Evaluation of Oncolytic and Immunomodulatory Potential of the HSV-1 Live-Attenuated Vaccine Strain VC2 in an Immunocompetent Murine Melanoma Model

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses with enhanced immune-stimulating properties and improved efficacy and safety profiles are needed. Further, the lack of concordance of preclinical murine studies with results in human clinical trials highlights the need for improved murine tumor modeling strategies. Our laboratory developed the live-attenuated HSV-1 (VC2) vaccine strain, which has shown efficacy in protection against lethal intravaginal HSV-1 and HSV-2 challenge after a single intramuscular injection in mice. VC2 replicate efficiently in permissible cells but does not enter ganglionic axons. Further, VC2 is highly immunogenic generating strong cell-mediated and humoral immune responses. We developed an immunocompetent double-labeled murine melanoma model for testing the immune-modulating and adjuvant effects of oncolytic herpesviruses. Intratumoral virotherapy using VC2 resulted in significant increases in CD3+ T cells and IBA-1+ macrophages in the tumor microenvironment, but reduced expression of arginase-1, a marker of the M2, pro-tumorigenic macrophage phenotype. Median survival times (MST) of VC2 treated mice were nearly twice that of mock-treated controls. We also found that bioluminescence allows for more sensitive assessment of anti-tumor responses during the acute inflammatory phase of treatment during which pseudoprogression can result in misleading increases in tumor volumes using traditional caliper measurements. Our findings suggest that the remarkable immunogenicity of VC2 makes it a good candidate as a vector for tumor vaccine development and our model allows for sensitive assessment of response to therapy in the face of marked acute inflammation. These findings represent significant progress in viral vector development for cancer therapy and in modeling strategies for testing immune-stimulating anti-cancer therapies

Alexithymia and posttraumatic stress disorder following asthma attack

This study examined the levels of posttraumatic stress disorder (PTSD) following asthma attack (post-asthma attack PTSD) and psychiatric co-morbidity among college students. It also investigated the association between these variables and alexithymia. One hundred and six college students participated in the study and completed an on-line survey comprising the Asthma Symptom Checklist, PTSD Checklist, General Health Questionnaire-28 and Toronto Alexithymia Scale. Ninety-one students without asthma and major illness formed the control group. 2 % met the diagnostic criteria for full-PTSD, while 42 and 56 % met the partial and no-PTSD criteria respectively. Compared with the control, the asthma group reported significantly more somatic problems, social dysfunction and depression and was five times more likely to have an elevated risk of developing a general psychiatric disorder. After adjusting age, marital status, asthma experience and symptoms, alexithymia did not predict PTSD, while difficulty identifying feelings predicted psychiatric co-morbidity. Mediational analyses showed that asthma symptoms partially mediated the link between difficulty identifying feelings and psychiatric co-morbidity. People can develop PTSD symptoms and other psychological difficulties following asthma attack. Alexithymia influenced general psychological difficulties independently of PTSD symptoms. © 2012 Springer Science+Business Media New York

Barriers to the Self

This article explores Sylvia Plath’s The Bell Jar (1967) and Elizabeth Wurtzel’s Prozac Nation (1994) through the effects that depression has on the creation and perception of self in young women. Depression is explored in terms of the barriers it erects around young women’s attempts to conceptualise selfhood as it forms in adolescence. This article particularly focuses on the problem of productivity in both texts as protagonists Esther Greenwood and Elizabeth Wurtzel appear to view productivity, particularly academic and literary, as the means through which they will create and establish a coherent self. This fetishised productivity is halted by their depressions, illustrating a further tension between the wider capitalist society which demands productivity and the destabilising nature of depression. Whilst Esther and Elizabeth have different experiences, due to the periods of composition, both characters and texts have striking similarities which suggest that there is a common thread which unites the experiences of female depression in the late twentieth century

Posttraumatic stress disorder following asthma attack (post-asthma attack PTSD) and psychiatric co-morbidity: The impact of alexithymia and coping

This study investigated the prevalence of post-asthma attack posttraumatic stress disorder (PTSD) and the severity of psychiatric co-morbidity among a group of college students and whether alexithymia and coping strategies would relate to health outcomes. This is a cross-sectional study in which 156 college students who had previously experienced asthma attack were recruited. They completed a demographic page, Asthma Symptom Checklist, PTSD Checklist, General Health Questionnaire-28, Toronto Alexithymia Scale and the COPE. They were also matched with 141 students without asthma. The results showed that 3% met the criteria for full-PTSD, 44% for partial and 53% for no-PTSD. There were no significant differences between the asthma and control groups in severity of psychiatric co-morbid symptoms. Path analyses showed that asthma severity was significantly correlated with PTSD and psychiatric co-morbidity. It was also correlated with alexithymia which was in turn associated with psychiatric co-morbidity but not PTSD. Coping strategies were not correlated with health outcomes. To conclude, people can develop PTSD symptoms and degrees of psychiatric co-morbid symptoms after suffering asthma attack. The severity of these symptoms relates to people\u27s perceptions of asthma severity and alexithymia. © 2012 Elsevier Ltd

Mid-Career Adult Learners in an Online Doctoral Program and the Drivers of Their Academic Self-Regulation: The Importance of Social Support and Parent Education Level

Adult professionals enroll in online graduate programs and rely on social support and on their ability to self-regulate to be successful. The literature on academic self-regulation among emerging adults (traditional college age) is ample, but we do not know how social support interacts with academic self- regulation among adult graduate students at mid-career, particularly among those students who are first generation college goers. This study addressed the following questions: (1) To what degree do parental education level and cohort progression predict academic self-regulation? and (2) What sources of social support – family, friends, loved one (significant other), and classmates – are predictive of academic self- regulation for adult students in an online doctoral program? Findings include evidence that the influence of parental educational level on academic self-regulation persists through midlife. Also, that perceived social support from family, friends, and peers predicts academic self-regulation. We conclude with implications for the design of online programs

Occupation-Based Learning Modules in Preparation for Parole: A Program Evaluation

A qualitative research study was conducted that examined occupational therapy students’ fieldwork rotation at Muskegon Correctional Facility, where they implemented a 15-week pre-parole program. One focus group with three participants was conducted. Transcription, coding, and theming followed, providing five themes; restriction, OT perceptions, learning styles, future needs, and relationships. Results showed areas of needs within this population, ways occupational therapy can address this need, and general improvements that can be made to pre-release programs

Re-mystifying the exhibition of medieval sacred objects

Through this study, I identify and ascertain contexts found within the medieval church, specifically focusing on the architectural experience of the Abbey of St.-Denis, and the design characteristics and features of three medieval objects, in order to see how museums can translate the messages of sacred medieval objects. In this work, I use theories of material culture and visual culture studies, museum practices, design observation and analysis to reveal a broader, conceptual way of applying curatorial and exhibition design practices. In addition, I rely heavily on a textual analysis of Abbot Suger's diary about St.-Denis to both provide a context for the artifacts under scrutiny and then to inspire contemporary curatorial and design practices. As objects shift from their place of origin to a museum setting, and then from one institution to another through museum loans and purchases, I posit that exhibit designers and curators must take great care in placement and display of these relics. Reverent and sacred presentation of inspirational and transcendent artifacts requires great sensitivity and scrutiny to translate both authentic context and material meaning for visitors. Of particular import, I show the connections between the medieval and contemporary worlds and the value inherent in the original contexts of objects as a catalyst for exhibition design. In doing so, I shed light to "re-mystify" the rich promise of artifacts to tell important stories in the museum, helping visitors to understand other worlds - and maybe more of their own - through meaningful exchange