To refine selection criteria for adult living liver donors and improve donor quality of care, risk factors for poor postdonation health-related quality of life (HRQOL) must be identified. This cross-sectional study examined donors who underwent a right hepatectomy at the University of Toronto between 2000 and 2007 (n = 143), and investigated predictors of (1) physical and mental health postdonation, as well as (2) willingness to participate in the donor process again. Participants completed a standardized HRQOL measure (SF-36) and measures of the pre-and postdonation process. Donor scores on the SF-36 physical and mental health indices were equivalent to, or greater than, population norms. Greater predonation concerns, a psychiatric diagnosis and a graduate degree were associated with lower mental health postdonation whereas older donors reported better mental health. The majority of donors (80%) stated they would donate again but those who perceived that their recipient engaged in risky health behaviors were more hesitant. Prospective donors with risk factors for lower postdonation satisfaction and mental health may require more extensive predonation counseling and postdonation psychosocial follow-up. Risk factors identified in this study should be prospectively evaluated in future research. participate (n = 204). Procedures used by our center to determine donor suitability for right hepatectomy have been reported elsewhere (1). Eleven donors who had been either lost to follow-up (n = 9) or who informed our program that they were doing well and no longer required follow-up (n = 2) were not contacted. Study designThis is a cross-sectional study in which donors who were at least 3 months postdonation were mailed a package of materials that contained a cover letter explaining the study objectives, a consent form and a written questionnaire. Only those measures that were analyzed in this report will be described here. Postdonation questionnaireLiving liver donors completed a one-time comprehensive questionnaire assessing demographics (sex, age, marital status, ethnicity, education, income and employment

Early-life environmental events can induce profound long-lasting changes in several behavioral and neuroendocrine systems. The neonatal handling procedure, which involves repeated brief maternal separations followed by experimental manipulations, reduces stress responses and sexual behavior in adult rats. The purpose of this study was to analyze the effects of neonatal handling on social behaviors of male and female rats in adulthood, as manifest by the results of social memory and social interaction tests. The number of oxytocin (OT) and vasopressin (VP) neurons in the paraventricular (PVN) and supraoptic (SON) nuclei of hypothalamus were also analyzed. The results did not demonstrate impairment of social memory. Notwithstanding, handling did reduce social investigative interaction and increase aggressive behavior in males, but did not do so in females. Furthermore, in both males and females, handling was linked with reduced number of OT-neurons in the parvocellular region of the PVN, while no differences were detected in the magnocellular PVN or the SON. On the other hand, handled males exhibited increased number of VP-neurons in the magnocellular zone of the PVN. We may conclude that the repeated brief maternal separations can reduce affiliative social behavior in adult male rats. Moreover, the disruption of the mother-infant relationship caused by the handling procedure induced long-lasting morphological changes in critical neuroendocrine areas that are involved in social bonding in mammals.

Paulin R, Meloche J, Jacob MH, Bisserier M, Courboulin A, Bonnet S. Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol 301: H1798 -H1809, 2011. First published September 2, 2011; doi:10.1152/ajpheart.00654.2011.-Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation and suppressed apoptosis. This phenotype is sustained by the activation of the Src/signal transducer and activator of transcription 3 (STAT3) axis, maintained by a positive feedback loop involving miR-204 and followed by an aberrant expression/activation of its downstream targets such as Pim1 and nuclear factor of activated T-cells (NFATc2). Dehydroepiandrosterone (DHEA) is a steroid hormone shown to reverse vascular remodeling in systemic vessels. Since STAT3 has been described as modulated by DHEA, we hypothesized that DHEA reverses human pulmonary hypertension by inhibiting Src/STAT3 constitutive activation. Using PASMCs isolated from patients with PAH (n ϭ 3), we demonstrated that DHEA decreases both Src and STAT3 activation (Western blot and nuclear translocation assay), resulting in a significant reduction of Pim1, NFATc2 expression/activation (quantitative RT-PCR and Western blot), as well as Survivin and upregulation of bone morphogenetic protein receptor 2 (BMPR2) and miR-204. Src/STAT3 axis inhibition by DHEA is associated with 1) mitochondrial membrane potential (tetramethylrhodamine methyl-ester perchlorate; n ϭ 150; P Ͻ 0.05) depolarization increasing apoptosis by 25% (terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling; n ϭ 150; P Ͻ 0.05); and 2) decreased intracellular Ca 2ϩ concentration (fluo-3 AM; n ϭ 150; P Ͻ 0.05) and proliferation by 30% (PCNA). Finally, in vivo similarly to STAT3 inhibition DHEA improves experimental PAH (monocrotaline rats) by decreasing mean PA pressure and right ventricle hypertrophy. These effects were associated with the inhibition of Src, STAT3, Pim1, NFATc2, and Survivin and the upregulation of BMPR2 and miR-204. We demonstrated that DHEA reverses pulmonary hypertension in part by inhibiting the Src/STAT3.