Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice

INTRODUCTION Treatment with estrogen and progesterone (E+P) mimics the protective effect of parity on mammary tumors in rodents and depends upon the activity of p53. The following experiments tested whether exogenous E+P primes p53 to be more responsive to DNA damage and whether these pathways confer resistance to mammary tumors in a mouse model of Li-Fraumeni syndrome. METHODS Mice that differ in p53 status (Trp53+/+, Trp53+/-, Trp53-/-) were treated with E+P for 14 days and then were tested for p53-dependent responses to ionizing radiation. Responses were also examined in parous and age-matched virgins. The effects of hormonal exposures on tumor incidence were examined in BALB/c-Trp53+/- mammary tissues. RESULTS Nuclear accumulation of p53 and apoptotic responses were increased similarly in the mammary epithelium from E+P-treated and parous mice compared with placebo and age-matched virgins. This effect was sustained for at least 7 weeks after E+P treatment and did not depend on the continued presence of ovarian hormones. Hormone stimulation also enhanced apoptotic responses to ionizing radiation in BALB/c-Trp53+/- mice but these responses were intermediate compared with Trp53+/+ and Trp-/- tissues, indicating haploinsufficiency. The appearance of spontaneous mammary tumors was delayed by parity in BALB/c-Trp53+/- mice. The majority of tumors lacked estrogen receptor (ER), but ER+ tumors were observed in both nulliparous and parous mice. However, apoptotic responses to ionizing radiation and tumor incidence did not differ among outgrowths of epithelial transplants from E+P-treated donors and nulliparous donors. CONCLUSION Therefore, E+P and parity confer a sustained increase in p53-mediated apoptosis within the mammary epithelium and suppress mammary tumorigenesis, but this effect was not retained in epithelial outgrowths.This work was supported by grants from the US Army Medical Research and Materiel Command (W81XWH0410385 to KAD and DAMD17-01-1-0315 to ACB) and the National Institutes of Health (RO1-CA095164 to DJJ)

Compassionate wound care: An integrated intervention for people who self-injure

This article discusses how an integrated physical, psychological and social approach to wound care can help improve the quality of life for people who self-injure. The health professional should demonstrate compassion while teaching the person who self-injures how to provide their own wound care. Compassionate care may help the patient improve their self-compassion and reduce shame associated with this coping strategy, which may in turn avoid exacerbating self-harm when seeking healthcare

"You can't work with my people if you don't know how to" : enhancing transfer of care from hospital to primary care for Aboriginal Australians with chronic disease

Indigenous Australians experience significantly poorer health compared to other Australians, with chronic disease contributing to two-thirds of the health gap. We report on an evaluation of an innovative model that leverages mainstream and Aboriginal health resources to enable safe, supported transfer of care for Aboriginal adults with chronic conditions leaving hospital. The multisite evaluation was Aboriginal-led and underpinned by the principles of self-determination and equity and Indigenous research protocols. The qualitative study documented processes and captured service user and provider experiences. We found benefits for patients and their families, the hospital and the health system. The new model enhanced the patient journey and trust in the health service and was a source of staff satisfaction. Challenges included staff availability, patient identification and complexity and the broader issue of cultural safety. Critical success factors included strong governance with joint cultural and clinical leadership and enduring relationships and partnerships at the service delivery, organisation and system levels. A holistic model of care, bringing together cultural and clinical expertise and partnering with Indigenous community organisations, can enhance care coordination and safety across the hospital–community interface. It is important to consider context as well as specific program elements in design, implementation and evaluation

