217 research outputs found

    Recruitment of regulatory and conventional T cells to colon adenocarcinomas

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    Colorectal cancer is one of the most common malignant diseases, with an annual incidence of over one million cases worldwide. Although survival depends strongly on tumor stage at diagnosis, lymphocyte infiltration has been clearly correlated to a favourable prognosis in several studies. The aim of this thesis was to determine the mechanisms for lymphocyte infiltration in colon adenocarcinomas, with emphasis on the effect of regulatory T (Treg) cells on the recruitment of conventional T cells. First, we characterized the lymphocyte infiltrate in human colon adenocarcinomas compared to surrounding unaffected tissue. In tumors, we detected substantial accumulation of CD4+ FOXP3+CTLA4+CCR4+ CD39+ Tregs with potential to suppress anti-tumor immunity. Also, the frequencies of activated intratumoral, Th1 like T cells, important for anti-tumor immune responses, were decreased. The accumulation of CCR4+ Tregs may be due to increased production of the ligand CCL22 in the tumor. Furthermore, MAdCAM-1 expression, an adhesion molecule used by lymphocytes to migrate to the gut, was decreased in tumor tissue, potentially contributing to shaping the repertoire of tumor infiltrating lymphocytes. Since directed lymphocyte migration is controlled by chemokines and chemokine receptors, we decided to investigate alternative mechanisms for lymphocyte recruitment to tumors by examining the mRNA levels of chemokine decoy receptors D6, DARC and CCX-CKR. By using real time RT-PCR, we detected strongly decreased levels of the chemokine decoy receptor D6, with affinity for inflammatory chemokines, in human colon tumors compared to unaffected mucosa, whereas there was no change in expression of DARC and CCX-CKR. Further, we observed that Treg isolated from colon cancer patients inhibited transendothelial migration of conventional T cells in vitro, while Tregs from healthy control subjects had no such effect. Also, we detected elevated levels of the adenosine-generating enzyme CD39 on circulating Tregs from cancer patients. Adenosine suppress lymphocyte functions and indeed, exogenous adenosine resulted in inhibition of conventional T cell migration in our system, while blocking of adenosine receptors restored the migration of T cells from cancer patients. To directly assess the function of Tregs in colon cancer, we crossed APCMin/+ mice, a model of intestinal cancer, with DEREG mice that allow selective depletion of Tregs. The tumor tissue in these mice presents a similar distribution of T cells as human colon tumors, since there is decreased infiltration of activated T cells and accumulation of Tregs in intestinal tumor tissues. When depleting Tregs for 10 days, we detected improved CD4+ and CD8+ lymphocyte infiltration to tumors, indicating that accumulation of Treg impairs migration of conventional T cells into tumors. Taken together, results from this thesis show differential lymphocyte composition in colon tumors compared to surrounding unaffected mucosa, possibly induced by accumulated Tregs and modulated chemokine decoy receptor and homing molecule expression in the local environment

    Antioxidant and Hepatoprotective Activity of Veronica ciliata Fisch Extracts Against Carbon Tetrachloride-Induced Liver Injury in Mice

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    Veronica ciliata Fisch. has been traditionally used in Traditional Chinese Medicine prescriptions due to its curative effects for hepatitis, cholecystitis, rheumatism, and urticaria. The present study was focused on investigating the role of ethyl acetate and aqueous extracts of Veronica ciliata Fisch. Furthermore, in vitro antioxidant activity (scavenging of DPPH, ABTS, superoxide, and nitrite radicals; reducing power; beta-carotene bleaching) and the hepatoprotective effect of the ethyl acetate extract by means of CCl4-induced oxidative stress in mice were investigated. The ethyl acetate extract of Veronica ciliata Fisch. displayed more noteworthy in vitro antioxidant activities than the aqueous extract. Moreover, it significantly prevented the increase in serum T-AOC, ALT, AST and ALP level in acute liver damage induced by CCl4, decreased the extent of MDA formation in liver and elevated the activities of SOD and GSH in liver. This activity was found to be comparable to that of bifendate. Histopathological observation of the liver was also performed to further support the evidence from the biochemical analysis. The results indicated that strong antioxidant activities and a significant protective effect against acute hepatotoxicity induced by CCl4 of Veronica ciliata Fisch. were concentrated in the ethyl acetate extract. The results suggested that this activity may be due to free radical-scavenging and antioxidant properties

