Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

They were Saying that I was a ‘typical Chinese mum’: Chinese Parents’ Experiences of Parent-Teacher Partnerships for Their Autistic Children

Effective parent-teacher partnerships improve outcomes for autistic students. Yet, we know little about what effective partnerships look like for parents of autistic children from different backgrounds. We conducted interviews with 17 Chinese parents of autistic children attending Australian kindergartens/schools to understand their experiences. Parents appreciated the acceptance, opportunities and supports they received in Australia. They had high expectations of children; expectations not often shared by educators. Parents were respectful of teachers’ expertise and polite and undemanding in interactions. Nevertheless, parents were frustrated by inconsistent teaching quality and inadequate communication. Navigating systems was also challenging and parents faced discrimination from teachers and their community. Recommendations include fostering open home-school communication, proactively seeking parents’ expertise about children and explicitly scaffolding parents’ self-advocacy

NCF1 gene and pseudogene pattern: association with parasitic infection and autoimmunity

<p>Abstract</p> <p>Background</p> <p>Neutrophil cytosolic factor 1, p47^phox(NCF1) is a component of the leukocyte NADPH oxidase complex mediating formation of reactive oxygen intermediates (ROI) which play an important role in host defense and autoimmunity. An individual genomic pattern of <it>ncf1 </it>and its two types of pseudogenes (reflected by the ΔGT/GTGT ratio) may influence the individual capacity to produce ROI.</p> <p>Methods</p> <p>NCF1ΔGT/GTGT ratios were correlated with clinical parameters and ROI production during <it>Plasmodium falciparum </it>malaria and with susceptibility to the autoimmune disease multiple sclerosis (MS).</p> <p>Results</p> <p>Among Gabonese children with severe malaria, ROI production from peripheral blood tended to be higher in individuals with a ΔGT/GTGT ratio ≤ 1:1. ΔGT/GTGT ratios were not associated with susceptibility to MS, but to age-of-onset among MS patients.</p> <p>Conclusion</p> <p>The genomic pattern of <it>NCF1 </it>and its pseudogenes might influence ROI production but only marginally influence susceptibility to and outcome of malaria and MS.</p

Smoking and health-related quality of life in English general population: Implications for economic evaluations

Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

Characterising the impact of heatwaves on work-related injuries and illnesses in three Australian cities using a standard heatwave definition- Excess Heat Factor (EHF)

BACKGROUND AND AIMS:Heatwaves have potential health and safety implications for many workers, and heatwaves are predicted to increase in frequency and intensity with climate change. There is currently a lack of comparative evidence for the effects of heatwaves on workers' health and safety in different climates (sub-tropical and temperate). This study examined the relationship between heatwave severity (as defined by the Excess Heat Factor) and workers' compensation claims, to define impacts and identify workers at higher risk. METHODS:Workers' compensation claims data from Australian cities with temperate (Melbourne and Perth) and subtropical (Brisbane) climates for the years 2006-2016 were analysed in relation to heatwave severity categories (low and moderate/high severity) using time-stratified case-crossover models. RESULTS:Consistent impacts of heatwaves were observed in each city with either a protective or null effect during heatwaves of low-intensity while claims increased during moderate/high-severity heatwaves compared with non-heatwave days. The highest effect during moderate/high-severity heatwaves was in Brisbane (RR 1.45, 95% CI: 1.42-1.48). Vulnerable worker subgroups identified across the three cities included: males, workers aged under 34 years, apprentice/trainee workers, labour hire workers, those employed in medium and heavy strength occupations, and workers from outdoor and indoor industrial sectors. CONCLUSION:These findings show that work-related injuries and illnesses increase during moderate/high-severity heatwaves in both sub-tropical and temperate climates. Heatwave forecasts should signal the need for heightened heat awareness and preventive measures to minimise the risks to workers.Blesson M. Varghese, Adrian G. Barnett, Alana L. Hansen, Peng Bi, John Nairn, Shelley Rowett, Monika Nitschke, Scott Hanson-Easey, Jane S. Heyworth, Malcolm R. Sim, Dino L. Pisaniell

Maximum running intensities during English academy rugby union match-play

Purpose: To quantify and compare the maximum running intensities during rugby union match-play. Methods: Running intensity was quantified using micro-technology devices (S5 Optimeye, Catapult) from 202 players during 24 matches (472 observations). Instantaneous speed was used to calculate relative distance (m·min-1) using a 0.1 s rolling mean for different time durations (15 and 30 s and 1, 2, 2.5, 3, 4, 5, and 10 min). Data were analysed using a linear mixed-model and assessed with magnitude-based inferences and Cohen’s d effect sizes (ES). Results: Running intensity for consecutive durations (e.g., 15 s vs. 30 s, 30 s vs. 1 min, etc.) decreased as time increased (ES = 0.48-2.80). Running intensity was lower in forwards than backs during all durations (-0.74 ±0.21 to -1.19 ±0.21). Running intensity for the second row and back row positions was greater than the front row players at all durations (-0.58 ±0.38 to -1.18 ±0.29). Running intensity for scrum-halves was greater (0.46 ±0.43 to 0.86 ±0.39) than inside and outside backs for all durations besides 15 and 30 s. Conclusions: Front rowers and scrum-halves were markedly different from other sub-positional groups and should be conditioned appropriately. Coaches working in academy rugby can use this information to appropriately overload the intensity of running, specific to time durations and positions

The bone marrow compartment is modified in the absence of galectin-3

Galectin-3 (gal-3) is a β-galactoside binding protein present in multivalent complexes with an extracellular matrix and with cell surface glycoconjugates. In this context, it can deliver a variety of intracellular signals to modulate cell activation, differentiation and survival. In the hematopoietic system, it was demonstrated that gal-3 is expressed in myeloid cells and surrounding stromal cells. Furthermore, exogenous and surface gal-3 drive the proliferation of myeloblasts in a granulocyte–macrophage colony-stimulating factor (GM-CSF)-dependent manner. Here, we investigated whether gal-3 regulates the formation of myeloid bone marrow compartments by studying galectin-3−/− mice (gal-3−/−) in the C57BL/6 background. The bone marrow histology of gal-3−/− mice was significantly modified and the myeloid compartments drastically disturbed, in comparison with wild-type (WT) animals. In the absence of gal-3, we found reduced cell density and diaphyseal disorders containing increased trabecular projections into the marrow cavity. Moreover, myeloid cells presented limited capacity to differentiate into mature myeloid cell populations in gal-3−/− mice and the number of hematopoietic multipotent progenitors was increased relative to WT animals. In addition, bone marrow stromal cells of these mice had reduced levels of GM-CSF gene expression. Taken together, our data suggest that gal-3 interferes with hematopoiesis, controlling both precursors and stromal cells and favors terminal differentiation of myeloid progenitors rather than proliferation

Genetic polymorphisms and susceptibility to lung disease

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease