During embryonic development the myocardium enlarges by the proliferation of cardiac myocytes. Shortly after birth, cardiac myocytes lose their capacity for mitogenesis, and further growth of the myocardium to meet the increasing hemodynamic demand of an elevated blood pressure and blood volume occurs by enlargement of existing muscle cells (hypertrophy). Similarly, the restoration of myocardial contractile performance lost to ischemia or viral infection is dependent on the recovery of injured myocytes and on the compensatory enlargement of agonist myocytes. Thus, an understanding of the controlling factors of myocardial protein synthesis and growth has implications for cardiac ontogeny, adaptation to chronic physiologic and pathophysiologic stimuli, and recovery from injury.Cardiac hypertrophy is produced by a variety of stimuli in culture and in vivo (1), including, but not limited to, mechanical stretch (2, 3), neurotransmitters (4, 5), and hormones (6, 7). As the biochemistry of myocardial growth is experimentally revealed, some common intracellular signaling pathways appear among primary stimuli. For example, stretch-induced cardiomyocyte hypertrophy is mediated, in part, by the local production of angiotensin II (8), and several hypertrophic stimuli, angiotensin II, norepinephrine, and endothelin-1, act through G q protein-coupled receptors (9 -11) and activate mitogen-activated protein kinases (12, 13). Direct evidence of G q involvement in cardiac growth was provided by microinjection of G q neutralizing antibodies to block the hypertrophic response of neonatal rat ventricular myocytes to the ␣ 1 -adrenergic agonist phenylephrine (9). Thus cardiac hypertrophy appears to be mediated, at least for several stimuli, by agonists of G q proteincoupled receptors.In addition to promoting myocardial growth, angiotensin II, norepinephrine, and endothelin-1 are vasoactive substances. Interestingly, Katz (14) speculated that angiotensin II evolved from a primitive growth factor and assumed additional regulatory roles in the cardiovascular system, such as stimulation of aldosterone production and smooth muscle contraction. It is conceivable that other vasoactive substances went through a similar evolutionary process, especially in consideration of the finding that Ca 2ϩ signaling is important for angiotensin II activation of mitogen-activated protein kinase in cardiac myocytes (13).Prostaglandin F 2␣ (PGF 2␣ ) 1 is a vasoactive substance that stimulates protein synthesis in skeletal and smooth muscle cells in culture (15,16). Moreover, PGF 2␣ regulates, in part, stretch-induced skeletal myoblast growth (16), and the effects of exogenous PGF 2␣ on vascular smooth muscle hypertrophy are most likely mediated by a PGF-specific receptor (15). As to the heart, PGF 2␣ was increased in the left ventricles of rabbits by acute pressure overload (17), and PG synthase inhibitors blocked cardiac growth induced by hypertension (18) and clenbuterol (19). These observations and others suggested that PGF 2␣ may play a role in the con...

This study evaluated the effectiveness of a group parenting intervention designed to strengthen the home learning environment of children from disadvantaged families. Two cluster randomised controlled superiority trials were conducted in parallel and delivered within existing services: a 6-week parenting group (51 locations randomised; 986 parents) for parents of infants (aged 6–12 months), and a 10-week facilitated playgroup (58 locations randomised; 1200 parents) for parents of toddlers (aged 12–36 months). Each trial had three conditions: intervention (smalltalk group-only); enhanced intervention with home coaching (smalltalk plus); and ‘standard’/usual practice controls. Parent-report and observational measures were collected at baseline, 12 and 32 weeks follow-up. Primary outcomes were parent verbal responsivity and home learning activities at 32 weeks. In the infant trial, there were no differences by trial arm for the primary outcomes at 32 weeks. In the toddler trial at 32-weeks, participants in the smalltalk group-only trial showed improvement compared to the standard program for parent verbal responsivity (effect size (ES) = 0.16; 95% CI 0.01, 0.36) and home learning activities (ES = 0.17; 95% CI 0.01, 0.38) but smalltalk plus did not. For the secondary outcomes in the infant trial, several initial differences favouring smalltalk plus were evident at 12 weeks, but not maintained to 32 weeks. For the toddler trial, differences in secondary outcomes favouring smalltalk plus were evident at 12 weeks and maintained to 32 weeks. These trials provide some evidence of the benefits of a parenting intervention focused on the home learning environment for parents of toddlers but not infants. Trial Registration: 8 September 2011; ACTRN12611000965909.Electronic supplementary materialThe online version of this article (doi:10.1007/s11121-017-0753-9) contains supplementary material, which is available to authorized users.

Background The long‐term clinical performance of transcatheter heart valves (THV) is unknown. Aims This study assessed the clinical outcomes, rate of structural valve deterioration (SVD) and bioprosthetic valve failure in patients after transcatheter aortic valve replacement (TAVR) to 10‐year follow‐up. Methods Consecutive patients undergoing TAVI for native aortic valve stenosis or failed aortic surgical bioprosthesis, between 2005 and 2009 at our institution were included. A total of 235 consecutive patients. Results At the time of TAVI mean age was 82.4 ± 7.9 years. All patients were judged to be high risk, with a STS score > 8 in 53.6%. THVs implanted were the Cribier‐Edwards (20.9%), Edwards SAPIEN (77.4%) or CoreValve (1.7%). Mortality at 1, 5, and 10‐year follow‐up was 23.4%, 63%, and 91.6%, respectively. Of the total cohort, 15 patients had structural valve deterioration/bioprosthetic valve failure, with a cumulative incidence at 10‐years of 6.5% (95% CI 3.3%, 9.6%). The rate of SVD/BVF at 4, 6, 8, and 10 years was 0.4%, 1.7%, 4.7%, and 6.5%, respectively. Nine patients had moderate SVD and six patients had severe SVD. Of the six patients with severe SVD, two patients had reintervention (one patient had redo TAVR, and the second had surgical aortic valve replacement). Survivors (n = 19) at 10‐year follow‐up, had a mean gradient of 14.0 ± 7.6 mmHg and aortic regurgitation ≥moderate in 5%. Quality of life measures in 10‐year survivors demonstrated ADLs 6/6 in 43.8%, and ambulation without a mobility aid of 62.5%. Conclusion Using early generation balloon expandable THVs in a high‐risk population, there was a low rate of structural valve deterioration and valve failure at 10‐year follow‐up. This study provides insights into the long‐term performance of transcatheter heart valves and patients self‐reported derived benefits.