A Comparative Study on Emerging Electric Vehicle Technology Assessments

Numerous organizations have published reports in recent years that investigate the ever changing world of electric vehicle (EV) technologies and their potential effects on society. Specifically, projections have been made on greenhouse gas (GHG) emissions associated with these vehicles and how they compare to conventional vehicles or hybrid electric vehicles (HEVs). Similar projections have been made on the volumes of oil that these vehicles can displace by consuming large amounts of grid electricity instead of petroleum-based fuels. Finally, the projected rate that these new vehicle fleets will enter the market varies significantly among organizations. New ideas, technologies, and possibilities are introduced often, and projected values are likely to be refined as industry announcements continue to be made. As a result, over time, a multitude of projections for GHG emissions, oil displacement, and market penetration associated with various EV technologies has resulted in a wide range of possible future outcomes. This leaves the reader with two key questions: (1) Why does such a collective range in projected values exist in these reports? (2) What assumptions have the greatest impact on the outcomes presented in these reports? Since it is impractical for an average reader to review and interpret all the various vehicle technology reports published to date, Sentech Inc. and the Oak Ridge National Laboratory have conducted a comparative study to make these interpretations. The primary objective of this comparative study is to present a snapshot of all major projections made on GHG emissions, oil displacement, or market penetration rates of EV technologies. From the extensive data found in relevant publications, the key assumptions that drive each report's analysis are identified and 'apples-to-apples' comparisons between all major report conclusions are attempted. The general approach that was taken in this comparative study is comprised of six primary steps: (1) Search Relevant Literature - An extensive search of recent analyses that address the environmental impacts, market penetration rates, and oil displacement potential of various EV technologies was conducted; (2) Consolidate Studies - Upon completion of the literature search, a list of analyses that have sufficient data for comparison and that should be included in the study was compiled; (3) Identify Key Assumptions - Disparity in conclusions very likely originates from disparity in simple assumptions. In order to compare 'apples-to-apples,' key assumptions were identified in each study to provide the basis for comparing analyses; (4) Extract Information - Each selected report was reviewed, and information on key assumptions and data points was extracted; (5) Overlay Data Points - Visual representations of the comprehensive conclusions were prepared to identify general trends and outliers; and (6) Draw Final Conclusions - Once all comparisons are made to the greatest possible extent, the final conclusions were draw on what major factors lead to the variation in results among studies

Infoliteracy@adistance: Creating Opportunities to Reach (Instruct) Distance Students

This article offers a theoretical model of online, graduate student information seeking behavior. The qualitative methodology used to gather data for the development of the model included an electronic survey and semi-structured interviews conducted online using Adobe Connect Pro™. Participating in the study were 238 graduate students enrolled in at least one online course at a mid-western university. Data analysis included use of Zoomerang™ reports to interpret survey data, and content analysis of interview transcriptions. The resulting evolution of the Bates’ (2002) theoretical model includes new two modes of information seeking: scrutinizing (directed, dynamic), and being alert (undirected, dynamic). The researchers conclude that the essence of online, graduate student information seeking is the gathering and processing of information by humans using computer technologies and the resulting impact on the human brain. This study shows the necessity of linking online, graduate student information-seeking research to psychological theory to examine reasons why online graduate students engage in various information behaviors

No evidence of XMRV in prostate cancer cohorts in the Midwestern United States

Background: Xenotropic murine leukemia virus (MLV)-related virus (XMRV) was initially identified in prostate cancer (PCa) tissue, particularly in the prostatic stromal fibroblasts, of patients homozygous for the RNASEL R462Q mutation. A subsequent study reported XMRV antigens in malignant prostatic epithelium and association of XMRV infection with PCa, especially higher-grade tumors, independently of the RNASEL polymorphism. Further studies showed high prevalence of XMRV or related MLV sequences in chronic fatigue syndrome patients (CFS), while others found no, or low, prevalence of XMRV in a variety of diseases including PCa or CFS. Thus, the etiological link between XMRV and human disease remains elusive. To address the association between XMRV infection and PCa, we have tested prostate tissues and human sera for the presence of viral DNA, viral antigens and anti-XMRV antibodies.Results: Real-time PCR analysis of 110 PCa (Gleason scores > 4) and 40 benign and normal prostate tissues identified six positive samples (5 PCa and 1 non-PCa). No statistical link was observed between the presence of proviral DNA and PCa, PCa grades, and the RNASEL R462Q mutation. The amplified viral sequences were distantly related to XMRV, but nearly identical to endogenous MLV sequences in mice. The PCR positive samples were also positive for mouse mitochondrial DNA by nested PCR, suggesting contamination of the samples with mouse DNA. Immuno-histochemistry (IHC) with an anti-XMRV antibody, but not an anti-MLV antibody that recognizes XMRV, sporadically identified antigen-positive cells in prostatic epithelium, irrespectively of the status of viral DNA detection. No serum (159 PCa and 201 age-matched controls) showed strong neutralization of XMRV infection at 1: 10 dilution.Conclusion: The lack of XMRV sequences or strong anti-XMRV neutralizing antibodies indicates no or very low prevalence of XMRV in our cohorts. We conclude that real-time PCR- and IHC-positive samples were due to laboratory contamination and non-specific immune reactions, respectively

Building validity evidence for the use of aggregate scores in accountability

High stakes test-based accountability systems primarily rely on aggregates and derivatives of scores from tests that were originally developed to measure individual student mastery of content specifications. Current validity models do not explicitly address this use of aggregate scores to measure the performance of teachers, administrators, and schools. Empirical methodologies that allow evaluation of test-based accountability systems need to be identified and developed. One empirical method that lends itself to the comparison of individual and group-level outcomes is hierarchical generalized linear modeling (HGLM). This research explores the validation of aggregate scores used in accountability

Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling.

Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor-mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine-induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada -/- and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder