Determining epigenetic instability in normal and diseased human vulva

Epigenetics is defined as the study of heritable changes of DNA. One such component of epigenetic regulation is DNA methylation in humans. In neoplastic cells epigenetic controls are often dysregulated, especially in the promoter region of CpG islands. Global hypomethylation along with region specific hypermethylation of CpG islands in the promoter region of tumor suppressor is often indicative of neoplastic cells. In cancer, CpG island cytosine hypermethylation has been observed in more than fifty genes, including known tumor suppressor and DNA repair genes. Squamous cell carcinoma (SCC), lichen sclerosis (LS), and adjacent normal tissues were obtained by radical vulvectomies of over one hundred patients. Normal unassociated tissues were also collected in the same manner. The disease process of LS provides an environment conducive to oxidative damage and increases in free radicals. Increased methylation in the promoter regions of specific tumor suppressor and DNA repair genes were anticipated to display a progression to malignancy from normal tissue to LS to SCC. Hypermethylation patterns of p16, p15, O6 methyl guanine methyl transferase (MGMT), glutathione S-transferase pi (GSTP1) were examined by methylation specific polymerase chain reaction (MSP) to obtain an etiological model of vulvar cancer. SCC samples exhibited 26% and 34% methylation in p16 and p15 genes. LS samples displayed 22% and 31% methylation in p16 and p15. The level of hypermethylation in SCC and LS associated samples was significantly different from normal samples in both p16 and p15 genes, suggesting that silencing of these two genes is an early and important event in vulvar squamous cell carcinoma. GSTP1 and MGMT were not found to have a statistically significant difference in any of the tissues tested

Algorithms and Public Service Media

Algorithms increasingly shape the flow of information in societies. Recently, public service media organisations have begun to develop algorithmic recommender systems and automated systems in their internet services, which makes sense given their importance as mediators of information. In the emerging era of big data and growing personalisation, this makes sense strategically and can have instrumental importance for networked societies. This chapter draws on relevant development projects in European and Australian public service media organisations. In relation to the core principles of public service media, five challenges in operationalising automated rulebased systems are identified: 1) balancing popularity and distinctiveness, 2) diversity of exposure to programming, 3) transparency of the logic underlying recommendations, 4) user sovereignty and, 5) the issue of dependence on or independence from commercial intermediaries. The chapter examines a new set of conditions that affect provision public service provision in societies that feature growing use and reliance on networked media

Myocardial Dysfunction in an Animal Model of Cancer Cachexia

Aims Fatigue is a common occurrence in cancer patients regardless of tumor type or anti-tumor therapies and is an especially problematic symptom in persons with incurable tumor disease. In rodents, tumor-induced fatigue is associated with a progressive loss of skeletal muscle mass and increased expression of biomarkers of muscle protein degradation. The purpose of the present study was to determine if muscle wasting and expression of biomarkers of muscle protein degradation occur in the hearts of tumor-bearing mice, and if these effects of tumor growth are associated with changes in cardiac function. Main methods The colon26 adenocarcinoma cell line was implanted into female CD2F1 mice and skeletal muscle wasting, in vivo heart function, in vitro cardiomyocyte function, and biomarkers of muscle protein degradation were determined. Key findings Expression of biomarkers of protein degradation were increased in both the gastrocnemius and heart muscle of tumor-bearing mice and caused systolic dysfunction in vivo. Cardiomyocyte function was significantly depressed during both cellular contraction and relaxation. Significance These results suggest that heart muscle is directly affected by tumor growth, with myocardial function more severely compromised at the cellular level than what is observed using echocardiography

Should we scale-up? A mixed methods process evaluation of an intervention targeting sedentary office workers using the RE-AIM QuEST framework

Background: Interventions targeting a reduction in sedentary behaviour in office workers need to be scaled-up to have impact. In this study, the RE-AIM QuEST framework was used to evaluate the potential for further implementation and scale-up of a consultation based workplace intervention which targeted both the reduction, and breaking up of sitting time.  Methods: To evaluate the Springfield College sedentary behaviour intervention across multiple RE-AIM QuEST indicators; intervention participant, non-participant (employees who did not participate) and key informant (consultation delivery team; members of the research team and stakeholders in workplace health promotion) data were collected using interviews, focus groups and questionnaires. Questionnaires were summarized using descriptive statistics and interviews and focus groups were transcribed verbatim, and thematically analysed.  Results: Barriers to scale-up were: participant burden of activity monitoring; lack of management support; influence of policy; flexibility (scheduling/locations); time and cost. Facilitators to scale up were: visible leadership; social and cultural changes in the workplace; high acceptability; existing health and wellbeing programmes; culture and philosophy of the participating college.  Conclusion: There is potential for scale-up, however adaptations will need to be made to address the barriers to scale-up. Future interventions in office workers should evaluate for scalability during the pilot phases of research

