Applying Systems Thinking to Improve a Hospital Food Retail Environment.

OBJECTIVE: To identify factors influencing the availability and sales of healthy food and drinks in a café located in a hospital setting in a rural area. METHODS: Three online and 1 in-person group model building workshops were conducted with hospital staff members to develop a causal loop diagram. RESULTS: Four areas in the causal loop diagram were identified, 5 teams were created to implement 15 identified action ideas, and an action registry was created to track their progress. By May 2023, 4 actions were active, 6 inactive, 4 completed, and 1 abandoned. CONCLUSIONS AND IMPLICATIONS: The group model building process identified factors and actions to improve the healthiness of the hospital's café and motivated staff members to act for change. However, progress was limited by staff turnover, recruitment, and inadequate participation from decision-makers. Better leadership and support by senior management can ensure that long-term objectives are achieved and healthier hospital food environments are sustained.

CO-Creation and Evaluation of Food Environments to Advance Community Health (COACH).

Introduction: Food environments are a key determinant of food intake and diet-related health. This paper describes the development of an iterative, adaptive, context-specific framework for health-enabling food environments embedded in cocreation theory. Methods: A 3-stage multimethod framework for the coproduction and prototyping of public health interventions was followed in an iterative manner during the development of the framework. These 3 stages were (1) evidence review, including systematic review, consultation with experts, and observation of current work; (2) codesign of the framework prototype with multiple stakeholders; and (3) coproduction through refinement of the prototype through stakeholder workshops and expert reviews with incorporation of researcher notes and workshop evaluation. We use the term prototype during the development phase and the term framework to report on the final product. Results: COACH (CO-creation and evaluation of food environments to Advance Community Health) is a process framework that describes what best practice application of cocreation in health-enabling food retail environments should involve. COACH consists of 10 interdependent factors within a 4-phase continuous quality improvement cycle. The 4 phases of the cycle are engagement and governance establishment, communication and policy alignment, codesign and implementation, and monitoring and evaluation. Conclusions: Utilizing cocreation theory represents an innovative step in research and practice to improve the healthiness of food retail environments. COACH provides a specific, unique, and comprehensive guide to the utilization of cocreation to improve the healthiness of food environments in practice.

Combining systems thinking approaches and implementation science constructs within community-based prevention: a systematic review.

BACKGROUND: Systems science offers methods for designing population health interventions while implementation science provides specific guidance for successful implementation. Integrating systems and implementation science may strengthen implementation and enhance and sustain systemic change to achieve system-level outcomes. Little is known about the extent to which these two approaches have been integrated to date. This review aimed to identify and synthesise the peer-reviewed literature that has reported the combined use of systems thinking approaches and implementation science constructs (within the same study), to deliver population health interventions. METHODS: A systematic literature search of peer-reviewed original research was conducted across six databases from 2009 to 2021. Journal manuscripts were included if they: (1) reported on a population health study conducted in a community, (2) reported the use of a systems method in the design of the intervention, and (3) used an implementation science theory, framework or model in the delivery of the intervention. Data extracted related to the specific systems methods and definitions and implementation science constructs used. The Mixed Methods Appraisal Tool (MMAT) was used to assess study quality. RESULTS: Of the 9086 manuscripts returned, 320 manuscripts were included for full-text review. Of these, 17 manuscripts that reported on 14 studies were included in the final extraction. The most frequently reported systems methods were a 'whole of community systems approach' (n = 4/14) and 'community-based system dynamics' (n = 2/14). Nineteen different implementation science theories, frameworks and models were used for intervention delivery, with RE-AIM being the only framework used in more than one study. CONCLUSION: There are few published peer-reviewed studies using systems thinking and implementation science for designing and delivering population health interventions. An exploration of synergies is worthwhile to operationalise alignment and improve implementation of systems thinking approaches. Review protocol registration PROSPERO CRD42021250419.

Perceived impacts of COVID-19 and bushfires on the implementation of an obesity prevention trial in Northeast Victoria, Australia.

BACKGROUND: Calls for the adoption of a systems approach to chronic disease prevention date back at least ten years because of the potential to empower communities to identify and address the complex causes of overnutrition, undernutrition and climate change. Australia, like many countries, has high levels of obesity and extreme climate events. The Reflexive Evidence and Systems interventions to Prevent Obesity and Non-communicable Disease (RESPOND) trial aims to prevent unhealthy weight gain in children in 10 intervention and two pilot communities in north-east Victoria, Australia using community-based participatory approaches informed by systems science. Intervention activities co-designed in 2019 were disrupted by COVID-19 and bushfires. This paper explores the impacts of these 'shocks' on the local prevention workforce to implement actions within communities. METHODS: A case study design involving one-hour online focus groups and an on-line survey (November 2021-February 2022). Purposive sampling was used to achieve diverse representation from RESPOND stakeholders including local council, health services, primary care partnerships and department of health. The focus group interview schedule and survey questions were based on Durlak and DuPre's implementation factors. RESULTS: Twenty-nine participants from seven different communities participated in at least one of nine focus groups to discuss the impacts of COVID-19 and bushfires on localised implementation. Twenty-eight participants (97% of focus group sample) also completed the on-line survey. Implementation of RESPOND stalled or stopped in most communities due to bushfires and/or COVID-19. These shocks resulted in organisational priorities changing, loss of momentum for implementation, redeployment of human resources, culminating in fatigue and exhaustion. Participants reported adaptation of RESPOND, but implementation was slowed due to limited resources. CONCLUSION: Further research is needed to advance risk management strategies and protect resources within health promotion. System shocks such as bushfires and COVID-19 are inevitable, and despite multiple adaptation opportunities, this intervention approach was not 'shock proof'.

Developing Co-Creation Research in Food Retail Environments: A Descriptive Case Study of a Healthy Supermarket Initiative in Regional Victoria, Australia.

Research into the co-creation of healthy food retail is in its early stages. One way to advance co-creation research is to explore and understand how co-creation was applied in developing, implementing, and evaluating a heath-enabling initiative in a supermarket in regional Victoria, Australia. A case study design was used to explore and understand how co-creation was applied in the Eat Well, Feel Good Ballarat project. Six documents and reports related to the Eat Well, Feel Good Ballarat project were analyzed with findings from the focus groups and interviews. Motivations to develop or implement health-enabling supermarket initiatives differed among the participants. Participants considered that initial negotiations were insufficient to keep the momentum going and to propose the value to the retailers to scale up the project. Presenting community-identified needs to the supermarket helped gain the retailer's attention, whilst the co-design process helped the implementation. Showcasing the project to the community through media exposure kept the supermarket interested. Retailers' time constraints and staff turnover were considered significant barriers to partnership building. This case study contributes insights into applying co-creation to health-enabling strategies in food retail outlets using two co-creation frameworks.

Lived experience of participants who engaged in the co-creation of initiatives to improve children's health in a rural Australian community.

OBJECTIVE: To describe participants' lived experience of co-creating and implementing initiatives to improve children's health. DESIGN: This manuscript reports an embedded case study design, which aims to describe participants' lived experiences of co-creating community-based initiatives. Information was gathered from an online survey and two focus groups. The two transcribed discussions from the focus groups were analysed using a 6-step phenomenological process. SETTING: Mansfield, Australia, population 4787, is one of ten local government areas (LGA) participating in the Reflexive Evidence and Systems Interventions to Prevent Obesity and Non-communicable Disease (RESPOND) project. PARTICIPANTS: Participants were purposively selected from established community groups previously engaged by RESPOND using a co-creation approach. The recruitment for the focus groups was a convenient sampling from participants that provided their email addresses in the online survey. RESULTS: Eleven participants completed the online survey. A total of ten participants attended the two focus groups of 1-h duration: five participants in each. Participants reported feeling empowered to create unique, locally relevant and readily adaptable community-wide change. They were supported by a strong partnership that mobilised funding for a part-time health promotion employee. Strengthened social connections were an unexpected though highly valued outcome. CONCLUSION: Co-creation processes may assist stakeholders in delivering prevention strategies in ways that are empowering for them, responsive to the changing needs of the community, strengthen organisational partnerships and enhance community participation, social inclusion and engagement.

Co-creation of health-enabling initiatives in food retail: academic perspectives.

INTRODUCTION: Co-creation of healthy food retail comprises the systematic collaboration between retailers, academics and other stakeholders to improve the healthiness of food retail environments. Research into the co-creation of healthy food retail is in its early stages. Knowledge of the roles and motivations of stakeholders in intervention design, implementation and evaluation can inform successful co-creation initiatives. This study presents academic experiences of stakeholder roles and motivations in the co-creation of healthy food retail environments. METHODS: Purposive sampling of academics with research experience in the co-creation of healthy food retail initiatives. Semi-structured interviews conducted between October and December 2021 gathered participants' experiences of multi-stakeholder collaborative research. Thematic analysis identified enablers, barriers, motivations, lessons and considerations for future co-creation of healthy food retail. RESULTS: Nine interviewees provided diverse views and applications of co-creation research in food retail environments. Ten themes were grouped into three overarching areas: (i) identification of stakeholders required for changes to healthier food retail; (ii) motivations and interactions, which included the intrinsic desire to build healthier communities along with recognition of their work; and (iii) barriers and enablers included adequate resourcing, effective and trusting working relationships and open communications. CONCLUSION: This study provides insights that could help future co-creation in healthy food retail environments. Trusting and respectful relationships and reciprocal acknowledgement between stakeholders are key practices in the co-creation process. These constructs should be considered in developing and testing a model that helps to systematically co-create healthy food retail initiatives that ensure all parties meet their needs while also delivering research outcomes.

Adoption, implementation, and sustainability of early childhood feeding, nutrition and active play interventions in real-world settings: a systematic review.

BACKGROUND: Instilling healthy dietary habits and active play in early childhood is an important public health focus. Interventions supporting the establishment of nutrition and active play behaviours in the first years of life have shown positive outcomes and long-term cost-effectiveness, however, most are research trials, with limited evidence regarding real-world application. Implementation science theories, models and frameworks (TMFs) can guide the process of research translation from trial to real-world intervention. The application of TMFs within nutrition and active play intervention studies in early childhood (< 5 years) is currently unknown. This systematic review identified the use of TMFs and barriers/ enablers associated with intervention adoption, implementation, and sustainability in early childhood nutrition and active play interventions implemented under real-world conditions. METHODS: Six databases were searched for peer-reviewed publications between 2000-2021. Studies were included if primary outcomes reported improvement in diet, physical activity or sedentary behaviours amongst children aged < 5 years and interventions were delivered under real-world conditions within a community and/or healthcare setting. Two reviewers extracted and evaluated studies, cross checked by a third and verified by all authors. Quality assessment of included studies was completed by two authors using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Eleven studies comprising eleven unique interventions were included. Studies represented low, middle and high-income countries, and were conducted across a range of settings. Five TMFs were identified representing four of Nilsen's implementation model categories, predominantly 'evaluation models'. Ninety-nine barriers/facilitators were extracted across the three intervention phases-Implementation (n = 33 barriers; 33 facilitators), Sustainability (n = 19 barriers; n = 9 facilitators), Adoption (n = 2 barriers; n = 3 facilitators). Identified barriers/facilitators were mapped to the five domains of the Durlak and DuPre framework, with 'funding', 'compatibility' and 'integration of new programming' common across the three intervention phases. CONCLUSIONS: Findings demonstrate that there is no systematic application of TMFs in the planning, implementation and/or evaluation of early childhood nutrition and active play interventions in real-world settings, and selective and sporadic application of TMFs occurs across the intervention lifespan. This apparent limited uptake of TMFs is a missed opportunity to enhance real-world implementation success. TRIAL REGISTRATION: PROSPERO (CRD42021243841).

A mixed-methods evaluation of a health-promoting café located in a small health service in rural Victoria, Australia.

