regional hospice. Using the Kendall's tau correlation, employee satisfaction scores for care teams trended toward a positive correlation with family overall satisfaction scores from the Family Evaluation of Hospice Care (tau=0.47, P=0.10). A trend for differences in employee satisfaction between the care teams to associate with differences in overall family perceptions of the quality of care also was found using the Kruskal-Wallis analysis of variance (chi(2)(K-W)=9.236, P=0.075). Post hoc tests indicated that overall family perceptions of quality of care differed between the hospice's Residence Team and Non-Hospice Facilities Team. Finally, positive associations between employee satisfaction and the families' Intent to recommend hospice (tau=0.55, P=0.059) and Inform and communicate about patient (tau=0.55, P=0.059) were noted. Selected employee and family comments provide complementarity to further clarify or explain the respondent data. These results suggest that employee satisfaction is associated with family perceptions of the quality of hospice care. Opportunities for improving both employee job satisfaction and family perceptions of the quality of care are discussed.