Health care delivery of kidney transplantation to indigenous Maori in Aotearoa New Zealand: A qualitative interview study with clinician stakeholders.

OBJECTIVES: Indigenous people experience higher rates of kidney failure than do non-Indigenous Peoples. However, compared to Indigenous patients, health care systems deliver kidney transplantation to non-Indigenous patients at a substantially higher rate and more frequently as the first treatment of kidney failure. Indigenous Maori patients in Aotearoa New Zealand report numerous barriers to kidney transplantation. We explore the perspectives of clinicians as stakeholders in the delivery of kidney transplantation. METHODS: In 2021/2022 we conducted in-depth qualitative interviews with key stakeholder clinicians within kidney transplantation services in Aotearoa New Zealand, asking them about the issues for Maori patients. We used thematic analysis informed by critical theory to identify key findings and used structural coding to categorize the themes at the level of society, health system, and health services. RESULTS: We interviewed 18 clinicians (nine nephrologists, including two transplant nephrologists, and nine nurses, including six transplant coordinators). We identified nine themes from stakeholders related to delivery of kidney transplantation services to Maori patients and whanau (family), categorized according to three main levels: Firstly, at the level of society (the impact of colonization and distrust). Secondly, the health care system (failure to prevent and manage kidney disease, health care model delivers inequitable outcomes, and inadequate Maori health professional workforce). Thirdly, health care services (transplantation reliant on patient and family resources, complex assessment causes untimely delays, clinical criteria for transplantation, and lack of clinician ability to effect change). CONCLUSIONS: Delivery of kidney transplantation to Indigenous Peoples is impacted at the level of society, health care system, and health care service. To address inequities, a broad approach that addresses each of these levels is required.

Stimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its poor survival and intense pain at the primary cancer site. Cancer pain is debilitating, contributes to diminished quality of life, and causes opioid tolerance. The stimulator of interferon genes (STING) agonism has been investigated as an anti-cancer strategy. We have developed STINGel, an extended-release formulation that prolongs the availability of STING agonists, which has demonstrated an enhanced anti-tumor effect in OSCC compared to STING agonist injection. This study investigates the impact of intra-tumoral STINGel on OSCC-induced pain using two separate OSCC models and nociceptive behavioral assays. Intra-tumoral STINGel significantly reduced mechanical allodynia in the orofacial cancer model and alleviated thermal and mechanical hyperalgesia in the hind paw model. To determine the cellular signaling cascade contributing to the antinociceptive effect, we performed an in-depth analysis of immune cell populations via single-cell RNA-seq. We demonstrated an increase in M1-like macrophages and N1-like neutrophils after STINGel treatment. The identified regulatory pathways controlled immune response activation, myeloid cell differentiation, and cytoplasmic translation. Functional pathway analysis demonstrated the suppression of translation at neuron synapses and the negative regulation of neuron projection development in M2-like macrophages after STINGel treatment. Importantly, STINGel treatment upregulated TGF-ß pathway signaling between various cell populations and peripheral nervous system (PNS) macrophages and enhanced TGF-ß signaling within the PNS itself. Overall, this study sheds light on the mechanisms underlying STINGel-mediated antinociception and anti-tumorigenic impact.

Differentiating Dyes: A Spectroscopic Investigation into the Composition of Scarlet Bloodroot (Haemodorum coccineum R.Br.) Rhizome.

Haemodorum coccineum, commonly known as scarlet bloodroot, is a plant native to New Guinea and the northern most parts of Australia. The highly coloured H. coccineum is used by communities in Larrakia country for dyeing garments and occasionally to treat snake bites. Previous studies into H. coccineum have focused on its taxonomic classification, with this being the first evaluation of the chemical composition of the plant. Haemodoraceae plants are reported to contain phenylphenalenones (PhPs), which are highly conjugated polycyclic oxygenated aromatic hydrocarbons. We report the characterisation of 20 compounds extracted from the rhizome of H. coccineum: four sugars and 16 compounds belonging to the PhP family. The compounds include five aglycones and seven glycosylated compounds, of which four contain malonate esters in their structures. Characterisation of these compounds was achieved through 1D and 2D NMR, MS analysis and comparison to the known phytochemistry of other species from the Haemodorum genus. Preliminary anti-microbial activity of the crude extract shows significant inhibition of the growth of both gram-positive and gram-negative bacteria, but no activity against Candida albicans.