Application of the Beer–Lambert Model to Attenuation of Photosynthetically Active Radiation in a Shallow, Eutrophic Lake

Models of primary production in aquatic systems must include a means to estimate subsurface light. Such models often use the Beer–Lambert law, assuming exponential attenuation of light with depth. It is further assumed that the diffuse attenuation coefficient may be estimated as a summation of scattering/absorbing constituent concentrations multiplied by their respective specific attenuation coefficients. While theoretical deviations from these assumptions have been documented, it is useful to consider the empirical performance of this common approach. Photosynthetically active radiation (PAR) levels and water quality conditions were recorded weekly from six to eight monitoring stations in western Lake Erie between 2012 and 2016. Exponential PAR extinction models yielded a mean attenuation coefficient of 1.55 m (interquartile range = 0.74–1.90 m). While more complex light attenuation models are available, analysis of residuals indicated that the simple Beer–Lambert model is adequate for shallow, eutrophic waters similar to western Lake Erie (R2 > 0.9 for 96% of samples). Three groups of water quality variables were predictive of PAR attenuation: total and nonvolatile suspended particles, dissolved organic substances (dissolved organic carbon and chromophoric dissolved organic matter), and organic solids (volatile suspended solids and chlorophyll). Multiple regression models using these variables predicted 3–90% of the variability in PAR attenuation, with a median adjusted R2 = 0.86. Explanatory variables within these groups may substitute for each other while maintaining similar model performance, indicating that various combinations of water quality variables may be useful to predict PAR attenuation, depending on availability within a model framework or monitoring program.Key PointsThe Beer–Lambert law effectively models photosynthetically active radiation in western Lake Erie, despite some systematic deviationsField‐obtained water quality parameters can predict photosynthetically active radiation attenuation with a high degree of confidenceSuspended particle concentration is most predictive of photosynthetically active radiation attenuation in this turbid, eutrophic basinPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147097/1/wrcr23654_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147097/2/wrcr23654-sup-0001-2018WR023024-SI.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147097/3/wrcr23654.pd

Endurance exercise accelerates myocardial tissue oxygenation recovery and reduces ischemia reperfusion injury in mice

Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K(+)channel on vascular smooth muscle cells, VSMC sarc-K(ATP)) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-K(ATP) channels and reperfusion recovery

The Role of PETE in Developing and Sustaining Physical Literacy Informed Practitioners

This paper discusses teacher preparation in relation to encouraging and empowering future teachers to appreciate the potential and value of adopting physical literacy as the goal of PE. The paper addresses the issue of the role of schools and teacher training programs in developing the next generation of PE teachers entering PE Teacher Education (PETE) with respect to thoughts, feelings, perceptions, and beliefs that underpin the concept of physical literacy, and providing high quality learning experiences that are crucial to continuing physical activity throughout the life course for all children, not just those that have a natural aptitude in this area. Many advocates for radical change in physical education have repeatedly argued that physical education curricula around the world are too focused on a traditional, one size fits all, sport technique based, multi-activity form. Others have argued that the traditional curricula have a primary focus on physical competence in running, jumping, and balls skills rather than providing experience in a wide range of physical activities including, inter alia, those with a focus on aesthetic awareness and those related to outdoor adventure

Diamond Line - Fall 2020

In following up the premier issue of The Diamond Line, the fall 2020 editorial staff had big shoes to fill. We took on the challenge of creating something that would uphold the framework of Issue 1 while simultaneously branching out from its margins. Like the editors before us, we had a vision, but ours took a new form — bright, warm colors. Sunset colors. Moons. Playful lines. Isolation and introspection. A stroll through an art gallery. A coming-of-age story bound between two groovy orange bookends. While Issue 2 does not have an overarching theme, we chose the cover art, “Pandemic Prom” by Autumn Blaylock, because it beautifully encompassed the pages within and the vision we were working toward

Diamond Line - Fall 2020

In following up the premier issue of The Diamond Line, the fall 2020 editorial staff had big shoes to fill. We took on the challenge of creating something that would uphold the framework of Issue 1 while simultaneously branching out from its margins. Like the editors before us, we had a vision, but ours took a new form — bright, warm colors. Sunset colors. Moons. Playful lines. Isolation and introspection. A stroll through an art gallery. A coming-of-age story bound between two groovy orange bookends. While Issue 2 does not have an overarching theme, we chose the cover art, “Pandemic Prom” by Autumn Blaylock, because it beautifully encompassed the pages within and the vision we were working toward