The common drivers of children and young people's health and wellbeing across 13 local government areas: a systems view.

BACKGROUND: System dynamics approaches, including group model building (GMB) and causal loop diagrams (CLDs), can be used to document complex public health problems from a community perspective. This paper aims to apply Social Network Analysis (SNA) methods to combine multiple CLDs created by local communities into a summary CLD, to identify common drivers of the health and wellbeing of children and young people. METHODS: Thirteen community CLDs regarding children and young people health and wellbeing were merged into one diagram involving three steps: (1) combining variable names; (2) CLD merging, where multiple CLDs were combined into one CLD with a set of unique variables and connections; (3) paring, where the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method was used to generate a cut-point to reduce the number of variables and connections and to rank the overall importance of each variable in the merged CLD. RESULTS: Combining variable names resulted in 290 variables across the 13 CLDS. A total of 1,042 causal links were identified in the merged CLD. The DEMATEL analysis of the merged CLD identified 23 common variables with a net importance between 1.0 and 4.5 R + C values and 57 causal links. The variables with the highest net importance were 'mental health' and 'social connection & support' classified as high net receivers of influence within the system. CONCLUSIONS: Combining large CLDs into a simple diagram represents a generalisable model of the drivers of complex health problems.

Healthy together Victoria and childhood obesity study: effects of a large scale, community-based cluster randomised trial of a systems thinking approach for the prevention of childhood obesity among secondary school students 2014-2016.

BACKGROUND: Healthy Together Victoria (HTV) was a Victorian Government initiative that sought to reduce the prevalence of overweight and obesity through targeting chronic disease risk factors including physical activity, poor diet quality, smoking, and harmful alcohol use. The intervention involved a boosted workforce of > 170 local-level staff in 12 communities; employed to deliver system activation around health and wellbeing for individuals, families and communities. A cluster randomised trial (CRT) of a systems thinking approach to obesity prevention was embedded within HTV. We present the two-year changes in overweight and obesity and associated behaviours among secondary school students across Victoria, Australia. METHODS: Twenty-three geographically bounded areas were randomised to intervention (12 communities) or comparison (11 communities). Randomly selected secondary schools within each community were invited to participate in the trial in 2014 and 2016. Students in Grade 8 (aged approximately 13-15 years) and Grade 10 (aged approximately 15-16 years) at participating schools were recruited using an opt-out approach across July-September 2014 and 2016. Primary outcomes were body mass index (BMI) and waist circumference. Secondary outcomes were physical activity, sedentary behaviour, diet quality, health-related quality of life, and depressive symptoms. Linear mixed models were fit to estimate the intervention effect adjusting for child/school characteristics. RESULTS: There were 4242 intervention children and 2999 control children in the final analysis. For boys, the two-year change showed improvement in intervention versus control for waist circumference (difference in change: - 2.5 cm; 95% confidence interval [CI]: - 4.6, - 0.5) and consumption of sugar-sweetened beverages per day (< 1 serve: 8.5 percentage points; 95% CI: 0.6, 16.5). For girls, there were no statistically significant differences between conditions. CONCLUSIONS: HTV seemed to produce favourable changes in waist circumference and sugar-sweetened beverage consumption for boys, however, no effect on BMI was observed. Although the HTV intervention was cut short, and the period between data collection points was relatively short, the changes observed in HTV contribute to the growing evidence of whole-of-community interventions targeting childhood obesity. TRIAL REGISTRATION: This trial is unregistered. The intervention itself was a policy setting delivered by government and our role was the collection of data to evaluate the effect of this natural experiment. That is, this study was not a trial from the classical point of view and we were not responsible for the intervention.

Systems thinking in local government: intervention design and adaptation in a community-based study.

BACKGROUND: Systems thinking approaches are increasingly being used by communities to address complex chronic disease. This paper reports on the VicHealth Local Government Partnership (VLGP) which sought to co-create improvements in the health and well-being of children and young people by working with local government in Victoria, Australia. METHODS: The VLGP included a series of health promotion modules, aimed at creating policy, programme and practice changes across local government. One of these modules, Connecting the Dots - creating solutions for lasting change, aimed to build capacity for systems thinking in municipal public health and well-being planning across 13 councils. The approach was adapted and data were collected on the stimuli for, and results of, adaptation. RESULTS: The council adapted the systems thinking approach to meet geographic characteristics, priority health issue/s and participant target group needs. Adaptions applied to workshop materials, training delivery, existing and new resources, and to align with other community-based approaches. Stimuli for adaptation included the COVID-19 pandemic, needs of children and young people, capacity of council to deliver the workshop series, and time available within the project or for the participant group. CONCLUSIONS: Systems thinking was used and adapted by councils to improve the health and well-being of children and young people and increase the voices of children and young people in decision-making. Flexible delivery is critical to ensure communities can adapt the approach to meet local needs.

When primary healthcare meets queerstory: community-based system dynamics influencing regional/rural LGBTQ + people's access to quality primary healthcare in Australia.

BACKGROUND: Lesbian, gay, bisexual, transgender, Queer, and people of any other minority sexuality or gender identity (LGBTQ + or "Queer") are often marginalised from accessing quality primary healthcare (PHC) in their local community. This is largely due to Queerphobic, cis-heteronormative/sexist systems pathologising Queer life and identities. The study aims were to: (1) identify key priorities for increasing Queer people's access to quality PHC as told by Queer people themselves, (2) identify the feedback loops that reduce or support Queer people's access to quality PHC in non-metropolitan, regional/rural communities, and (3) identify potential action areas to improve system structures to increase Queer people's access to quality PHC. METHODS: Group Model Building (GMB) workshops were held with a small group (n = 8) of LGBTQ + people in regional Victoria with lived experience of using PHC services. This participatory approach permits exploration and visual mapping of local structures causing behaviour patterns of community concern over time - in this case, Queer people's ability to access quality PHC in the Geelong-Barwon region. This is the first study that specially applies GMB in Queer PHC in the non-metropolitan regional/rural context. RESULTS: Key community identified PHC priorities were: (a) providers' level of Queer Literacy, (b) the responsibility of Queer Advocacy (at individual, systemic, and collective levels), (c) support from safe Queer Spaces, (d) strength from a Queer Presence, and (e) power from Intersectional Queer Life. These priorities interconnected, creating system-level feedback loops reinforcing barriers and enablers to Queer people's access to quality PHC in the Geelong-Barwon region; with potential action areas identified. CONCLUSIONS: Improving Queer people's access to quality PHC in the Geelong-Barwon region requires embedding principles of Queer Literacy, Queer Advocacy, Queer Space, Queer Presence, and Intersectional Queer Life within practices and service systems. The study findings were distilled into a novel, preliminary set of Queer Equity Principles. These need to be taken back to regional Queer communities for further co-design and planning for translation across PHC practices and systems, with potential applicability in other areas of the healthcare spectrum.

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.

Building capacity for the use of systems science to support local government public health planning: a case study of the VicHealth Local Government Partnership in Victoria, Australia.

OBJECTIVE: To present an approach to build capacity for the use of systems science to support local communities in municipal public health and well-being planning. DESIGN: Case study. SETTING: Local government authorities participating in the VicHealth Local Government Partnership in Victoria, Australia. PARTICIPANTS: Local government staff members were trained in community-based system dynamics (CBSD), and group model building (GMB) techniques to mobilise local community efforts. The trained local government facilitation teams then delivered GMB workshops to community stakeholder groups from 13 local government areas (LGA)s. MAIN OUTCOMES: Training in CBSD was conducted with council facilitation teams in 13 LGAs, followed by the local delivery of GMB workshops 1-3 to community stakeholders. Causal loop diagrams (CLD) representing localised drivers of mental well-being, healthy eating, active living or general health and well-being of children and young people were developed by community stakeholders. Locally tailored action ideas were generated such as well-being classes in school, faster active transport and access to free and low-cost sporting programmes RESULTS: Overall, 111 local government staff participated in CBSD training. Thirteen CLDs were developed, with the stakeholders that included children, young people and community members, who had participated in the GMB workshops across all 13 council sites. Workshop 3 had the highest total number of participants (n=301), followed by workshop 1 (n=287) and workshop 2 (n=171). CONCLUSIONS: Local facilitation of the CBSD process has developed community informed and locally relevant CLDs that will be used to lead local action to improve the well-being of children and young people. Training employees in CBSD is one approach to increase systems thinking capacity within local government.

Unique Evolution of Antiviral Tetherin in Bats.

Bats are recognized as important reservoirs of viruses deadly to other mammals, including humans. These infections are typically nonpathogenic in bats, raising questions about host response differences that might exist between bats and other mammals. Tetherin is a restriction factor which inhibits the release of a diverse range of viruses from host cells, including retroviruses, coronaviruses, filoviruses, and paramyxoviruses, some of which are deadly to humans and transmitted by bats. Here, we characterize the tetherin genes from 27 bat species, revealing that they have evolved under strong selective pressure, and that fruit bats and vesper bats express unique structural variants of the tetherin protein. Tetherin was widely and variably expressed across fruit bat tissue types and upregulated in spleen tissue when stimulated with Toll-like receptor agonists. The expression of two computationally predicted splice isoforms of fruit bat tetherin was verified. We identified an additional third unique splice isoform which includes a C-terminal region that is not homologous to known mammalian tetherin variants but was functionally capable of restricting the release of filoviral virus-like particles. We also report that vesper bats possess and express at least five tetherin genes, including structural variants, more than any other mammal reported to date. These findings support the hypothesis of differential antiviral gene evolution in bats relative to other mammals. IMPORTANCE Bats are an important host of various viruses which are deadly to humans and other mammals but do not cause outward signs of illness in bats. Furthering our understanding of the unique features of the immune system of bats will shed light on how they tolerate viral infections, potentially informing novel antiviral strategies in humans and other animals. This study examines the antiviral protein tetherin, which prevents viral particles from escaping their host cell. Analysis of tetherin from 27 bat species reveals that it is under strong evolutionary pressure, and we show that multiple bat species have evolved to possess more tetherin genes than other mammals, some of which encode structurally unique tetherins capable of activity against different viral particles. These data suggest that bat tetherin plays a potentially broad and important role in the management of viral infections in bats.

Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression.

BACKGROUND: Women with a cervicovaginal microbiota dominated by Lactobacillus spp. are at reduced risk of acquiring sexually transmitted infections including HIV, but the biological mechanisms involved remain poorly defined. Here, we performed metaproteomics on vaginal swab samples from young South African women (n = 113) and transcriptomics analysis of cervicovaginal epithelial cell cultures to examine the ability of lactic acid, a metabolite produced by cervicovaginal lactobacilli, to modulate genital epithelial barrier function. RESULTS: Compared to women with Lactobacillus-depleted microbiota, women dominated by vaginal lactobacilli exhibit higher abundance of bacterial lactate dehydrogenase, a key enzyme responsible for lactic acid production, which is independently associated with an increased abundance of epithelial barrier proteins. Physiological concentrations of lactic acid enhance epithelial cell culture barrier integrity and increase intercellular junctional molecule expression. CONCLUSIONS: These findings reveal a novel ability of vaginal lactic acid to enhance genital epithelial barrier integrity that may help prevent invasion by sexually transmitted pathogens. Video abstract.

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.

Designing Virtual Reality Assisted Psychotherapy for Anxiety in Older Adults Living with Parkinson's Disease: Integrating Literature for Scoping.

Objective: This review integrates literature to discuss the potential use of virtual reality (VR) in treatment of anxiety in Parkinson's disease (PD) and inform next steps.Methods: A systematic search was performed to identify studies of VR use in PD, using four databases. Data were reported in accordance to the Preferred Reporting Items for Systematic reviews and Meta-Analyzes extension for Scoping Reviews (PRISMA-ScR).Results: Thirty-two studies met the inclusion criteria with four VR studies from the same study group directly assessing the effects of anxiety on motor symptoms in PD. Primary studies implementing a VR protocol in PD identified focus areas of understanding and alleviating freezing of gait (FOG), balance training, and cognitive and motor rehabilitation, and informed design considerations.Conclusion: VR in PD studies suggested established feasibility. With appropriate design considerations, a VR based protocol could improve anxiety outcomes in PD.Clinical implications: VR in PD provides control of a patient's field of view, which can be exploited to induce specific responses, provide visual feedback, analysis of patient actions, and introduce safe challenges in the context of training. VR assisted Cognitive Behavioral Therapy (CBT) tailored to suit subtypes of anxiety disorders in PD have the potential to improve the efficacy and effectiveness of psychotherapy in PD.

Retroviruses of Bats: a Threat Waiting in the Wings?

Bats are infamous reservoirs of deadly human viruses. While retroviruses, such as the human immunodeficiency virus (HIV), are among the most significant of virus families that have jumped from animals into humans, whether bat retroviruses have the potential to infect and cause disease in humans remains unknown. Recent reports of retroviruses circulating in bat populations builds on two decades of research describing the fossil records of retroviral sequences in bat genomes and of viral metagenomes extracted from bat samples. The impact of the global COVID-19 pandemic demands that we pay closer attention to viruses hosted by bats and their potential as a zoonotic threat. Here we review current knowledge of bat retroviruses and explore the question of whether they represent a threat to humans.

HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer.

Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47-70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker.

Identifying the views of adolescents in five European countries on the drivers of obesity using group model building.

BACKGROUND: To make effective progress towards a global reduction in obesity prevalence, there needs to be a focus on broader structural factors, beyond individual-level drivers of diet and physical activity. This article describes the use of a systems framework to develop obesity prevention policies with adolescents. The aim of this research was to use the group model building (GMB) method to identify young people's perceptions of the drivers of adolescent obesity in five European countries, as part of the EU-funded Co-Create project. METHODS: We used GMB with four groups of 16-18-year-olds in schools in each of the five European countries (The Netherlands, Norway, Poland, Portugal and the UK) to create causal loop diagrams (CLDs) representing their perceptions of the drivers of adolescent obesity. The maps were then merged into one, using a new protocol. RESULTS: Two hundred and fifty-seven participants, aged 16-18 years, engaged in 20 separate system mapping groups, each of which generated 1 CLD. The findings were largely congruent between the countries. Three feedback loops in the merged diagram particularly stand out: commercial drivers of unhealthy diets; mental health and unhealthy diets; social media use, body image and motivation to exercise. CONCLUSIONS: GMB provides a novel way of eliciting from young people the system-based drivers of obesity that are relevant to them. Mental health issues, social media use and commercial practices were considered by the young people to be key drivers of adolescent obesity, subjects that have thus far had little or no coverage in research and policy.

Tenth Scientific Biennial Meeting of the Australasian Virology Society-AVS10 2019.

The Australasian Virology Society (AVS) aims to promote, support and advocate for the discipline of virology in the Australasian region. The society was incorporated in 2011 after 10 years operating as the Australian Virology Group (AVG) founded in 2001, coinciding with the inaugural biennial scientific meeting. AVS conferences aim to provide a forum for the dissemination of all aspects of virology, foster collaboration, and encourage participation by students and post-doctoral researchers. The tenth Australasian Virology Society (AVS10) scientific meeting was held on 2-5 December 2019 in Queenstown, New Zealand. This report highlights the latest research presented at the meeting, which included cutting-edge virology presented by our international plenary speakers Ana Fernandez-Sesma and Benjamin tenOever, and keynote Richard Kuhn. AVS10 honoured female pioneers in Australian virology, Lorena Brown and Barbara Coulson. We report outcomes from the AVS10 career development session on "Successfully transitioning from post-doc to lab head", winners of best presentation awards, and the AVS gender equity policy, initiated in 2013. Plans for the 2021 meeting are underway which will celebrate the 20th anniversary of AVS where it all began, in Fraser Island, Queensland, Australia.

Infectious KoRV-related retroviruses circulating in Australian bats.

Bats are reservoirs of emerging viruses that are highly pathogenic to other mammals, including humans. Despite the diversity and abundance of bat viruses, to date they have not been shown to harbor exogenous retroviruses. Here we report the discovery and characterization of a group of koala retrovirus-related (KoRV-related) gammaretroviruses in Australian and Asian bats. These include the Hervey pteropid gammaretrovirus (HPG), identified in the scat of the Australian black flying fox (Pteropus alecto), which is the first reproduction-competent retrovirus found in bats. HPG is a close relative of KoRV and the gibbon ape leukemia virus (GALV), with virion morphology and Mn2+-dependent virion-associated reverse transcriptase activity typical of a gammaretrovirus. In vitro, HPG is capable of infecting bat and human cells, but not mouse cells, and displays a similar pattern of cell tropism as KoRV-A and GALV. Population studies reveal the presence of HPG and KoRV-related sequences in several locations across northeast Australia, as well as serologic evidence for HPG in multiple pteropid bat species, while phylogenetic analysis places these bat viruses as the basal group within the KoRV-related retroviruses. Taken together, these results reveal bats to be important reservoirs of exogenous KoRV-related gammaretroviruses.

Tools and analytic techniques to synthesise community knowledge in CBPR using computer-mediated participatory system modelling.

Participatory systems thinking methods are often used in community-based participatory research to engage and respond to complexity. Participation in systems thinking activities creates opportunities for participants to gain useful insights about complexity. It is desirable to design activities that extend the benefits of this participation into communities, as these insights are predictive of success in community-based prevention. This study tests an online, computer-mediated participatory system modelling platform (STICKE) and associated methods for collating and analysing its outputs. STICKE was trialled among a group of community members to test a computer-mediated system modelling exercise. The causal diagrams resulting from the exercise were then merged, and network analysis and DEMATEL methods applied to inform the generation of a smaller summary model to communicate insights from the participant group as a whole. Participants successfully completed the online modelling activity, and created causal diagrams consistent with expectations. The DEMATEL analysis was identified as the participant-preferred method for converging individuals causal diagrams into a coherent and useful summary. STICKE is an accessible tool that enabled participants to create causal diagrams online. Methods trialled in this study provide a protocol for combining and summarising individual causal diagrams that was perceived to be useful by the participant group. STICKE supports communities to consider and respond to complex problems at a local level, which is cornerstone of sustainable effective prevention. Understanding how communities perceive their own health challenges will be important to better support and inform locally owned prevention efforts.

Campbelltown - Changing our Future: study protocol for a whole of system approach to childhood obesity in South Western Sydney.

BACKGROUND: In Australia, around 67% of adults and 25% of children (5-17 years) are currently overweight or obese (Australian Bureau of Statistics, 4364.0.55.001 - National Health Survey: First Results, 2017-18, 2018). The Campbelltown - Changing our Future study will translate 'a whole of system' approach, previously trialed in rural communities in Victoria and the Australian Capital Territoty, to Campbelltown Local Government Area (LGA), a socioeconomically and ethnically diverse urban community in south western Sydney, NSW. METHODS: The study intervention will use a five-step approach; 1 - set up a childhood obesity monitoring system by collecting baseline data from children in primary schools across Campbelltown LGA to give a local context to the community when developing the systems map; 2 - key stakeholders develop systems maps which inform the development of the interventions; 3 - key stakeholders and community groups identify priority areas for action and form working groups; 4 - implementation of the interventions; 5 - evaluation of the interventions. The study will adopt a longitudinal pre/post design with repeated measures at baseline, 2 years and 4 years. Both qualitative and quantitative methods will be used to collect and analyse the data. DISCUSSION: Addressing childhood overweight and obesity is complex and requires a multifaceted intervention. This approach has the capacity to impact a range of factors that influence childhood overweight and obesity utilising existing capacity of multiple partners with broad community reach. Findings will develop local responses which capture the complexity of obesity at a community level and further our understanding of the interrelationships and relative importance of local factors impacting childhood overweight and obesity. This study aims to provide evidence for systems methods and approaches suitable for adaption and scaling and may provide evidence of successful community intervention elements.

Host and Viral Proteins Modulating Ebola and Marburg Virus Egress.

The filoviruses Ebolavirus and Marburgvirus are among the deadliest viral pathogens known to infect humans, causing emerging diseases with fatality rates of up to 90% during some outbreaks. The replication cycles of these viruses are comprised of numerous complex molecular processes and interactions with their human host, with one key feature being the means by which nascent virions exit host cells to spread to new cells and ultimately to a new host. This review focuses on our current knowledge of filovirus egress and the viral and host factors and processes that are involved. Within the virus, these factors consist of the major matrix protein, viral protein 40 (VP40), which is necessary and sufficient for viral particle release, and nucleocapsid and glycoprotein that interact with VP40 to promote egress. In the host cell, some proteins are hijacked by filoviruses in order to enhance virion budding capacity that include members of the family of E3 ubiquitin ligase and the endosomal sorting complexes required for transport (ESCRT) pathway, while others such as tetherin inhibit viral egress. An understanding of these molecular interactions that modulate viral particle egress provides an important opportunity to identify new targets for the development of antivirals to prevent and treat filovirus infections.