Health, wellbeing and nutritional impacts after 2 years of free school meals in New Zealand.

In 2020, a government-funded healthy school lunch program was introduced in a quarter of New Zealand schools, selected due to high levels of socio-economic barriers. This study assesses the impact of the introduction of the school lunch program from family (whanau), student and school principal perspectives. Across four schools, we conducted five focus groups (two with secondary students and three with family members) and four school principal interviews. Participating schools represented a range of contexts: primary and secondary, schools with cooks in on-site kitchens and schools receiving meals delivered by external caterers. Thematic analysis was used to develop themes describing the health, wellbeing and nutritional impact of the program. Family participants were 82% Indigenous Maori and self-identified as having 'borderline' (73.5%) or no financial security (8.8%). Seven positive impact themes were identified: improved food security, enhanced equity, increased appreciation of healthy foods for students, enhanced mana (wellbeing) for all, reduced financial hardship/stress for families, opportunities for nutritional learning and recognition that appreciation and uptake happen over time. Four negative impact themes were identified: low uptake that created food waste, perception that healthy food is not palatable for students, lack of knowledge of the program and loss of agency for students. This is the largest intervention in nutrition and food security for children implemented in New Zealand since the 1930's. The first 2 years have offered wellbeing and financial benefits for students and families, particularly when school environments promote uptake. More involvement of students and family members in the program planning is essential.

6-Shogaol and 10-Shogaol Synergize Curcumin in Ameliorating Proinflammatory Mediators via the Modulation of TLR4/TRAF6/MAPK and NFκB Translocation.

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokinesuppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-É£-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaol-curcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

"We Need a System that's Not Designed to Fail Maori": Experiences of Racism Related to Kidney Transplantation in Aotearoa New Zealand.

BACKGROUND: Reported experiences of racism in Aotearoa New Zealand are consistently associated with negative measures of health, self-rated health, life satisfaction, and reduced access to high-quality healthcare with subsequent poor health outcomes. In this paper, we report on perceptions and experiences of prejudice and racism by Indigenous Maori with kidney disease and their family members and donors who took part in a wider study about experiences of kidney transplantation. METHODS: We conducted semi-structured interviews with 40 Maori between September and December 2020. Participants included those with kidney disease who had considered, were being worked up for, or who had already received a kidney transplant as well as family members and potential or previous donors. We examined the data for experiences of racism using a theoretical framework for racism on three levels: institutionalised racism, personally mediated racism, and internalised racism. RESULTS: We identified subthemes at each level of racism: institutional (excluded and devalued by health system; disease stigmatization; discriminatory body weight criteria, lack of power), personally mediated (experiencing racial profiling; explicit racism), and internalized racism (shame and unworthiness to receive a transplant). CONCLUSIONS: The wide-reaching experiences and perceptions of racism described by participants with kidney disease and their families in this research point to an unfair health system and suggest that racism may be contributing to kidney transplantation inequity in Aotearoa New Zealand. Addressing racism at all levels is imperative if we are to address inequitable outcomes for Maori requiring kidney transplantation.

Systems Mapping of the New Zealand Free and Healthy School Lunch Programme: Perspectives from Lunch Providers.

As part of the COVID-19 economic recovery package, the Aotearoa New Zealand Government rolled out a universal free and healthy lunch programme to the 25% least advantaged schools nationwide. This study explored experiences of school lunch providers in the Hawke's Bay region. The aim was to create a systems map identifying points of intervention through which the lunch programme could be improved to meet the goal of reducing child food insecurity. Twelve lunch providers were interviewed to generate casual loop diagrams which were examined and integrated to form a single systems map. Seven themes arose during analysis: teacher support, principal support, nutrition guidelines and government support, supply chain, ingredient suppliers, student feedback and food waste. Teacher support was important for getting students to try new foods and eat the nutritious lunches. Principal support was a strong theme impacting opportunities for broader student engagement. This study employed systems science to highlight the importance of support from different stakeholders within the lunch programme to achieve the goal of reduced child food insecurity. Further work is needed to ensure the programme meets the wider goals of the government and community, and to determine the potential broader benefits of the programme.

Synergistic Anti-Inflammatory Activity of Ginger and Turmeric Extracts in Inhibiting Lipopolysaccharide and Interferon-γ-Induced Proinflammatory Mediators.

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2−related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.

Synergistic Inhibition of Pro-Inflammatory Pathways by Ginger and Turmeric Extracts in RAW 264.7 Cells.

Synergy plays a prominent role in herbal medicines to increase potency and widen the therapeutic windows. The mechanism of synergy in herbal medicines is often associated with multi-targeted behavior and complex signaling pathways which are challenging to elucidate. This study aims to investigate the synergistic mechanism of a combination (GT) of ginger (G) and turmeric (T) extracts by exploring the modulatory activity in lipopolysaccharides (LPS)-induced inflammatory pathways and key molecular targets. A Bioplex ProTM mouse cytokine 23-plex assay was utilized to assess the broad anti-cytokine activity of GT in LPS and interferon (IFN)-É£ (both at 50 ng/mL)-activated RAW 264.7 cells. The inhibitory effects of individual and combined G and T on major proinflammatory mediators including nitric oxide (NO), tumor necrosis factor (TNF) and interleukin (IL)-6 were tested using Griess reagents and ELISA assays, respectively. Immunofluorescent staining and Western blot were used to investigate the modulatory effect of GT on key proteins in the LPS/TLR4 signaling transduction. The regulation of murine microRNA miR-155-5p was tested using real-time PCR. The IC50 value and combination index (CI) values were used to demonstrate potency and synergistic interaction, respectively. GT synergistically attenuated a range of pro-inflammatory mediators including inducible NO, major cytokines (TNF and IL-6) and secondary inflammatory cytokines (GM-CSF and MCP-1). GT significantly inhibited LPS-induced NF-kB p65 translocation, the activation of TLR4, TRAF6, and phosphorylation of JNK and c-JUN. Moreover, the suppressive effect of GT on each of the protein targets in this axis was stronger than that of the individual components. Real-time PCR analysis showed that GT suppressed miR-155-5p to a greater extent than G or T alone in LPS-stimulated cells. Our study demonstrates the synergistic mechanism of GT in downregulating LPS-induced proinflammatory pathways at the miRNA and protein levels. Our results establish a scientific basis for the combined application of G and T as an advanced therapeutic candidate in inflammatory diseases with broad and synergistic anti-inflammatory activity and multi-targeted mechanisms.

Culture of Healthy Eating and Food Environments, Policies, and Practices in Regional New Zealand Schools.

The school food environment plays an important role in shaping students' dietary choices, which often influence future dietary behaviours. We surveyed primary and secondary schools in Hawke's Bay, New Zealand, to measure the comprehensiveness and strength of food policies, describe the culture of food provision, and identify barriers to improving school food environments. Fifty-one schools were included in the final analysis, with 58.8% having a food policy, most of which used a generic template. Schools with food policies and those participating in the free and healthy lunch programme were more likely to have a strong culture around healthy eating. Common barriers to healthy eating were food outlets near school and resistance from students. Secondary schools reported facing more barriers to implementing healthy eating cultures, were more likely to use food as classroom rewards and to sell food to students, most of which was unhealthy. Hawke's Bay schools participating in food provision programmes are successfully improving their food environments through improved culture and delivery of healthy food; however, more action is needed to strengthen the wording and guidance in food policies and reduce the provision of unhealthy food in schools before effective change can be achieved.

Community Co-Design of Regional Actions for Children's Nutritional Health Combining Indigenous Knowledge and Systems Thinking.

Children's nutrition is highly influenced by community-level deprivation and socioeconomic inequalities and the health outcomes associated, such as childhood obesity, continue to widen. Systems Thinking using community-based system dynamics (CBSD) approaches can build community capacity, develop new knowledge and increase commitments to health improvement at the community level. We applied the formal structure and resources of a Group Model Building (GMB) approach, embedded within an Indigenous worldview to engage a high deprivation, high Indigenous population regional community in New Zealand to improve children's nutrition. Three GMB workshops were held and the youth and adult participants created two systems map of the drivers and feedback loops of poor nutrition in the community. Maori Indigenous knowledge (matauranga) and approaches (tikanga) were prioritized to ensure cultural safety of participants and to encourage identification of interventions that take into account social and cultural environmental factors. While the adult-constructed map focused more on the influence of societal factors such as cost of housing, financial literacy in communities, and social security, the youth-constructed map placed more emphasis on individual-environment factors such as the influence of marketing by the fast-food industry and mental wellbeing. Ten prioritized community-proposed interventions such as increasing cultural connections in schools, are presented with the feasibility and likely impact for change of each intervention rated by community leaders. The combination of community-based system dynamics methods of group model building and a matauranga Maori worldview is a novel Indigenous systems approach that engages participants and highlights cultural and family issues in the systems maps, acknowledging the ongoing impact of historical colonization in our communities.

