Objective. To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model.Methods. A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction.Results. Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived boneattachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased.Conclusion. The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.Injuries of the shoulder due to overuse are increasingly prevalent in both the sporting arena and the workplace. Occupational injury of the shoulder is second only to neck and low back pain in the frequency of consultation by general practitioners, with the most common injury involving the rotator cuff. (1,2) The prevalence of rotator cuff conditions increases with age, from 30-50% in the seventh decade of life to a staggering 70-80% by the ninth (3,4). Although most cases are treated conservatively, many patients undergo surgical repair with a prolonged convalescence. There are no drugs to specifically treat disorders of the rotator cuff or other tendons, and many surgical repairs fail within 12 months (5). Lack of knowledge of the fundamental mechanisms that underlie tendon breakdown results in limited and inadequate management options for tendon disorders.

BackgroundBiobanks provide an important foundation for genomic and personalised medicine. In order to enhance their scientific power and scope, they are increasingly becoming part of national or international networks. Public trust is essential in fostering public engagement, encouraging donation to, and facilitating public funding for biobanks. Globalisation and networking of biobanking may challenge this trust. MethodsWe report the results of an Australian study examining public attitudes to the networking and globalisation of biobanks. The study used quantitative and qualitative methods in conjunction with bioethical analysis in order to determine factors that may contribute to, and threaten, trust.ResultsOur results indicate a generally high level of trust in biobanks and in medical research more broadly. Key factors that can reduce perceived trustworthiness of biobanks are commercialisation and involvement in global networking. ConclusionsWe conclude that robust ethical oversight and governance standards can both promote trust in global biobanking and ensure that this trust is warranted.

Hawe et al. raise concerns about Human Research Ethics Committees (HRECs) taking a risk-averse and litigation-sensitive approach to ethical review of research proposals. HRECs are tasked with reviewing proposals for compliance with the National Statement on Ethical Conduct in Human Research for the purpose of promoting the welfare of participants. While these guidelines intentionally include a significant degree of discretion in HREC decision making, there is also evidence that HRECs sometimes request changes that go beyond the guidance provided by the National Statement. When HRECs request changes outside their remit, inconsistencies between individual HRECs become more common, contributing to delays in ethical review and reducing the quality of HREC decision making. Improvements to the HREC regulatory system are needed to promote transparency and accountability.

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