INTRODUCTION: Residents of rural areas internationally typically experience chronic disease risk profiles worse than city dwellers. Poor diet, a key driver of chronic disease, has been associated with unhealthy food environments, and rural areas often experience limited access to healthy, fresh and affordable food. OBJECTIVE: This study aimed to evaluate the first three years of a health promoting social enterprise café established in a small rural health service. DESIGN: A mixed-methods evaluation study. Quantitative sales data, surveys and key informant interviews that included both quantitative and qualitative responses. FINDINGS: Three years of sales data were included; 111customer surveys and five key informant interviews were conducted. Food and beverages on displayed and sold consistently met or exceeded the healthy criteria set by policy. Stakeholders supported the traffic light system, the social enterprise model and rated the likelihood of sustainability of the café as high. DISCUSSION: Customers used the 'traffic light' system to inform food choices, placed value on the warmth of the staff and on the welcoming environment created through the social enterprise model. Resources remain tight although all stakeholders are committed to the sustainability of the YarriYak café. CONCLUSION: The study shows the acceptability, feasibility and sustainability of a health promoting social enterprise café in a rural area.

System approaches to childhood obesity prevention: ground up experience of adaptation and real-world context.

OBJECTIVE: Childhood obesity prevention is critical to reducing the health and economic burden currently experienced by the Australian economy. System science has emerged as an approach to manage the complexity of childhood obesity and the ever-changing risk factors, resources and priorities of government and funders. Anecdotally, our experience suggests that inflexibility of traditional research methods and dense academic terminology created issues with those working in prevention practice. Therefore, this paper provides a refined description of research-specific terminology of scale-up, fidelity, adaptation and context, drawing from community-based system dynamics and our experience in designing, implementing and evaluating non-linear, community-led system approaches to childhood obesity prevention. DESIGN: We acknowledge the importance of using a practice lens, rather than purely a research design lens, and provide a narrative on our experience and perspectives on scale-up, fidelity, context and adaptation through a practice lens. SETTING: Communities. PARTICIPANTS: Practice-based researcher experience and perspectives. RESULTS: Practice-based researchers highlighted the key finding that community should be placed at the centre of the intervention logic. This allowed communities to self-organise with regard to stakeholder involvement, capacity, boundary identification, and co-creation of actions implemented to address childhood obesity will ensure scale-up, fidelity, context and adaptation are embedded. CONCLUSIONS: We need to measure beyond primary anthropometric outcomes and focus on evaluating more about implementation, process and sustainability. We need to learn more from practitioners on the ground and use an implementation science lens to further understand how actions work. This is where solutions to sustained childhood obesity prevention will be found.

Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND): protocol and baseline outcomes for a stepped-wedge cluster-randomised prevention trial.

INTRODUCTION: Systems science methodologies have been used in attempts to address the complex and dynamic causes of childhood obesity with varied results. This paper presents a protocol for the Reflexive Evidence and Systems interventions to Prevention Obesity and Non-communicable Disease (RESPOND) trial. RESPOND represents a significant advance on previous approaches by identifying and operationalising a clear systems methodology and building skills and knowledge in the design and implementation of this approach among community stakeholders. METHODS AND ANALYSIS: RESPOND is a 4-year cluster-randomised stepped-wedge trial in 10 local government areas in Victoria, Australia. The intervention comprises four stages: catalyse and set up, monitoring, community engagement and implementation. The trial will be evaluated for individuals, community settings and context, cost-effectiveness, and systems and implementation processes. Individual-level data including weight status, diet and activity behaviours will be collected every 2 years from school children in grades 2, 4 and 6 using an opt-out consent process. Community-level data will include knowledge and engagement, collaboration networks, economic costs and shifts in mental models aligned with systems training. Baseline prevalence data were collected between March and June 2019 among >3700 children from 91 primary schools. ETHICS AND DISSEMINATION: Ethics approval: Deakin University Human Research Ethics Committee (HREC 2018-381) or Deakin University's Faculty of Health Ethics Advisory Committee (HEAG-H_2019-1; HEAG-H 37_2019; HEAG-H 173_2018; HEAG-H 12_2019); Victorian Government Department of Education and Training (2019_003943); Catholic Archdiocese of Melbourne (Catholic Education Melbourne, 2019-0872) and Diocese of Sandhurst (24 May 2019). The results of RESPOND, including primary and secondary outcomes, and emerging studies developed throughout the intervention, will be published in the academic literature, presented at national and international conferences, community newsletters, newspapers, infographics and relevant social media. TRIAL REGISTRATION NUMBER: ACTRN12618001986268p.

