120 research outputs found
Subchondral bone remodelling in osteoarthritis
Subchondral bone remodelling is an integral part of osteoarthritis and involves the development of subchondral sclerosis seen on plain imaging, along with osteophyte formation. The development of these changes is due to persistent abnormal mechanical stresses which create a cellular and biomolecular response to microfractures in the subchondral bone and osteochondral junction. An early sign is bone marrow lesions seen on MRI scanning. Healing can occur at this stage by correcting the abnormal loads. Persistence leads to what is thought to be a delayed union or nonunion response by the bone. Microfractures of the osteochondral junction, coupled with articular cartilage fissuring and loss, allows synovial fluid to penetrate the subchondral bone along with cytokines and other molecules reacting with the bone cells to increase the pathological effects. This review gives an overview of the current thoughts on subchondral bone remodelling in osteoarthritis that is aimed at orthopaedic surgeons to help in the understanding of the pathogenesis of osteoarthritis and the role of surgical management
The potential use of microcalorimetry in rapid differentiation between septic arthritis and other causes of arthritis.
Current diagnostic methods in differentiating septic from non-septic arthritis are time-consuming (culture) or have limited sensitivity (Gram stain). Microcalorimetry is a novel method that can rapidly detect microorganisms by their heat production. We investigated the accuracy and time to detection of septic arthritis by using microcalorimetry. Patients older than 18 years of age with acute arthritis of native joints were prospectively included. Synovial fluid was aspirated and investigated by Gram stain, culture and microcalorimetry. The diagnosis of septic arthritis and non-septic arthritis were made by experienced rheumatologists or orthopaedic surgeons. Septic arthritis was diagnosed by considering the finding of acute arthritis together with findings such as positive Gram stain or positive culture of synovial fluid or positive blood culture. The sensitivity and specificity for diagnosing septic arthritis and the time to positivity of microcalorimetry were determined. Of 90 patients (mean age 64 years), nine had septic arthritis, of whom four (44 %) had positive Gram stain, six (67 %) positive synovial fluid culture and four (44 %) had positive blood culture. The sensitivity of microcalorimetry was 89 %, the specificity was 99 % and the mean detection time was 5.0 h (range, 2.2-8.0 h). Microcalorimetry is an accurate and rapid method for the diagnosis of septic arthritis. It has potential to be used in clinical practice in diagnosing septic arthritis
A next-generation inverse-geometry spallation-driven ultracold neutron source
The physics model of a next-generation spallation-driven high-current
ultracold neutron (UCN) source capable of delivering an extracted UCN rate of
around an-order-of-magnitude higher than the strongest proposed sources, and
around three-orders-of-magnitude higher than existing sources, is presented.
This UCN-current-optimized source would dramatically improve cutting-edge UCN
measurements that are currently statistically limited. A novel "Inverse
Geometry" design is used with 40 L of superfluid He (He-II), which acts as
a converter of cold neutrons (CNs) to UCNs, cooled with state-of-the-art
sub-cooled cryogenic technology to 1.6 K. Our design is optimized for a
100 W maximum heat load constraint on the He-II and its vessel. In our
geometry, the spallation target is wrapped symmetrically around the UCN
converter to permit raster scanning the proton beam over a relatively large
volume of tungsten spallation target to reduce the demand on the cooling
requirements, which makes it reasonable to assume that water edge-cooling only
is sufficient. Our design is refined in several steps to reach
s under our other restriction of 1 MW maximum
available proton beam power. We then study effects of the He-II scattering
kernel as well as reductions in due to pressurization to reach
s. Finally, we provide a design for the UCN
extraction system that takes into account the required He-II heat transport
properties and implementation of a He-II containment foil that allows UCN
transmission. We estimate a total useful UCN current from our source of
s from a 18 cm diameter guide 5 m from the source.
Under a conservative "no return" approximation, this rate can produce an
extracted density of cm in 1000~L external experimental
volumes with a Ni (335 neV) cut-off potential.Comment: Submitted to Journal of Applied Physic
CD11b Signaling Prevents Chondrocyte Mineralization and Attenuates the Severity of Osteoarthritis.
