Dickkopf-3 is upregulated in osteoarthritis and has a chondroprotective role

Objective Dickkopf-3 (Dkk3) is a non-canonical member of the Dkk family of Wnt antagonists and its upregulation has been reported in microarray analysis of cartilage from mouse models of osteoarthritis (OA). In this study we assessed Dkk3 expression in human OA cartilage to ascertain its potential role in chondrocyte signaling and cartilage maintenance. Methods Dkk3 expression was analysed in human adult OA cartilage and synovial tissues and during chondrogenesis of ATDC5 and human mesenchymal stem cells. The role of Dkk3 in cartilage maintenance was analysed by incubation of bovine and human cartilage explants with interleukin-1 (IL1) and oncostatin-M (OSM). Dkk3 expression was measured in cartilage following murine hip avulsion. Whether Dkk3 influenced Wnt, TGF and activin cell signaling was assessed in primary human chondrocytes and SW1353 chondrosarcoma cells using RT-qPCR and luminescence assays. Results Increased gene and protein levels of Dkk3 were detected in human OA cartilage, synovial tissue and synovial fluid. DKK3 expression was decreased during chondrogenesis of both ATDC5 cells and humans MSCs. Dkk3 inhibited IL1 and OSM-mediated proteoglycan loss from human and bovine cartilage explants and collagen loss from bovine cartilage explans. Cartilage DKK3 expression was decreased following hip avulsion injury. TGF signaling was enhanced by Dkk3 and Wnt3a and activin signaling were inhibited. Conclusions We provide evidence that Dkk3 is upregulated in OA and may have a protective effect on cartilage integrity by preventing proteoglycan loss and helping to restore OA-relevant signaling pathway activity. Targeting Dkk3 may be a novel approach in the treatment of OA

A multi-proxy approach to identifying short-lived marine incursions in the Early Carboniferous

This study is a contribution to the TW:eed Project (Tetrapod World: early evolution and diversification), which examines the rebuilding of Carboniferous ecosystems following a mass extinction at the end of the Devonian. The project focuses on the Tournaisian Ballagan Formation of Scotland and the Borders, which contains rare fish and tetrapod material. The Ballagan Formation is characterised by sandstones, dolomitic cementstones, paleosols, siltstones and gypsum deposits. The depositional environment ranges from fluvial, alluvial-plain to marginal-marine environments, with fluvial, floodplain and lacustrine deposition dominant

Increasing age and tear size reduce rotator cuff repair healing rate at 1 year : Data from a large randomized controlled trial

Peer reviewedPublisher PD

Comparison of cellular responses to TGF-β1 and BMP-2 between healthy and torn tendons

Background: Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-β) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation. Purpose: To understand how TGF-β and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons. Study Design: Controlled laboratory study. Methods: Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-β1 (10 ng/mL) or BMP-2 (100 ng/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting. Results: TGF-β1 treatment induced ACAN mRNA expression in both cell types but less in the diseased compared with healthy cells (P < .05). BMP-2 treatment induced BGN mRNA expression in healthy but not diseased cells (P < .01). In the diseased cells, TGF-β1 treatment induced increased ACTA2 mRNA expression (P < .01) and increased small mothers against decapentaplegic (SMAD) signaling (P < .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced ACTA2 mRNA expression in the diseased cells only (P < .05). Conclusion: Diseased tendon–derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-β1 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells. Clinical Relevance: Findings from this study suggest that diseased tendon–derived cells respond differently than healthy cells in the presence of TGF-β1 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing

Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial

BackgroundRotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to MethodsORVAC is a 2-stage, double-blind, randomized, placebo-controlled trial. Australian Aboriginal children 6 to ResultsBetween March 2018 and August 2020, a total of 253 infants were enrolled. Of these, 178 infants (70%) had analyzable serological results after follow-up; 89 were randomized to receive Rotarix, and 89 to receive placebo. The proportion with seroresponse was 85% after Rotarix compared with 72% after placebo. There were no occurrences of intussusception or any serious adverse events.ConclusionsAn additional dose of Rotarix administered to Australian Aboriginal infants 6 to Clinical trials registrationNCT02941107

Relationship of creative projects in anatomy to medical student professionalism, test performance and stress: an exploratory study

<p>Abstract</p> <p>Background</p> <p>The anatomy course offers important opportunities to develop professionalism at an early stage in medical education. It is an academically significant course that also engenders stress in some students.</p> <p>Methods</p> <p>Over a three-year period, 115 of 297 students completed creative projects. Thirty-four project completers and 47 non-completers consented to participate in the study. Projects were analyzed for professionalism themes using grounded theory. A subset of project completers and non-completers were interviewed to determine their views about the stress of anatomy and medical school, as well as the value of the creative projects. We also compared test performance of project completers and non-completers.</p> <p>Results</p> <p>Projects completed early in the course often expressed ambivalence about anatomy, whereas later projects showed more gratitude and sense of awe. Project completers tended to report greater stress than noncompleters, but stated that doing projects reduced stress and caused them to develop a richer appreciation for anatomy and medicine. Project completers performed significantly lower than non-completers on the first written exam (pre-project). Differences between groups on individual exams after both the first and second creative project were nonsignificant.</p> <p>Conclusion</p> <p>For some students, creative projects may offer a useful way of reflecting on various aspects of professionalism while helping them to manage stress.</p