Assessing the Cost of Healthy and Unhealthy Diets: A Systematic Review of Methods.

PURPOSE OF REVIEW: Poor diets are a leading risk factor for chronic disease globally. Research suggests healthy foods are often harder to access, more expensive, and of a lower quality in rural/remote or low-income/high minority areas. Food pricing studies are frequently undertaken to explore food affordability. We aimed to capture and summarise food environment costing methodologies used in both urban and rural settings. RECENT FINDINGS: Our systematic review of high-income countries between 2006 and 2021 found 100 relevant food pricing studies. Most were conducted in the USA (n = 47) and Australia (n = 24), predominantly in urban areas (n = 74) and cross-sectional in design (n = 76). All described a data collection methodology, with just over half (n = 57) using a named instrument. The main purpose for studies was to monitor food pricing, predominantly using the 'food basket', followed by the Nutrition Environment Measures Survey for Stores (NEMS-S). Comparatively, the Healthy Diets Australian Standardised Affordability and Price (ASAP) instrument supplied data on relative affordability to household incomes. Future research would benefit from a universal instrument reflecting geographic and socio-cultural context and collecting longitudinal data to inform and evaluate initiatives targeting food affordability, availability, and accessibility.

Co-creation of healthier food retail environments: A systematic review to explore the type of stakeholders and their motivations and stage of engagement.

OBJECTIVE: To synthesize peer-reviewed literature that utilize co-creation principles in healthy food retail initiatives. METHODS: Systematic review of six databases from inception to September 2021. Screening and quality assessment were carried out by two authors independently. Studies were included if they were conducted in food retail stores, used a collaborative model, and aimed to improve the healthiness of the food retail environment. Studies excluded were implemented in restaurants, fast food chains, or similar or did not utilize some form of collaboration. Extracted data included the type of stakeholders engaged, level of engagement, stakeholder motivation, and barriers and enablers of the co-creation process. FINDINGS: After screening 6951 articles by title and abstract, 131 by full text, 23 manuscripts that describe 20 separate studies from six countries were included. Six were implemented in low-income communities and eight among Indigenous people groups. A common aim was to increase access to, and availability of, healthy products. A diverse range of co-creation approaches, theoretical perspectives, and study designs were observed. The three most common stakeholders involved were researchers, corporate representatives or store owners, and governments. CONCLUSIONS: Some evidence exists of the benefits of co-creation to improve the healthiness of food retail environments. The field may benefit from structured guidance on the theory and practice of co-creation.

Generating change through collective impact and systems science for childhood obesity prevention: The GenR8 Change case study.

BACKGROUND: Community-based interventions have shown promise in reducing childhood overweight and obesity. However, they have been critiqued for using linear logic models. Participatory community-based systems approaches are posited as addressing the complexity of non-linear relationships in a local context. Community members are empowered to understand and describe obesity causation, identify and prioritise possible solutions. The application of such approaches to childhood obesity is in its infancy. AIM: To describe the first 12 months of a participatory whole-of-community systems approach to creating collective action to tackle childhood obesity, called GenR8 Change, in a local government area of Victoria, Australia. METHODS: Three group model building (GMB) sessions focused on the development of a causal loop diagram (CLD), prioritised evidence-informed actions, and developed implementation strategies. The collective impact framework underpinned the approach, with a local backbone group supporting community members to implement prioritised actions. RESULTS: The first two GMB sessions included 20 key community leaders where a CLD examining the factors contributing to childhood obesity in the community was constructed and refined (22 variables GMB1, 53 variables GMB2). In the third session, 171 members of the wider community further refined the CLD, identified priorities for childhood obesity prevention (72 variables in final CLD). One-hundred and thirteen individuals signed up across 13 working groups to plan and implement 53 prioritised actions. Agreed community actions included creating sugar free zones; developing healthy policies; increasing breastfeeding rates; improving drinking water access; and increasing physical activity options. Twelve months post-GMB3, 115 actions had been implemented. CONCLUSION: GenR8 Change is one of the first communities to apply systems thinking to childhood obesity prevention. Knowledge on how to collectively identify relevant leverage points to tackle childhood obesity can now be shared with other communities.

