Serum and synovial fluid lipidomic profiles predict obesity-associated osteoarthritis, synovitis, and wound repair

High-fat diet-induced obesity is a major risk factor for osteoarthritis (OA) and diminished wound healing. The objective of this study was to determine the associations among serum and synovial fluid lipid levels with OA, synovitis, adipokine levels, and wound healing in a pre-clinical obese mouse model of OA. Male C57BL/6 J mice were fed either a low-fat (10% kcal) or one of three high-fat (HF, 60% kcal) diets rich in saturated fatty acids (SFAs), ω-6 or ω-3 polyunsaturated FAs (PUFAs). OA was induced by destabilization of the medial meniscus. Mice also received an ear punch for evaluating wound healing. Serum and synovial fluid were collected for lipidomic and adipokine analyses. We demonstrated that the serum levels of ω-3 PUFAs were negatively correlated with OA and wound size, but positively correlated with adiponectin levels. In contrast, most ω-6 PUFAs exhibited positive correlations with OA, impaired healing, and inflammatory adipokines. Interestingly, levels of pentadecylic acid (C15:0, an odd-chain SFA) and palmitoleic acid were inversely correlated with joint degradation. This study extends our understanding of the links of FAs with OA, synovitis and wound healing, and reports newly identified serum and synovial fluid FAs as predictive biomarkers of OA in obesity

The Role of Stakeholders in HIA: A Landfill Site and Housing Development in Mundijong, Western Australia

The use of Health Impact Assessment (HIA) as a tool to identify and manage issues relating to health has not been widely adopted in Western Australia. Health Impact Assessment methodology was applied to two concurrent developments in the Shire of Serpentine Jarrahdale, Western Australia. Potential health impacts of the expansionof a sanitary landfill adjacent to a proposed housing development were identified following a literature review and stakeholder interviews. Recommendations to assess the risk to the community in the housing estate through quantitative analysis, and risk management strategies were provided to the Shire. The ability of an existing stakeholder group for the landfill, the South Cardup Landfill Stakeholder Consultative Group, to resolve concerns of the community relating to environmental and social issues were also evaluated. Recommendations to improve collaborative decision making were provided to the Stakeholder Group using the Framework for Democratic Science. The outcomes of the HIA informed the Shire of potential health impacts to assist decision making during the development application process and the design of a local District Structure Plan

Reviews

Judith Jeffcoate, Multimedia in Practice ‐Technology and Applications, BCS Practitioner Series, Prentice‐Hall International, 1995. ISBN: 0–13–123324–6. £24.95

Perception or reality? A frame analysis of leadership behavior, style, and effectiveness among selected community college administrators

The American community college has reached a pivotal point in its history, a juncture of conflicting forces pulling and pushing the institution in opposite directions, attacking and supporting its mission, and demanding more from yet providing less to the two-year sector of higher education. At this historical juncture, the community college is also confronted by the challenges inherent in an increasingly diverse student population, heightened external mandates for enhanced accountability, severe funding shortages, continually metamorphosing technological developments, and growing public skepticism. Compounded by an internal leadership crisis, the above forces have converged to create the proverbial “perfect storm,” an unprecedented turning point signaling the need for unprecedented leadership. Such leadership must be both situational and transformational, altering both the leader and the led and giving new credibility to the institution itself. To effectively transform their institutions and ensure the navigation of such turbulent times, current and future community college leaders must first transform themselves through multi-faceted evaluation involving both self-examination of their effectiveness and assessment by those with and for whom they work. This study utilized a multi-rater approach to investigate the leadership behavior, orientation, and effectiveness of sixteen selected administrators at a North Carolina community college. Those administrators included vice-presidents, associate deans, executive directors, executive officers, and one academic dean. The purpose of the researcher was to compare leaders? self-perceptions of their behavior, orientation/style, and managerial and leadership effectiveness with the perceptions expressed by their supervisors, peers, and subordinates. Bolman and Deal?s Leadership Orientation Instrument-Self (LOI-Self) was used to assess individual leaders? self-perceptions; the Leadership Orientation Instrument-Other (LOI-Other), the perceptions expressed by leaders? supervisors, peers, and subordinates. Leadership behavior and orientation were analyzed within Bolman and Deal?s four organizational frames: structural, human resource, political, and symbolic. Independent variables were the groups of raters (self, supervisors, peers, and subordinates). Dependent variables were the perceptions of leadership behavior, orientation, and effectiveness. Descriptive comparisons indicated that leaders and their supervisors considered leaders? preferred frame as the human resource frame, followed by the structural, symbolic, and political frames. Both peers and subordinates deemed the structural frame as leaders? preferred frame, followed by the human resource, symbolic, and political frames. Individual frame analyses revealed discrepancies in the level of rankings, with leaders often rated themselves higher than others. Discrepancies were also noted in leadership and managerial effectiveness, where leaders were more inclined to rate themselves in the top 20% of effective leaders they had known and peers were more inclined to rate leaders in the next to top 20% or middle 20%. A series of nine two-factor Analyses of Variance with Repeated Measures (ANOVR) was used to analyze the differences between leaders? perceptions and the perceptions of others. Results suggested statistically significant differences between leaders? self-perceptions of both their leadership behavior and their leadership orientation when compared with the perceptions of their supervisors, peers, and subordinates