Associations between combined overweight and obesity, lifestyle behavioural risk and quality of life among Australian regional school children: baseline findings of the Goulburn Valley health behaviours monitoring study.

INTRODUCTION: Health related quality of life is a multi-dimensional construct of particular interest in determining the consequences of illness and disease. This study aimed to determine the relationships between overweight/obesity, and associated obesogenic risk behaviours with health related quality of life and physical, social, emotional and school sub-domains, among a large cohort of Australian primary school children. METHODS: The data were derived from the Goulburn Valley Health Behaviours Monitoring study whereby a census-styled school recruitment process and high participatory opt-out (passive) procedure was employed. All primary schools in three Local Government Areas were invited to participate between July-September 2016 with 39/62 (62%) of schools participating and 1606/2034 (79%) students in Grade 2 (aged approx. 7-8 years), Grade 4 (aged approx. 9-10 years) and Grade 6 (aged approx. 11-12 years) participating. Measured height and weight were collected among participating students and older children (Grade 4 and 6) who also completed a self-report behavioural questionnaire, including the paediatric quality of life inventory. RESULTS: Among 809 children aged 9 to 12 years, there were 219 (27.1%) classified as overweight/obese. Male children classified as overweight/obese reported significantly lower health related quality of life in the physical functioning and global functioning scores, compared to normal weight males. Significantly higher quality of life scores were observed among all children who met the physical activity recommendations on five out of the seven previous days. Significantly higher scores were observed among males adhering to the daily screen time recommendations, and among those meeting daily recommendations for fruit consumption. Among male school children, soft drink consumption was associated to lower health related quality of life. CONCLUSION: Although cross-sectional, these findings highlight children with overweight/obesity and some underlying lifestyle behavioural risk factors, had significantly lower healthy-related quality of life, although this was observed most consistently among male school children. These findings have not previously been identified in young children and highlights the need to consider mental and emotional health in public health efforts to prevent obesity. TRIAL REGISTRATION: ANZCTR Trial Registry: ACTRN12616000980437 retrospectively registered 26 July 2016.

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota.

Non-optimal vaginal microbiota, as observed in bacterial vaginosis (BV), is typically characterized by a depletion of beneficial lactobacilli and an abundance of numerous anaerobes. These non-optimal conditions are associated with subclinical cervicovaginal inflammation and an increased risk of HIV infection compared to women colonized with optimal vaginal microbiota dominated by lactobacilli. Lactic acid (LA) is a major organic acid metabolite produced by vaginal lactobacilli that elicits anti-inflammatory effects from cervicovaginal epithelial cells and is dramatically depleted during BV. However, it is unclear if LA retains its anti-inflammatory activity in the presence of vaginal microbiota metabolites comprising short chain fatty acids (SCFAs) and succinic acid, which are also produced by an optimal vaginal microbiota. Furthermore, the immunomodulatory effect of SCFAs and succinic acid on cervicovaginal epithelial cells at higher concentrations present during BV is unknown. Here we report that in the presence of physiologically relevant concentrations of SCFAs and succinic acid at pH 3.9 (as found in women with lactobacillus-dominated microbiota) LA induced an anti-inflammatory state in cervicovaginal epithelial cells and inhibited inflammation elicited by the toll-like receptor (TLR) agonists polyinosinic:polycytidylic acid and Pam3CSK4. When cervicovaginal epithelial cells were treated with a vaginal microbiota metabolite mixture representative of BV, containing a lower concentration of LA but higher concentrations of SCFA/succinic acid at pH 7, no anti-inflammatory was observed. Rather, the vaginal microbiota metabolite mixture representative of BV dysregulated the immune response of cervicovaginal epithelial cells during prolonged and sustained treatments. This was evidenced by increased basal and TLR-induced production of pro-inflammatory cytokines including tumor necrosis factor-α, but decreased basal production of chemokines including RANTES and IP-10. Further characterization of individual components of the BV vaginal microbiota mixture suggested that acetic acid is an important vaginal microbiota metabolite capable of eliciting diverse immunomodulatory effects on a range of cervicovaginal epithelial cell targets. These findings indicate that elevated levels of SCFAs are a potential source of cervicovaginal inflammation in women experiencing BV, and support the unique anti-inflammatory properties of LA on cervicovaginal epithelial cells as well as a role for LA or LA-producing lactobacilli to reverse genital inflammation associated with increased HIV risk.