Publications

BACKGROUND

Unintended pregnancy has been significantly associated with subsequent female sterilization. Whether women who are sterilized after experiencing an unintended pregnancy are less likely to express desire for sterilization reversal is unknown.

METHODS

This study used national, cross-sectional data collected by the 2006-2010 National Survey of Family Growth. The study sample included women ages 15-44 who were surgically sterile from a tubal sterilization at the time of interview. Multivariable logistic regression was used to examine the relationship between a history of unintended pregnancy and desire for sterilization reversal while controlling for potential confounders.

RESULTS

In this nationally representative sample of 1,418 women who were sterile from a tubal sterilization, 78% had a history of at least one unintended pregnancy and 28% expressed a desire to have their sterilization reversed. In unadjusted analysis, having a prior unintended pregnancy was associated with higher odds of expressing desire for sterilization reversal (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.15-2.79). In adjusted analysis controlling for sociodemographic factors, unintended pregnancy was no longer significantly associated with desire for reversal (OR: 1.46; 95% CI: 0.91-2.34).

CONCLUSION

Among women who had undergone tubal sterilization, a prior history of unintended pregnancy did not decrease desire for sterilization reversal.

The sphingolipid metabolites ceramide, sphingosine, and sphingosine-1-phosphate (S1P) and its enzyme sphingosine kinase (SphK) play an important role in the regulation of cell proliferation, survival, inflammation, and cell death. Ceramide and sphingosine usually inhibit proliferation and promote apoptosis, while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis. Because these metabolites are interconvertible, it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate. The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations. A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat, as it not only produces the pro-growth, anti-apoptotic messenger S1P, but also decreases levels of pro-apoptotic ceramide and sphingosine. Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease, and these observations have considerable relevance for future potential therapeutic targets.

BACKGROUND

A-kinase anchoring proteins (AKAPs) are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA) and D (PKD) and an active Rho-guanine nucleotide exchange factor (Rho-GEF) domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.

METHODOLOGY/PRINCIPAL FINDINGS

To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.

CONCLUSIONS

These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

In this issue of Blood, Leonhardt et al report that neovascularization during graft-versus-host disease (GVHD) is regulated by av integrins and the micro RNA miR-100.