Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis

Introduction: The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage. Methods: Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions. Results: Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism. Conclusions: sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.

Prevalence and risk factors for foot and ankle musculoskeletal disorders experienced by nurses

Background Nurses are at high risk of musculoskeletal disorders (MSDs). Although the prevalence of MSDs of the lower back, upper limbs, neck and shoulders have been reported previously in nursing, few studies have evaluated MSDs of the foot and ankle. This study evaluated the prevalence of foot and ankle MSDs in nurses and their relation to individual and workplace risk factors. Methods A self-administered survey incorporating the Nordic Musculoskeletal Questionnaire (NMQ) was distributed, over a nine-week period, to all eligible nurses (n = 416) working in a paediatric hospital in Brisbane, Australia. The prevalence of MSDs for each of the NMQ body regions was determined. Bivariate and multivariable logistic regression analyses were conducted to examine the relationships between activity-limiting foot/ankle MSDs and risk factors related to the individual (age, body mass index, number of existing foot conditions, smoking history, general physical health [SF36 Physical Component Scale], footwear features) or the workplace (level of nursing position, work location, average hours worked, hours worked in previous week, time since last break from work). Results A 73% response rate was achieved with 304 nurses completing surveys, of whom 276 were females (91%). Mean age of the nurses was 37 years (±10), younger than the state average of 43 years. Foot/ankle MSDs were the most prevalent conditions experienced by nurses during the preceding seven days (43.8%, 95% CI 38.2-49.4%), the second most prevalent MSDs to impair physical activity (16.7%, 95% CI 13.0-21.3%), and the third most prevalent MSD, after lower-back and neck problems, during the preceding 12 months (55.3%, 95% CI 49.6-60.7%). Of the nurse and work characteristics investigated, obesity, poor general physical health, existing foot conditions and working in the intensive care unit emerged as statistically significant (p < 0.05) independent risk factors for activity-limiting foot/ankle MSDs. Conclusions Foot/ankle MSDs are common in paediatric hospital nurses and resulted in physical activity limitations in one out of every six nurses. We recommend targeted education programs regarding the prevention, self-management and treatment strategies for foot/ankle MSDs. Further research is needed into the impact of work location and extended shift durations on foot/ankle MSDs.

Errors in the knee joint forces and moments during gait depending on the foot and knee prosthetic components

Background Previously studies showed that inverse dynamics based on motion analysis and force-plate is inaccurate compared to direct measurements for individuals with transfemoral amputation (TFA). Indeed, direct measurements can appropriately take into account the absorption at the prosthetic foot and the resistance at the prosthetic knee. [1-3] However, these studies involved only a passive prosthetic knee. Aim The objective of the present study was to investigate if different types of prosthetic feet and knees can exhibit different levels of error in the knee joint forces and moments. Method Three trials of walking at self-selected speed were analysed for 9 TFAs (7 males and 2 females, 47±9 years old, 1.76±0.1 m 79±17 kg) with a motion analysis system (Qualisys, Goteborg, Sweden), force plates (Kitsler, Winterthur, Switzerland) and a multi-axial transducer (JR3, Woodland, USA) mounted above the prosthetic knee [1-17]. TFAs were all fitted with an osseointegrated implant system. The prostheses included different type of foot (N=5) and knee (N=3) components. The root mean square errors (RMSE) between direct measurements and the knee joint forces and moments estimated by inverse dynamics were computed for stance and swing phases of gait and expressed as a percentage of the measured amplitudes. A one-way Kruskal-Wallis ANOVA was performed (Statgraphics, Levallois-Perret, France) to analyse the effects of the prosthetic components on the RMSEs. Cross-effects and post-hoc tests were not analysed in this study. Results A significant effect (*) was found for the type of prosthetic foot on anterior-posterior force during swing (p=0.016), lateral-medial force during stance (p=0.009), adduction-abduction moment during stance (p=0.038), internal-external rotation moment during stance (p=0.014) and during swing (p=0.006), and flexion-extension moment during stance (p = 0.035). A significant effect (#) was found for the type of prosthetic knee on anterior-posterior force during swing (p=0.018) and adduction-abduction moment during stance (p=0.035). Discussion & Conclusion The RMSEs were larger during swing than during stance. It is because the errors on accelerations (as derived from motion analysis) become substantial with respect to the external loads. Thus, inverse dynamics during swing should be analysed with caution because the mean RMSEs are close to 50%. Conversely, there were fewer effects of the prosthetic components on RMSE during swing than during stance and, accordingly, fewer effects due to knees than feet. Thus, inverse dynamics during stance should be used with caution for comparison of different prosthetic components.

The role of IL-17-secreting mast cells in inflammatory joint disease

The proinflammatory cytokine IL-17 has an important role in pathogenesis of several inflammatory diseases. In immune-mediated joint diseases, IL-17 can induce secretion of other proinflammatory cytokines such as IL-1, IL-6 and TNF, as well as matrix metalloproteinase enzymes, leading to inflammation, cartilage breakdown, osteoclastogenesis and bone erosion. In animal models of inflammatory arthritis, mice deficient in IL-17 are less susceptible to development of disease. The list of IL-17-secreting cells is rapidly growing, and mast cells have been suggested to be a dominant source of IL-17 in inflammatory joint disease. However, many other innate sources of IL-17 have been described in both inflammatory and autoinflammatory conditions, raising questions as to the role of mast cells in orchestrating joint inflammation. This article will critically assess the contribution of mast cells and other cell types to IL-17 production in the inflammatory milieu associated with inflammatory arthritis, understanding of which could facilitate targeted therapeutic approaches. © 2013 Macmillan Publishers Limited. All rights reserved.

