Analysis of non-canonical three- and four-way DNA junctions.

The development of compounds that can selectively bind with non-canonical DNA structures has expanded in recent years. Junction DNA, including three-way junctions (3WJs) and four-way Holliday junctions (HJs), offer an intriguing target for developmental therapeutics as both 3WJs and HJs are involved in DNA replication and repair processes. However, there are a limited number of assays available for the analysis of junction DNA binding. Here, we describe the design and execution of multiplex fluorescent polyacrylamide gel electrophoresis (PAGE) and microscale thermophoresis (MST) assays that enable evaluation of junction-binding compounds. Two well characterised junction-binding compounds-a C6 linked bis-acridine ligand and an iron(II)-bound peptide helicate, which recognise HJs and 3WJs, respectively-were employed as probes for both MST and PAGE experiments. The multiplex PAGE assay expands beyond previously reported fluorescent PAGE as it uses four individual fluorophores that can be combined to visualise single-strands, pseudo-duplexes, and junction DNA present during 3WJ and HJ formation. The use of MST to identify the binding affinity of junction binding agents is, to our knowledge, first reported example of this technique. The combined use of PAGE and MST provides complementary results for the visualisation of 3WJ and HJ formation and the direct binding affinity (Kd and EC50) of these agents. These assays can be used to aid the discovery and design of new therapeutics targeting non-canonical nucleic acid structures.

Barriers and Facilitators to Integrative Oncology Services in Australia: A Changed Mind Set Required.

Objectives: This study aimed to explore barriers and facilitators to integrative oncology (IO) service provision and access in Australia. Design: The study design was mixed method with two substudies: a cross-sectional national cancer service survey of public and private sectors; and focus group interviews and an online survey of cancer survivors. Triangulation analysis of qualitative and quantitative data was used to identify and interrogate meta-themes. Subjects: The cancer service response rate was 93.2% (n = 275/295); 71/275 (25.8%) provided IO. Thirty-three cancer survivors from Anglo-European, Arabic, Vietnamese, and Chinese backgrounds were interviewed, and 121 survivors answered the online survey. Results: IO gaps were substantial, with no services in many regions and cities; a lack of diversity and availability of therapeutic options, including culturally appropriate services; and a mismatch between the high use of natural health products by survivors and types of IO services provided. Two overlapping meta-themes were identified: "barriers and facilitators" and "peoples and institutions"; each with four subthemes, respectively, "access/provision, affordability/funding, information/evidence, and culture/values" and "cancer survivors, healthcare professionals, organizations, and policies." While affordability/funding was the greatest barrier to survivors and providers, solutions varied (e.g., building a stronger evidence-base, business model advice) and often conflicted (e.g., public verses private sector funding). The most insidious barrier was professional/corporate cultures and values that influenced hospital policies (or lack thereof), conceptions of evidence and the therapeutic alliance. Survivors called for a change of mindset in the culture of medicine and value-based health care. Conclusions: The barriers and facilitators to IO services were more complex than building the evidence-base and demonstrating value to justify funding. To achieve a better alignment of patients' preferences with service provision, providers require more guidance on clinical governance, business models, local service gaps, and interprofessional collaboration. National strategies and funding models are needed to ensure appropriate, equitable IO service provision.

Australian integrative oncology services: a mixed-method study exploring the views of cancer survivors.

BACKGROUND: The significant use of traditional and complementary medicine (T&CM) by cancer survivors is well documented. The aim of this study was to explore cancer survivors' views on integrating T&CM services with conventional cancer care. METHOD: A mixed-method study design with an emphasis on qualitative methodology was used to conduct and analyse four focus group interviews and an on-line survey. Purposive sampling recruited 33 cancer survivors and caregivers from Arabic, Vietnamese, Chinese and Anglo-European Australian backgrounds who participated in one of four focus group interviews, and 121 cancer survivors who responded to an on-line survey. The inductive thematic analysis was augmented with a descriptive statistical analysis. RESULTS: Most participants had used T&CM therapies or consulted T&CM practitioners as an adjuvant during and/or after their initial cancer treatment. Two themes emerged: 'positive perceptions and experiences' and 'barriers and unmet needs'. Participants emphasised that T&CM was not a 'luxury item', rather it was considered important for managing side effects and comorbidities, rehabilitation and quality of life. A wide range of complex, interrelated barriers and solutions to IO service provision and access were identified. Structural barriers included inadequate service provision, medical practitioner attitudes, logistical constraints and funding. Personal barriers were influenced by the severity of impairment and disability; attitudes, beliefs and knowledge about T&CM; and available resources (e.g. finances, time, transport). Unmet need and inequitable access was exacerbated by geographical location, ethnicity and ability to pay. There was a mismatch between where participants were accessing T&CM services and their preference for IO service delivery. Participants perceived hospital-based IO services availability to have several benefits, including the T&CM practitioners having more expert knowledge about cancer care, the convenience of co-locating oncology services, and potentially lower out-of-pocket costs. CONCLUSION: Patients' use, preferences and needs for T&CM services in the oncology setting are important for informing service provision. Inequitable, unmet need reflected the increasing demand and expectation from patients for their oncology teams to be well informed about the benefits, risks and indications for T&CM use, and for the public and private health sectors to formally integrate and fund IO services.