The influence of comorbid conditions on racial disparities in endometrial cancer survival

There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race.

Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants

Antenatal magnesium (anteMg) is used for various obstetric indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg.

Maternal circulating angiogenic factors in twin and singleton pregnancies

The purpose of this study was to compare longitudinally sampled maternal angiogenic proteins between singleton and twin pregnancies.

Increasing Dietary Selenium Elevates Reducing Capacity and ERK Activation Associated with Accelerated Progression of Select Mesothelioma Tumors

To study the effect of the micronutrient selenium on malignant mesothelioma (MM) progression, we cultured four different MM cell lines in media containing increasing amounts of sodium selenite (30, 50, and 80 nmol/L). Increasing selenium levels increased density-dependent proliferation and mobility for CRH5 and EKKH5 but not AB12 and AK7. Comparing these cell lines revealed that extracellular regulated kinase (ERK) phosphorylation was sensitive to a selenium increase in CRH5 and EKKH5 but not AB12 and AK7 cells. Stable expression of a dominant-negative mutant ERK eliminated the effects of increasing selenium. Because ERK is redox sensitive, we compared the MM cell lines in terms of glutathione levels and the capacity to reduce exogenous hydrogen peroxide. Increasing selenium levels led to higher glutathione and reducing capacity in CRH5 and EKKH5 but not AB12 and AK7. The reducing agent N-acetylcysteine eliminated the effects of selenium on ERK activation, proliferation, and mobility. Mice fed diets containing increasing levels of selenium (0.08, 0.25, and 1.0 ppm) showed increased tumor progression for CRH5 but not AB12, MM cells, and in vivo N-acetylcysteine treatment eliminated these effects. These data suggest that the effects of dietary selenium on MM tumor progression depend on the arising cancer cells' redox metabolism, and the tumors able to convert increased selenium into a stronger reducing capacity actually benefit from increased selenium intake.

Conditional Knockout of Pik3c3 Causes a Murine Muscular Dystrophy

Abnormalities in phosphoinositide metabolism are an emerging theme in human neurodegenerative disease. Myotubular myopathy is a prototypical disorder of phosphoinositide dysregulation that is characterized by profound muscle pathology and weakness and that is caused by mutations in MTM1, which encodes a phosphatase that targets 3-position phosphoinositides, including phosphatidylinositol 3-phosphate. Although the association between MTM1 and muscle disease has become increasingly clarified, the normal role(s) of phosphatidylinositol 3-phosphate metabolism in muscle development and homeostasis remain poorly understood. To begin to address the function of phosphatidylinositol 3-phosphate in skeletal muscle, we focused on the primary kinase responsible for its production, and created a muscle-specific conditional knockout of the class III phosphatidylinositol 3-kinase, Pik3c3. Muscle-specific deletion of Pik3c3 did not disturb embryogenesis or early postnatal development, but resulted in progressive disease characterized by reduced activity and death by 2 months of age. Histopathological analysis demonstrated changes consistent with a murine muscular dystrophy. Examination for cellular mechanism(s) responsible for the dystrophic phenotype revealed significant alterations in the autophagolysosomal pathway with mislocation of known dystrophy proteins to the lysosomal compartment. In all, we present the first analysis of Pik3c3 in skeletal muscle, and report a novel association between deletion of Pik3c3 and muscular dystrophy.

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke.

Behavioral Research in Cancer Prevention and Control

Human behavior is central to the etiology and management of cancer outcomes and presents several avenues for targeted and sustained intervention. Psychosocial experiences such as stress and health behaviors including tobacco use, sun exposure, poor diet, and a sedentary lifestyle increase the risk of some cancers yet are often quite resistant to change. Cancer screening and other health services are misunderstood and over-utilized, and vaccination underutilized, in part because of the avalanche of information about cancer prevention. Coordination of cancer care is suboptimal, and only a small fraction of cancer patients enroll in clinical trials essential to the development of new cancer treatments. A growing population of cancer survivors has necessitated a fresh view of cancer as a chronic rather than acute disease. Fortunately, behavioral research can address a wide variety of key processes and outcomes across the cancer control continuum from prevention to end-of-life care. Here we consider effects at the biobehavioral and psychological, social and organizational, and environmental levels. We challenge the research community to address key behavioral targets across all levels of influence, while taking into account the many new methodological tools that can facilitate this important work.

The Influence of Health Disparities on Targeting Cancer Prevention Efforts

Despite the advances in cancer medicine and the resultant 20% decline in cancer death rates for Americans since 1991, there remain distinct cancer health disparities among African Americans, Hispanics, Native Americans, and the those living in poverty. Minorities and the poor continue to bear the disproportionate burden of cancer, especially in terms of stage at diagnosis, incidence, and mortality. Cancer health disparities are persistent reminders that state-of-the-art cancer prevention, diagnosis, and treatment are not equally effective for and accessible to all Americans. The cancer prevention model must take into account the phenotype of accelerated aging associated with health disparities as well as the important interplay of biological and sociocultural factors that lead to disparate health outcomes. The building blocks of this prevention model will include interdisciplinary prevention modalities that encourage partnerships across medical and nonmedical entities, community-based participatory research, development of ethnically and racially diverse research cohorts, and full actualization of the prevention benefits outlined in the 2010 Patient Protection and Affordable Care Act. However, the most essential facet should be a thoughtful integration of cancer prevention and screening into prevention, screening, and disease management activities for hypertension and diabetes mellitus because these chronic medical illnesses have a substantial prevalence in populations at risk for cancer disparities and cause considerable comorbidity and likely complicate effective treatment and contribute to disproportionate cancer death rates.

Public Health Surveillance of Nonmalignant Blood Disorders

Nonmalignant blood disorders currently affect millions of Americans, and their prevalence is expected to grow over the next several decades. This is owing to improvements in treatment leading to increased life expectancy of people with hereditary conditions, like sickle cell disease and hemophilia, but also the rising occurrence of risk factors for venous thromboembolism. The lack of adequate surveillance systems to monitor these conditions and their associated health indicators is a significant barrier to successfully assess, inform, and measure prevention efforts and progress toward national health goals. CDC is strengthening surveillance activities for blood disorders by improving and developing new methods that are tailored to best capture and monitor the epidemiologic characteristics unique to each disorder. These activities will provide a robust evidence base for public health action to improve the health of patients affected by or at risk for these disorders.

OP-265 Hybrid Treatment for Aortic Stenosis and CAD: Minimally Invasive Sutureless Aortic Valve Replacement and Delayed PCI