Stage-specific embryonic antigen-4 is not a marker for chondrogenic and osteogenic potential in cultured chondrocytes and mesenchymal progenitor cells

One important challenge for regenerative medicine is to produce a clinically relevant number of cells with consistent tissue-forming potential. Isolation and expansion of cells from skeletal tissues results in a heterogeneous population of cells with variable regenerative potential. A more consistent tissue formation could be achieved by identification and selection of potent progenitors based on cell surface molecules. In this study, we assessed the expression of stage-specific embryonic antigen-4 (SSEA-4), a classic marker of undifferentiated stem cells, and other surface markers in human articular chondrocytes (hACs), osteoblasts, and bone marrow-derived mesenchymal stromal cells (bmMSCs) and characterized their differentiation potential. Further, we sorted SSEA-4-expressing hACs and followed their potential to proliferate and to form cartilage in vitro. Cells isolated from cartilage and bone exhibited remarkably heterogeneous SSEA-4 expression profiles in expansion cultures. SSEA-4 expression levels increased up to approximately 5 population doublings, but decreased following further expansion and differentiation cultures; levels were not related to the proliferation state of the cells. Although SSEA-4-sorted chondrocytes showed a slightly better chondrogenic potential than their SSEA-4-negative counterparts, differences were insufficient to establish a link between SSEA-4 expression and chondrogenic potential. SSEA-4 levels in bmMSCs also did not correlate to the cells' chondrogenic and osteogenic potential in vitro. SSEA-4 is clearly expressed by subpopulations of proliferating somatic cells with a MSC-like phenotype. However, the predictive value of SSEA-4 as a specific marker of superior differentiation capacity in progenitor cell populations from adult human tissue and even its usefulness as a stem cell marker appears questionable.

Doctrinal research : researching the jury

This chapter examines the doctrinal methodology which many lawyers consider best typifies a distinctly legal approach to research. Legal research skills have been identified as a core skill for lawyers, and within the profession, such skills are regarded as synonymous with the doctrinal research method. Good legal research skills are a necessary step in attaining the ability to ‘think like a lawyer’ and achieving valid legal reasoning outcomes. For lawyers, therefore, the doctrinal method is an intuitive aspect of legal work. Yet as this chapter demonstrates, the doctrinal methodology is not without its detractors. There have been serious criticisms of the method put forward by exponents of the various critical legal theories, as well as a perception in some academic circles that the doctrinal research method is nothing more than mere ‘scholarship’ and as a result less compelling or respected than the research methods used by those in the sciences and social sciences. Despite these attacks, and the incursions on the method posed by the growth in the use of non-doctrinal and interdisciplinary research work by lawyers, the argument put forward in this chapter is that the doctrinal method still necessarily forms the basis for most, if not all, legal research projects.

Not all systematic reviews are systematic : a meta-review of the quality of current systematic reviews and meta-analyses for remote monitoring in heart failure

Background/aims: Remote monitoring for heart failure has not only been evaluated in a large number of randomised controlled trials, but also in many systematic reviews and meta-analyses. The aim of this meta-review was to identify, appraise and synthesise existing systematic reviews that have evaluated the effects of remote monitoring in heart failure. Methods: Using a Cochrane methodology, we electronically searched all relevant online databases and search engines, performed a forward citation search as well as hand-searched bibliographies. Only fully published systematic reviews of invasive and/or non-invasive remote monitoring interventions were included. Two reviewers independently extracted data. Results: Sixty-five publications from 3333 citations were identified. Seventeen fulfilled the inclusion and exclusion criteria. Quality varied with A Measurement Tool to Assess Systematic Reviews (AMSTAR scores) ranging from 2 to 11 (mean 5.88). Seven reviews (41%) pooled results from individual studies for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Four (24%) focused specifically on telemonitoring. Four (24%) included studies investigating both non-invasive and invasive technologies. Population characteristics of the included studies were not reported consistently. Mortality and hospitalisations were the most frequently reported outcomes 12 (70%). Only five reviews (29%) reported healthcare costs and compliance. A high degree of heterogeneity was reported in many of the meta-analyses. Conclusions: These results should be considered in context of two negative RCTs of remote monitoring for heart failure that have been published since the meta-analyses (TIM-HF and Tele-HF). However, high quality reviews demonstrated improved mortality, quality of life, reduction in hospitalisations and healthcare costs.

Physico-chemical/biological properties of tripolyphosphate cross-linked chitosan based

In this study, chitosan-PEO blend, prepared in a 15 M acetic acid, was electrospun into nanofibers (~ 78 nm diameter) with bead free morphology. While investigating physico-chemical parameters of blend solutions, effect of yield stress on chitosan based nanofiber fabrication was clearly evidenced. Architectural stability of nanofiber mat in aqueous medium was achieved by ionotropic cross-linking of chitosan by tripolyphosphate (TPP) ions. The TPP cross-linked nanofiber mat showed swelling up to ~ 300 % in 1h and ~ 40 % degradation during 30 d study period. 3T3 fibroblast cells showed good attachment, proliferation and viability on TPP treated chitosan based nanofiber mats. The results indicate non-toxic nature of TPP cross-linked chitosan based nanofibers and their potential to be explored as a tissue engineering matrix.

Chitosan-collagen scaffolds with nano/microfibrous architecture for skin tissue engineering

In this study, a hierarchical nano/microfibrous chitosan/collagen scaffold that approximates structural and functional attributes of native extracellular matrix (ECM), has been developed for applicability in skin tissue engineering. Scaffolds were produced by electrospinning of chitosan followed by imbibing of collagen solution, freeze-drying and subsequent cross-linking of two polymers. Scanning electron microscopy showed formation of layered scaffolds with nano/microfibrous architechture. Physico-chemical properties of scaffolds including tensile strength, swelling behavior and biodegradability were found satisfactory for intended application. 3T3 fibroblasts and HaCaT keratinocytes showed good in vitro cellular response on scaffolds thereby indicating the matrices′ cytocompatible nature. Scaffolds tested in an ex vivo human skin equivalent (HSE) wound model, as a preliminary alternative to animal testing, showed keratinocyte migration and wound re-epithelization — a pre-requisite for healing and regeneration. Taken together, the herein proposed chitosan/collagen scaffold, shows good potential for skin tissue engineering.

Using formative feedback to identify and support first year chemistry students with missing or misconceptions. A Practice Report

Students entering tertiary studies possess a diverse range of prior experiences in their academic preparation for tertiary chemistry so academics need tools to enable them to respond to issues in diversity in conceptual models possessed by entering students. Concept inventories can be used to provide formative feedback to help students identify concepts that they need to address to improve construction of subsequent understanding enabling their learning. Modular, formative learning activities that can be administered inside or outside of class in first year chemistry courses have been developed. These activities address key missing and mis-conceptions possessed by incoming student. Engagement in these learning activities by students and academics will help shift the culture of diagnostic and formative assessment within the tertiary context and address issues around the secondary/tertiary transition. This diagnostic/intervention framework is currently being trialed across five Australian tertiary institutions encompassing a large heterogeneous sample of students.

Boomtown

This creative work was commissioned by the Queensland Music Festival (artistic director: James Morrison) as the signature regional event for the 2013 festival. With book by David Burton and music by Scott Saunders, this original music theatre piece was creatively developed and directed by Sean Mee under the overall control of creative Producer, Marguerite Pepper. The production was created using the stories of Gladstone and performed by over 300 local artists, school children and industry partners on the foreshore of the Gladstone Marina on a purpose built stage, designed by Josh McIntosh. The production played over 4 nights (18-21 July 2013) to an estimated audience of just under 20,000.

Poly(2-oxazoline) hydrogels for controlled fibroblast attachment

Currently there is a lack of choice when selecting synthetic materials with the cell-instructive properties demanded by modern biomaterials. The purpose of this study was to investigate the attachment of cells onto hydrogels prepared from poly(2-oxazoline)s selectively-functionalized with cell adhesion motifs. A water-soluble macromer based on the microwave-assisted cationic ring-opening polymerization of 2-methyl-2-oxazoline and 2-(dec-9-enyl)-2-oxazoline was functionalized with the peptide CRGDSG or controls using thiol-ene photochemistry followed by facile crosslinking in the presence of a dithiol crosslinker. The growth of human fibroblasts on the hydrogel surfaces was dictated by the structure and amount of incorporated peptide. Controls without any peptide showed resistance to cellular attachment. The benignity of the crosslinking conditions was demonstrated by the incorporation of fibroblasts within the hydrogels to produce three-dimensional cell-polymer constructs.

Matrix metalloproteinase biosensor based on a porous silicon reflector

Matrix metalloproteinases (MMPs) are proteolytic enzymes important to wound healing. In non-healing wounds, it has been suggested that MMP levels become dysfunctional, hence it is of great interest to develop sensors to detect MMP biomarkers. This study presents the development of a label-free optical MMP biosensor based on a functionalised porous silicon (pSi) thin film. The biosensor is fabricated by immobilising a peptidomimetic MMP inhibitor in the porous layer using hydrosilylation followed by amide coupling. The binding of MMP to the immobilised inhibitor translates into a change of effective optical thickness (EOT) over the time. We investigate the effect of surface functionalisation on the stability of pSi surface and evaluate the sensing performance. We successfully demonstrate MMP detection in buffer solution and human wound fluid at physiologically relevant concentrations. This biosensor may find application as a point-of-care device that is prognostic of the healing trajectory of chronic wounds.

A retrospective cohort investigation of active range of motion within one week of open reduction and internal fixation of distal radius fractures

Distal radius fractures stabilized by open reduction internal fixation (ORIF) have become increasingly common. There is currently no consensus on the optimal time to commence range of motion (ROM) exercises post-ORIF. A retrospective cohort review was conducted over a five-year period to compare wrist and forearm range of motion outcomes and number of therapy sessions between patients who commenced active ROM exercises within the first seven days and from day eight onward following ORIF of distal radius fractures. One hundred and twenty-one patient cases were identified. Clinical data, active ROM at initial and discharge therapy assessments, fracture type, surgical approaches, and number of therapy sessions attended were recorded. One hundred and seven (88.4%) cases had complete datasets. The early active ROM group (n = 37) commenced ROM a mean (SD) of 4.27 (1.8) days post-ORIF. The comparator group (n = 70) commenced ROM exercises 24.3 (13.6) days post-ORIF. No significant differences were identified between groups in ROM at initial or discharge assessments, or therapy sessions attended. The results from this study indicate that patients who commenced active ROM exercises an average of 24 days after surgery achieved comparable ROM outcomes with similar number of therapy sessions to those who commenced ROM exercises within the first week.

Review : "The Adventures of Barry McKenzie" -- Bruce Beresford

Synopsis and review of the Australian ocker comedy The Adventures of Barry McKenzie (Bruce Beresford, 1972). Includes cast and credits. The Adventures of Barry McKenzie, adapted from a comic strip written by Barry Humphries, is a landmark film in the revival of Australian cinema. It was the first film to be fully funded by the new federal agency, the Australian Film Development Corporation (AFDC), and its unexpected success (in Britain as well as in Australia) both demonstrated that Australian films could be popular, and helped establish the ‘ocker comedy’ as the first indigenous (sub)genre of the Australian ‘new wave’. In common with other ocker comedies including Stork (Tim Burstall, 1971), and Alvin Purple (Tim Burstall, 1973), The Adventures of Barry McKenzie was derided by critics despite its popular success. But as Tom O’Regan has argued, these films were vitally important in developing a public profile for Australian films, for encouraging private investment in production, and for convincing exhibitors to screen Australian films...

Quality of life for older people in residential care is related to connectedness, willingness to enter care, and co-residents

Aim: To establish associations with quality of life (QOL) of older people in long-term residential care facilities in two New Zealand cities. Methods: The outcome measure of QOL was the Life Satisfaction Index. We used multiple linear regression to explore how broad categories of factors might contribute to QOL. Results: A total of 599 people (median age of 85 years; 74% women) participated. Response rates were 85% for facilities and 83% for residents. A resident's QOL was significantly related to the QOL of co-residents. QOL was higher for people who were more positive about entry to residential care, more physically able, and not depressed, and for those with more family and emotional support. Conclusion: Attending to the circumstances around entry to residential care may enhance QOL, as may promoting physical activity, treating depression and ensuring older people remain emotionally connected to their families. In choosing a facility, noting the QOL of co-residents is important.

Approaches to reducing the most important patient errors in primary health care : patient and professional perspectives

We have previously reported a preliminary taxonomy of patient error. However, approaches to managing patients' contribution to error have received little attention in the literature. This paper aims to assess how patients and primary care professionals perceive the relative importance of different patient errors as a threat to patient safety. It also attempts to suggest what these groups believe may be done to reduce the errors, and how. It addresses these aims through original research that extends the nominal group analysis used to generate the error taxonomy. Interviews were conducted with 11 purposively selected groups of patients and primary care professionals in Auckland, New Zealand, during late 2007. The total number of participants was 83, including 64 patients. Each group ranked the importance of possible patient errors identified through the nominal group exercise. Approaches to managing the most important errors were then discussed. There was considerable variation among the groups in the importance rankings of the errors. Our general inductive analysis of participants' suggestions revealed the content of four inter-related actions to manage patient error: Grow relationships; Enable patients and professionals to recognise and manage patient error; be Responsive to their shared capacity for change; and Motivate them to act together for patient safety. Cultivation of this GERM of safe care was suggested to benefit from 'individualised community care'. In this approach, primary care professionals individualise, in community spaces, population health messages about patient safety events. This approach may help to reduce patient error and the tension between personal and population health-care.

Electrospraying of polymers with therapeutic molecules : state of the art

The encapsulation and release of bioactive molecules from polymeric vehicles represents the holy grail of drug and growth factor delivery therapies, whereby sustained and controlled release is crucial in eliciting a positive therapeutic effect. To this end, electrospraying is rapidly emerging as a popular technology for the production of polymeric particles containing bioactive molecules. Compared with traditional emulsion fabrication techniques, electrospraying has the potential to reduce denaturation of protein drugs and affords tighter regulation over particle size distribution and morphology. In this article, we review the importance of the electrospraying parameters that enable reproducible tailoring of the particles' physical and in vitro drug release characteristics, along with discussion of existing in vivo data. Controlled morphology and monodispersity of particles can be achieved with electrospraying, with high encapsulation efficiencies and without unfavorable denaturation of bioactive molecules throughout the process. Finally, the combination of electrospraying with electrospun scaffolds, with an emphasis on tissue regeneration is reviewed, depicting a technique in its relative infancy but holding great promise for the future of regenerative medicine.

Composites for delivery of therapeutics : combining melt electrospun scaffolds with loaded electrosprayed microparticles

A novel strategy is reported to produce biodegradable microfiber-scaffolds layered with high densities of microparticles encapsulating a model protein. Direct electrospraying on highly porous melt electrospun scaffolds provides a reproducible scaffold coating throughout the entire architecture. The burst release of protein is significantly reduced due to the immobilization of microparticles on the surface of the scaffold and release mechanisms are dependent on protein-polymer interactions. The composite scaffolds have a positive biological effect in contact with precursor osteoblast cells up to 18 days in culture. The scaffold design achieved with the techniques presented here endorses these new composite scaffolds as promising templates for growth factor delivery.