Fructose Alters Cell Survival and Gene Expression in Microglia and Neuronal Cells Lines

Purpose: Microglia are macrophages that are found primarily in the CNS and play a crucial role in maintaining a healthy brain by engulfing invading microorganisms, releasing inflammatory mediators, and pruning dead cells. Microglia can become activated in response to certain stimuli which causes them to transition into a pro-inflammatory state, and can sometimes become chronically activated which can result in neuronal damage. Studies have shown a causal relationship between this activation and sugars such as fructose and glucose. We sought to understand the role of sugars in microglial activation and the subsequent effects on neuron health. Methods: Rat microglia (HAPI) and neuronal (B35) cell lines were treated with varying concentrations of fructose (25 mM, 12.5 mM, and 6.25 mM) or glucose (25 mM and 12.5 mM)as a positive control to determine their effects on the cells. Following treatment and incubation for 3 or 24 hours, the cells were analyzed using an MTT assay to measure cell survival or real-time polymerase chain reaction (RT-PCR) to measure gene expression levels. Effects of fructose were measured in HAPI microglia after direct treatment with the sugar. The genes investigated by the RT-PCR in the HAPI cells included: glucose transporter 5 (GLUT5), and the inflammatory markers high mobility group box 1 (HMGB1), and prostaglandin E receptor 2 (Ptger2). To evaluate the effects of microglial activation on neuronal function, the B35 neurons were treated either directly with sugars or with the supernatant collected from fructose-treated HAPI microglia. This allows examination of the effects of soluble neuron-injury factors released by microglia. The genes investigated by RT-PCR in B35 neurons included nuclear factor-κB (NFκB) and enolase 2 (Eno2). Results: Cell survival assays showed that 24-hour direct fructose treatment increased B35 cell survival by up to 13%, while groups treated with microglia supernatant increased cell survival by up to 33%. In HAPI microglia, 3 hours of treatment with fructose caused GLUT5 expression to be suppressed by up to 32% in all treatment groups except for 6.25 mM fructose, while Ptger2 and HMGB1 expression was increased by as much as 65% and 15%, respectively. After 24-hours of treatment with fructose, the HAPI microglia showed a maximum of 80% increased expression of HMGB1, while Ptger2 expression was mostly unchanged. In B35 neurons, 3 hours of treatment with fructose caused a decrease of up to 26% in NFκB and an increase of up to 46% in Eno2 expression. Conclusion: Cell survival results indicate that the microglia may provide a short term protective effect on the B35 neurons. However, data from the gene expression assays show evidence of cellular dysfunction in neurons and pro-inflammatory activity in microglia which may lead to neuronal death on a longer timeline. As seen in the gene expression results, microglia had increased expression of pro-inflammatory genes and B35 neuronal cells had increased expression of markers of cellular damage. Future studies will further explore the effects of fructose on expression of other genes and examine the effects on neuron survival at later time points

New Technologies and International Broadcasting: Reflections on Adaptations and Transformations

International broadcasters, like all media institutions, adjust to reflect the existence of new distribution technologies. Technological change is part of a new media landscape that has rendered older definitions and contexts of international broadcasting insufficient. The pace and extent of adjustment differs among the players. Adaptations range from the superficial to the highly integrative and, on the other hand, from the merely adaptive to the pervasively transformative. Can one compare, among institutions, how this process takes place and what factors influence the patterns of accommodation? Theories of organizational structure shed light on which factors lead international broadcasters to which path. This article considers U.S. international broadcasting as a model to tease out some of these factors, among them organizational complexity, political influence, and control and contradictions embedded in institutional purpose. In this scenario, technological adaptation can mask a critical need to address institutional transformation

Teaching Resident Self-Assessment Through Triangulation of Faculty and Patient Feedback

Problem: To accurately determine one\u27s ability in any clinical competency, an individual must be able to self-assess performance and identify personal limitations. Existing research demonstrates that physicians of all levels are unreliable self-assessors. This poses a concern in medical practice, which requires continuous updates to clinical competencies and awareness of personal limitations. Few published studies examine graduate medical education curricula designed to develop self-assessment skills. Intervention: Conceptual models, such as self-determination theory, suggest that self-assessment is most effectively learned through reflective processes. The Family Medicine Residency Program at Lehigh Valley Health Network developed a learner-centered competency assessment process that integrates advising and performance review. The multisource, observable behavior-based process encourages conversation between resident and advisor. Utilizing feedback from clinical preceptors and patient surveys, advisors guide residents in determining individual learning needs in core competency areas, including relationship-centered care. Development of medical learners\u27 capacity to form relationships is one means to improving the patient experience. Context: This retrospective case study evaluates the accuracy of senior residents\u27 self-assessment in relationship-centered care compared with that of junior residents. The study population includes the 34 residents enrolled from AY 2009–2012. Data sets represent specific 6-month periods and have 3 component scores—Self, Faculty, and Patient—which were triangulated to determine concordance rates by postgraduate year level. Outcome: The concordance rate among first-years was 26.7%, whereas third-years saw 60.0% concordance. A discordance analysis found the Patient score most often deviated from the other 2 scores, whereas the Faculty score was never the sole dissenter. When all 3 scores differed, the Self score frequently fell between the other 2 scores. Lessons Learned: The principles of self-determination theory provide a valuable framework for understanding the development of residents\u27 intrinsic motivation to become lifelong learners. The trend in improved concordance rates among senior residents suggests that prompting learners to triangulate feedback from multiple sources can lead to a shift in perspective about competency. Further study is needed to determine whether our results are generalizable to other competencies and educational setting

SUPER BOWL CITY: THE REAL FACES OF XLVI UNMASKED

poster abstract111.3 million viewers watched as Indianapolis went from Naptown to Super City when they hosted the 2012 Super Bowl XLVI. As visitors poured into Indianapolis, they were greeted with the smiling faces of Hoosiers. Throughout the weeks preceding the Super Bowl Indianapolis residents worked together to bring the Super Bowl legacy to life. While the media focused on Lucas Oil stadium and the events in Super Bowl Village because it grabbed the attention of the public, the lives of unnoticed Indianapolis residents were impacted by their involvement with the mega sports event. To investigate the effects of the Super Bowl on Indianapolis and its residents, we interviewed residents who were involved with the Super Bowl through the areas of philanthropy, low-wage workers, and the residents of the Near-East Side. Data was collected through interviews, participant observations, ethnographic research methods, surveys, and resources collected from residents and organizations. Our project is an ongoing process and is a start to understanding the impact of large sporting events on Indianapolis and its residents

The TLR4 D299G and T399I SNPs Are Constitutively Active to Up-Regulate Expression of Trif-Dependent Genes

Peer reviewedPublisher PD

Information Security in Nonprofits: A First Glance at the State of Security in Two Illinois Regions

Information security is a hot button topic across all industries and new reports of security incidents and data breaches is a near daily occurrence. Much is known about recent trends and shortcomings in information security in the public and private sectors, but relatively little research examines the state of information security in nonprofit organizations. The underlying missions of nonprofit organizations, composition of their workforce, and their reliance on grants and donations for revenue generation streams set nonprofits apart from private business. These facts warrant an examination of information security of nonprofit organizations separate from private or commercial groups. This paper examines the state of information security in nonprofit organizations with results obtained by surveying volunteers or employees at nonprofit groups in two areas of Illinois. A qualitative discussion using observations gained from direct analysis of the security status of three organizations as part of student service learning projects is presented as well