HSV1716 Prevents Myeloma Cell Regrowth When Combined with Bortezomib In Vitro and Significantly Reduces Systemic Tumor Growth in Mouse Models.

Multiple myeloma remains largely incurable due to refractory disease; therefore, novel treatment strategies that are safe and well-tolerated are required. Here, we studied the modified herpes simplex virus HSV1716 (SEPREHVIR®), which only replicates in transformed cells. Myeloma cell lines and primary patient cells were infected with HSV1716 and assessed for cell death using propidium iodide (PI) and Annexin-V staining and markers of apoptosis and autophagy by qPCR. Myeloma cell death was associated with dual PI and Annexin-V positivity and increased expression of apoptotic genes, including CASP1, CASP8, CASP9, BAX, BID, and FASL. The combination of HSV1716 and bortezomib treatments prevented myeloma cell regrowth for up to 25 days compared to only transient cell growth suppression with bortezomib treatment. The viral efficacy was tested in a xenograft (JJN-3 cells in NSG mice) and syngeneic (murine 5TGM1 cells in C57BL/KaLwRijHsd mice) systemic models of myeloma. After 6 or 7 days, the post-tumor implantation mice were treated intravenously with the vehicle or HSV1716 (1 × 107 plaque forming units/1 or 2 times per week). Both murine models treated with HSV1716 had significantly lower tumor burden rates compared to the controls. In conclusion, HSV1716 has potent anti-myeloma effects and may represent a novel therapy for multiple myeloma.

Ironbark: Developing a healthy community program for older Aboriginal people.

ISSUE ADDRESSED: Programs by, with and for Aboriginal older people must be culturally safe and relevant. Successful elements include being Aboriginal specific and group based. Co-design with Aboriginal people and stakeholders is essential. We describe the co-design process of developing the Ironbark: Healthy Community program. METHODS: Aboriginal ways of knowing, being and doing and yarning conversational methods guided the development process, during 2018. A desktop review provided details of current group characteristics and key community stakeholders. Stakeholder engagement regarding views about group operations, participants and benefits also occurred. Aboriginal Elders views of their groups were gathered through yarning circles in New South Wales (NSW). Grounded theory approach was used to ascertain key themes. RESULTS: Initial engagement occurred with 13 different community stakeholders and organisations in three Australian states (NSW, South Australia (SA), Western Australia (WA)). Three yarning circles occurred with Elders from urban (N = 10), regional coastal (N = 10) and regional country (N = 4) groups. Six key themes were organised in three groups according to an Aboriginal ontology. 1. Knowing: groups provide opportunities to share knowledge and connect socially. Adequate program resourcing and sustainability are valued. 2. Being: groups strengthen culture, providing important social, emotional and other forms of support to age well. 3. Doing: previous program experiences inform perceptions for new program operations. Group venues and operational aspects should be culturally safe, acknowledging diversity among Elders, their preferences and community control. Themes were used to develop the program and its resource manual that were finalised with stakeholders, including steering committee approval. CONCLUSIONS: Stakeholder feedback at multiple stages and Aboriginal Elders' perspectives resulted in a new co-designed community program involving weekly yarning circles and social activities. So what?: Co-design, guided by Aboriginal ways of knowing, being and doing, can develop programs relevant for Aboriginal people.

The Use of Oncolytic Viruses in the Treatment of Multiple Myeloma.

Multiple myeloma accounts for 1% of all new cancers worldwide. It is the second most common haematological malignancy and has a low five-year survival rate (53.2%). Myeloma remains an incurable disease and is caused by the growth of malignant plasma cells in the bone marrow. Current anti-myeloma therapies (conventional chemotherapies, immunomodulatory drugs i.e., thalidomide and its' analogues, proteasome inhibitors, monoclonal antibodies, and radiotherapy) initially substantially debulk tumour burden, but after a period of remission 'plateau phase' disease invariably relapses due to tumour recrudescence from foci of minimal residual disease (MRD) and accumulating drug resistance. Therefore, there is a compelling clinical need for the development of novel treatment regimens to target MRD and effectively eliminate all remaining tumour cells. This review will discuss the potential use of oncolytic virus (OV) therapies in the treatment of myeloma. Specifically, it will focus on preclinical studies using DNA viruses (adenovirus (Ad), vaccinia virus (VV), myxoma virus (MYXV), and herpes simplex virus (HSV)), RNA viruses (reovirus (reo), coxsackie virus, measles virus (MV) and bovine viral diarrhoea virus (BVDV), and vesicular stomatitis virus (VSV)), and on four types of viruses (VV, reo, MV-NIS and VSV-IFNß-NIS) that have been assessed clinically in a small number of myeloma patients.

