Osteoarthritic cartilage chondrocytes alter subchondral bone osteoblast differentiation via MAPK signalling pathway involving ERK1/2

Osteoarthritic subchondral bone is characterized by abnormal bone density and enhanced production of bone turnover markers, an indication of osteoblast dysfunction. Several studies have proposed that pathological changes in articular cartilage influence the subchondral bone changes, which are typical of the progression of osteoarthritis; however, direct evidence of this has yet to be reported. The aim of the present study was to investigate what effects articular cartilage cells, isolated from normal and osteoarthritic joints, may have on the subchondral bone osteoblast phenotype, and also the potential involvement of the mitogen activated protein kinase (MAPK) signalling pathway during this process. Our results suggest that chondrocytes isolated from a normal joint inhibited osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic joint enhanced osteoblast differentiation, both via a direct and indirect cell interaction mechanisms. Furthermore, the interaction of subchondral bone osteoblasts with osteoarthritic chondrocyte conditioned media appeared to significantly activate ERK1/2 phosphorylation. On the other hand, conditioned media from normal articular chondrocytes did not affect ERK1/2 phosphorylation. Inhibition of the MAPK–ERK1/2 pathways reversed the phenotype changes of subchondral bone osteoblast, which would otherwise be induced by the conditioned media from osteoarthritic chondrocytes. In conclusion, our findings provide evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast metabolism via an ERK1/2 dependent pathway.

Theoretical critique of the work of art : co-producers in research

The ways in which the "traditional" tension between words and artwork can be perceived has huge implications for understanding the relationship between critical or theoretical interpretation, art and practice, and research. Within the practice-led PhD this can generate a strange sense of disjuncture for the artist-researcher particularly when engaged in writing the exegesis. This paper aims to explore this tension through an introductory investigation of the work of the philosopher Andrew Benjamin. For Benjamin criticism completes the work of art. Criticism is, with the artwork, at the centre of our experience and theoretical understanding of art – in this way the work of art and criticism are co-productive. The reality of this co-productivity can be seen in three related articles on the work of American painter Marcia Hafif. In each of these articles there are critical negotiations of just how the work of art operates as art and theoretically, within the field of art. This focus has important ramifications for the writing and reading of the exegesis within the practice-led research higher degree. By including art as a significant part of the research reporting process the artist-researcher is also staking a claim as to the critical value of their work. Rather than resisting the tension between word and artwork the practice-led artist-researcher need to embrace the co-productive nature of critical word and creative work to more completely articulate their practice and its significance as research. The ideal venue and opportunity for this is the exegesis.

Structural and cellular features in metaphyseal and diaphyseal periosteum of osteoporotic rats

Despite the important physiological role of periosteum in the pathogenesis and treatment of osteoporosis, little is known about the structural and cellular characteristics of periosteum in osteoporosis. To study the structural and cellular differences in both diaphyseal and metaphyseal periosteum of osteoporotic rats, samples from the right femur of osteoporotic and normal female Lewis rats were collected and tissue sections were stained with hematoxylin and eosin, antibodies or staining kit against tartrate resistant acid phosphatase (TRAP), alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), von Willebrand (vWF), tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP). The results showed that the osteoporotic rats had much thicker and more cellular cambial layer of metaphyseal periosteum compared with other periosteal areas and normal rats (P\0.001). The number of TRAP? osteoclasts in bone resorption pits, VEGF? cells and the degree of vascularization were found to be greater in the cambial layer of metaphyseal periosteum of osteoporotic rats (P\0.05), while no significant difference was detected in the number of ALP? cells between the two groups. Sympathetic nerve fibers identified by TH staining were predominantly located in the cambial layer of metaphyseal periosteum of osteoporotic rats. No obvious difference in the expression of CGRP between the two groups was found. In conclusion, periosteum may play an important role in the cortical bone resorption in osteoporotic rats and this pathological process may be regulated by the sympathetic nervous system.

Complexity and learning behaviors in product innovation

Successful product innovation and the ability of companies to continuously improve their innovation processes are rapidly becoming essential requirements for competitive advantage and long-term growth in both manufacturing and service industries. It is now recognized that companies must develop innovation capabilities across all stages of the product development, manufacture, and distribution cycle. These Continuous Product Innovation (CPI) capabilities are closely associated with a company’s knowledge management systems and processes. Companies must develop mechanisms to continuously improve these capabilities over time. Using results of an international survey on CPI practices, sets of companies are identified by similarities in specific contingencies related to their complexity of product, process, technological, and customer interface. Differences between the learning behaviors found present in the company groups and in the levers used to develop and support these behaviors are identified and discussed. This paper also discusses appropriate mechanisms for firms with similar complexities, and some approaches they can use to improve their organizational learning and product innovation.

The strategic mindset of Australian manufacturing managers : some missing links

Manufacturing managers have a measurable mindset (or frame) that structures their response to the manufacturing environment. Most importantly, this frame represents a set of assumptions about the relative prominence of concepts in the manufacturing domains, about the nature of people, and about the sensemaking processes required to understand the nature of the manufacturing environment as seen through the eyes of manufacturing managers. This paper uses work in the area of text analysis and extends the scope of a methodology that has been approached from two different directions by Carley ( Journal of Organizational Behavior , 18 (51), 533-558, 1997) and Gephart ( Journal of Organizational Behavior , 18 (51), 583-622, 1997). This methodology is termed collocate analysis. Based on the analysis of transcripts of interviews of Australian manufacturing managers mind maps of the concepts used by these managers have been constructed. From an analysis of these mind maps it is argued that strategy plays a minor role in their thinking second only to the improvement domain, whereas design and related concepts play a dominant role in their day-to-day thinking.

Practice-led research and the innovation agenda : beyond the postgraduate research degree in the arts, design and media

The rise of the ‘practice-led’ research approach has given us a new way of understanding what creative practice in art, design and media can do in the academy and the world— it can materialise new ideas and forms into being as a form of experimental research. Yet, to date, attention around the world, and especially in Australia, has been chiefly directed at the postgraduate research degrees, most notably the PhD or doctoral equivalents. Recent mapping projects and surveys of practice-led research in Australia reveal much about the institutional conditions of higher degree researchers, supervisors, examiners and research training (Baker et al 2009; Evans et al 2003; Dally et al 2004; Paltridge et al 2009; Phillips et al 2009). Given this focus, we might well ask: is the practice-led approach destined to be a part of the higher degree ghetto only, or does it have an afterlife? What is the place of ‘practice-led’ beyond the postgraduate degree? After all postgraduate researchers do not remain postgraduates forever, and perhaps the practice-led approach to research may have benefits in wider university, professional and communal contexts.

Bioactive mesopore-glass microspheres with controllable protein-delivery properties by biomimetic surface modification

Microsphere systems with the ideal properties for bone regeneration need to be bioactive, and at the same time possess the capacity for controlled protein/drug-delivery; however, the current crop of microsphere system fails to fulfill these properties. The aim of this study was to develop a novel protein-delivery system of bioactive mesoporous glass (MBG) microspheres by a biomimetic method through controlling the density of apatite on the surface of microspheres, for potential bone tissue regeneration. MBG microspheres were prepared by using the method of alginate cross-linking with Ca2+ ions. The cellular bioactivity of MBG microspheres was evaluated by investigating the proliferation and attachment of bone marrow stromal cell (BMSC). The loading efficiency and release kinetics of bovine serum albumin (BSA) on MBG microspheres were investigated after coprecipitating with biomimetic apatite in simulated body fluids (SBF). The results showed that MBG microspheres supported BMSC attachment and the Si containing ionic products from MBG microspheres stimulated BMSCs proliferation. The density of apatite on MBG microspheres increased with the length of soaking time in SBF. BSA-loading efficiency of MBG was significantly enhanced by co-precipitating with apatite. Furthermore, the loading efficiency and release kinetics of BSA could be controlled by controlling the density of apatite formed on MBG microspheres. Our results suggest that MBG microspheres are a promising protein-delivery system as a filling material for bone defect healing and regeneration.

Porous PLGA microspheres effectively loaded with BSA protein by electrospraying combined with phase separation in liquid nitrogen

Polymer microspheres loaded with bioactive particles, biomolecules, proteins, and/or growth factors play important roles in tissue engineering, drug delivery, and cell therapy. The conventional double emulsion method and a new method of electrospraying into liquid nitrogen were used to prepare bovine serum albumin (BAS)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres. The particle size, the surface morphology and the internal porous structure of the microspheres were observed using scanning electron microscopy (SEM). The loading efficiency, the encapsulation efficiency, and the release profile of the BSA-loaded PLGA microspheres were measured and studied. It was shown that the microspheres from double emulsion had smaller particle sizes (3-50 m), a less porous structure, a poor loading efficiency (5.2 %), and a poor encapsulation efficiency (43.5%). However, the microspheres from the electrospraying into liquid nitrogen had larger particle sizes (400-600 m), a highly porous structure, a high loading efficiency (12.2%), and a high encapsulation efficiency (93.8%). Thus the combination of electrospraying with freezing in liquid nitrogen and subsequent freeze drying represented a suitable way to produce polymer microspheres for effective loading and sustained release of proteins.

The consequences of substance use among gay and bisexual men : a consensual qualitative research analysis

- Background Substance use is common among gay/bisexual men and is associated with significant health risks (e.g. HIV transmission). The consequences of substance use, across the range of substances commonly used, have received little attention. The purpose of this study is to map participant’s beliefs about the effects of substance use to inform prevention, health promotion and clinical interventions. - Methods Participants were interviewed about experiences regarding their substance use and recruited through medical and sexual health clinics. Data were collected though a consumer panel and individual interviews. Responses regarding perceived consequences of substance use were coded using Consensual Qualitative Research (CQR) methodology. - Results Most participants reported lifetime use of alcohol, cannabis, stimulants and amyl nitrite, and recent alcohol and cannabis use. A wide range of themes were identified regarding participant’s thoughts, emotions and behaviours (including sexual behaviours) secondary to substance use, including: cognitive functioning, mood, social interaction, physical effects, sexual activity, sexual risk-taking, perception of sexual experience, arousal, sensation, relaxation, disinhibition, energy/activity level and numbing. Analyses indicated several consequences were consistent across substance types (e.g. cognitive impairment, enhanced mood), whereas others were highly specific to a given substance (e.g. heightened arousal post amyl nitrite use). - Conclusions Prevention and interventions need to consider the variety of effects of substance use in tailoring effective education programs to reduce harms. A diversity of consequences appear to have direct and indirect impacts on decision-making, sexual activity and risk-taking. Findings lend support for the role of specific beliefs (e.g. expectancies) related to substance use on risk-related cognitions, emotions and behaviours.

Brain-derived neurotrophic factor (BDNF) gene : no major impact on antidepressant treatment response

The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p=0.01) particularly in anxious depression (p=0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TT

The cost effectiveness of Naltrexone added to cognitive-behavioral therapy in the treatment of alcohol dependence

he purpose of this study was to evaluate the comparative cost of treating alcohol dependence with either cognitive behavioral therapy (CBT) alone or CBT combined with naltrexone (CBT+naltrexone). Two hundred ninety-eight outpatients dependent on alcohol who were consecutively treated for alcohol dependence participated in this study. One hundred seven (36%) patients received adjunctive pharmacotherapy (CBT+naltrexone). The Drug Abuse Treatment Cost Analysis Program was used to estimate treatment costs. Adjunctive pharmacotherapy (CBT+naltrexone) introduced an additional treatment cost and was 54% more expensive than CBT alone. When treatment abstinence rates (36.1% CBT; 62.6% CBT+naltrexone) were applied to cost effectiveness ratios, CBT+naltrexone demonstrated an advantage over CBT alone. There were no differences between groups on a preference-based health measure (SF-6D). In this treatment center, to achieve 100 abstainers over a 12-week program, 280 patients require CBT compared with 160 CBT+naltrexone. The dominant choice was CBT+naltrexone based on modest economic advantages and significant efficiencies in the numbers needed to treat.

Mechanisms of change in negative thinking and urinary monoamines in depressed patients during acute treatment with group cognitive behavior therapy and antidepressant medication

This naturalistic study investigated the mechanisms of change in measures of negative thinking and in 24-h urinary metabolites of noradrenaline (norepinephrine), dopamine and serotonin in a sample of 43 depressed hospital patients attending an eight-session group cognitive behavior therapy program. Most participants (91%) were taking antidepressant medication throughout the therapy period according to their treating Psychiatrists' prescriptions. The sample was divided into outcome categories (19 Responders and 24 Non-responders) on the basis of a clinically reliable change index [Jacobson, N.S., & Truax, P., 1991. Clinical significance: a statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19.] applied to the Beck Depression Inventory scores at the end of the therapy. Results of repeated measures analysis of variance [ANOVA] analyses of variance indicated that all measures of negative thinking improved significantly during therapy, and significantly more so in the Responders as expected. The treatment had a significant impact on urinary adrenaline and metadrenaline excretion however, these changes occurred in both Responders and Non-responders. Acute treatment did not significantly influence the six other monoamine metabolites. In summary, changes in urinary monoamine levels during combined treatment for depression were not associated with self-reported changes in mood symptoms.

A psychometric comparison of the Toronto Alexithymia Scale (TAS-20) and the Observer Alexithymia Scale (OAS) in an alcohol-dependent sample

Alexithymia is characterised by deficits in emotional insight and self reflection, that impact on the efficacy of psychological treatments. Given the high prevalence of alexithymia in Alcohol Use Disorders, valid assessment tools are critical. The majority of research on the relationship between alexithymia and alcohol-dependence has employed the self-administered Toronto Alexithymia Scale (TAS-20). The Observer Alexithymia Scale (OAS) has also been recommended. The aim of the present study was to assess the validity and reliability of the OAS and the TAS-20 in an alcohol-dependent sample. Two hundred and ten alcohol-dependent participants in an outpatient Cognitive Behavioral Treatment program were administered the TAS-20 at assessment and upon treatment completion at 12 weeks. Clinical psychologists provided observer assessment data for a subsample of 159 patients. The findings confirmed acceptable internal consistency, test-retest reliability and scale homogeneity for both the OAS and TAS-20, except for the low internal consistency of the TAS-20 EOT scale. The TAS-20 was more strongly associated with alcohol problems than the OAS.