Identification of vitronectin as a novel insulin-like growth factor-II binding protein

We have previously reported the presence of a 70 kDa insulin-like growth factor (IGF)-II-specific binding protein in chicken serum using Western ligand blotting approaches. In order to ascertain the identity of this 70 kDa IGF-II binding species, the protein has been purified from chicken serum using a combination of ion-exchange and gel-permeation chromatography. Interestingly, amino acid sequencing of the purified protein revealed that it has the same N-terminal sequence as chicken vitronectin (VN). The protein has the ability to specifically bind IGF-II and not IGF-I as determined by ligand blotting, cross-linking and competitive binding assay approaches. In addition, the protein binds 125I-des(l-6)-IGF-II, suggesting that the interaction with IGF-II is different to those with other characterized IGF-binding proteins. Importantly, we have ascertained that both human and bovine VN also specifically bind IGF-II. These results are particularly relevant in the light of the recent report that the urokinase-type plasminogen activator receptor, a protein that also binds VN, has been shown to associate with the cation-independent mannose-6-phosphate/GF-II receptor and suggest a possible role for IGF-II in cell adhesion and invasion.

The "free-factor" impact on value in health services

Purpose - This paper seeks to understand the impact of financial cost on customer value in health prevention services by comparing free government services with private fee-charging providers. This is important as there is a common belief that a free health service is of lower quality and thus lower value than a paid service. However there is no evidence to verify this notion. Design / Methodology / Approach - A large-scale online survey was administered nationwide to Australian women. The respondents were asked about the functional and emotional value derived from their service experiences. Findings - Structural equation modelling (SEM) revealed non significant relationships between fee/free services and functional and emotional value (FV/EV). The non-significant relationship with FV is contrary to the theory of price quality relationship in services. This could be attributed to consumer perceptions that the technical quality of health professionals is comparable across free and paid services. The non-significant relationship with EV could be explained by the indicators used to reflect EV. These indicators were reflective of breast screening behaviour, not breast screening services. Subsequently, it may be posited that the act of having a breast screen is sufficient for consumers to derive emotional value, regardless of the financial cost. Originality / Value - This research fills an important gap in the literature by investigating the impact of financial cost on a service that consumers use proactively(prevention), rather than reactively (treatment). Insights are provided into the impact of cost on customer value in preventive health services, which are valuable to social marketing academics, health practitioners, and governments

Stress and addiction : contribution of the corticotropin releasing factor (CRF) system in neuroplasticity

Corticotropin releasing factor (CRF) has been shown to induce various behavioral changes related to adaptation to stress. Dysregulation of the CRF system at any point can lead to a variety of psychiatric disorders, including substance use disorders (SUDs). CRF has been associated with stress-induced drug reinforcement. Extensive literature has identified CRF to play an important role in the molecular mechanisms that lead to an increase in susceptibility that precipitates relapse to SUDs. The CRF system has a heterogeneous role in SUDs. It enhances the acute effects of drugs of abuse and is also responsible for the potentiation of drug-induced neuroplasticity evoked during the withdrawal period. We present in this review the brain regions and circuitries where CRF is expressed and may participate in stress-induced drug abuse. Finally, we attempt to evaluate the role of modulating the CRF system as a possible therapeutic strategy for treating the dysregulation of emotional behaviors that result from the acute positive reinforcement of substances of abuse as well as the negative reinforcement produced by withdrawal.

Is diurnal temperature range a risk factor for childhood diarrhea?

Background Previous studies have found that high and cold temperatures increase the risk of childhood diarrhea. However, little is known about whether the within-day variation of temperature has any effect on childhood diarrhea. Methods A Poisson generalized linear regression model combined with a distributed lag non-linear model was used to examine the relationship between diurnal temperature range and emergency department admissions for diarrhea among children under five years in Brisbane, from 1st January 2003 to 31st December 2009. Results There was a statistically significant relationship between diurnal temperature range and childhood diarrhea. The effect of diurnal temperature range on childhood diarrhea was the greatest at one day lag, with a 3% (95% confidence interval: 2%–5%) increase of emergency department admissions per 1°C increment of diurnal temperature range. Conclusion Within-day variation of temperature appeared to be a risk factor for childhood diarrhea. The incidence of childhood diarrhea may increase if climate variability increases as predicted.

Exploratory factor analysis and psychometric evaluation of the Teachers Reporting Attitude Scale for Child Sexual Abuse

This paper presents an evaluation of an instrument to measure teachers’ attitudes towards reporting child sexual abuse and discusses the instrument’s merit for research into reporting practice. Based on responses from 444 Australian teachers, the Teachers’ Reporting Attitude Scale for Child Sexual Abuse (TRAS - CSA) was evaluated using exploratory factor analysis. The scale isolated three dimensions: commitment to the reporting role; confidence in the system’s response to reports; and concerns about reporting. These three factors accounted for 37.5% of the variance in the 14-item measure. Alpha coefficients for the subscales were 0.769 (commitment), 0.617 (confidence), and 0.661 (concerns). The findings provide insights into the complexity of studying teachers’ attitudes towards reporting of child sexual abuse, and have implications for future research.

Lifestyle risk factor modification in midlife women with type 2 diabetes : theoretical modelling of perceived barriers

Objective: The aim of this paper is to propose a ‘Perceived barriers and lifestyle risk factor modification model’ that could be incorporated into existing frameworks for diabetes education to enhance lifestyle risk factor education in women. Setting: Diabetes education, community health. Primary argument: ‘Perceived barriers’ is a health promotion concept that has been found to be a significant predictor of health promotion behaviour. There is evidence that women face a range of perceived barriers that prevent them from engaging in healthy lifestyle activities. Despite this, current evidence based models of diabetes education do not explicitly incorporate the concept of perceived barriers. A model of risk factor reduction that incorporates ‘perceived barriers’ is proposed. Conclusion: Although further research is required, current approaches to risk factor reduction in type 2 diabetes could be enhanced by identification and goal setting to reduce an individual’s perceived barriers.

Fibroblast growth factor receptor inhibition synergizes with paclitaxel and doxorubicin in endometrial cancer cells

OBJECTIVE: The fibroblast growth factor (FGF) family of signaling molecules has been associated with chemoresistance and poor prognosis in a number of cancer types, including lung, breast, ovarian, prostate, and head and neck carcinomas. Given the identification of activating mutations in the FGF receptor 2 (FGFR2) receptor tyrosine kinase in a subset of endometrial tumors, agents with activity against FGFRs are currently being tested in clinical trials for recurrent and progressive endometrial cancer. Here, we evaluated the effect of FGFR inhibition on the in vitro efficacy of chemotherapy in endometrial cancer cell lines. METHODS: Human endometrial cancer cell lines with wild-type or activating FGFR2 mutations were used to determine any synergism with concurrent use of the pan-FGFR inhibitor, PD173074, and the chemotherapeutics, doxorubicin and paclitaxel, on cell proliferation and apoptosis. RESULTS: FGFR2 mutation status did not alter sensitivity to either chemotherapeutic agent alone. The combination of PD173074 with paclitaxel or doxorubicin showed synergistic activity in the 3 FGFR2 mutant cell lines evaluated. In addition, although nonmutant cell lines were resistant to FGFR inhibition alone, the addition of PD173074 potentiated the cytostatic effect of paclitaxel and doxorubicin in a subset of FGFR2 wild-type endometrial cancer cell lines. CONCLUSIONS: Together these data suggest a potential therapeutic benefit to combining an FGFR inhibitor with standard chemotherapeutic agents in endometrial cancer therapy particularly in patients with FGFR2 mutation positive tumors.

S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice.

Purpose To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model. Methods Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

Factor analysis of the Self Report Version of the Strengths and Difficulties Questionnaire in a sample of children with intellectual disability

The rate of emotional and behavioral disturbance in children with intellectual disability (ID) is up to four times higher than that of their typically developing peers. It is important to identify these difficulties in children with ID as early as possible to prevent the chronic co-morbidity of ID and psychopathology. Children with ID have traditionally been assessed via proxy reporting, but appropriate and psychometrically rigorous instruments are needed so that children can report on their own emotions and behaviors. In this study, the factor structure of the self-report version of the Strengths and Difficulties Questionnaire (SDQ) was examined in a population of 128 children with ID (mean age = 12 years). Exploratory and Confirmatory Factor Analysis showed a three factor model (comprising Positive Relationships, Negative Behavior and Emotional Competence) to be a better measure than the original five factor SDQ model in this population.

Reducing road related injuries for young adolescents : an investigation of truancy as a risk factor

Truancy is recognised as an indicator of engagement in high-risk behaviours for adolescents. Injuries from road related risk behaviours continue to be a leading cause of death and disability for early adolescents (13-14 years). The aim of this research is to determine the extent to which truancy relates to increased risk of road related injuries for early adolescents. Four hundred and twenty-seven Year 9 students (13-14 years) from five high schools in Queensland, Australia, completed a questionnaire about their perceptions of risk and recent injury experience. Self-reported injuries were assessed by the Extended Adolescent Injury Checklist (E-AIC). Injuries resulting from motorcycle use, bicycle use, vehicle use (as passenger or driver), and as a pedestrian were measured for the preceding three months. Students were also asked to indicate whether they sought medical attention for their injuries. Truancy rates were assessed from self-reported skipping class or wagging school over the same three month period. The findings explore the relationship between early adolescent truancy and road related injuries. The relationship between road related injuries and truancy was analysed separately for males and females. Results of this study revealed that road related injuries and reports of associated medical treatment are higher for young people who engage in truancy when compared with non-truant adolescents. The results of this study contribute knowledge about truancy as a risk factor for engagement in road related risks. The findings have the potential to enhance school policies and injury prevention programs if emphasis is placed on increasing school attendance as a safety measure to decrease road related injuries for young adolescents.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.