Vitronectin modulates human mesenchymal stem cell response to insulin-like growth factor-I and transforming growth factor beta 1 in a serum-free environment

The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.

Comparison of three expert elicitation methods for logistic regression on predicting the presence of the threatened brush-tailed rock-wallaby petrogale penicillata

Numerous expert elicitation methods have been suggested for generalised linear models (GLMs). This paper compares three relatively new approaches to eliciting expert knowledge in a form suitable for Bayesian logistic regression. These methods were trialled on two experts in order to model the habitat suitability of the threatened Australian brush-tailed rock-wallaby (Petrogale penicillata). The first elicitation approach is a geographically assisted indirect predictive method with a geographic information system (GIS) interface. The second approach is a predictive indirect method which uses an interactive graphical tool. The third method uses a questionnaire to elicit expert knowledge directly about the impact of a habitat variable on the response. Two variables (slope and aspect) are used to examine prior and posterior distributions of the three methods. The results indicate that there are some similarities and dissimilarities between the expert informed priors of the two experts formulated from the different approaches. The choice of elicitation method depends on the statistical knowledge of the expert, their mapping skills, time constraints, accessibility to experts and funding available. This trial reveals that expert knowledge can be important when modelling rare event data, such as threatened species, because experts can provide additional information that may not be represented in the dataset. However care must be taken with the way in which this information is elicited and formulated.

The evaluation of a biphasic osteochondral implant coupled with an electrospun membrane in a large animal model

Conventional clinical therapies are unable to resolve osteochondral defects adequately, hence tissue engineering solutions are sought to address the challenge. A biphasic implant which was seeded with Mesenchymal Stem Cells (MSC) and coupled with an electrospun membrane was evaluated as an alternative. This dual phase construct comprised of a Polycaprolactone (PCL) cartilage scaffold and a Polycaprolactone - Tri Calcium Phosphate (PCL - TCP) osseous matrix. Autologous MSC was seeded into the entire implant via fibrin and the construct was inserted into critically sized osteochondral defects located at the medial condyle and patellar groove of pigs. The defect was resurfaced with a PCL - collagen electrospun mesh that served as a substitute for periosteal flap in preventing cell leakage. Controls either without implanted MSC or resurfacing membrane were included. After 6 months, cartilaginous repair was observed with a low occurrence of fibrocartilage at the medial condyle. Osteochondral repair was promoted and host cartilage degeneration was arrested as shown by the superior Glycosaminoglycan (GAG) maintenance. This positive morphological outcome was supported by a higher relative Young's modulus which indicated functional cartilage restoration. Bone in growth and remodeling occurred in all groups with a higher degree of mineralization in the experimental group. Tissue repair was compromised in the absence of the implanted cells or the resurfacing membrane. Moreover healing was inferior at the patellar groove as compared to the medial condyle and this was attributed to the native biomechanical features.

Prison foodservice in Australia : systems, menus and inmate attitudes

This paper presents results from three studies in 25 custodial facilities in three Australian states, including nutrient analyses of menus and focus groups exploring inmate attitudes. Both cook-fresh and cook-chill production systems are used. Non-selective cycle menus of 4-6 weeks are common but inmates can supplement meals by purchase of additional food items (‘buy-ups’). Menus included adequate variety and met most nutritional standards, with the possible exception of fruit. The sodium content of menus is above recommended levels. Protein, fibre, vitamins A, C, thiamin, riboflavin, calcium, iron and zinc were more than adequate, and the percentage energy from fat is close to or meets national recommendations. Focus groups identified 16 themes, including meal quality, food available at ‘buy-ups’, cooking facilities, and concerns about possible food safety risks associated with inmates storing food in cells. Many complaints were about factors not under the control of the foodservice manager.

Diagramming the interior

Mark Taylor's new essay assesses the impact of the diagram on interior design from the late 19th century to the present. Taylor identifies the pop-cultural discourse of advice writing in both books and magazines as a starting point for his analysis. Drawing on diverse sources, his analysis focuses on texts relating to the dynamics of use and flexibility by Catherine Beecher, Harriet Beecher Stowe, Melusina Fay Peirce, Mary Haweis and Christine Frederick among others. The examples in these texts use the home, domestic housekeeping and kitchens as the sites and practices of intervention through which interior design innovations can be enacted. Taylor's analysis identified the innovations in both the social and the political aspects of space and the critique of static space behind these seemingly amateurish and innocuous texts. Identifying these contributions as early precursors of Modernism's open-plan and flexible, dynamic spaces, Taylor also interprets them with a critical concern for the oppositions and hierarchies that can exist in spatial design, and which are the hallmarks of recent Postmodern, phenomenological approaches to interior design and its theorisations. The progressive and subversive "paradigms for living" implicit in these diagrams can be argued to present a model of greater economic, social and political equality as well as representing a more balanced set of power relations in the home. Progressing through the 20th century to the present, Taylor's analysis shifts byond the dressed body and on to the more intimate rituals of the revealed body to further examine how diagrams of the interior, and the interior as a set of diagrams, are also mediators, sites and grounds for the design of social and sexual intimacy. Through a consideration of the link between design, indentity and intimacy (whether of the invisible, fashioned or sexualised body), the diagrms of interiors are reconfigured as radical and critical tools for an animate, material and emancipatory "redressing" of the balance between the body, identity, sexuality, gender, function, mis(use), aesthetics and the interior.

