Awareness of Pregnancy-Associated Health Risks Among Pregnant Women and Male Partners Surveyed in a Prenatal Clinic.

Background: Underestimation of pregnancy-associated health risks could compromise informed decision-making and reduce demand for preconception care. We assessed the knowledge of pregnant women and male partners about several health risks posed by pregnancy to identify potential gaps in reproductive health literacy. Materials and Methods: Pregnant women and male partners were surveyed about their knowledge of seven common health risks associated with pregnancy (venous thromboembolism [VTE], diabetes, gallstones, hemorrhoids, hypertension [HTN], kidney infection, and anemia) in either English or Spanish in a prenatal clinic at Harbor-UCLA Medical Center in Torrance, California. Results: The response rate for women was estimated to be 66% and was 85% for men. Of the 285 respondents, 5.0% of women and 5.6% of men were able to correctly report that all seven health risks increased during pregnancy. Overall, 30.6% of women and 24% of men recognized that pregnancy increased the risks of the three most serious conditions (VTE, diabetes, and HTN). While higher education was associated with a higher awareness of these three serious risks, the majority of individuals with the highest education nonetheless incorrectly reported that these risks were reduced or unchanged in pregnancy. Age, parity, language, gender, and gestational age did not impact study findings. Overall, 77.9% of respondents rated oral birth control pills more hazardous to a woman's health than pregnancy. Conclusions: Surveyed pregnant women and male partners have significant knowledge deficiencies concerning common and serious health hazards associated with pregnancy that may hamper women's ability to make informed choices about their reproductive health options.

Perceptions of health risks associated with pregnancy compared to oral contraceptive use.

OBJECTIVE: To assess beliefs about the safety of oral contraceptives compared to pregnancy to determine if men and women possess accurate information to make informed choices. STUDY DESIGN: In each of six surveys conducted in Southern California from 2008 to 2017, participants were asked "Which do you think is more hazardous to a woman's health - birth control pills or pregnancy?" RESULTS: A total of 28.4% of all 1839 male and female respondents and 29.1% of the 1712 female respondents answered correctly that the health risks posed by pregnancy were greater. In subgroup analyses, 64.4%-81.9% rated oral contraceptives at least as hazardous to a woman's health as pregnancy. CONCLUSION: The vast majority of respondents incorrectly believed that oral contraceptives are more hazardous than pregnancy. IMPLICATIONS: Health decision making relies upon patients' understanding of the relative risks and benefits of each available option. Most sexually active women do not understand that there is no contraceptive method current guidelines would offer them that is as hazardous to their health as pregnancy. Such misconceptions can lead to risky decisions. Clinicians need to explicitly provide their sexually active patients more accurate and balanced information, putting contraception in the context of its probable alternative - pregnancy.

Dual PI3K/mTOR Inhibitors Induce Rapid Overactivation of the MEK/ERK Pathway in Human Pancreatic Cancer Cells through Suppression of mTORC2.

The PI3K/AKT/mTOR pathway, which is aberrantly stimulated in many cancer cells, has emerged as a target for therapy. However, mTORC1/S6K also mediates negative feedback loops that attenuate upstream signaling. Suppression of these feedback loops opposes the growth-suppressive effects of mTOR inhibitors and leads to drug resistance. Here, we demonstrate that treatment of PANC-1 or MiaPaCa-2 pancreatic ductal adenocarcinoma (PDAC) cells with the dual PI3K/mTOR kinase inhibitor (PI3K/TOR-KI) BEZ235 blocked mTORC1/S6K activation (scored by S6 phosphorylation at Ser(240/244)), mTORC1/4E-BP1 (assayed by 4E-BP1 phosphorylation at Thr(37/46)), and mTORC2-mediated AKT phosphorylation at Ser(473), in a concentration-dependent manner. Strikingly, BEZ235 markedly enhanced the MEK/ERK pathway in a dose-dependent manner. Maximal ERK overactivation coincided with complete inhibition of phosphorylation of AKT and 4E-BP1. ERK overactivation was induced by other PI3K/TOR-KIs, including PKI-587 and GDC-0980. The MEK inhibitors U126 or PD0325901 prevented ERK overactivation induced by PI3K/TOR-KIs. The combination of BEZ235 and PD0325901 caused a more pronounced inhibition of cell growth than that produced by each inhibitor individually. Mechanistic studies assessing PI3K activity in single PDAC cells indicate that PI3K/TOR-KIs act through a PI3K-independent pathway. Doses of PI3K/TOR-KIs that enhanced MEK/ERK activation coincided with those that inhibited mTORC2-mediated AKT phosphorylation on Ser(473), suggesting a role of mTORC2. Knockdown of RICTOR via transfection of siRNA markedly attenuated the enhancing effect of BEZ235 on ERK phosphorylation. We propose that dual PI3K/mTOR inhibitors suppress a novel negative feedback loop mediated by mTORC2, thereby leading to enhanced MEK/ERK pathway activity in pancreatic cancer cells.