Healthy Food Environments in Early Learning Services: An Analysis of Manager Survey Responses, Menus and Policies in Regional New Zealand Early Childhood Education and Care Centres.

Healthy food environments in early childhood play an important role in establishing health-promoting nutritional behaviours for later life. We surveyed Early Learning Services (ELS) in the Hawke's Bay region of New Zealand and describe common barriers and facilitators to providing a healthy food environment, through descriptive survey analysis and thematic analysis of open-ended questions. We used a policy analysis tool to assess the strength and comprehensiveness of the individual centre's nutrition policies and we report on the healthiness of menus provided daily in the centres. Sixty-two centres participated and 96.7% had policies on nutrition compared to 86.7% with policies on drinks. Of the 14 full policies provided for analysis, identified strengths were providing timelines for review and encouraging role modelling by teachers. The main weaknesses were communication with parents and staff, lack of nutrition training for staff and absence of policies for special occasion and fundraising food. With regard to practices in the ELS, food for celebrations was more likely to be healthy when provided by the centre rather than brought from home. Food used in fundraising was more likely to be unhealthy than healthy, though <20% of centres reported using food in fundraising. Only 40% of menus analysed met the national guidelines by not including any 'red' (unhealthy) items. Centre Managers considered the biggest barriers to improving food environments to be a lack of parental support and concerns about food-related choking. These results highlight the need for future focus in three areas: policies for water and milk-only, celebration and fundraising food; increased nutrition-focused professional learning and development for teachers; and communication between the centre and parents, as a crucial pathway to improved nutrition for children attending NZ early childhood education and care centres.

Values, Perspectives, and Experiences of Indigenous Maori Regarding Kidney Transplantation: A Qualitative Interview Study in Aotearoa/New Zealand.

RATIONALE & OBJECTIVE: In Aotearoa/New Zealand, Indigenous Maori experience inequitable delivery of kidney transplantation despite disproportionately higher rates of kidney failure. This study describes Maori patients' and families' values, perspectives, and experiences related to kidney transplantation. STUDY DESIGN: Qualitative interview study. SETTING & PARTICIPANTS: We conducted 40 in-depth interviews of 40 Maori: 8 who had received a transplant, 20 with chronic kidney disease (which included 10 on the deceased donor transplant list, 9 who were interested in transplantation and not currently waitlisted or who were ineligible for waitlisting, and 1 who was not interested in transplantation), 4 live-kidney donors, and 8 family members including 6 who had experiences with donor assessment. ANALYTICAL APPROACH: Data were analyzed inductively to generate themes and a conceptual framework. RESULTS: We identified 5 major themes: actively seeking a kidney transplant; evolving attitudes toward traditional values and practices; being confronted by interpersonal and systemic racism; poor information and communication; and challenged by social determinants of health. LIMITATIONS: Participants were recruited nationally through patient advocacy organizations and 1 regional kidney service. Potential participants unrelated to these groups or region could not be included. CONCLUSIONS: Maori participants were highly motivated to seek kidney transplantation and were inspired by positive experiences through donating and receiving a kidney. However, they faced barriers including social determinants, racism, and lack of information that impacted both direct experiences of transplantation and access to transplantation services.

Exploring rural and remote patients' experiences of health services for kidney disease in Aotearoa New Zealand: An in-depth interview study.

AIMS: People with chronic kidney disease (CKD) living in rural communities have increased risks of death, morbidity, hospitalization and poorer quality of life compared with people with CKD living in urban areas. This study explores the experiences and perceptions of rural and remote patients and families in relation to accessing health services for kidney disease in Aotearoa New Zealand. METHODS: We conducted an In-depth interview study. We purposively sampled adult patients with CKD and their caregivers who lived further than 100 km (62 miles) or more than 1 h drive from their nearest dialysis or transplant centre. Qualitative data were analyzed inductively to generate themes, subthemes and a conceptual framework. RESULTS: Of 35 participants, including 26 patients and nine caregivers, 51% were female, 71% travelled between 1 and 3 h to their nearest renal unit, and the remainder, between 3 and 6 h. We identified five themes and related subthemes: intense psychological impact of rurality; pressure of extended periods away from home; services not designed for rural and remote living; suffering from financial losses; and poor communication. CONCLUSION: Rural and remote patients with CKD and their caregivers face the added challenges of separation from family, social and community support and financial burden, which can have profound consequences on their psychological and physical well-being and that of their families.

A diagnosis of prediabetes when combined with lifestyle advice and support is considered helpful rather than a negative label by a demographically diverse group: A qualitative study.

AIMS: The aim of this study was to explore the experience and perceptions of a diagnosis of prediabetes among a demographically diverse sample of New Zealanders who had, and had not, regressed to normoglycaemia following participation in a primary care nurse-delivered intervention for 6 months. The sample included Indigenous Maori who have high rates of diabetes and associated co-morbidities. METHODS: A purposefully selected sample of 58 people with prediabetes and BMI >25 kg/m2, stratified by male/female, Maori/non-Maori, and those who had/had not regressed to normoglycaemia, after completing 6-months of a prediabetes intervention were interviewed. Interviews were audio-recorded and transcribed. Data were analysed by thematic analysis. RESULTS: Most participants recalled being shocked when told they had prediabetes, but they did not perceive the diagnosis to be a label in a negative sense, and some, described the diagnosis as helpful. Participants appreciated knowing that prediabetes could be reversed, and the opportunity to be able to take supported action and make lifestyle changes through the nurse-delivered prediabetes lifestyle intervention. Participants' clear preference was to take control and make dietary changes, not to take Metformin. CONCLUSIONS: Prediabetes was not considered a negative label, but an opportunity, when coupled with a primary care nurse-delivered dietary intervention.

Combining Cognitive Mapping and indigenous knowledge to improve food environments in regional New Zealand.

ISSUE ADDRESSED: Hawke's Bay has one of the highest rates of childhood obesity in New Zealand. While several initiatives exist aiming to decrease obesity through physical activity, there are few nutritional interventions. This study adopted a systems science and matauranga Maori approach to identify and target underlying drivers of rising childhood obesity and engage the community to improve the food environment. METHODS: Cognitive mapping interviews (CM) with local stakeholders (school principals, Iwi and district health board representatives, education managers and local councillors) were conducted. The aim was to map participants' mental models of the causes of rising childhood obesity and to identify key principles for engaging with the local community in a meaningful, impactful and culturally appropriate way for future action. RESULTS: Eleven interviews were conducted face-to-face and cognitive maps were constructed. Follow-up interviews were carried out online, due to COVID restrictions, to present the maps and for interviewees to make any adjustments. Four composite themes emerged through centrality and cluster analysis of the resulting cognitive maps: the importance of building in matauranga Maori (Maori knowledge and ways of being), the "hauora" of children, working with the community and integrating existing initiatives. Two contextual factors are also considered: the growing need for food security in our communities and the opportunity to start interventions in the school setting. CONCLUSION: Cognitive mapping can produce useful insights in the early stages of community engagement. The six "pou" (pillars) underscore the importance of incorporating indigenous knowledge when embarking on public health interventions, particularly around obesity and in regional communities. SO WHAT?: When designing a public health initiative with a community with a high indigenous population, indigenous knowledge should be promoted to focus on holistic health, working with the community and creating opportunities for cohesion. These founding principles will be used to structure future community actions to improve children's food environments in regional New Zealand.

Distribution of Holliday junctions and repair forks during Escherichia coli DNA double-strand break repair.

Accurate repair of DNA double-strand breaks (DSBs) is crucial for cell survival and genome integrity. In Escherichia coli, DSBs are repaired by homologous recombination (HR), using an undamaged sister chromosome as template. The DNA intermediates of this pathway are expected to be branched molecules that may include 4-way structures termed Holliday junctions (HJs), and 3-way structures such as D-loops and repair forks. Using a tool creating a site-specific, repairable DSB on only one of a pair of replicating sister chromosomes, we have determined how these branched DNA intermediates are distributed across a DNA region that is undergoing DSB repair. In cells, where branch migration and cleavage of HJs are limited by inactivation of the RuvABC complex, HJs and repair forks are principally accumulated within a distance of 12 kb from sites of recombination initiation, known as Chi, on each side of the engineered DSB. These branched DNA structures can even be detected in the region of DNA between the Chi sites flanking the DSB, a DNA segment not expected to be engaged in recombination initiation, and potentially degraded by RecBCD nuclease action. This is observed even in the absence of the branch migration and helicase activities of RuvAB, RadA, RecG, RecQ and PriA. The detection of full-length DNA fragments containing HJs in this central region implies that DSB repair can restore the two intact chromosomes, into which HJs can relocate prior to their resolution. The distribution of recombination intermediates across the 12kb region beyond Chi is altered in xonA, recJ and recQ mutants suggesting that, in the RecBCD pathway of DSB repair, exonuclease I stimulates the formation of repair forks and that RecJQ promotes strand-invasion at a distance from the recombination initiation sites.

Proximal and distal influences on dietary change among a diverse group with prediabetes participating in a pragmatic, primary care nurse-led intervention: a qualitative study.

OBJECTIVE: To understand motivators, facilitators and challenges to dietary change amongst a diverse sample of New Zealanders with prediabetes participating in a primary care nurse-led individualised dietary intervention. DESIGN: A qualitative study involving semi-structured, face-to-face interviews with a stratified sample of adults with prediabetes and BMI ≥ 25 kg/m2, purposefully selected from a larger 2-year primary care-based prediabetes dietary intervention study. Thematic analysis was undertaken. A socio-ecological model guided interpretation. SETTING: Hawke's Bay, Aotearoa/New Zealand, April 2018-March 2020. PARTICIPANTS: Fifty-eight people aged 28-69 years, with similar numbers of men and women, indigenous Maori and non-Maori, and those who had and had not regressed to normoglycaemia at 6 months. RESULTS: Motivators for wanting to make dietary changes were determination not to progress to diabetes; wanting to be healthy and contribute to others and encouragement by others. Facilitators for adopting and maintaining changes were a strong desire to be healthy; personal determination and feeling supported. Challenges were compromised control over life and environmental factors; feeling unsupported by others; social occasions; financial constraints and living with other health conditions. Developing their own strategies to overcome challenges was empowering, enabling a sense of control. These factors were similar across demographic and glycaemic outcome groups. CONCLUSIONS: Influences on dietary change involved personal, interpersonal, organisational, environmental and policy factors. Although findings appeared similar across groups, dietary interventions need to address the specific ways motivators, facilitators and challenges manifest for individuals and social groups and be tailored accordingly within the context of the wider obesogenic and socio-economic environment.

Local Anti-PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model.

Although the principle of systemic treatment to prevent the progression of oral premalignant lesions (OPL) has been demonstrated, there remains a lack of consensus about an optimal approach that balances clinical efficacy with toxicity concerns. Recent advances in cancer therapy using approaches targeting the tumor immune microenvironment (TIME) including immune-checkpoint inhibitors indicate that these agents have significant clinically activity against different types of cancers, including oral cancer, and therefore they may provide an effective oral cancer prevention strategy for patients with OPLs. Our past work showed that systemic delivery of a monoclonal antibody to the programmed death receptor 1 (PD-1) immune checkpoint can inhibit the progression of OPLs to oral cancer in a syngeneic murine oral carcinogenesis model. Here we report a novel approach of local delivery of a PD-1 immune-checkpoint inhibitor loaded using a hydrogel, which significantly reduces the progression of OPLs to carcinomas. In addition, we detected a significant infiltration of regulatory T cells associated with oral lesions with p53 mutation, and a severe loss of expression of STING, which correlated with a decreased infiltration of dendritic cells in the oral lesions. However, a single local dose of PD-1 inhibitor was found to restore stimulator of interferon response cGAMP interactor 1 (STING) and CD11c expression and increase the infiltration of CD8+ T cells into the TIME irrespective of the p53 mutational status. Overall, we provide evidence for the potential clinical value of local delivery of biomaterials loaded with anti-PD-1 antibodies to prevent malignant progression of OPLs. PREVENTION RELEVANCE: Oral cancer is an aggressive disease, with an overall survival rate of 50%. Preinvasive histologic abnormalities such as tongue dysplasia represent an early stage of oral cancer; however, there are no treatments to prevent oral carcinoma progression. Here, we combined biomaterials loaded with an immunotherapeutic agent preventing oral cancer progression.