    How to be a woman. Models of masochism and sacrifice in young adult fiction

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    Buffy, Bella, Veronica, Katniss, Clary, Tris and Saba : For two decades post-feminist heroines have faced life-threatening trials as part of their progress to womanhood. In this chapter I consider how young adult popular fictions operate as forms of pedagogy for young women by offering them particular models of maturity and womanhood. I explore the recurrence and reformulation of a persistent pattern of behaviour in which heroines engage in risky and/or masochistic behaviours for which they are emotionally rewarded.. These recurrences function as a form of vicarious experiential learning in which readers and viewers learn that emotional gratification and adult status are conferred through self-harm and self-sacrifice. Popular culture is not a monolithic form and young adult fictions are no exception. An analysis of fictional examples of this behaviour pattern challenges the idea that heroines today are empowered agents as a result of the legacy of feminism. At the same time, the analysis belies any notion that fictions are universally hegemonic and oppressive – fictions can and do disrupt and interrogate this pattern of emotional masochism. Scholars of public pedagogy have explored the complexities, contradictions and subtleties of the pedagogical process. Sandlin O’Malley and Burdick (2011) in their review of public pedagogy literature acknowledge that some scholarship has demonstrated how “the teaching and learning inherent within daily life can be both oppressive and resistant” (p. 144). Jubas and Knutson (2012) also see public pedagogy as an arena where contradictions and tensions are in play. They argue that we can see “New examples of dialectic or tensions … between the authority of the producer and the consumer; between traditional structures which ground identities and help people make sense of cultural texts, and personal agency which frees people to choose and invent identities and meanings” (p. 86). This analysis aims to contribute to understandings of the complexities of public pedagogy by showing how fictions aimed primarily at young women both resist and accommodate patriarchy

    Towards an understanding of embodied heritage language reclamation: implications for heritage language learners

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    This paper is the autoethnographic report of a heritage language learner during an academic year of self-directed study of the Bàsàa, a developing language in Cameroon, and a participatory youth language and art camp. The author developed two practice-based theories. The first theory is based on the author’s embodiment of the heritage language reclamation, while the second is based on youth’s creativity and capacity to adapt their social and environmental constraints to learn Bàsàa. Embodied heritage language reclamation (EmHLR) is an emerging scholarship to document the benefits of inherited cultural aesthetics, including language. As a practice-based theory, EmHLR advocates for art-literacy as a domain of use for the preservation of cultural heritage. The social convenience pedagogy (SCP), on the other hand, reflects youth “lives, selves, and identities” (Choi, 2016, p.116). Consequently, applying SCP is the action of “giving account of oneself” (p. 116). The SCP, likewise, generates new domains of use for language reclaimers. Both theories aim to 1) assist heritage language learners in their reclamation journey and 2) change their attitude toward their heritage language 3) to personally safeguard their cultural heritage aesthetically. EmHLR and SCP are a reminder that, as a heritage language learner, I cannot just throw away the foreign languages my parents gave me. I can, nonetheless, enhance my cultural identity and revitalize Bàsàa through art literacy (visualizing language), music literacy (listening to language), dance literacy (communicating nonverbally) and theater literacy (performing language). This shift in attitude allows me, as a reclaimer, to reconnect to my native land, language, culture and traditions. EmHLR and SCP are, therefore, ethnographic approaches that follow Smith’s (1999) parameters of culturally sensitive research. It uses multiple forms of literacies to document and safeguard cultural heritage (Piazza, 1999). EmHLR and SCP combine arts with language, so that the reclaimer embodies the language at the same time it is being produced. This presentation will explain the reason for both theories and, using film literacy (imaging language), illustrate the embodiment of heritage language reclamation using the social convenience pedagogy. References: Choi, J. (2016). Creating a Multivocal Self: Autoethnography as Method. New York, NY: Routledge. Piazza, C. L. (1999). Multiple Forms of Literacy: Teaching Literacy and the Arts. Upper Saddle River, NJ: Prentice-Hall, Inc. Smith, L. T. (1999). Deconstructing Methodologies: Research and Indigenous Peoples New York, NY: Zed Books

