Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies

Dioxin risk reduction programme at the most severe dioxin hot spot in Vietnam: Residual knowledge, attitude and practices five years post intervention

Bien Hoa Airbase was one of the bulk storage and supply facilities for defoliants during the Vietnam War. Environmental and biological samples taken around the airbase have elevated levels of dioxin. In 2007, a pre-intervention knowledge, attitude and practice (KAP) survey of local residents living in Trung Dung and Tan Phong wards was undertaken regarding appropriate strategies to reduce dioxin exposure. A risk reduction programme was implemented in 2008 and post-intervention KAP surveys were undertaken in 2009 and 2013 to evaluate the longer term impacts. Quantitative assessment was undertaken via a KAP survey in 2013 among 600 local residents randomly selected from the two intervention wards and one control ward (Buu Long). Eight in-depth interviews and two focus group discussions were also undertaken for qualitative assessment. Most programme activities had ceased and dioxin risk communication activities had not been integrated into local routine health education programmes; however, main results generally remained and were better than that in Buu Long. In total, 48.2% of households undertook measures to prevent exposure, higher than those in pre- and post-intervention surveys (25.8% and 39.7%) and the control ward (7.7%). Migration and the sensitive nature of dioxin issues were the main challenges for the programme's sustainability

Submission to the draft Migration Assurance Policy - Improving the transition to the fixed-line national broadband network review

The rights of individuals to self-determination and participation in social, political and economic life are recognised and supported by Articles 1, 3 and 25 of the International Covenant on Civil and Political Rights 1966.4 Article 1 of the United Nations’ Human Rights Council’s Resolution on the Promotion and Protection of Human Rights on the Internet of July 2012 confirms individuals have the same rights online as offline. Access to the internet is essential and as such the UN: Calls upon all States to promote and facilitate access to the Internet and international cooperation aimed at the development of media and information and communications facilities in all countries (Article 3) Accordingly, access to the internet per se is a fundamental human right, which requires direct State recognition and support.5 The obligations of the State to ensure its citizens are able, and are enabled, to access the internet, are not matters that should be delegated to commercial parties. Quite simply – access to the internet, and high-speed broadband, by whatever means are “essential services” and therefore “should be treated as any other utility service”...

The cross-talk of LDL-cholesterol with cell migration: Insights from the Niemann Pick Type C1 mutation

Cholesterol is considered indispensible for the recruitment and functioning of integrins in focal adhesions for cell migration. However, the physiological cholesterol pools that control integrin trafficking and focal adhesion assembly remain unclear. Using Niemann Pick Type C1 (NPC) mutant cells, which accumulate Low Density lipoprotein (LDL)-derived cholesterol in late endosomes (LE), several recent studies indicate that LDL-cholesterol has multiple roles in regulating focal adhesion dynamics. Firstly, targeting of endocytosed LDL-cholesterol from LE to focal adhesions controls their formation at the leading edge of migrating cells. Other newly emerging literature suggests that this may be coupled to vesicular transport of integrins, Src kinase and metalloproteases from the LE compartment to focal adhesions. Secondly, our recent work identified LDL-cholesterol as a key factor that determines the distribution and ability of several Soluble NSF Attachment Protein (SNAP) Receptor (SNARE) proteins, key players in vesicle transport, to control integrin trafficking to the cell surface and extracellular matrix (ECM) secretion. Collectively, dietary, genetic and pathological changes in cholesterol metabolism may link with efficiency and speed of integrin and ECM cell surface delivery in metastatic cancer cells. This commentary will summarize how direct and indirect pathways enable LDL-cholesterol to modulate cell motility.

Neighbourliness and Australia’s contribution to regional migration strategies for climate displacement in the Pacific

The prospect of widespread displacement in the Pacific as a result of climate change is becoming increasingly likely and it is possible that many will eventually need to relocate to other countries. Regional migration strategies not only offer the potential to minimise the harms of relocation, while acknowledging existing relationships of friendship and regional cooperation. This article examines the use of the language of ‘neighbourliness’ in Australia’s regional climate change strategies and argues that, while it expresses friendship, such language can also be employed to avoid the creation of stronger obligations. The article considers the international doctrine of good neighbourliness and concludes that, while international legal obligations may not yet exist, Australia should nonetheless begin planning for regional migration within the Pacific to allow people to migrate with dignity.

Family-based programmes for preventing smoking by children and adolescents: Evidence and implications for public health

- P -General population, nonsmoking children (aged 5 to 12) and adolescents (aged 13 to 18) with their parents - I -Interventions with children and family members intended to deter tobacco use. Any components to change parenting behaviour, parental or sibling smoking behaviour, or family communication and interaction. - C -Usual practice, or a program of no family intervention - O -Smoking status of children who reported no use of tobacco at baseline.

Enhancing skill acquisition and expertise in high performance programmes

Our research programme with elite athletes has investigated and implemented learning design from an ecological dynamics perspective, examining its effects on movement coordination and control and the acquisition of expertise. Ecological dynamics is a systemsoriented theoretical rationale for understanding the emergent relations in a complex system formed by each performer and a performance environment. This approach has identified the individual-environment relationship as the relevant scale of analysis for modelling how processes of perception, cognition and action underpin expert performance in sport (Davids et al., 2014; Zelaznik, 2014). In this chapter we elucidate key concepts from ecological dynamics and exemplify how they have informed our understanding of relevant psychological processes including: movement coordination and its acquisition, learning and transfer, impacting on practice task design in high performance programmes.

A systematic literature review of alcohol education programmes in middle and high school settings (2000-2014)

Purpose Social marketing benchmark criteria were used to understand the extent to which single-substance alcohol education programmes targeting adolescents in middle and high school settings sought to change behaviour, utilised theory, included audience research and applied the market segmentation process. The paper aims to discuss these issues. Design/methodology/approach A systematic literature review retrieved a total of 1,495 identified articles; 565 duplicates were removed. The remaining 930 articles were then screened. Articles detailing formative research or programmes targeting multiple substances, parents, families and/or communities, as well as elementary schools and universities were excluded. A total of 31 articles, encompassing 16 qualifying programmes, were selected for detailed evaluation. Findings The majority of alcohol education programmes were developed on the basis of theory and achieved short- and medium-term behavioural effects. Importantly, most programmes were universal and did not apply the full market segmentation process. Limited audience research in the form of student involvement in programme design was identified. Research limitations/implications This systematic literature review focused on single-substance alcohol education programmes targeted at middle and high school student populations, retrieving studies back to the year 2000. Originality/value The results of this systematic literature review indicate that application of the social marketing benchmark criteria of market segmentation and audience research may represent an avenue for further extending alcohol education programme effectiveness in middle and high school settings.

The need for cost-effectiveness analyses of antimicrobial stewardship programmes: A structured review

The cost effectiveness of antimicrobial stewardship (AMS) programmes was reviewed in hospital settings of Organisation for Economic Co-operation and Development (OECD) countries, and limited to adult patient populations. In each of the 36 studies, the type of AMS strategy and the clinical and cost outcomes were evaluated. The main AMS strategy implemented was prospective audit with intervention and feedback (PAIF), followed by the use of rapid technology, including rapid polymerase chain reaction (PCR)-based methods and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology, for the treatment of bloodstream infections. All but one of the 36 studies reported that AMS resulted in a reduction in pharmacy expenditure. Among 27 studies measuring changes to health outcomes, either no change was reported post-AMS, or the additional benefits achieved from these outcomes were not quantified. Only two studies performed a full economic evaluation: one on a PAIF-based AMS intervention; and the other on use of rapid technology for the selection of appropriate treatment for serious Staphylococcus aureus infections. Both studies found the interventions to be cost effective. AMS programmes achieved a reduction in pharmacy expenditure, but there was a lack of consistency in the reported cost outcomes making it difficult to compare between interventions. A failure to capture complete costs in terms of resource use makes it difficult to determine the true cost of these interventions. There is an urgent need for full economic evaluations that compare relative changes both in clinical and cost outcomes to enable identification of the most cost-effective AMS strategies in hospitals.

Auditing design and innovation programmes within a multinational insurance provider

The financial services industry is key to the success of the Australian economy, however even established businesses need to continually push to innovate. At present, design is becoming widely accepted as means to innovate and many companies currently have design and innovation programmes. The goal of these programmes is to foster a design capability amongst staff members. However, little is known as to the impact of the innovation capabilities such design programmes claim to instil. Therefore, this paper seeks to investigate how a financial services firm is currently attempting to build a design capability amongst staff members. Using a case study approach the research team audited four design capability programmes currently being deployed by the case firm. The study highlights the strengths and weaknesses of current efforts by the firm and current barriers to achieving design capability. The implications of this paper include key insights for both academics and industry.

The oxygen migration in the apatite-type lanthanum silicate with the cation substitution

A theoretical model is proposed to determine the effects of Si substitution with Al on the oxygen diffusion in apatite-type lanthanum silicates based on density-functional theory (DFT) calculations for La10(SiO 4)4(AlO4)2O2. Substitution changes the stable configuration for excess oxygen from the split interstitial to a new cluster form with the original cluster. Al doping completely changes the migration mechanism from the interstitialcy one, which was proposed for the La9.33(SiO4)6O2 starting material, to a mechanism which contains an interstitial process. Nevertheless, the migration barrier is calculated to be 0.81 eV, which indicates small changes in oxygen conduction and is consistent with the observations. The present study indicates that the cation substitution on silicon site alone does not promise the improvement of the oxide ion conduction in the lanthanum silicate.

Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance

Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.