Assessment of tumor prevention in Type 1 Neurofibromatosis using a nitroxide compound

Background Type 1 Neurofibromatosis (NF1) is a genetic disorder linked to mutations of the NF1 gene. Clinical symptoms are varied, but hallmark features of the disease include skin pigmentation anomalies (café au lait macules, skinfold freckling) and dermal neurofibromas. Method These dermal manifestations of NF1 have previously been reported in a mouse model where Nf1+/− mice are topically treated with dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). We adopted this mouse model to test the protective effects of a nitroxide antioxidant, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Antioxidants have previously been shown to increase longevity in nf1-deficient fruitflies. Doses of 4 μM and 40 μM CTMIO provided ad libitum in drinking water were given to Nf1-deficient mice. Results Consistent with previous reports, Nf1-deficient mice showed a 4.7-fold increase in papilloma formation (P < 0.036). However, neither dose of CTMIO had any significant affect on papilloma formation. A non-significant decrease in skin pigmentation abnormalities was seen with 4 μM but not 40 μM CTMIO. Subsequent analysis of genomic DNA isolated from papillomas indicated that DMBA/TPA induced tumors did not exhibit a local loss of heterozygosity (LOH) at the Nf1 locus. Conclusion These data reveal that oral antioxidant therapy with CTMIO does not reduce tumor formation in a multistage cancer model, but also that this model does not feature LOH for Nf1.

Orals ain’t orals : the role of prepared oral presentations in the classroom and beyond. How do instruction and feedback practices guide delivery choices?

Despite an ostensibly technology-driven society, the ability to communicate orally continues to feature as an essential ability for students at school and university, as it is for graduates in the workplace. Pedagogically, one rationale is that the need to develop effective oral communication skills is tied to life-long learning which includes successful participation in future work-related tasks. One tangible way that educators have assessed proficiency in the area of communication is through prepared oral presentations. While much of the literature uses the terms 'oral communication' and 'oral presentation' interchangeably, some writers question the role more formal presentations play in the overall development of oral communication skills. However, such formal speaking tasks continue to be a recognised assessment practice in both the secondary school and academy, and, therefore, worthy of further investigation. Adding to the discussion, this thesis explores the knowledge and skills students bring into the academy from previous educational experiences. It examines some of the teaching and assessment methods used in secondary schools to develop oral communication skills through the use of formal oral presentations. Specifically, it investigates criterion-referenced assessment sheets and how these tools are used as a form of instruction, as well as their role and effectiveness in the evaluation of student ability. The focus is on the student's perspective and includes 12 semi-structured interviews with school students. The purpose of this thesis is to explore key thematics underpinning oral communication and to identify tensions between expectations and practice. While acknowledging the breadth and depth of material available under the heading of 'communication theory', this study specifically draws on an expanded view of the rhetorical tradition to fully interrogate the assumptions supporting the practice of assessing oral presentations. Finally, this thesis recommends reconnecting with an updated understanding of rhetoric as a way of assisting in the development of expressive, articulate and discerning communicators.

Jogging alongside or bumping off? oral history and fiction in dialogue

This paper emerges from my practice-led PhD thesis investigating the ways fiction writers can enter a dialogue with the project of oral history in Australia. In this paper, I survey the current literature in order to identify the status of fiction within the practice of oral history in Australia. I argue that oral historians and fiction writers are, among other things, both concerned with understanding subjectivity. I consider how one of the specific qualities of fiction, that of character, can provide a space to explore subjectivity, and rely on my own writing practice in order to demonstrate how oral history theory can enrich fictive writings. This paper, while positioned in the field of oral history, exists within a wider debate around how the past can legitimately be represented; I argue oral historians and fiction writers can enter a dialogue around shared concerns.

More men than women make mucosal IgA antibodies to human papillomavirus type 16 (HPV-16) and HPV-18: A study of oral HPV and oral HPV antibodies in a normal healthy population

Background: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. Methods: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. Results: Oral HPV infection was h ighest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09-12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97-6.2, P = 0.04). Conclusion: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation. © 2006 Marais et al; licensee BioMed Central Ltd.

Efficacy of oral or intrauterine device-delivered progestin in patients with complex endometrial hyperplasia with atypia or early endometrial adenocarcinoma : a meta-analysis and systematic review of the literature

Objectives: To investigate the efficacy of progestin treatment to achieve pathological complete response (pCR) in patients with complex atypical endometrial hyperplasia (CAH) or early endometrial adenocarcinoma (EC). Methods: A systematic search identified 3245 potentially relevant citations. Studies containing less than ten eligible CAH or EC patients in either oral or intrauterine treatment arm were excluded. Only information from patients receiving six or more months of treatment and not receiving other treatments was included. Weighted proportions of patients achieving pCR were calculated using R software. Results: Twelve studies met the selection criteria. Eleven studies reported treatment of patients with oral (219 patients, 117 with CAH, 102 with grade 1 Stage I EC) and one reported treatment of patients with intrauterine progestin (11 patients with grade 1 Stage IEC). Overall, 74% (95% confidence interval [CI] 65-81%) of patients with CAH and 72% (95% CI 62-80%) of patients with grade 1 Stage I EC achieved a pCR to oral progestin. Disease progression while on oral treatment was reported for 6/219 (2.7%), and relapse after initial complete response for 32/159 (20.1%) patients. The weighted mean pCR rate of patients with grade 1 Stage I EC treated with intrauterine progestin from one prospective pilot study and an unpublished retrospective case series from the Queensland Centre of Gynaecologic Oncology (QCGC) was 68% (95% CI 45- 86%). Conclusions: There is a lack of high quality evidence for the efficacy of progestin in CAH or EC. The available evidence however suggests that treatment with oral or intrauterine progestin is similarly effective. The risk of progression during treatment is small but longer follow-up is required. Evidence from prospective controlled clinical trials is warranted to establish how the efficacy of progestin for the treatment of CAH and EC can be improved further.

Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75(NTR) in malignancy

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75NTR, CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75NTR was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75NTR, CD24 antigens and ALDH activity (ALDEFLUOR® assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells.

Words and Silences : The journal of the International Oral History Association

Words and Silences is the official on-line journal of the International Oral History Association. It is an internationally peer reviewed, high quality forum for oral historians from a wide range of disciplines and a means for the professional community to share projects and current trends of oral history from around the world. We are extremely pleased to release the first online issue of Word &Silences. This e-journal is the result of long standing discussion and debate about the best way to publish a quality bilingual oral history journal (including a blind peer reviewed section) as a viable solution to mounting difficulties associated with publishing in print. We have discovered that an online version is also not without its challenges and requires tremendous labor intensive dedication. We strongly encourage members to assist us with small review process tasks in the future, so that we can ensure the sustainability of an annual W&S publication for our members and beyond.

Disaster strikes, then what? Using evaluation in narrative driven (oral history & digital storytelling) community-based projects

In 2011 Queensland suffered both floods and cyclones, leaving residents without homes and their communities in ruins (2011). This paper presents how researchers from QUT, who are also members of the Oral History Association of Australia (OHAA) Queensland’s chapter, are using oral history, photographs, videography and digital storytelling to help heal and empower rural communities around the state and how evaluation has become a key element of our research. QUT researchers ran storytelling workshops in the capital city of Brisbane i early 2011, after the city suffered sever flooding. Cyclone Yasi then struck the town of Cardwell (in February 2011) destroying their historical museum and recording equipment. We delivered an 'emergency workshop', offering participants hands on use of the equipment, ethical and interviewing theory, so that the community could start to build a new collection. We included oral history workshops as well as sessions on how best to use a video camera, digital camera and creative writing sessions, so the community would also know how to make 'products' or exhibition pieces out of the interviews they were recording. We returned six months later to conduct follow-up workshops and the material produced by and with the community had been amazing. More funding has now been secured to replicate audio/visual/writing workshops in other remote rural Queensland communities including Townsville, Mackay and Cunnamulla and Toowoomba in 2012, highlighting the need for a multi media approach, to leverage the most out of OH interviews as a mechanism to restore and promote community resilience and pride.

Yasi : Digital stories and oral histories collection

"The second of the Oral History Workshops conducted by Associate Professor Helen Klaebe and the Oral History team from the Queensland University of Technology in Brisbane, was conducted in El Arish on the last weekend in September 2011. The first workshop was held in Cardwell in March 2011. Historical Society members and other researchers from both the Cardwell and El Arish areas combined to organise and fund the workshops, which have produced a growing collection of recordings of personal stories from people with a wide variety of experiences during and after cyclone Yasi. Aside from being productive in documenting history, the workshops have offered a greatly appreciated educational opportunity for many people, most of whom have never before had access to such benefits. Not only were they able to learn history gathering methodologies and the relevant technical skills, but they also gained new experience in the use of computers to apply these skills. These far northern oral history workshops took the form of a shortened version of the 5 series workshops being presented at QUT in Brisbane this year. The agenda was aligned to the wishes and requirements of the participants who attended from the Cassowary Coast and Tableland regions."

