Technical pre-study for the ExMS project

This report aims to give an overview of software and hardware platforms available now or in the near future for building a prototype of an ExMS application (for an overview of the ExMS project, see Appendix). The report also gives an overview of the different technologies for building third-party mobile client software applications that are in use today. The report is composed of three sections. The first section is a general discussion on mobile client software and the different technologies that can be used to develop third-party mobile client software. The next section continues with a specific discussion on ExMS and answers the following questions: What is the general architecture of the ExMS application? What alternatives exist for implementing the ExMS prototype? The final section of the report is a recommendation of hardware and software platform for building the ExMS prototype

Micro-CT Characterization of Human Trabecular Bone in Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment

Influence of thresholding in mass and entropy dimension of 3-D soil images

With the advent of modern non-destructive tomography techniques, there have been many attempts to analyze 3-D pore space features mainly concentrating on soil structure. This analysis opens a challenging opportunity to develop techniques for quantifying and describe pore space properties, one of them being fractal analysis. Undisturbed soil samples were collected from four horizons of Brazilian soil and 3-D images at 45μm resolution. Four different threshold criteria were used to transform computed tomography (CT) grey-scale imagery into binary imagery (pore/solid) to estimate their mass fractal dimension (Dm) and entropy dimension (D1). Each threshold criteria had a direct influence on the porosity obtained, varying from 8 to 24% in one of the samples, and on the fractal dimensions. Linear scaling was observed over all the cube sizes, however depending on the range of cube sizes used in the analysis, Dm could vary from 3.00 to 2.20, realizing that the threshold influenced mainly the scaling in the smallest cubes (length of size from 1 to 16 voxels). Dm and D1 showed a logarithmic relation with the apparent porosity in the image, however, the increase of both values respect to porosity defined a characteristic feature for each horizon that can be related to soil texture and depth

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

Methods for reduced platen compression (RPC) test specimen cutting locations using micro-CT and planar radiographs

This study looks at improving reduced platen compression (RPC) specimen preparation procedures by developing a better method for locating the ideal RPC specimen on each bone. These improvements are aimed at decreasing the amount of time required to complete an RPC analysis and improving the quality of the obtained results. High-resolution micro-CT scans are used to gain a better understanding of rat long bone anatomy by quantifying the location, shape, and orientation of the growth plate, primary spongiosa, and secondary spongiosa. Micro-CT analysis shows that there are easily identifiable external landmarks on the anterior side of both tibias and femurs that identify the end of the growth plate and the point at which the top of an ideal RPC specimen should be located. The landmarks are the most proximal tip of the patellar surface for the femur and the base of the tibial tuberosity for the tibia. This study also analyzes the effect of variations in the actual RPC specimen location from the ideal location and the effect of different platen sizes on test results using BMD as a surrogate for mechanical properties. The analysis shows that the BMD increases as the target RPC specimen location approaches the growth plate and decreases on moving away from the growth plate. The study also indicates that consistency is necessary when obtaining RPC specimens to avoid error due to variation from the specified landmark. Additionally, the BMD decreased as the diameter of the platen is reduced. Choosing platen size then becomes a trade off between testing the greatest amount of cancellous bone possible and potentially higher load sharing by the cortical shell with larger platen sizes as well as the risk of compressing cortical bone during the test

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

IntroductionThe interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.MethodsHuman CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice.ResultsIL-17A upregulates the receptor activator for NF-kappaB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts.ConclusionsCollectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases