An association of intrapartum synthetic oxytocin dosing and the odds of developing autism.

Oxytocin is a hormone naturally produced in the human body that can make the womb (uterus) contract during labor. Manufactured oxytocin is frequently given to mothers in labor to strengthen the contractions or in some cases to start labor. This study compared children with a diagnosis of autism and children without autism to see whether children with autism received more oxytocin during labor.

The impact of a psychosocial program on clinical outcomes for severe psychiatric disorders.

Background: This retrospective study evaluated the impact of a psychosocial program on individuals with severe and chronic psychiatric disorders. This study also examined potential modifiable predictors of hospitalization.

Methods: The sample was comprised of 94 individuals with severe and chronic mental illness who were followed in the Community Support Network (CSN), a psychosocial program.

Production of Recombinant Adeno-associated Virus Vectors Using Suspension HEK293 Cells and Continuous Harvest of Vector From the Culture Media for GMP FIX and FLT1 Clinical Vector.

Adeno-associated virus (AAV) has shown great promise as a gene therapy vector in multiple aspects of preclinical and clinical applications. Many developments including new serotypes as well as self-complementary vectors are now entering the clinic. With these ongoing vector developments, continued effort has been focused on scalable manufacturing processes that can efficiently generate high-titer, highly pure, and potent quantities of rAAV vectors.

Primer for the Interim Chair.

Objective: Being successful in the role of an Interim Chair requires an approach to transitional leadership that is different from that of individuals filling the Chair role permanently. This article reviews pertinent literature on the topic.

Method: The author reviewed the literature, cited pertinent articles, and supplemented with personal experiences as an Interim Chair.

Transitioning between clerkship directors.

Objective: The authors report on succession-planning for mid-level academic positions.

Method: The authors describe the process of succession-planning between clerkship directors and the smooth transition resulting in one case.

Results: Gradually transitioning allowed a new faculty person to assume the clerkship-director position with minimal disruption of the clerkship.

Nonadherence to medication in hypothyroidism: a case report.

This case report reviews the consequences of nonadherence to a hypothyroidism medication schedule and examines the complexity of hypothyroidism treatment. Both biologic and psychosocial aspects are discussed. The physician-patient relationship is a key to improving adherence, and medication alone is not sufficient to improve outcomes.

Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart.

Cardiac gene transfer is an attractive tool for developing novel heart disease treatments. Adeno-associated viral (AAV) vectors are widely used to mediate transgene expression in animal models and are being evaluated for human gene therapy. However, it is not clear which serotype displays the best cardiac tropism.

An adrenal beta-arrestin 1-mediated signaling pathway underlies angiotensin II-induced aldosterone production in vitro and in vivo.

Aldosterone produces a multitude of effects in vivo, including promotion of postmyocardial infarction adverse cardiac remodeling and heart failure progression. It is produced and secreted by the adrenocortical zona glomerulosa (AZG) cells after angiotensin II (AngII) activation of AngII type 1 receptors (AT(1)Rs). Until now, the general consensus for AngII signaling to aldosterone production has been that it proceeds via activation of G(q/11)-proteins, to which the AT(1)R normally couples.

Negative regulation of VEGF signaling in human coronary artery endothelial cells by G protein-coupled receptor kinase 5.

G protein-coupled receptor kinase 5 (GRK5) is present in endothelial cells (ECs) and has the potential to regulate EC function through seven transmembrane-spanning receptor (7TMR) signaling. Recently, it has been appreciated that GRKs can affect receptor tyrosine kinases (RTKs). VEGF, an RTK, is one of the most potent mediators for EC function and angiogenesis; therefore, we determined the role GRK5 plays in VEGF signaling in human coronary artery ECs (HCAECs).

Myocardial adeno-associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure.

Background: The upregulation of G protein-coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional beta-adrenergic receptor (betaAR) signaling and cardiac function. The peptide betaARKct, which can inhibit the activation of G protein-coupled receptor kinase 2 and improve betaAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term betaARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6).

Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection.

This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1-9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection.

Targeted inhibition of cardiomyocyte Gi signaling enhances susceptibility to apoptotic cell death in response to ischemic stress.

Background: A salient characteristic of dysfunctional myocardium progressing to heart failure is an upregulation of the adenylyl cyclase inhibitory guanine nucleotide (G) protein alpha subunit, G alpha(i2). It has not been determined conclusively whether increased Gi activity in the heart is beneficial or deleterious in vivo. Gi signaling has been implicated in the mechanism of cardioprotective agents; however, no in vivo evidence exists that any of the G alpha subunits are cardioprotective.

Modulation of adrenal catecholamine secretion by in vivo gene transfer and manipulation of G protein-coupled receptor kinase-2 activity.

We recently reported that the upregulation of adrenal G protein-coupled receptor kinase-2 (GRK2) causes enhanced catecholamine (CA) secretion by desensitizing sympatho-inhibitory alpha (2)-adrenergic receptors (alpha (2)ARs) of chromaffin cells, and thereby aggravating heart failure (HF). In this study, we sought to develop an efficient and reproducible in vivo adrenal gene transfer method to determine whether manipulation of adrenal GRK2 levels/activity regulates physiological CA secretion in rats. We specifically investigated two different in vivo gene delivery methods: direct injection into the suprarenal glands, and retrograde delivery through the suprarenal veins.

Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue.

Background: The incidence of heart failure is ever-growing, and it is urgent to develop improved treatments. An attractive approach is gene therapy; however, the clinical barrier has yet to be broken because of several issues, including the lack of an ideal vector supporting safe and long-term myocardial transgene expression.

Methods And Results: Here, we show that the use of a recombinant adeno-associated viral (rAAV6) vector containing a novel cardiac-selective enhancer/promoter element can direct stable cardiac expression of a therapeutic transgene, the calcium (Ca2+)-sensing S100A1, in a rat model of heart failure.