Understanding implementation factors and participant experiences of a cluster randomised controlled trial to prevent falls among older Aboriginal people: a process evaluation protocol.

INTRODUCTION: Process evaluations examining programme implementation are often conducted in conjunction with effectiveness studies. Their inclusion in studies with Aboriginal participants can give an understanding of programme delivery in Aboriginal community contexts. The Ironbark: Standing Strong and Tall programme was codesigned with Aboriginal communities and includes exercise and facilitated 'yarning' discussion about fall risk and prevention strategies. The programme pilot showed favourable outcomes and acceptability for Aboriginal people aged 45 years and over. The Ironbark: Standing Strong and Tall programme is now being compared with a 'Healthy Community' programme in a cluster randomised controlled trial within Aboriginal health and community services. An embedded process evaluation aims to explore relationships between participation and programme outcomes and the quality of programme implementation. METHODS AND ANALYSIS: The process evaluation will use a mixed methods design, guided by Indigenous research methodology. It will evaluate quantitative data (number of completed sessions, site coaching checklist tool, participant and facilitator questionnaire data and a participant habit formation scale), as well as qualitative data (open-ended responses from project and site staff and semistructured interviews using yarning with study participants and site managers). A programme logic model was developed to explain the intended inputs, activities, outputs and outcomes, which guided this process evaluation design. CONCLUSION: This process evaluation of a fall prevention programme for older Aboriginal people using a mixed methods design and data triangulation will allow for a comprehensive understanding of study findings. Multiple study sites allow for generalisability of findings and exploration of variation across sites. TRIAL REGISTRATION NUMBER: ACTRN12619000349145.

Obtaining fruit and vegetables for the lowest prices: pricing survey of different outlets and geographical analysis of competition effects.

AIMS: Inadequate fruit and vegetable (F&V) consumption is an important dietary risk factor for disease internationally. High F&V prices can be a barrier to dietary intake and so to improve understanding of this topic we surveyed prices and potential competition between F&V outlet types. METHODS: Over a three week early autumn period in 2013, prices were collected bi-weekly for 18 commonly purchased F&Vs from farmers' markets (FM) selling local produce (n = 3), other F&V markets (OFVM) (n = 5), supermarkets that neighbored markets (n = 8), and more distant supermarkets (n = 8), (in urban Wellington and Christchurch areas of New Zealand). Prices from an online supermarket were also collected. RESULTS: A total of 3120 prices were collected. Most F&Vs (13/18) were significantly cheaper at OFVMs than supermarkets. Over half of the F&Vs (10/18) were significantly cheaper at nearby compared to distant supermarkets, providing evidence of a moderate 'halo effect' in price reductions in supermarkets that neighbored markets. Weekend (vs midweek) prices were also significantly cheaper at nearby (vs distant) supermarkets, supporting evidence for a 'halo effect'. Ideal weekly 'food basket' prices for a two adult, two child family were: OFVMs (NZ$76), online supermarket ($113), nearby supermarkets ($124), distant supermarkets ($127), and FMs ($138). This represents a savings of $49 per week (US$26) by using OFVMs relative to (non-online) supermarkets. Similarly, a shift from non-online supermarkets to the online supermarket would generate a $13 saving. CONCLUSIONS: In these locations general markets appear to be providing some substantially lower prices for fruit and vegetables than supermarkets. They also appear to be depressing prices in neighboring supermarkets. These results, when supplemented by other needed research, may help inform the case for interventions to improve access to fruit and vegetables, particularly for low-income populations.