    The Feasibility of Conducting Task-Oriented Training at Home for Patients with Stroke

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    Background: Task-oriented training for upper extremity hemiparesis following a stroke is an effective intervention with evidence of its application in the clinic setting. However, the home provides an enriched and practical environment to implement this intervention. This report presents the feasibility of implementing task-oriented training at home. Method: Stroke survivors with limitations in upper extremity movement and function were assessed before and after a Task-Oriented Training and Evaluation at Home (TOTE Home) program, and 1 month later. Areas of process, resources, management, and scientific value were analyzed for the feasibility of a larger randomized clinical trial (RCT). Results: The process of this study was acceptable but demonstrated a need for more personnel for a larger trial to accommodate a larger sample over a shorter period. Adjusting the amount of intervention dosing may reduce the amount of resources required to achieve participants’ goals. A large RCT examining TOTE Home would require management from multiple professionals. TOTE Home proved to be a safe scientific endeavor with no adverse side effects. Conclusion: The implementation of TOTE Home is a feasible endeavor. A larger clinical trial is justified to determine the generalizability and effectiveness of this intervention in a home-based setting

    Task oriented training and evaluation at home (TOTE Home)

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    Hemiparesis following a stroke frequently leads to “learned non-use” of the weaker arm and hand. Task oriented training has been suggested as a contemporary neurorehabilitation technique. A single-subject AB series design with a follow-up was conducted to assess the effectiveness of a task oriented training program administered in participants’ homes. This intervention, Task Oriented Training at Home (TOTE Home), incorporated current experience-dependent plasticity aspects (Kleim & Jones, 2008) modeled after the ASAP protocol parameters as described in Winstein et al. (2013) and principles of task oriented training as suggested by Lang and Birkenmeier (2014). Repeated measures of accelerometry and level of confidence on a priority task were analyzed with visual analysis of changes in level, trend, and slope (Portney & Watkins, 2009). Change scores from standardized assessments for the upper extremity (Fugl-Meyer, 1980), Motor Activity Log (van der lee, Beckerman, Knol, de Vet, & Bouter, 2004), Stroke Impact Scale question of recovery (Duncan et al., 1999), Functional Test for the Hemiparetic Upper Extremity (Wilson, Baker, & Craddock, 1984), and Canadian Occupational Performance Measure (Law et al., 2005) were evaluated on data collected at baseline, post-intervention, and follow-up time periods (Portney & Watkins, 2009). Four participants completed TOTE Home and each demonstrated improvement in movement and function of their affected upper extremity as measured by accelerometry, self-efficacy, and other standardized measures. The degree of improvement varied between each participant. A detectable change was evident in all outcome measures following intervention. Each participant’s progress throughout the TOTE Home study was supported by aspects of both Motor Learning Theory (Bass-Haugen, Mathiowetz, & Flinn, 2008; Carr & Shepherd, 1989) and the Theory of Occupational Adaptation (Schkade & Schultz, 1992; Schultz & Schkade, 1992)

    Madonna’s Music Videos as Audiovisual “Performances”. Forty years of popular culture

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    In recent years, the concept of “performance” has taken on an increasingly specific value in reference to issues of education, evaluation, and perception. It is a word recalling not only the performances we do, when necessary, but the entertainment world, where music and vision combine to generate sensational events and the magic of fiction. In The Society of the Spectacle, written by Guy Debord in 1967, the author claimed that the spectacle had become an “integral part of our very existence”. That was true at the time, and it is still true today. However, in the contemporary visual age we are hyper-and-radically-connected and we are transformed into “sounding images” projected onto screens without our interrelational human parts. Madonna Louise Veronica Ciccone’s career began in the Early 80s and it has not ended yet. Over those forty years, Madonna has constructed an innovative “poetics of performance” that has been studied by numerous sociologists around the world
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