Osteoarthritis (OA) is a progressive joint disease that is strongly associated with calcium-containing crystal formation (mineralization) by chondrocytes leading ultimately to cartilage calcification. However, this calcification process is poorly understood and treatments targeting the underlying disease mechanisms are lacking. The CD11b/CD18 integrin (Mac-1 or αMβ2), a member of the beta 2 integrin family of adhesion receptors, is critically involved in the development of several inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus. We found that in a collagen-induced arthritis, CD11b-deficient mice exhibited increased cartilage degradation compared to WT control animals. However, the functional significance of CD11b integrin signaling in the pathophysiology of chondrocytes remains unknown. CD11b expression was found in the extracellular matrix and in chondrocytes in both healthy and damaged human and murine articular cartilage. Primary murine CD11b KO chondrocytes showed increased mineralization when induced in vitro by secondary calciprotein particles (CPP) and quantified by Alizarin Red staining. This increased propensity to mineralize was associated with an increased alkaline phosphatase (Alp) expression (measured by qRT-PCR and activity assay) and an enhanced secretion of the pro-mineralizing IL-6 cytokine compared to control wild-type cells (measured by ELISA). Accordingly, addition of an anti-IL-6 receptor antibody to CD11b KO chondrocytes reduced significantly the calcification and identified IL-6 as a pro-mineralizing factor in these cells. In the same conditions, the ratio of qRT-PCR expression of collagen X over collagen II, and that of Runx2 over Sox9 (both ratio being indexes of chondrocyte hypertrophy) were increased in CD11b-deficient cells. Conversely, the CD11b activator LA1 reduced chondrocyte mineralization, Alp expression, IL-6 production and collagen X expression. In the meniscectomy (MNX) model of murine knee osteoarthritis, deficiency of CD11b led to more severe OA (OARSI scoring of medial cartilage damage in CD11b: 5.6 ± 1.8, in WT: 1.2 ± 0.5, p < 0.05, inflammation in CD11b: 2.8 ± 0.2, in WT: 1.4 ± 0.5). In conclusion, these data demonstrate that CD11b signaling prevents chondrocyte hypertrophy and chondrocyte mineralization in vitro and has a protective role in models of OA in vivo
Alterations of Subchondral Bone Progenitor Cells in Human Knee and Hip Osteoarthritis Lead to a Bone Sclerosis Phenotype.
Subchondral bone tissue plays a key role in the initiation and progression of human and experimental osteoarthritis and has received considerable interest as a treatment target. Elevated bone turnover and remodeling leads to subchondral bone sclerosis that is characterized by an increase in bone material that is less mineralized. The aim of this study was to investigate whether perturbations in subchondral bone-resident progenitor cells might play a role in aberrant bone formation in osteoarthritis. Colony formation assays indicated similar clonogenicity of progenitor cells from non-sclerotic and sclerotic subchondral trabecular bone tissues of osteoarthritic knee and hip joints compared with controls from iliac crest bone. However, the osteogenic potential at the clonal level was approximately two-fold higher in osteoarthritis than controls. An osteogenic differentiation assay indicated an efficient induction of alkaline phosphatase activity but blunted in vitro matrix mineralization irrespective of the presence of sclerosis. Micro-computed tomography and histology demonstrated the formation of de novo calcified tissues by osteoblast-like cells in an ectopic implantation model. The expression of bone sialoprotein, a marker for osteoblast maturation and mineralization, was significantly less in sclerotic progenitor cells. Perturbation of resident progenitor cell function is associated with subchondral bone sclerosis and may be a treatment target for osteoarthritis
Mapping of functionalized regions on carbon nanotubes by scanning tunneling microscopy
Scanning tunneling microscopy (STM) gives us the opportunity to map the
surface of functionalized carbon nanotubes in an energy resolved manner and
with atomic precision. But this potential is largely untapped, mainly due to
sample stability issues which inhibit reliable measurements. Here we present a
simple and straightforward solution that makes away with this difficulty, by
incorporating the functionalized multiwalled carbon nanotubes (MWCNT) into a
few layer graphene - nanotube composite. This enabled us to measure energy
resolved tunneling conductance maps on the nanotubes, which shed light on the
level of doping, charge transfer between tube and functional groups and the
dependence of defect creation or functionalization on crystallographic
orientation.Comment: Keywords: functionalization, carbon nanotubes, few layer graphene,
STM, CITS, ST
Association between drug intake and incidence of malignancies in patients with Juvenile Idiopathic Arthritis: a nested case–control study
Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course
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