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BackgroundThe present study demonstrates that the ubiquitin E3 ligase, Pellino‐1 (Peli1), is an important angiogenic molecule under the control of vascular endothelial growth factor (VEGF) receptor 2/Flk‐1. We have previously reported increased survivability of ischemic skin flap tissue by adenovirus carrying Peli1 (Ad‐Peli1) gene therapy in Flk‐1+/− mice.Methods and ResultsTwo separate experimental groups of mice were subjected to myocardial infarction (MI) followed by the immediate intramyocardial injection of adenovirus carrying LacZ (Ad‐LacZ) (1×109 pfu) or Ad‐Peli1 (1×109 pfu). Heart tissues were collected for analyses. Compared with wild‐type (WTMI) mice, analysis revealed decreased expressions of Peli1, phosphorylated (p‐)Flk‐1, p‐Akt, p‐eNOS, p‐MK2, p‐IκBα, and NF‐κB and decreased vessel densities in Flk‐1+/− mice subjected to MI (Flk‐1+/− MI). Mice (CD1) treated with Ad‐Peli1 after the induction of MI showed increased β‐catenin translocation to the nucleus, connexin 43 expression, and phosphorylation of Akt, eNOS, MK2, and IκBα, that was followed by increased vessel densities compared with the Ad‐LacZ–treated group. Echocardiography conducted 30 days after surgery showed decreased function in the Flk1+/− MI group compared with WTMI, which was restored by Ad‐Peli1 gene therapy. In addition, therapy with Ad‐Peli1 stimulated angiogenic and arteriogenic responses in both CD1 and Flk‐1+/− mice following MI. Ad‐Peli1 treatment attenuated cardiac fibrosis in Flk‐1+/− MI mice. Similar positive results were observed in CD1 mice subjected to MI after Ad‐Peli1 therapy.ConclusionOur results show for the first time that Peli1 plays a unique role in salvaging impaired collateral blood vessel formation, diminishes fibrosis, and improves myocardial function, thereby offering clinical potential for therapies in humans to mend a damaged heart following MI.

BACKGROUND AND OBJECTIVES:Little is known about the effect of circumcision on breastfeeding in the hours and days after the procedure. Factors with the potential to negatively impact breastfeeding success in the newborn period may result in higher rates of jaundice requiring phototherapy and formula supplementation, both of which can potentially extend the length of initial hospitalization. Our objective was to determine the impact of circumcision on rates of exclusive breastfeeding, neonatal jaundice requiring phototherapy, and length of stay at hospital discharge immediately after birth.METHODS: Term male newborn infants whose mothers intended to exclusively breastfeed were included in this retrospective cohort. Bivariate analysis and multivariate logistic regression modeling were used to evaluate target behaviors, comparing infant boys who were circumcised with those who were uncircumcised. RESULTS:Of the 1109 breastfed male newborns included, 846 (76.6%) were circumcised. There was no significant effect of circumcision status or circumcision timing on the rate of in-hospital formula supplementation. There were no differences in peak bilirubin levels, phototherapy requirement, or length of hospital stay for male newborns based on circumcision status. CONCLUSIONS: Circumcision did not affect the rate of exclusive breastfeeding, neonatal jaundice, phototherapy requirement, or length of hospital stay in this retrospective analysis of breastfed male newborns.

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