Inhibition of SARS-CoV-2 Infection in Vero Cells by Bovine Lactoferrin under Different Iron-Saturation States.

Despite the rapid mass vaccination against COVID-19, the emergence of new SARS-CoV-2 variants of concern, such as omicron, is still a great distress, and new therapeutic options are needed. Bovine lactoferrin (bLf), a multifunctional iron-binding glycoprotein available in unsaturated (apo-bLf) and saturated (holo-bLf) forms, has been shown to exert broad-spectrum antiviral activity against many viruses. In this study, we evaluated the efficacy of both forms of bLf at 1 mg/mL against infection of Vero cells by SARS-CoV-2. As assessed with antiviral assays, an equivalent significant reduction in virus infection by about 70% was observed when either form of bLf was present throughout the infection procedure with the SARS-CoV-2 ancestral or omicron strain. This inhibitory effect seemed to be concentrated during the early steps of virus infection, since a significant reduction in its efficiency by about 60% was observed when apo- or holo-bLf were incubated with the cells before or during virus addition, with no significant difference between the antiviral effects of the distinct iron-saturation states of the protein. However, an ultrastructural analysis of bLf treatment during the early steps of virus infection revealed that holo-bLf was somewhat more effective than apo-bLf in inhibiting virus entry. Together, these data suggest that bLf mainly acts in the early events of SARS-CoV-2 infection and is effective against the ancestral virus as well as its omicron variant. Considering that there are no effective treatments to COVID-19 with tolerable toxicity yet, bLf shows up as a promising candidate.

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy.

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Lumbar spinal fusion surgery outcomes in a cohort of injured workers in the Victorian workers' compensation system.

BACKGROUND: Lumbar spinal fusion (LSF) outcomes for workers' compensation patients are worse than for the general population. The objectives were to examine the long-term work capacity, opioid prescription and mental health outcomes of injured workers who have undergone LSF surgery in Victoria, Australia, and to identify demographic and pre- and post-operative characteristics associated with these outcomes. METHODS: Retrospective study of 874 injured workers receiving elective LSF from 2008 to 2016 in the Victorian workers' compensation system. WorkSafe Victoria's claims data were used to infer outcomes for recovery. Association of demographics, pre-surgery and surgery variables with outcomes were modelled using multivariate multinomial logistic regression analyses. RESULTS: Twenty-four months after LSF surgery, 282 (32.3%) of the 874 injured workers had substantial work capacity, 388 (44.4%) were prescribed opioids, and 330 (37.8%) were receiving mental health treatment. Opioid prescription and limited work capacity before surgery were independent strong predictors of opioid prescription, reduced work capacity and mental health treatment 24 months after LSF. Pre-operative mental health treatment was associated with the use of mental health treatment at 24 months. Other predictors for poor outcomes included a greater than 12-month duration from injury to surgery, LSF re-operation and common law or impairment benefit lodgement before surgery. CONCLUSION: An association between pre-operative factors and post-operative outcomes after LSF in a Victorian workers' compensation population was identified, suggesting that pre-operative status may influence outcomes and should be considered in LSF decisions. The high opioid use indicates that opioid management before and after surgery needs urgent review.

Two-Step In Vitro Model to Evaluate the Cellular Immune Response to SARS-CoV-2.

The cellular immune response plays an important role in COVID-19, caused by SARS-CoV-2. This feature makes use of in vitro models' useful tools to evaluate vaccines and biopharmaceutical effects. Here, we developed a two-step model to evaluate the cellular immune response after SARS-CoV-2 infection-induced or spike protein stimulation in peripheral blood mononuclear cells (PBMC) from both unexposed and COVID-19 (primo-infected) individuals (Step1). Moreover, the supernatants of these cultures were used to evaluate its effects on lung cell lines (A549) (Step2). When PBMC from the unexposed were infected by SARS-CoV-2, cytotoxic natural killer and nonclassical monocytes expressing inflammatory cytokines genes were raised. The supernatant of these cells can induce apoptosis of A549 cells (mock vs. Step2 [mean]: 6.4% × 17.7%). Meanwhile, PBMCs from primo-infected presented their memory CD4+ T cells activated with a high production of IFNG and antiviral genes. Supernatant from past COVID-19 subjects contributed to reduce apoptosis (mock vs. Step2 [ratio]: 7.2 × 1.4) and to elevate the antiviral activity (iNOS) of A549 cells (mock vs. Step2 [mean]: 31.5% × 55.7%). Our findings showed features of immune primary cells and lung cell lines response after SARS-CoV-2 or spike protein stimulation that can be used as an in vitro model to study the immunity effects after SARS-CoV-2 antigen exposure.

Health promotion competencies for promoting child-oral health: Victorian multidisciplinary workforce perspectives.

ISSUE ADDRESSED: Population oral health (OH) improvements depend on successful, coordinated execution of oral health promotion (OHP) programs by both oral and general health professionals with key competencies (skills, abilities, knowledge and values). This study explored multidisciplinary professionals' perspectives of the competencies required for the successful implementation of a community-based OHP program called Smiles 4 Miles (S4M) in early childhood settings in Victoria, Australia. METHODS: Convenience sampling was used to recruit multidisciplinary professionals working in the S4M early childhood health promotion program in Victoria. Semi-structured focus groups were conducted with program managers/coordinators (n = 26) from 21 S4M sites and the state-wide program coordination team (n = 5). Focus groups explored OHP competency needs, capacity to promote child OH and strategies for enhancing OHP competencies. The competencies identified through focus groups were then compared to the International Union for Health Promotion and Education (IUHPE) competencies framework. RESULTS: Strategies to enhance individual and organisational OHP competencies included intersectoral collaborations; working in multidisciplinary teams; support networks and partnerships; sharing skills and expertise between health professionals. The OHP competencies identified by the participants were consistent with key IUHPE domains including ethical values and health promotion knowledge base underpinning, enabling change, advocacy for health, mediating through partnerships, communication, leadership, assessment, planning, implementation, evaluation and research. CONCLUSION: A multidisciplinary workforce based in community settings can play key and complementary roles in OHP and widen avenues for oral disease prevention. SO WHAT?: Integrated collaborative workforce models involving multidisciplinary professionals beyond the OH sector can more effectively support efforts to address the burden of oral disease.

Family-centred oral health promotion through Victorian child-health services: a pilot.

Maternal and Child Health Services (MCHS) provide ideal settings for oral disease prevention. In Victoria (Australia), child mouth-checks (Lift-the-Lip) and oral health promotion (OHP) occur during MCHS child visits. This study trialled Tooth-Packs (OHP resources, toothbrushes, toothpastes) distribution within MCHS to (i) assess the impacts of Tooth-Packs distribution on child and family oral health (OH) behaviours and knowledge, including Maternal and Child Health Nurses (MCHN) child referral practices to dental services, and (ii) determine the feasibility and acceptability of incorporating Tooth-Packs distribution into MCHN OHP practices. A mixed-methods evaluation design was employed. MCHN from four high-needs Victorian Local Government Areas distributed Tooth-Packs to families of children attending 18-month and/or 24-month MCHS visits (baseline). Families completed a questionnaire on OH and dietary practices at baseline and 30-month follow-up. Tooth-Packs distribution, Lift-the-lip mouth-checks and child OH referrals were conducted. Guided discussions with MCHN examined intervention feasibility. Overall, 1585 families received Tooth-Packs. Lift-the-lip was conducted on 1493 children (94.1%). Early childhood caries were identified in 142 children (9.5%) and these children were referred to dental services. Baseline to follow-up behavioural improvements (n = 230) included: increased odds of children having ever seen an OH professional (OR 28.0; 95% CI 7.40-236.88; p < 0.001), parent assisted toothbrushing twice/day (OR 1.76; 95% CI 1.05-3.00; p = 0.030) and toothpaste use >once/day (OR 2.82; 95% CI 1.59-5.24; p < 0.001). MCHN recommendations included distribution of Tooth-Packs to at-risk children <12-months of age. MCHS provide an ideal setting to enable timely family-centred OHP intervention and adoption of good OH behaviours at an early age.

Addressing disparities in oral disease in Aboriginal people in Victoria: where to focus preventive programs.

