Anna S. Aledia

Prevascularization of a Fibrin-Based Tissue Construct Accelerates the Formation of Functional Anastomosis with Host Vasculature

One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.

Cut points for Asthma Control Tests in Mexican children in Orange County, California

BACKGROUND The Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) are validated measures of asthma control in which a score of 19 is defined as uncontrolled according to published reports. However, different cut points may exist in different ethnic populations. OBJECTIVE To determine the cut point for uncontrolled asthma in a Mexican descent population from Orange Country, California, compared with an age- and asthma severity-matched non-Hispanic cohort. METHODS The C-ACT (in children 6-11 years old) and ACT (in children 12-17 years old) scores were collected from 151 children of Mexican descent and 48 non-Hispanic controls with mild-to-moderate asthma who lived in Orange County. Physicians were masked to C-ACT and ACT scores while assessing control based on National Asthma Education and Prevention program guidelines. The receiver operating characteristic method was used to examine the screening accuracy of the tests to detect uncontrolled asthma. The optimal cut points were selected by maximizing the total sensitivity and specificity. RESULTS Cronbach α values for the C-ACT (0.76) and the ACT (0.80) confirmed that both tests were reliable in our study population. The C-ACT and ACT scores were statistically higher in children of Mexican descent than non-Hispanic children (P = .008). A cut point of 22 was optimal to detect uncontrolled asthma in children of Mexican descent 6 to 11 years old (group 1: sensitivity, 0.74; specificity, 0.86; area under the curve [AUC], 0.83) and children 12 to 17 years old (group 3: sensitivity, 0.78; specificity, 0.68; AUC, 0.79). For non-Hispanic controls, a cut point of 20 were optimal to detect uncontrolled asthma in children 6 to 11 years old (group 2: sensitivity, 0.70; specificity, 0.91; AUC, 0.86) and children 12 to 17 years old (group 4: sensitivity, 0.83; specificity, 0.87; AUC, 0.91). CONCLUSION In this cross-ethnic validation study, children of Mexican descent in Orange County seem to underreport asthma symptoms compared with a non-Hispanic population and may require higher C-ACT and ACT cut points to detect uncontrolled asthma.