Human milk xanthine oxidase and neonatal salivary nucleotide precursors generate hydrogen peroxide; a novel pathway with potential role in regulating oral microflora

Background: Xanthine oxidase (XO) is a complex molybdeno-flavoprotein occurring with high activity in the milk fat globule membrane (MFGM) in all mammalian milk and is involved in the final stage of degradation of purine nucleotides. It catalyzes the sequential oxidation of hypoxanthine to xanthine and uric acid, accompanied by production of hydrogen peroxide and superoxide anion. Human saliva has been extensively described for its composition of proteins, electrolytes, cortisol, melatonin and some metabolites such as amino acids, but little is known about nucleotide metabolites. Method: Saliva was collected with swabs from babies; at full-term 1-4 days, 6-weeks, 6-months and 12-months. Unstimulated fasting (morning) saliva samples were collected directly from 77 adults. Breast milk was collected from 24 new mothers. Saliva was extracted from swabs and ultra-filtered. Nucleotide metabolites were analyzed by RP-HPLC with UV-photodiode array and ESI-MS/MS. XO activity was measured as peroxide production from hypoxanthine. Bacterial inhibition over time was assessed using CFU/mL or OD. Results: Median concentrations (μmol/L) of salivary nucleobases and nucleosides for neonates/6-weeks/6-months/12-months/adult respectively were: uracil 5.3/0.8/1.4/0.7/0.8, hypoxanthine 27/7.0/1.1/0.8/2.0, xanthine 19/7.0/2.0/2.0/2.0, adenosine 12/7.0/0.9/0.8/0.1, inosine 11/5.0/0.3/0.4/0.2, guanosine 7.0/6.0/0.5/0.4/0.1, uridine 12/0.8/0.3/0.9/0.4. Deoxynucleosides and dihydropyrimidines concentrations were essentially negligible. XO activity (Vmax:mean ± SD) in breast milk was 8.9 ± 6.2 μmol/min/L and endogenous peroxide was 27 ± 12 μmol/L; mixing breast milk with neonate saliva generated ~40 μmol/L peroxide,which inhibited Staphylococcus aureus. Conclusions: Salivary metabolites, particularly xanthine/hypoxanthine, are high in neonates, transitioning to low adult levels between 6-weeks to 6-months (p < 0.001). Peroxide occurs in breast milk and is boosted during suckling as an antibacterial system.

When Can Oral Health Education Begin? Relative effectiveness of three oral health education strategies starting pre-partum

Objective: To test the impact of oral health education provided to pregnant mothers on subsequent practices within the infant’s family. Research design: A quasi-experimental intervention trial comparing the effectiveness of ‘usual care’ to one, or both, of two oral health education resources: a ‘sample bag’ of information and oral health care products; and/or a nine-minute “Healthy Teeth for Life” video on postnatal oral health issues. Participants: Women attending the midwife clinic at approximately 30 weeks gestation were recruited (n=611) in a public hospital providing free maternity services. Results and Conclusions: Four months after the birth of their infant, relative to the usual care condition, each of the oral health education interventions had independent or combined positive impacts on mother’s knowledge of oral health practices. However young, single, health care card-holder or unemployed mothers were less likely to apply healthy behaviours or to improve knowledge of healthy choices, as a result of these interventions. The video intervention provided the strongest and most consistent positive impact on mothers’ general and infant oral health knowledge. While mothers indicated that the later stage of pregnancy was a good time to receive oral health education, many suggested that this should also be provided after birth at a time when teeth were a priority issue, such as when “baby teeth” start to erupt.

The artful life story : the oral history interview as fiction

This practice-led PhD project consists of two parts. The first is an exegesis documenting how a fiction writer can enter a dialogue with the oral history project in Australia. I identify two philosophical mandates of the oral history project in Australia that have shaped my creative practice: an emphasis on the analysis of the interviewee’s subjective experience as a means of understanding the past, and the desire to engage a wide audience in order to promote empathy towards the subject. The discussion around fiction in the oral history project is in its infancy. In order to deepen the debate, I draw on the more mature discussion in ethnographic fiction. I rely on literary theorists Steven Greenblatt, Dorrit Cohn and Gerard Genette to develop a clear understanding of the distinct narrative qualities of fiction, in order to explore how fiction can re-present and explore an interviewee’s subjective experience, and engage a wide readership. I document my own methodology for producing a work of fiction that is enriched by oral history methodology and theory, and responds to the mandates of the project. I demonstrate the means by which fiction and the oral history project can enter a dialogue in the truest sense of the word: a two-way conversation that enriches and augments practice in both fields. The second part of the PhD is a novel, set in Brisbane and based on oral history interviews and archival material I gathered over the course of the project. The novel centres on Brisbane artist Evelyn, who has been given an impossible task: a derelict old house is about to be demolished, and she must capture its history in a sculpture that will be built on the site. Evelyn struggles to come up with ideas and create the sculpture, realising that she has no way to discover who inhabited the house. What follows is a series of stories, each set in a different era in Brisbane’s history, which take the reader backwards through the house’s history. Hidden Objects is a novel about the impossibility of grasping the past and the powerful pull of storytelling. The novel is an experiment in a hybrid form and is accompanied by an appendix that identifies the historically accurate sources informing the fiction. The decisions about the aesthetics of the novel were a direct result of my engagement with the mandates of the oral history project in Australia. The novel was shortlisted in the 2012 Queensland Literary Awards, unpublished manuscript category.