The aim of this study is to determine where Aboriginal people living in Victoria attend public oral health services; whether they access Aboriginal-specific or mainstream services; and the gap between dental caries (tooth decay) experience in Aboriginal and non-Aboriginal people. Analysis was undertaken on routinely collected clinical data for Aboriginal patients attending Victorian public oral health services and the distribution of Aboriginal population across Victoria. Approximately 27% of Aboriginal people attended public oral health services in Victoria across a 2-year period, with approximately one in five of those accessing care at Aboriginal-specific clinics. In regional Victoria, 6-year-old Aboriginal children had significantly higher levels of dental caries than 6-year-old non-Aboriginal children. There was no significant difference in other age groups. This study is the first to report where Aboriginal people access public oral health care in Victoria and the disparity in disease between Aboriginal and non-Aboriginal users of the Victorian public oral healthcare system. Aboriginal people largely accessed mainstream public oral healthcare clinics highlighting the importance for culturally appropriate services and prevention programs to be provided across the entire public oral healthcare system. The findings will guide development of policy and models of care aimed at improving the oral health of Aboriginal people living in Victoria.

Caries and periodontal disease in Indigenous adults in Australia: a case of limited and non-contemporary data.

Objective The aim of the present study was to identify all evidence about the prevalence and severity of clinically measured caries and periodontal disease in Indigenous adults in Australia published in peer-reviewed journals and to summarise trends over time. In addition, we examined whether the studies investigated associations between putative risk factors and levels of caries and periodontal disease. Methods PubMed was searched in September 2014, with no date limitations, for published peer-reviewed articles reporting the prevalence rates and/or severity of caries and periodontal disease in Indigenous adults living in Australia. Articles were excluded if measurement was not based on clinical assessment and if oral disease was reported only in a specific or targeted sample, and not the general population. Results The search identified 18 papers (reporting on 10 primary studies) that met the inclusion criteria. The studies published clinical data about dental caries and/or periodontal disease in Australian Indigenous adults. The studies reported on oral health for Indigenous adults living in rural (40%), urban (10%) and both urban and rural (50%) locations. Included studies showed that virtually all Indigenous adults living in rural locations had periodontal disease. The data also showed caries prevalence ranged from 46% to 93%. Although 10 studies were identified, the peer-reviewed literature was extremely limited and no published studies were identified that provided statistics for a significant proportion of Australia (Victoria, Tasmania, Queensland or the Australian Capital Territory). There were also inconsistencies in how the data were reported between studies, making comparisons difficult. Conclusions This review highlights a lack of robust and contemporary data to inform the development of policies and programs to address the disparities in oral health in Indigenous populations living in many parts of Australia. What is known about the topic? Many studies report that Indigenous people in Australia have poorer general health compared with non-Indigenous people. What does this paper add? This paper documents the available caries and periodontal disease prevalence and experience for Indigenous adults in Australia published in peer-reviewed journals. It demonstrates significant limitations in the data, including no data in several large Australian jurisdictions, inconsistency with reporting methods and most data available being for Indigenous adults living in rural locations. Therefore, the oral health data available in the peer-reviewed literature do not reflect the situation of all Indigenous people living in Australia. What are the implications for practitioners? It is important for oral health practitioners to have access to current and relevant statistics on the oral health of Indigenous Australians. However, we have highlighted significant evidence gaps for this population group within the peer-reviewed literature and identified the limitations of the available data upon which decisions are currently being made. This paper also identifies ways to capture and report oral health data in the future to enable more meaningful comparisons and relevance for use in policy development.

WITHDRAWN: Community-based population-level interventions for promoting child oral health.

BACKGROUND: Dental caries and gingival and periodontal disease are commonly occurring, preventable chronic conditions. Even though much is known about how to treat oral disease, currently we do not know which community-based population-level interventions are most effective and equitable in preventing poor oral health. OBJECTIVES: Primary • To determine the effectiveness of community-based population-level oral health promotion interventions in preventing dental caries and gingival and periodontal disease among children from birth to 18 years of age. Secondary • To determine the most effective types of interventions (environmental, social, community and multi-component) and guiding theoretical frameworks.• To identify interventions that reduce inequality in oral health outcomes.• To examine the influence of context in the design, delivery and outcomes of interventions. SEARCH METHODS: We searched the following databases from January 1996 to April 2014: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Education Resource Information Center (ERIC), BIOSIS Previews, Web of Science, the Database of Abstracts of Reviews of Effects (DARE), ScienceDirect, Sociological Abstracts, Social Science Citation Index, PsycINFO, SCOPUS, ProQuest Dissertations & Theses and Conference Proceedings Citation Index - Science. SELECTION CRITERIA: Included studies were individual- and cluster-randomised controlled trials (RCTs), controlled before-and-after studies and quasi-experimental and interrupted time series. To be included, interventions had to target the primary outcomes: dental caries (measured as decayed, missing and filled deciduous teeth/surfaces, dmft/s; Decayed, Missing and Filled permanent teeth/surfaces, DMFT/S) and gingival or periodontal disease among children from birth to 18 years of age. Studies had to report on one or more of the primary outcomes at baseline and post intervention, or had to provide change scores for both intervention and control groups. Interventions were excluded if they were solely of a chemical nature (e.g. chlorhexidine, fluoride varnish), were delivered primarily in a dental clinical setting or comprised solely fluoridation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed screening, data extraction and assessment of risk of bias of included studies (a team of six review authors - four review authors and two research assistants - assessed all studies). We calculated mean differences with 95% confidence intervals for continuous data. When data permitted, we undertook meta-analysis of primary outcome measures using a fixed-effect model to summarise results across studies. We used the I2 statistic as a measure of statistical heterogeneity. MAIN RESULTS: This review includes findings from 38 studies (total n = 119,789 children, including one national study of 99,071 children, which contributed 80% of total participants) on community-based oral health promotion interventions delivered in a variety of settings and incorporating a range of health promotion strategies (e.g. policy, educational activities, professional oral health care, supervised toothbrushing programmes, motivational interviewing). We categorised interventions as dietary interventions (n = 3), oral health education (OHE) alone (n = 17), OHE in combination with supervised toothbrushing with fluoridated toothpaste (n = 8) and OHE in combination with a variety of other interventions (including professional preventive oral health care, n = 10). Interventions generally were implemented for less than one year (n = 26), and only 11 studies were RCTs. We graded the evidence as having moderate to very low quality.We conducted meta-analyses examining impact on dental caries of each intervention type, although not all studies provided sufficient data to allow pooling of effects across similar interventions. Meta-analyses of the effects of OHE alone on caries may show little or no effect on DMFT (two studies, mean difference (MD) 0.12, 95% confidence interval (CI) -0.11 to 0.36, low-quality evidence), dmft (three studies, MD -0.3, 95% CI -1.11 to 0.52, low-quality evidence) and DMFS (one study, MD -0.01, 95% CI -0.24 to 0.22, very low-quality evidence). Analysis of studies testing OHE in combination with supervised toothbrushing with fluoridated toothpaste may show a beneficial effect on dmfs (three studies, MD -1.59, 95% CI -2.67 to -0.52, low-quality evidence) and dmft (two studies, MD -0.97, 95% CI -1.06 to -0.89, low-quality evidence) but may show little effect on DMFS (two studies, MD -0.02, 95% CI -0.13 to 0.10, low-quality evidence) and DMFT (three studies, MD -0.02, 95% CI -0.11 to 0.07, moderate-quality evidence). Meta-analyses of two studies of OHE in an educational setting combined with professional preventive oral care in a dental clinic setting probably show a very small effect on DMFT (-0.09 weighted mean difference (WMD), 95% CI -0.1 to -0.08, moderate-quality evidence). Data were inadequate for meta-analyses on gingival health, although positive impact was reported. AUTHORS' CONCLUSIONS: This review provides evidence of low certainty suggesting that community-based oral health promotion interventions that combine oral health education with supervised toothbrushing or professional preventive oral care can reduce dental caries in children. Other interventions, such as those that aim to promote access to fluoride, improve children's diets or provide oral health education alone, show only limited impact. We found no clear indication of when is the most effective time to intervene during childhood. Cost-effectiveness, long-term sustainability and equity of impacts and adverse outcomes were not widely reported by study authors, limiting our ability to make inferences on these aspects. More rigorous measurement and reporting of study results would improve the quality of the evidence.

Community-based population-level interventions for promoting child oral health.

BACKGROUND: Dental caries and gingival and periodontal disease are commonly occurring, preventable chronic conditions. Even though much is known about how to treat oral disease, currently we do not know which community-based population-level interventions are most effective and equitable in preventing poor oral health. OBJECTIVES: Primary • To determine the effectiveness of community-based population-level oral health promotion interventions in preventing dental caries and gingival and periodontal disease among children from birth to 18 years of age. Secondary • To determine the most effective types of interventions (environmental, social, community and multi-component) and guiding theoretical frameworks.• To identify interventions that reduce inequality in oral health outcomes.• To examine the influence of context in the design, delivery and outcomes of interventions. SEARCH METHODS: We searched the following databases from January 1996 to April 2014: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Education Resource Information Center (ERIC), BIOSIS Previews, Web of Science, the Database of Abstracts of Reviews of Effects (DARE), ScienceDirect, Sociological Abstracts, Social Science Citation Index, PsycINFO, SCOPUS, ProQuest Dissertations & Theses and Conference Proceedings Citation Index - Science. SELECTION CRITERIA: Included studies were individual- and cluster-randomised controlled trials (RCTs), controlled before-and-after studies and quasi-experimental and interrupted time series. To be included, interventions had to target the primary outcomes: dental caries (measured as decayed, missing and filled deciduous teeth/surfaces, dmft/s; Decayed, Missing and Filled permanent teeth/surfaces, DMFT/S) and gingival or periodontal disease among children from birth to 18 years of age. Studies had to report on one or more of the primary outcomes at baseline and post intervention, or had to provide change scores for both intervention and control groups. Interventions were excluded if they were solely of a chemical nature (e.g. chlorhexidine, fluoride varnish), were delivered primarily in a dental clinical setting or comprised solely fluoridation. DATA COLLECTION AND ANALYSIS: Two review authors independently performed screening, data extraction and assessment of risk of bias of included studies (a team of six review authors - four review authors and two research assistants - assessed all studies). We calculated mean differences with 95% confidence intervals for continuous data. When data permitted, we undertook meta-analysis of primary outcome measures using a fixed-effect model to summarise results across studies. We used the I2 statistic as a measure of statistical heterogeneity. MAIN RESULTS: This review includes findings from 38 studies (total n = 119,789 children, including one national study of 99,071 children, which contributed 80% of total participants) on community-based oral health promotion interventions delivered in a variety of settings and incorporating a range of health promotion strategies (e.g. policy, educational activities, professional oral health care, supervised toothbrushing programmes, motivational interviewing). We categorised interventions as dietary interventions (n = 3), oral health education (OHE) alone (n = 17), OHE in combination with supervised toothbrushing with fluoridated toothpaste (n = 8) and OHE in combination with a variety of other interventions (including professional preventive oral health care, n = 10). Interventions generally were implemented for less than one year (n = 26), and only 11 studies were RCTs. We graded the evidence as having moderate to very low quality.We conducted meta-analyses examining impact on dental caries of each intervention type, although not all studies provided sufficient data to allow pooling of effects across similar interventions. Meta-analyses of the effects of OHE alone on caries may show little or no effect on DMFT (two studies, mean difference (MD) 0.12, 95% confidence interval (CI) -0.11 to 0.36, low-quality evidence), dmft (three studies, MD -0.3, 95% CI -1.11 to 0.52, low-quality evidence) and DMFS (one study, MD -0.01, 95% CI -0.24 to 0.22, very low-quality evidence). Analysis of studies testing OHE in combination with supervised toothbrushing with fluoridated toothpaste may show a beneficial effect on dmfs (three studies, MD -1.59, 95% CI -2.67 to -0.52, low-quality evidence) and dmft (two studies, MD -0.97, 95% CI -1.06 to -0.89, low-quality evidence) but may show little effect on DMFS (two studies, MD -0.02, 95% CI -0.13 to 0.10, low-quality evidence) and DMFT (three studies, MD -0.02, 95% CI -0.11 to 0.07, moderate-quality evidence). Meta-analyses of two studies of OHE in an educational setting combined with professional preventive oral care in a dental clinic setting probably show a very small effect on DMFT (-0.09 weighted mean difference (WMD), 95% CI -0.1 to -0.08, moderate-quality evidence). Data were inadequate for meta-analyses on gingival health, although positive impact was reported. AUTHORS' CONCLUSIONS: This review provides evidence of low certainty suggesting that community-based oral health promotion interventions that combine oral health education with supervised toothbrushing or professional preventive oral care can reduce dental caries in children. Other interventions, such as those that aim to promote access to fluoride, improve children's diets or provide oral health education alone, show only limited impact. We found no clear indication of when is the most effective time to intervene during childhood. Cost-effectiveness, long-term sustainability and equity of impacts and adverse outcomes were not widely reported by study authors, limiting our ability to make inferences on these aspects. More rigorous measurement and reporting of study results would improve the quality of the evidence.

Examining the relationship between childhood health conditions and health service utilisation at school entry and subsequent academic performance in a large cohort of Australian children.

AIM: Chronic health conditions are associated with poor academic outcomes. This study examines the relationship between health conditions, specialist health service utilisation and academic performance in Australian children. METHODS: This was a quasi-longitudinal study where School Entrant Health Questionnaire (a survey tool with parent report on children's health) data for 24 678 children entering school in 2008 was matched with the 2011 National Assessment Program - Literacy and Numeracy (NAPLAN). Linear and logistic regressions were used to examine associations between health conditions, use of a specialist health service and reading and numeracy scores. RESULTS: The study comprised 24 678 children. Children with allergies, very low birth weight, developmental delay, diabetes, spina bifida, cystic fibrosis, birth abnormality, speech problems, intellectual disability and attention-deficit/hyperactivity disorder had lower numeracy scores than those without any of these conditions (P < 0.05). The same children had higher odds (1.2-5.8) of being at or below the national minimum standard for numeracy. Children with developmental delay, epilepsy, dental problems, speech, intellectual disabilities and low birth weight had lower reading scores than those without these conditions (P < 0.05) and had higher odds of being at (odds ratio: 1.3) or below (odds ratio: 3.7) the national minimum standard for reading. Children with health conditions who had ever accessed specialist health services did not differ in their academic performance from those that had not used specialist health services. CONCLUSIONS: Some health conditions put children at risk of poorer academic performance, and interventions to prevent this such as appropriate support services in schools should be considered.

Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson's disease.

Convincing evidence indicates that advanced glycation end-products and danger-associated protein S100B play a role in Parkinson's disease (PD). These agents operate through the receptor for advanced glycation end-products (RAGE), which displays distinct isoforms playing protective/deleterious effects. However, the nature of RAGE variants has been overlooked in PD studies. Hence, we attempted to characterize RAGE regulation in early stages of PD striatal pathology. A neurotoxin-based rodent model of PD was used in this study, through administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice. Animals were killed 6 h post-MPTP to assess S100B/RAGE contents (RT-qPCR, ELISA) and RAGE isoform density (WB) and cellular distribution (immunohistochemistry). Dopaminergic and gliotic status were also mapped (HPLC-ED, WB, immunohistochemistry). At this preliminary stage of MPTP-induced PD in mice, RAGE inhibitory isoforms were increased whereas full-length RAGE was not affected. This putative cytoprotective RAGE phenotype paired an inflammatory and pro-oxidant setting fueling DAergic denervation. Increased RAGE inhibitory variants occur in astrocytes showing higher S100B density but no overt signs of hypertrophy or NF-κB activation, a canonical effector of RAGE. These findings expand our understanding of the toxic effect of MPTP on striatum and offer first in vivo evidence of RAGE being a responder in early stages of astrogliosis dynamics, supporting a protective rather tissue-destructive phenotype of RAGE in the initial phase of PD degeneration. These data lay the groundwork for future studies on the relevance of astrocytic RAGE in DAergic neuroprotection strategies. We report increased antagonistic RAGE variants paralleling S100B up-regulation in early stages of MPTP-induced astrogliosis dynamics . We propose that selective RAGE regulation reflects a self-protective mechanism to maintain low levels of RAGE ligands , preventing long-term inflammation and oxidative stress arising from sustained ligands/flRAGE activation . Understanding loss of RAGE protective response to stress may provide new therapeutic options to halt or slow down dopaminergic axonopathy and, ultimately, neuronal death .

Developing a model to assess community-level risk of oral diseases for planning public dental services in Australia.

BACKGROUND: Poor oral health is a chronic condition that can be extremely costly to manage. In Australia, publicly funded dental services are provided to community members deemed to be eligible-those who are socio-economically disadvantaged or determined to be at higher risk of dental disease. Historically public dental services have nominally been allocated based on the size of the eligible population in a geographic area. This approach has been largely inadequate for reducing disparities in dental disease, primarily because the approach is treatment-focused, and oral health is influenced by a variety of interacting factors. This paper describes the developmental process of a multi-dimensional community-level risk assessment model, to profile a community's risk of poor oral health. METHODS: A search of the evidence base was conducted to identify robust frameworks for conceptualisation of risk factors and associated performance indicators. Government and other agency websites were also searched to identify publicly available data assets with items relevant to oral diseases. Data quality and analysis considerations were assessed for the use of mixed data sources. RESULTS: Several frameworks and associated indicator sets (twelve national and eight state-wide data collections with relevant indicators) were identified. Determination of the system inputs for the Model were primarily informed by the World Health Organisation's (WHO) operational model for an Integrated Oral Health-Chronic Disease Prevention System, and Australia's National Oral Health Plan 2004-2013. Data quality and access informed the final selection of indicators. CONCLUSIONS: Despite limitations in the quality and regularity of data collections, there are numerous data sources available that provide the required data inputs for community-level risk assessment for oral health. Assessing risk in this way will enhance our ability to deliver appropriate public oral health care services and address the uneven distribution of oral disease across the social gradient.

Presymptomatic MPTP Mice Show Neurotrophic S100B/mRAGE Striatal Levels.

AIMS: Astrocytic S100B and receptor for advanced glycation endproducts (RAGE) have been implicated in Parkinson׳s disease (PD) pathogenesis through yet unclear mechanisms. This study attempted to characterize S100B/mRAGE (signaling isoform) axis in a dying-back dopaminergic (DAergic) axonopathy setting, which mimics an early event of PD pathology. METHODS: C57BL/6 mice were submitted to a chronic MPTP paradigm (20 mg/kg i.p., 2 i.d-12 h apart, 5 days/week for 2 weeks) and euthanized 7 days posttreatment to assess mRAGE cellular distribution and S100B/mRAGE density in striatum, after probing their locomotor activity (pole test and rotarod). Dopaminergic status, oxidative stress, and gliosis were also measured (HPLC-ED, WB, IHC). RESULTS: This MPTP regimen triggered increased oxidative stress (augmented HNE levels), gliosis (GS/Iba1-reactive morphology), loss of DAergic fibers (decreased tyrosine hydroxylase levels), and severe hypodopaminergia. Biochemical deficits were not translated into motor abnormalities, mimicking a presymptomatic PD period. Remarkably, striatal neurotrophic S100B/mRAGE levels and major neuronal mRAGE localization coexist with compensatory responses (3-fold increase in DA turnover), which are important to maintain normal motor function. CONCLUSION: Our findings rule out the involvement of S100B/mRAGE axis in striatal reactive gliosis, DAergic axonopathy and warrant further exploration of its neurotrophic effects in a presymptomatic compensatory PD stage, which is a fundamental period for successful implementation of therapeutic strategies.

The evaluation of an oral health education program for midwives in Australia.

BACKGROUND: Antenatal care providers are now recommended to promote oral health during pregnancy and provide dental referrals. However, midwives in Australia are not trained to undertake this role. To address this shortcoming, an online evidence based midwifery initiated oral health (MIOH) education program was systematically developed as a professional development activity. AIM: This study aimed to evaluate the effectiveness of the program in improving the oral health knowledge of midwives and assess their confidence to promote maternal oral health post training. METHODS: The program was evaluated using a pre-post test design involving 50 midwives purposively recruited from two states in Australia. The pre-post questionnaire contained 24 knowledge items previously pilot tested as well as items exploring confidence in promoting oral health and perceptions of the program. FINDINGS: The results showed a significant improvement in the oral health knowledge (↑21.5%, p<0.001) of midwives after completion of the program. The greatest improvement in knowledge occurred in key areas vital in promoting maternal oral health namely the high prevalence of dental problems and its impact on birth and infant outcomes. The majority also reported being confident in introducing oral health into antenatal care (82%) and referring women to dental services (77.6%) after undertaking the education program. CONCLUSION: The MIOH education program is a useful resource to equip midwives with the necessary knowledge and skills to promote oral health during pregnancy. The program is accessible and acceptable to midwives and can potentially be transferable to other antenatal care providers.

Reviewing public policy for promoting population oral health in Victoria, Australia (2007-12).

OBJECTIVE: Government policy and planning set the direction for community decisions related to resource allocation, infrastructure, services, programs, workforce and social environments. The aim ofthe present study was to examine the policy and planning context for oral health promotion in Victoria, Australia, over the period 2007-12. METHODS: Key Victorian policies and plans related to oral health promotion in place during the 2007-12 planning cycle were identified through online searching, and content analysis was performed. Inclusion of oral health (and oral health-related) promotion initiatives was assessed within the goals, objectives and strategies sections of each plan. RESULTS: Six of the 223 public health plans analysed (3%) included oral health 'goals' (including one plan representing nine agencies). Oral health was an 'objective' in 10 documents. Fifty-six plan objectives, and 70 plan strategies related to oral health or healthy eating for young children. Oral health was included in municipal plans (44%) more frequently than the other plans examined. CONCLUSION: There is a policy opportunity to address oral health at a community level, and to implement population approaches aligned with the Ottawa Charter that address the social determinants of health.

