There is an increasing body of evidence that synovitis plays a role in the progression of osteoarthritis and that overproduction of cytokines and growth factors from the inflamed synovium can ...influence the production of degradative enzymes and the destruction of cartilage. In this study, we investigate the role of synovial macrophages and their main proinflammatory cytokines, interleukin (IL)-1 and tumour necrosis factor-alpha (TNF-alpha), in driving osteoarthritis synovitis and influencing the production of other pro- and anti-inflammatory cytokines, production of matrix metalloproteinases, and expression of aggrecanases in the osteoarthritis synovium. We established a model of cultures of synovial cells from digested osteoarthritis synovium derived from patients undergoing knee or hip arthroplasties. By means of anti-CD14-conjugated magnetic beads, specific depletion of osteoarthritis synovial macrophages from these cultures could be achieved. The CD14+-depleted cultures no longer produced significant amounts of macrophage-derived cytokines like IL-1 and TNF-alpha. Interestingly, there was also significant downregulation of several cytokines, such as IL-6 and IL-8 (p < 0.001) and matrix metalloproteinases 1 and 3 (p < 0.01), produced chiefly by synovial fibroblasts. To investigate the mechanisms involved, we went on to use specific downregulation of IL-1 and/or TNF-alpha in these osteoarthritis cultures of synovial cells. The results indicated that neutralisation of both IL-1 and TNF-alpha was needed to achieve a degree of cytokine (IL-6, IL-8, and monocyte chemoattractant protein-1) and matrix metalloproteinase (1, 3, 9, and 13) inhibition, as assessed by enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction (RT-PCR), similar to that observed in CD14+-depleted cultures. Another interesting observation was that in these osteoarthritis cultures of synovial cells, IL-1beta production was independent of TNF-alpha, in contrast to the situation in rheumatoid arthritis. Using RT-PCR, we also demonstrated that whereas the ADAMTS4 (a disintegrin and metalloprotease with thrombospondin motifs 4) aggrecanase was driven mainly by TNF-alpha, ADAMTS5 was not affected by neutralisation of IL-1 and/or TNF-alpha. These results suggest that, in the osteoarthritis synovium, both inflammatory and destructive responses are dependent largely on macrophages and that these effects are cytokine-driven through a combination of IL-1 and TNF-alpha.
Health claims and front-of-pack labels (FoPLs) may lead consumers to hold more positive attitudes and show a greater willingness to buy food products, regardless of their actual healthiness. A ...potential negative consequence of this positivity bias is the increased consumption of unhealthy foods. This study investigated whether a positivity bias would occur in unhealthy variations of four products (cookies, corn flakes, pizzas and yoghurts) that featured different health claim conditions (no claim, nutrient claim, general level health claim, and higher level health claim) and FoPL conditions (no FoPL, the Daily Intake Guide (DIG), Multiple Traffic Lights (MTL), and the Health Star Rating (HSR)). Positivity bias was assessed via measures of perceived healthiness, global evaluations (incorporating taste, quality, convenience, etc.) and willingness to buy. On the whole, health claims did not produce a positivity bias, while FoPLs did, with the DIG being the most likely to elicit this bias. The HSR most frequently led to lower ratings of unhealthy foods than the DIG and MTL, suggesting that this FoPL has the lowest risk of creating an inaccurate positivity bias in unhealthy foods.
Policies restricting children's exposure to unhealthy food marketing have been impeded by the lack of evidence showing a direct link between food advertising exposure and children's energy intake and ...body weight. Food advertising exposure increases children's immediate food consumption, but whether this increased intake is compensated for at later eating occasions is not known; consequently the sustained effect on diets remains unclear.
We conducted a within-subject, randomised, crossover, counterbalanced study across four, six-day holiday camps in New South Wales, Australia between April 2016 and January 2017. Children (7-12 years, n = 160) were recruited via local schools, email networks and social media. Two gender- and age-balanced groups were formed for each camp (n = 20), randomised to either a multiple- or single- media condition and exposed to food and non-food advertising in an online game and/or a television cartoon. Children's food consumption (kilojoules) was measured at a snack immediately after exposure and then at lunch later in the day. Linear mixed models were conducted to examine relationships between food advertising exposure and dietary intake, taking into account gender, age and weight status.
All children in the multiple-media condition ate more at a snack after exposure to food advertising compared with non-food advertising; this was not compensated for at lunch, leading to additional daily food intake of 194 kJ (95% CI 80-308, p = 0.001, d = 0.2). Exposure to multiple-media food advertising compared with a single-media source increased the effect on snack intake by a difference of 182 kJ (95% CI 46-317, p = 0.009, d = 0.4). Food advertising had an increased effect among children with heavier weight status in both media groups.
Online ('advergame') advertising combined with TV advertising exerted a stronger influence on children's food consumption than TV advertising alone. The lack of compensation at lunch for children's increased snack intake after food advertising exposure suggests that unhealthy food advertising exposure contributes to a positive energy-gap, which could cumulatively lead to the development of overweight.
Australian New Zealand Clinical Trials Registry, number ACTRN12617001230347 (Retrospectively registered).
Chondroitin sulphate (CS) proteoglycans with variable sulphation-motifs along their glycosaminoglycan (GAG) chains are closely associated with the stem cell niche of articular cartilage, where they ...are believed to influence the characteristics of the resident stem cells. Here, we investigated the immunohistochemical distribution of hybrid CS/dermatan sulphate (DS) GAGs in the periphery of the adult chicken cornea, which is the location of the cornea's stem cell niche in a number of species, using a monoclonal antibody, 6C3, that recognises a sulphation motif-specific CS/DS GAG epitope. This revealed positive labelling that was restricted to the subepithelial corneal stroma, as well as nearby bony structures within the sclera, called ossicles. When cultivated on cell culture dishes coated with 6C3-rich CS/DS, corneal stromal cells (keratocytes) that had been isolated from embryonic chicken corneas formed circular colonies, which took several days to reach confluency. A flow cytometric analysis of these keratocytes revealed changes in their expression levels of the indicative stem cell markers, Connexin 43 (Cx43), Paired Box 6 (
), B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1), and C-X-C Chemokine Receptor 4 (CXCR4) suggestive of a less-differentiated phenotype compared with expression levels in cells not exposed to CS/DS. These findings support the view that CS/DS promotes the retention of a stem cell phenotype in corneal cells, much as it has been proposed to do in other connective tissues.
The circadian clock, a collection of endogenous cellular oscillators with an approximate 24‐h cycle, involves autoregulatory transcriptional/translational feedback loops to enable synchronization ...within the body. Circadian rhythmicity is controlled by a master clock situated in the hypothalamus; however, peripheral tissues are also under the control of autonomous clocks which are coordinated by the master clock to regulate physiological processes. Although light is the primary signal required to entrain the body to the external day, non‐photic zeitgeber including exercise also entrains circadian rhythmicity. Cellular mechano‐sensing is imperative for functionality of physiological systems including musculoskeletal tissues. Over the last decade, mechano‐regulation of circadian rhythmicity in skeletal muscle, intervertebral disc, and bone has been demonstrated to impact tissue homeostasis. In contrast, few publications exist characterizing the influence of mechanical loading on the circadian rhythm in articular cartilage, a musculoskeletal tissue in which loading is imperative for function; importantly, a dysregulated cartilage clock contributes to development of osteoarthritis. Hence, this review summarizes the literature on mechano‐regulation of circadian clocks in musculoskeletal tissues and infers on their collective importance in understanding the circadian clock and its synchronicity for articular cartilage mechanobiology.
To investigate the New South Wales (NSW) community's support for obesity prevention policies and concern for food marketing and promotion issues, and to determine any demographic differences or ...changes over time.
In 2013 (n=2474), 2016 (n=1602) and 2019 (n=1613) a sample of adults who were representative of the NSW population for age, gender, education and location was asked about support for policy initiatives that influence the food environment. Analysis identified the characteristics of those who supported policies and variation in support over time.
There were limited changes in support over time; however, support for many policies was strong and sustained. In 2019, support was highest for regulation of claims about nutrition (77.2%), and health warning labels (75.7%). Support for a ban on unhealthy food advertising that targets children (64.6%) had decreased since 2013. Women, older people and those who were aware that obesity was a risk factor for cancer were generally more likely to support policies. Parents were more likely than non‐parents to be concerned about positioning unhealthy food at supermarket checkouts (OR 1.32) and unhealthy outdoor advertisements (OR 1.22). Concern increased in 2019 for unhealthy marketing on the internet (OR 1.21).
This study shows public support for policy options at moderate to high levels but not increasing in the six‐year study period.
These results form part of a package that, along with the well‐established evidence, makes the case for policy action in Australia.
To analyse the case reports of complaints regarding food marketing to children over six years and compare Australian marketing Codes to best practice recommendations.
Case reports on complaints about ...food marketing to children under the five industry Codes – the Responsible Children's Marketing Initiative, the Quick Service Restaurant Initiative and the Australian Association of National Advertisers Code of Ethics, Code of Advertising and Marketing to Children and Food and Beverages Code – were qualitatively analysed. Reports on the Ad Standards website in the food/beverage groceries and food/beverage venues categories from 2015‐2020 were investigated. The most common clauses from the Codes were identified and quotes from reports used to illustrate the determinations. Codes were compared with World Cancer Research Fund recommendations on policy to protect children.
Only 14 of 119 complaints resulted in a reported breach of industry Codes. The most common reason for dismissing complaints involved clauses requiring advertisements to be ‘primarily’ directed to children. The Codes did not align with best practice recommendations.
Complaints by the public show concern for food advertising to children but the Australian industry Codes fall short of addressing those concerns.
Government regulation is required to protect children from unhealthy food marketing.
Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct ...collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury.
The diets of Australian children, including their lunch boxes have a disproportionate amount of discretionary foods. Packaged snacks have marketing directed to both children and parents.
Packaged ...school lunch box snacks were identified on supermarket websites. Nutrition information and child-directed and parent-directed marketing on the package were analysed. The "healthiness" of products was analysed using the Health Star Rating (HSR) (presently on packaging in Australia), two criteria designed for assessing food suitable for marketing to children (the Australian Health Council and the World Health Organization Western Pacific region) and Chilean criteria (used for broad food regulation).
The average HSR of the 135 products was 2.2% and 79% had a HSR <3.5. About 39% of products had child-directed marketing. Child-directed marketing would be removed from 89% sweet snacks, and 91% savoury snacks if products with a HSR <3.5 were not allowed to carry that marketing. This is less than the proportion not allowed using criteria from Chile (100%), World Health Organization Western Pacific Region (99%) and the Australian Health Council (93%).
A policy that disallows marketing tactics on unhealthy food based on any of the criteria studied would remove most of both child-directed and parent-directed marketing on packaged lunch box snacks. SO WHAT?: Removing child-directed marketing from unhealthy products would help parents when shopping and contribute to addressing the high proportion of discretionary foods eaten by children at school. Child-directed marketing on packaging should be a part of comprehensive regulation to protect children from the marketing of unhealthy foods.
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