Identity and text : developing self-conscious readers

Globalisation and societal change suggest the language and literacy skills needed to make meaning in our lives are increasing and changing radically. Multiliteracies are influencing the future of literacy teaching. One aspect of the pedagogy of multiliteracies is recruiting learners’ previous and current experiences as an integral part of the learning experience. This paper examines the implications of results from a project that examined student responses to a postmodern picture book, in particular, ways teachers might develop students’ self-knowledge about reading. It draws on Freebody and Luke’s Four Resources Model of Reading and recently developed models for teaching multiliteracies.

Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells

The growth and differentiation of mesenchymal stem cells is controlled by various growth factors, the activities of which can be modulated by heparan sulfates. We have previously underscored the necessity of sulfated glycosaminoglycans for the FGF-2-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of heparan sulfate to cultures of primary rat MSCs stimulates their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation. FGF-2 can also increase the proliferation and osteogenic differentiation of rMSCs when applied exogenously during their linear growth. However, as opposed to exogenous HS, the continuous use of FGF-2 during in vitro differentiation completely blocked rMSC mineralization. Furthermore, we show that the effects of both FGF-2 and HS are mediated through FGF receptor 1 (FGFR1) and that inhibition of signaling through this receptor arrests cell growth resulting in the cells being unable to reach the critical density necessary to induce differentiation. Interestingly, blocking FGFR1 signaling in post-confluent osteogenic cultures significantly increased calcium deposition. Taken together our data clearly suggests that FGFR1 signaling plays an important role during osteogenic differentiation, firstly by stimulating cell growth that is closely followed by an inhibitory affect once the cells have reached confluence. It also underlines the importance of HS as a co-receptor for the signaling of endogenous FGF-2 and suggests that purified glycosaminoglycans may be attractive alternatives to growth factors for improved ex vivo growth and differentiation of MSCs.

Protective behavior in adolescent friendships : the influence of attitudes toward the consequences, friendship norms and perceived control

The current study sought to understand adolescent protective behavior in friendship using a Theory of Planned Behavior framework. In particular, the study sought to consider a young persons’ direct and active intervention to inhibit their friends’ risky behavior or to assist them when the behavior leads to injury. The role of attitudes regarding the consequences, norms and control about protective behavior were examined both qualitatively through focus groups (n= 50) and quantitatively through surveys from a sample of 540 Year 9 students (13-14 years old). There was some support for the theory with attitudes regarding the consequences of the behavior and norms predicting intended protective behavior. A path analysis was conducted with a sub-sample of 140 students which showed that intentions to be protective and perceived control to undertake protective behavior directly predicted such behavior after a 3 month interval. Attitudes towards the consequences and norms only indirectly predicted protective behavior via intention. The findings provide important applied information for interventions designed to increase adolescent protective behavior in their friendships.

An adolescent injury intervention : selecting targeted behaviours with implications for program design and evaluation

Objectives: This paper sought to identify the behaviour change targets for an injury prevention program; Skills for Preventing Injury in Youth, SPIY. The aim was to explore how such behaviours could subsequently be implemented and evaluated in the program. Methods and Design: The quantitative procedure involved a survey with 267 Year 8 and 9 students (mean age 13.23 years) regarding their engagement in risk-taking behaviours that may lead to injury. The qualitative study involved 30 students aged 14 to 17 years reporting their experiences of injury and risk-taking. Results: Injury risk behaviours co-occurred among three-quarters of those who reported engaging in any alcohol use or transport or violence related injury risk behaviour. Students described in detail some of these experiences. Conclusions: The selection process of identifying target behaviours for change for an injury prevention program is described. Adolescents’ description of such risk behaviours can inform the process of operationalising and contextualising program content and deciding on evaluation methodology. The design of an effective injury prevention program involves considerable preparatory work and this paper was able to describe the process of identifying the behavioural targets for change that can be operationalised and evaluated in the injury prevention program, SPIY.

Factors associated with recurrence of venous leg ulcers : a survey and retrospective chart review

Background: Chronic venous leg ulcers have a significant impact on older individuals’ well-being and health care resources. Unfortunately after healing, up to 70% recur. ----- Objective: To examine the relationships between leg ulcer recurrence and physical activity, compression, nutrition, health, psychosocial indicators and self-care activities in order to provide information for preventive strategies. ----- Design: Survey and retrospective chart review Settings: Two metropolitan hospital and three community-based leg ulcer clinics. ----- Subjects: A sample of 122 community living patients with leg ulcer of venous aetiology which had healed between 12 and 36 months prior to the survey. ---- Methods: Data were collected from medical records on demographics, medical history and previous ulcer history and treatments; and from self-report questionnaires on physical activity, nutrition, psychosocial measures, ulcer recurrences and history, compression and other self-care activities. All variables significantly associated with recurrence at the bivariate level were entered into a logistic regression model to determine their independent influences on recurrence. ----- Results: Median follow-up time was 24 months (range 12–40 months). Sixty-eight percent of participants had recurred. Bivariate analysis found recurrence was positively associated with ulcer duration, cardiac disease, a Body Mass Index ≤20, scoring as at-risk of malnutrition and depression; and negatively associated with increased physical activity, leg elevation, wearing Class 2 (20–25mmHg) or Class 3 (30–40mmHg) compression hosiery, and higher self-efficacy scores. After adjusting for all variables, an hour/day of leg elevation (OR=0.04, 95% CI=0.01–0.17), days/week in Class 2 or 3 compression hosiery (OR=0.53, 95% CI=0.34–0.81), Yale Physical Activity Survey score (OR=0.95, 95% CI=0.92–0.98), cardiac disease (OR=5.03, 95% CI=1.01–24.93) and General Self-Efficacy scores (OR=0.83, 95% CI=0.72–0.94) remained significantly associated (p<0.05) with recurrence. ----- Conclusions: Results indicate a history of cardiac disease is a risk factor for recurrence; while leg elevation, physical activity, compression hosiery and strategies to improve self-efficacy are likely to prevent recurrence.

A short-term evaluation of a school-based early adolescent injury prevention program

This paper reports on the development of a school-based intervention to reduce risk-taking and associated injuries. There is limited but important evidence that intervention design should ensure participation does not lead to an increase in target risk behaviors with some studies in alcohol and drug prevention finding unexpected negative effects. The short-term evaluation of Skills for Preventing Injury in Youth (SPIY) examined change in interpersonal violence, alcohol and transport-related risks. Intervention (n = 360) and comparison (n = 180) students were surveyed pre/post-intervention. A qualitative analysis based on focus groups (70 students) explored experiences of change. Findings indicate significant positive changes reinforced by students’ reports. A decrease in reported risk-taking for the intervention group and an increase in the comparison group were observed. These findings endorse SPIY as a useful curriculum approach to reducing injuries and lend support to the future conduct of a long-term outcome evaluation.

Bicycle helmet wearing among adolescents

Adolescents experience many benefits from bicycling; however, there are also potentially significant injury consequences. One effective counter-measure for the prevention of adolescent bicycling injuries is to promote bicycle helmet wearing. An overview is provided of injury risks of bicycle riding with particular attention to the role of helmet wearing and associated countermeasures such as legislation and school and community approaches. The findings are presented of a study conducted in Australia that examined the effectiveness of a theory-based injury prevention program, Skills for Preventing Injury in Youth (SPIY) for ninth-grade students (age 13 to 14 years). The findings showed a significant, 20.2% decrease in cycling without a helmet among the intervention students (n = 360) and no change for the students in the comparison group (n = 363) after 6 months. In addition, it was found that failing to wear a helmet was significantly associated with engaging in other transport-related risks, being male, having friends who do not wear a helmet and are specific targets of change in the SPIY program, showing a negative attitude toward risk, failing to intervene in friends' risk-taking, and having low knowledge of first aid. Overall, the SPIY program appeared to be an effective theory-based intervention to increase helmet wearing among early adolescents, a group not often targeted in school and community helmet-wearing programs.

Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critically-sized femoral defects

The repair of large non-unions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause bone marrow stromal cells to lose their differentiation ability. To overcome these limitations, we have genetically engineered bone marrow stromal cells to constitutively overexpress the osteoblast specific transcription factor Runx2. In the present study, we examined Runx2-modified bone marrow stromal cells, delivered via poly(caprolactone) scaffolds loaded with type I collagen meshes, in critically-sized segmental defects in rats compared to unmodified cells, cell-free scaffolds and empty defects. Runx2 expression in bone marrow stromal cells accelerated healing of critically-sized defects compared to unmodified bone marrow stromal cells and defects receiving cell-free treatments. These findings provide an accelerated method for healing large bone defects which may reduce recovery time and the need for external fixation of critically-sized defects.

Stem cell–related gene expression in clonal populations of mesenchymal stromal cells from bone marrow

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.