Mechanical properties of a hollow-cylindrical-joint honeycomb

In this paper, we constructed a new honeycomb by replacing the three-edge joint of the conventional regular hexagonal honeycomb with a hollow-cylindrical joint, and developed a corresponding theory to study its mechanical properties, i.e., Young's modulus, Poisson's ratio, fracture strength and stress intensity factor. Interestingly, with respect to the conventional regular hexagonal honeycomb, its Young's modulus and fracture strength are improved by 76% and 303%, respectively; whereas, for its stress intensity factor, two possibilities exist for the maximal improvements which are dependent of its relative density, and the two improvements are 366% for low-density case and 195% for high-density case, respectively. Moreover, a minimal Poisson's ratio exists. The present structure and theory could be used to design new honeycomb materials.

Exploring methods of preparing functional cartilage-bone xenografts for joint repair

This thesis explores the feasibility of donor-receiver concept for joint replacement where cartilage-bone tissues can be taken from either human or other mammals and prepared scientifically for repairing focal joint defects in knees, hips and shoulders. The manufactured construct is immunologically inert and is capable of acting as a scaffold for engineering new cartilage-bone laminates when placed in the joint. Innovative manufacturing procedures and assessment techniques were developed for appraising this tissue-based scaffold. This research has demonstrated that tissue replacement technology can be applied in situations where blood vessels are absent such as in articular cartilage.

Improving the outcomes of foot and ankle surgery. Professional impact of the Australasian College of Podiatric Surgeons' audit tool

Background Surgery is an example of expanded practice scope that enhances podiatry and incorporates inter-professional collaboration. By 2050 demand for foot and ankle procedures is predicted to rise nationally by 61.9%. Performance management of this increase motivated the development of an online audit tool. Developed in collaboration with the Australasian College of Podiatric Surgeons (ACPS), the ACPS audit tool provides real-time data capture and reporting. It is the first audit tool designed in Australia to support and improve the outcomes of foot and ankle surgery. Methods Audit activity in general, orthopaedic, plastic and podiatric surgery was examined using a case study design. Audit participation enablers and barriers were explored. Case study results guided a Delphi survey of international experts experienced or associated with foot and ankle surgery. Delphi survey-derived consensus informed modification of a generic data set from the Royal Australasian College of Surgeons (RACS). Based on the Delphi survey findings the ACPS online audit tool was developed and piloted. Reliability and validity of data entry and usability of this new tool was then assessed with an online survey. Results The case study found surgeon attitudes and behaviours positively impacted audit participation, and also indicated that audit data should be: (1) available in real time, (2) identify practice change, (3) applicable for safety and quality management, and; (4) useful for peer review discussion. The Delphi process established consensus on audit variables to be captured, including the modified RACS generic data set. 382 cases of foot and ankle surgery were captured across 3 months using the new tool. Data entry was found to be valid and reliable. Real-time outcome reporting and practice change identification impacted positively on safety and quality management and assisted peer review discussion. An online survey showed high levels of usability. Conclusions Surgeon contribution to audit tool development resulted in 100% audit participation. The data from the ACPS audit tool supported the ACPS submission to the Medical Services Advisory Committee to list podiatric surgery under Medicare, an outcome noted by the Federal Minister of Health.

Morphology-based interslice interpolation on manual segmentations of joint bones and muscles in MRI

This paper presents a validation study on the application of a novel interslice interpolation technique for musculoskeletal structure segmentation of articulated joints and muscles on human magnetic resonance imaging data. The interpolation technique is based on morphological shape-based interpolation combined with intensity based voxel classification. Shape-based interpolation in the absence of the original intensity image has been investigated intensively. However, in some applications of medical image analysis, the intensity image of the slice to be interpolated is available. For example, when manual segmentation is conducted on selected slices, the segmentation on those unselected slices can be obtained by interpolation. We proposed a two- step interpolation method to utilize both the shape information in the manual segmentation and local intensity information in the image. The method was tested on segmentations of knee, hip and shoulder joint bones and hamstring muscles. The results were compared with two existing interpolation methods. Based on the calculated Dice similarity coefficient and normalized error rate, the proposed method outperformed the other two methods.

Gravity-induced coronal plane joint moments in adolescent idiopathic scoliosis

Background Adolescent Idiopathic Scoliosis is the most common type of spinal deformity, and whilst the risk of progression appears to be biomechanically mediated (larger deformities are more likely to progress), the detailed biomechanical mechanisms driving progression are not well understood. Gravitational forces in the upright position are the primary sustained loads experienced by the spine. In scoliosis they are asymmetrical, generating moments about the spinal joints which may promote asymmetrical growth and deformity progression. Using 3D imaging modalities to estimate segmental torso masses allows the gravitational loading on the scoliotic spine to be determined. The resulting distribution of joint moments aids understanding of the mechanics of scoliosis progression. Methods Existing low-dose CT scans were used to estimate torso segment masses and joint moments for 20 female scoliosis patients. