Links Between Maternal Cardiovascular Disease and the Health of Offspring.

Maternal cardiovascular disease (CVD) during pregnancy is on the rise worldwide, as both more women with congenital heart disease are reaching childbearing age, and conditions such as diabetes, hypertension, and obesity are becoming more prevalent. However, the extent to which maternal CVD influences offspring health, as a neonate and later in childhood and adolescence, remains to be fully understood. The thrifty phenotype hypothesis, by which a fetus adapts to maternal and placental changes to survive a nutrient-starved environment, may provide an answer to the mechanism of maternal CVD and its impact on the offspring. In this narrative review, we aim to provide a review of the literature pertaining to the impact of maternal cardiovascular and hypertensive disease on the health of neonates, children, and adolescents. This review demonstrates that maternal CVD leads to higher rates of complications among neonates. Ultimately, our review supports the hypothesis that maternal CVD leads to intrauterine growth restriction (IUGR), which, through the thrifty phenotype hypothesis and vascular remodelling, can have health repercussions, including an impact on CVD risk, both in the immediate newborn period as well as later throughout the life of the offspring. Further research remains crucial in elucidating the mechanism of maternal CVD long-term effects on offspring, as further understanding could lead to preventive measures to optimise offspring health, including modifiable lifestyle changes. Potential treatments for this at-risk offspring group could mitigate risk, but further studies to provide evidence are needed.

Comparing methods of performing geographically targeted rural health surveillance.

BACKGROUND: Worsening socioeconomic conditions in rural America have been fueling increases in chronic disease and poor health. The goal of this study was to identify cost-effective methods of deploying geographically targeted health surveys in rural areas, which often have limited resources. These health surveys were administered in New York's rural Sullivan County, which has some of the poorest health outcomes in the entire state. METHODS: Comparisons were made for response rates, estimated costs, respondent demographics, and prevalence estimates of a brief health survey delivered by mail and phone using address-based sampling, and in-person using convenience sampling at a sub-county level in New York's rural Sullivan County during 2017. RESULTS: Overall response rates were 27.0% by mail, 8.2% by phone, and 71.4% for convenience in-person surveys. Costs to perform phone surveys were substantially higher than mailed or convenience in-person surveys. All modalities had lower proportions of Hispanic respondents compared to Census estimates. Unadjusted and age-adjusted prevalence estimates were similar between mailed and in-person surveys, but not for phone surveys. CONCLUSIONS: These findings are consistent with declining response rates of phone surveys, which obtained an inadequate sample of rural residents. Though in-person surveys had higher response rates, convenience sampling failed to obtain a geographically distributed sample of rural residents. Of modalities tested, mailed surveys provided the best opportunity to perform geographically targeted rural health surveillance.

Preclinical Metrics Correlate With Drug Activity in Phase II Trials of Targeted Therapies for Non-Small Cell Lung Cancer.

Novel oncology drugs often fail to progress from preclinical experiments to FDA approval. Therefore, determining which preclinical or clinical factors associate with drug activity could accelerate development of effective therapies. We investigated whether preclinical metrics and patient characteristics are associated with objective response rate (ORR) in phase II clinical trials of targeted therapies for non-small cell lung cancer (NSCLC). We developed a reproducible process to select a single phase II trial and supporting preclinical publication for a given drug-indication pair, which we defined as the pairing of a small molecule inhibitor (e.g., crizotinib) with the specific patient population for which it was designed to work (e.g., patients with an ALK aberration). We demonstrated that robust drug activity in mice, as measured by change in tumor size, is independently associated with improved ORR in phase II clinical trials. The number of mice utilized in experiments, the number of publications referencing the drug for NSCLC before the phase II clinical trial, and whether the drug was approved for a cancer other than NSCLC also significantly correlated with ORR. Among clinical characteristics, sex, race, histology, and smoking history were significantly associated with ORR. Further research into metrics that correlate with drug activity has the potential to optimize selection of novel therapies for clinical trials and enrich the drug development pipeline, particularly for patients with targetable genetic aberrations and rare cancers.

Combination of Rapamycin and Resveratrol for Treatment of Bladder Cancer.

Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1-/- MEF cells, and not in wild-type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436-446, 2017. © 2016 Wiley Periodicals, Inc.