The Public Health 12 framework: interpreting the 'Meadows 12 places to act in a system' for use in public health.

BACKGROUND: Systems science approaches have demonstrated effectiveness in identifying underlying drivers of complex problems and facilitating the emergence of potential interventions that are locally tailored, feasible, sustainable and evidence informed. Despite the potential usefulness of system dynamics simulation modelling and other systems science modelling techniques in guiding implementation, time and cost constraints have limited its ability to provide strong guidance on how to implement complex interventions in communities. Guidance is required to ensure systems interventions lead to impactful systems solutions, implemented utilising strategies from the intersecting fields of systems science and implementation science. To provide cost-effective guidance on how and where to implement in systems, we offer a translation of the 'Meadows 12 places to act in a system' (Meadows 12) into language useful for public health. METHODS: This translation of Meadows 12 was informed by our experience in working with 31 communities across two complex large scale randomised control trials and one large whole of community case study. These research projects utilised systems science and implementation science to co-create childhood obesity prevention interventions. The team undertaking this translation comprised research academics, implementation specialists and practitioners, practice-based researchers and a systems dynamicist. Our translation of each of the Meadows 12 levels to act in the system maintains the fidelity and nuance of the 12 distinct levels. We provide examples of each level of the Public Health 12 framework (PH12) drawn from 31 communities. All research was conducted in Victoria, Australia between 2016 and 2020. RESULTS: PH12 provides a framework to guide both research and practice in real world contexts to implement targeted system level interventions. PH12 can be used with existing implementation science theory to identify relevant strategies for implementation of these interventions to impact the system at each of the leverage points. CONCLUSION: To date little guidance for public health practitioners and researchers exists regarding how to implement systems change in community-led public health interventions. PH12 enables operationalisation Meadows 12 systems theory into public health interventions. PH12 can help research and practice determine where leverage can be applied in the system to optimise public health systems level interventions and identify gaps in existing efforts. TRIAL REGISTRATION: WHO STOPS: ANZCTR: 12616000980437 . RESPOND: ANZCTR: 12618001986268p .

A Theory of Change for Community-Based Systems Interventions to Prevent Obesity.

INTRODUCTION: Applying systems science in public health trials is a recent innovation in childhood obesity prevention. This paper aims to use systems science conventions to propose a theory of change for community-based interventions aiming to build capacity and use exemplars from systems science for obesity prevention to describe how this approach works. METHODS: Participants were community-based researchers. A dynamic hypothesis was created in workshops conducted in 2020 and 2021 by identifying variables critical to building community capacity for systems thinking. These were used to develop stock and flow diagrams representing individual causal relationships, feedback loops, and the overall theory of change. RESULTS: The resultant model identified 9 stocks and 4 pairs of central balancing and reinforcing feedback loops. These represented building commitment through relationships, mutual learning, strengthening collaboration, and embedding capacity. The model is described using examples from 3 trials involving 25 communities across Victoria, Australia. CONCLUSIONS: This nonlinear and practice-based model illustrates the process of community-based obesity prevention. The model integrates >20 years of community-based intervention implementation experience, providing an overarching theory of how such interventions work to create change and prevent obesity.

Adenovirus prevents dsRNA formation by promoting efficient splicing of viral RNA.

Eukaryotic cells recognize intracellular pathogens through pattern recognition receptors, including sensors of aberrant nucleic acid structures. Sensors of double-stranded RNA (dsRNA) are known to detect replication intermediates of RNA viruses. It has long been suggested that annealing of mRNA from symmetrical transcription of both top and bottom strands of DNA virus genomes can produce dsRNA during infection. Supporting this hypothesis, nearly all DNA viruses encode inhibitors of dsRNA-recognition pathways. However, direct evidence that DNA viruses produce dsRNA is lacking. Contrary to dogma, we show that the nuclear-replicating DNA virus adenovirus (AdV) does not produce detectable levels of dsRNA during infection. In contrast, abundant dsRNA is detected within the nucleus of cells infected with AdV mutants defective for viral RNA processing. In the presence of nuclear dsRNA, the cytoplasmic dsRNA sensor PKR is relocalized and activated within the nucleus. Accumulation of viral dsRNA occurs in the late phase of infection, when unspliced viral transcripts form intron/exon base pairs between top and bottom strand transcripts. We propose that DNA viruses actively limit dsRNA formation by promoting efficient splicing and mRNA processing, thus avoiding detection and restriction by host innate immune sensors of pathogenic nucleic acids.

Zika virus employs the host antiviral RNase L protein to support replication factory assembly.

Infection with the flavivirus Zika virus (ZIKV) can result in tissue tropism, disease outcome, and route of transmission distinct from those of other flaviviruses; therefore, we aimed to identify host machinery that exclusively promotes the ZIKV replication cycle, which can inform on differences at the organismal level. We previously reported that deletion of the host antiviral ribonuclease L (RNase L) protein decreases ZIKV production. Canonical RNase L catalytic activity typically restricts viral infection, including that of the flavivirus dengue virus (DENV), suggesting an unconventional, proviral RNase L function during ZIKV infection. In this study, we reveal that an inactive form of RNase L supports assembly of ZIKV replication factories (RFs) to enhance infectious virus production. Compared with the densely concentrated ZIKV RFs generated with RNase L present, deletion of RNase L induced broader subcellular distribution of ZIKV replication intermediate double-stranded RNA (dsRNA) and NS3 protease, two constituents of ZIKV RFs. An inactive form of RNase L was sufficient to contain ZIKV genome and dsRNA within a smaller RF area, which subsequently increased infectious ZIKV release from the cell. Inactive RNase L can interact with cytoskeleton, and flaviviruses remodel cytoskeleton to construct RFs. Thus, we used the microtubule-stabilization drug paclitaxel to demonstrate that ZIKV repurposes RNase L to facilitate the cytoskeleton rearrangements required for proper generation of RFs. During infection with flaviviruses DENV or West Nile Kunjin virus, inactive RNase L did not improve virus production, suggesting that a proviral RNase L role is not a general feature of all flavivirus infections.

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes.

Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection; induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung; and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease. Robust activation of IFN or OAS-RNase L is not observed in these cell types, whereas PKR activation is evident in iAT2 and iCM. In SARS-CoV-2-infected Calu-3 and A549ACE2 lung-derived cell lines, IFN induction remains relatively weak; however, activation of OAS-RNase L and PKR is observed. This is in contrast to Middle East respiratory syndrome (MERS)-CoV, which effectively inhibits IFN signaling and OAS-RNase L and PKR pathways, but is similar to mutant MERS-CoV lacking innate immune antagonists. Remarkably, OAS-RNase L and PKR are activated in MAVS knockout A549ACE2 cells, demonstrating that SARS-CoV-2 can induce these host antiviral pathways despite minimal IFN production. Moreover, increased replication and cytopathic effect in RNASEL knockout A549ACE2 cells implicates OAS-RNase L in restricting SARS-CoV-2. Finally, while SARS-CoV-2 fails to antagonize these host defense pathways, which contrasts with other coronaviruses, the IFN signaling response is generally weak. These host-virus interactions may contribute to the unique pathogenesis of SARS-CoV-2.

The Impact of COVID-19 on Rural Food Supply and Demand in Australia: Utilising Group Model Building to Identify Retailer and Customer Perspectives.

Prior to the 2020 outbreak of COVID-19, 70% of Australians' food purchases were from supermarkets. Rural communities experience challenges accessing healthy food, which drives health inequalities. This study explores the impact of COVID-19 on food supply and purchasing behaviour in a rural supermarket. Group model building workshops explored food supply experiences during COVID-19 in a rural Australian community with one supermarket. We asked three supermarket retailers "What are the current drivers of food supply into this supermarket environment?" and, separately, 33 customers: "What are the current drivers of purchases in this supermarket environment?" Causal loop diagrams were co-created with participants in real time with themes drawn afterwards from coded transcripts. Retailers' experience of COVID-19 included 'empty shelves' attributed to media and government messaging, product unavailability, and community fear. Customers reported fear of contracting COVID-19, unavailability of food, and government restrictions resulting in cooking more meals at home, as influences on purchasing behaviour. Supermarket management and customers demonstrated adaptability and resilience to normalise demand and combat reduced supply.