Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models.

Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans

Smooth Versus Rocky Transitions to Parenthood: Family Systems in Developmental Context

Using family systems theory and a dyadic growth curve, the authors examined factors associated with a smooth versus rocky transition to parenthood for 125 couples. The authors identified significant variability in couples\u27 experiences. Although many parents reported declines in love and increases in conflict, 23% of mothers and 37% of fathers reported equal or increased love; 20% of mothers and 28% of fathers reported equal or lower conflict. Fathers of reactive infants reported higher levels of conflict, and fathers of daughters reported increasing conflict over time. Fathers\u27 marital love decreased when their expectations were violated, and fathers\u27 conflict increased when mothers reported violated expectations. Finally, mothers\u27 marital conflict increased with greater changes in depressive symptoms. Despite potential gender differences, within‐couple analyses showed synchrony between partners suggesting that potential gender differences may be best treated within the couple

Violated wishes about division of childcare labor predict early coparenting process during stressful and nonstressful family evaluations.

Prior research has indicated that expectant parents overestimate the extent to which fathers will take part in the “work” of parenting, with mothers often becoming disenchanted when these expectations are violated following the baby’s arrival. In this study, we examine the role of violated wishes concerning childcare involvement in accounting for variability in maternal and paternal marital satisfaction, and in early coparenting behavior as assessed during family-interaction sessions. The results indicate possible negative effects of violated wishes on the enacted family process and confirm previous findings regarding the effects of marital satisfaction. In addition, we uncovered differences in the way that violated maternal wishes are related to coparenting during playful and mildly stressful family interactions

The transition to parenthood: What does it mean for fathers?

Title. The transition to parenthood: what does it mean for fathers? Aim. This paper is a report of a study to explore the needs of first-time fathers in relation to the care, support and education provided by healthcare professionals during the antenatal period, particularly in relation to preparing them for the transition to fatherhood. Background. Pregnancy and transition to parenthood are major developmental periods within families throughout the world. Previous research suggests that fathers in many different countries feel unprepared for parenthood. Methods. Purposive sampling was used to recruit 20 partners of primiparous women from two healthcare provider organizations in South-West England between December 2005 and July 2006. Recruitment took place at about 28 weeks gestation. Semi-structured interviews were undertaken at home in the last trimester of pregnancy and 3-4 months postpartum. Content analysis of the interview data was undertaken. Findings. Several common themes emerged from both the ante- and postnatal data, including lack of support mechanisms, involvement in antenatal provision and the need for more information given in the antenatal period on parenting, baby care and relationships. Conclusions. Adequately preparing new fathers for parenthood in advance of the birth of their baby is important, and healthcare professionals can contribute to this by involving and supporting new fathers. Further study is needed to explore the role of fathers in antenatal education and the types of interventions that are effective in improving their early experiences of parenthood. The study needs to be repeated with fathers from black and ethnic minority groups. © 2008 Blackwell Publishing Ltd