Flying blind: trying to find solutions to Indigenous oral health.

Objective The aim of the present study was to identify all published evidence about oral health in Indigenous children in Australia and to determine trends in Indigenous oral health over time. Methods PubMed was used to search for published peer-reviewed articles that reported caries (decay) prevalence rates and/or caries experience (based on caries indices) in Indigenous children. Studies included in the analysis needed to report clinical oral health data (not self-reported dental experiences), and articles were excluded if they reported caries in only a select, specific or targeted sample (e.g. only children undergoing hospital admissions for dental conditions). Results The review identified 32 studies that met the inclusion criteria. These studies reported data from the Northern Territory (n=14), Western Australia (n=7), South Australia (n=7), Queensland (n=7), New South Wales (n=1), Australian Capital Territory (n=1) and Tasmania (n=1). Of the studies, 47% were in rural locations, 9% were in urban locations and 44% were in both rural and urban locations. Data are limited and predominantly for Indigenous children living in rural locations, and there are no published studies on caries in Indigenous children living in Victoria. Conclusions The present study documents the published prevalence and severity of caries in Indigenous children living in Australia and highlights that limited oral health data are available for this priority population. Although risk factors for oral disease are well known, most of the studies did not analyse the link between these factors and oral disease present. There is also inconsistency in how caries is reported in terms of age and caries criteria used. We cannot rely on the available data to inform the development of policies and programs to address the oral health differences in Indigenous populations living contemporary lives in metropolitan areas. What is known about the topic? Many studies report that Indigenous people have poorer general health in Australia compared with non-Indigenous people. What does this paper add? This paper documents the available published prevalence and experience of caries for Indigenous children in Australia. It demonstrates significant limitations in the data, including no Victorian data, inconsistency with reporting methods and most data being for Indigenous children who are living in rural locations. What are the implications for practitioners? It is important for practitioners to have access to oral health data for Indigenous children in Australia. However, the present study highlights significant knowledge gaps for this population group and identifies ways to collect data in future studies to enable more meaningful comparisons and policy development.

Economic Models of Preventive Dentistry for Australian Children and Adolescents: A Systematic Review.

PURPOSE: To identify economic evaluation models and parameters that could be replicated or adapted to construct a generic model to assess cost-effectiveness of and prioritise a wide range of community-based oral disease prevention programmes in an Australian context. METHODS: The literature search was conducted using MEDLINE, ERIC, PsycINFO, CINHAL (EBSCOhost), EMBASE (Ovid), CRD, DARE, NHSEED, HTA, all databases in the Cochrane library, Scopus and ScienceDirect databases from their inception to November 2012. RESULTS: Thirty-three articles met the criteria for inclusion in this review (7 were Australian studies, 26 articles were international). Existing models focused primarily on dental caries. Periodontal disease, another common oral health problem, was lacking. Among caries prevention studies, there was an absence of clear evidence showing continuous benefits from primary through to permanent dentition and the long-term effects of oral health promotion. CONCLUSION: No generic model was identified from previous studies that could be immediately adopted or adapted for our purposes of simulating and prioritising a diverse range of oral health interventions for Australian children and adolescents. Nevertheless, data sources specified in the existing Australian-based models will be useful for developing a generic model for such purposes.

Critical design features for establishing a childhood obesity monitoring program in Australia.

Efforts to combat childhood obesity in Australia are hampered by the lack of quality epidemiological data to routinely monitor the prevalence and distribution of the condition. This paper summarises the literature on issues relevant to childhood obesity monitoring and makes recommendations for implementing a school-based childhood obesity monitoring program in Australia. The primary purpose of such a program would be to collect population-level health data to inform both policy and the development and evaluation of community-based obesity prevention interventions. Recommendations are made for the types of data to be collected, data collection procedures and program management and evaluation. Data from an obesity monitoring program are crucial for directing and informing policies, practices and services, identifying subgroups at greatest risk of obesity and evaluating progress towards meeting obesity-related targets. Such data would also increase the community awareness necessary to foster change.