44 research outputs found

    Vocational pathways in the early part of a career: An Australian study

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    The vocational pathways of a representative national sample of Australian school students (N = 1,201) were examined over a 7-year period after the students left school. Results indicated that there was a disparity between the students' initial vocational interests and their occupations at the beginning of their careers. Only 21% of the students were in identical high-point interest areas at initial assessment and 7 years later. The results suggested that there was a period of career exploration that was followed by adjustment to the labor market

    Roles of hyaluronan in bone resorption

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    BACKGROUND: Hyaluronan, an unsulfated glycosaminoglycan, while being closely linked to osteoclast function several years ago, has received little attention lately. Given recent new knowledge of hyaluronan's possible cell binding abilities, it is important to re-examine the role of this polysaccharide in bone homeostasis. DISCUSSION: Previously published data demonstrating a linkage between induction of hyaluronan synthesis and osteoclast-mediated bone resorption are reviewed. Suggestions are made involving the cell binding ability of hyaluronan and its potential to mediate osteoclast binding to bone surfaces and its potential to serve as a diffusion barrier and participate in the sealing zone required for osteoclast-mediated bone resorption. SUMMARY: This brief article summarizes previous studies linking HA to bone resorption and suggests roles for hyaluronan in the process of bone resorption

    Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

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    BACKGROUND: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. RESULTS: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45-55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. CONCLUSION: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs

    Guidelines for histopathological specimen examination and diagnostic reporting of primary bone tumours

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    This review is intended to provide histopathologists with guidelines for clinical assessment, specimen handling and diagnostic reporting of benign and malignant primary bone tumours. Information from radiology, surgical, oncology and other clinical colleagues involved in the diagnosis and treatment of primary bone tumours should be properly assessed before undertaking a structured approach to specimen handling and histological reporting. This ensures that the information needed for planning appropriate treatment of these complex tumours is provided. Consistency in diagnostic evaluation with respect to both terminology and report content facilitates liaison at multidisciplinary bone tumour meetings and collaboration between cancer units and networks, as well as providing a common database for audit of the clinical, radiological and pathological aspects of bone tumours

    Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes

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    BackgroundOsteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint.Methodology/Principal FindingsOA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was performed using transwell chambers. Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. CORM-2 reduced the proliferation and migration of OA synoviocytes, the expression of IL-8, CCL2, CCL20, matrix metalloproteinase(MMP)-1 and MMP-3, and the production of oxidative stress. We found that CORM-2 reduced the phosphorylation of extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase1/2 and to a lesser extent p38. Our results also showed that CORM-2 significantly decreased the activation of nuclear factor-κB and activator protein-1 regulating the transcription of chemokines and MMPs in OA synoviocytes.Conclusion/SignificanceA number of synoviocyte functions relevant in OA synovitis and articular degradation can be down-regulated by CORM-2. These results support the interest of this class of agents for the development of novel therapeutic strategies in inflammatory and degenerative conditions

    One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

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    BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research

    Perspectives on the mesenchymal origin of metastatic cancer

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    Adult language, literacy, numeracy and problem-solving skills in the workplace

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    This paper examines the performance of the eight major occupational categories across the four skill areas of the Adult Literacy and Life Skills Survey. The results indicated that some 38-64% of employed Australians were below minimal competence (at Level 1 or Level 2) in one of the four skill areas of prose literacy, document literacy, numeracy or problem-solving skills. A pattern of greatest need was identified amongst two occupational groups, namely, machinery operators/drivers and labourers. There was also a clear occupational hierarchy in the area of problem-solving skills that was considered to reflect a social bias since it was inconsistent with the three other skill areas. The findings also highlight pockets of social disadvantage and inequality with many labourers outperforming managers and professionals. It was concluded that the pattern of performance across occupations and skill levels was statistically and significantly different than chance

    Young people in transition: Factors influencing the educational-vocational pathways of Australian school-leavers

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    The educational achievements of a representative national sample of Australian school-leavers were examined after leaving school. The study was part of the longitudinal Youth in Transition study – a national probability sample of Australian youth. There was sufficient evidence to argue that the educational and occupational achievements were related to gender, socio-economic status, ethnicity, geographical location (rurality), completion of the highest level of secondary schooling, vocational interests in high school and even levels of literacy and numeracy in primary school. A tentative model of educational-vocational achievement is outlined. © 2001, MCB UP Limite

    Rehabilitation Judgments With Incomplete Information: A Case Study

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    This case study outlines the accuracy of a rehabilitation counsellor in judgments of the quality of life of actual cases comprising accident victims. Up to seven cues of information relating to health, energy, daily activities, self, personal relations, money and living conditions were provided to the counsellor. He/she had to decide whether the clients considered their own quality of life to be poor or good. The counsellor was consistent in his/her judgments (test–retest reliability = .79). The counsellor was accurate in 60% of cases, but this is only marginally better than an automatic decision that every accident victim is dissatisfied with his/her quality of life. The judgment accuracy was suboptimal. It was influenced by a reliance (93%) on satisfaction with personal relationships, whereas basic issues such as money for everyday living were more important in predicting quality of life. It did not appear that increasing the amount of information led to an increase in accuracy. The correlation between accuracy and the number of cues was very low (-.160). © 2011, Cambridge University Press. All rights reserved
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