Aging and obesity prime the methylome and transcriptome of adipose stem cells for disease and dysfunction

The epigenome of stem cells occupies a critical interface between genes and environment, serving to regulate expression through modification by intrinsic and extrinsic factors. We hypothesized that aging and obesity, which represent major risk factors for a variety of diseases, synergistically modify the epigenome of adult adipose stem cells (ASCs). Using integrated RNA- and targeted bisulfite-sequencing in murine ASCs from lean and obese mice at 5- and 12-months of age, we identified global DNA hypomethylation with either aging or obesity, and a synergistic effect of aging combined with obesity. The transcriptome of ASCs in lean mice was relatively stable to the effects of age, but this was not true in obese mice. Functional pathway analyses identified a subset of genes with critical roles in progenitors and in diseases of obesity and aging. Specifically, Mapt, Nr3c2, App, and Ctnnb1 emerged as potential hypomethylated upstream regulators in both aging and obesity (AL vs. YL and AO vs. YO), and App, Ctnnb1, Hipk2, Id2, and Tp53 exhibited additional effects of aging in obese animals. Furthermore, Foxo3 and Ccnd1 were potential hypermethylated upstream regulators of healthy aging (AL vs. YL), and of the effects of obesity in young animals (YO vs. YL), suggesting that these factors could play a role in accelerated aging with obesity. Finally, we identified candidate driver genes that appeared recurrently in all analyses and comparisons undertaken. Further mechanistic studies are needed to validate the roles of these genes capable of priming ASCs for dysfunction in aging- and obesity-associated pathologies

Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis

Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA

Tendon mechanobiology: Current knowledge and future research opportunities: TENDON MECHANOBIOLOGY

Tendons mainly function as load-bearing tissues in the muscloskeletal system, transmitting loads from muscle to bone. Tendons are dynamic structures that respond to the magnitude, direction, frequency, and duration of physiologic as well as pathologic mechanical loads via complex interactions between cellular pathways and the highly specialized extracellular matrix. This paper reviews the evolution and current knowledge of mechanobiology in tendon development, homeostasis, disease, and repair. In addition, we review several novel mechanotransduction pathways that have been identified recently in other tissues and cell types, providing potential research opportunities in the field of tendon mechanobiology. We also highlight current methods, models, and technologies being used in a wide variety of mechanobiology research that could be investigated in the context of their potential applicability for answering some of the fundamental unanswered questions in this field. The article concludes with a review of the major questions and future goals discussed during the recent ORS/ISMMS New Frontiers in Tendon Research Conference held September 10–11, 2014 in New York City

Biological resurfacing in a canine model of hip osteoarthritis

[Figure: see text]

Cartilage-specific knockout of the mechanosensory ion channel TRPV4 decreases age-related osteoarthritis

Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA

Defining the effect and mediators of two knowledge translation strategies designed to alter knowledge, intent and clinical utilization of rehabilitation outcome measures: a study protocol [NCT00298727]

BACKGROUND: A substantial number of valid outcome measures have been developed to measure health in adult musculoskeletal and childhood disability. Regrettably, national initiatives have merely resulted in changes in attitude, while utilization remains unacceptably low. This study will compare the effectiveness and mediators of two different knowledge transfer (KT) interventions in terms of their impact on changing knowledge and behavior (utilization and clinical reasoning) related to health outcome measures. METHOD/DESIGN: Physical and occupational therapists (n = 144) will be recruited in partnership with the national professional associations to evaluate two different KT interventions with the same curriculum: 1) Stakeholder-Hosted Interactive Problem-Based Seminar (SHIPS), and 2) Online Problem-Based course (e-PBL). SHIPS will consist of face-to-face problem-based learning (PBL) for 2 1/2 days with outcome measure developers as facilitators, using six problems generated in consultation with participants. The e-PBL will consist of a 6-week web-based course with six generic problems developed by content experts. SHIPS will be conducted in three urban centers in Canada. Participants will be block-allocated by a minimization procedure to either of the two interventions to minimize any prognostic differences. Trained evaluators at each site will conduct chart audits and chart-stimulated recall. Trained interviewers will conduct semi-structured interviews focused on identifying critical elements in KT and implementing practice changes. Interviews will be transcribed verbatim. Baseline predictors including demographics, knowledge, attitudes/barriers regarding outcome measures, and Readiness to Change will be assessed by self-report. Immediately post-intervention and 6 months later, these will be re-administered. Primary qualitative and quantitative evaluations will be conducted 6-months post-intervention to assess the relative effectiveness of KT interventions and to identify elements that contribute to changing clinical behavior. Chart audits will determine the utilization of outcome measures (counts). Incorporation of outcome measures into clinical reasoning will be assessed using an innovative technique: chart-stimulated recall. DISCUSSION: A strategy for optimal transfer of health outcome measures into practice will be developed and shared with multiple disciplines involved in primary and specialty management of musculoskeletal and childhood disability