Vascular remodeling of the mouse yolk sac requires hemodynamic force

The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a^(–/–)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sa

The Design of a Cognitive Apprenticeship to Facilitate Storytime Programming for Librarians

The majority of research that has been conducted on structuring mentorship programs has been on career support in terms of transferring tacit and explicit knowledge from the supervisor to the protégé. While the instructional design literature touts that cognitive apprenticeships provide a great framework for constructivist and situated learning environments, little research has been done examining how much time should be allocated to the various phases of the apprenticeship framework. The purpose of this study was to explore whether the use of a cognitive apprenticeship framework could be used to mentor new librarians. Data was collected and analyzed in three phases. Phase 1 consisted of a needs assessment to determine the skills necessary for programmers to deliver a curriculum based storytime. Phase 2 data collected during the implementation of the cognitive apprenticeship included observation and reflective journals. Data collected during Phase 3 consisted of participant interviews immediately following the implementation of the cognitive apprenticeship, and three months after the conclusion of the study. All data was coded and analyzed using a phenemonological approach. The researchers found the need for flexibility when utilizing a cognitive apprenticeship model, based on participant prior knowledge and experience, the importance of the modeling and coaching stages of the model, participant desire for working with other programmers being trained

Physician-led patient experience improvement efforts: The CONNECT program, an emerging innovation

In 2009, the leadership of the Children’s University Medical Group (CUMG) embarked on an effort to answer the question, “What would it take to promote and foster a culture of service amongst the medical staff?” The challenge was to engage the physician group in leading patient and family experience improvements within Seattle Children’s. In this article, an innovative, physician-designed and led approach to improving the patient experience is described. The effort focuses on encouraging local, grass roots strategies rooted in readily available and validated best practices. In support of that effort, novel tools that were developed and deployed to elicit input, engagement and self-assessment are also described

The Interaction of Retention, Recruitment, and Density-Dependent Mortality in the Spatial Placement of Marine Reserves

Population density can affect rates of mortality and individual growth. We measured these for the non-exploited bluehead wrasse, Thalassoma bifasciatum, at three sites around St. Croix, US Virgin Islands. Previous work demonstrated that differences in the degree of larval retention in these sites results in very large differences in recruitment intensity. Post-settlement mortality differed among sites and was positively related to recruitment density. Post-settlement growth differences were small. Because of strong mortality effects early in life, adult densities and size/age distributions differed among sites and did not reflect differences in recruitment rate. The site with the highest retention and recruitment (Butler Bay) had many small fish, while the two other sites with lower recruitment rates (Jacks Bay and Green Cay) had proportionally more large fish. These differences resulted in large differences in egg production. Per capita production was highest at the lowest density site (Green Cay). Total egg production at Green Cay was 75% that at Butler Bay, despite only having half the population size, and the highest overall production was at Jacks Bay, with low retention and moderate recruitment. In terms of marine reserve location, sites predicted to have high retention and recruitment may not always be the sites of highest egg production due to density-dependent processes, and it is important to consider the relative values of self-recruitment and larval export in reserve design

Metformin as a Therapeutic Target in Endometrial Cancers.

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer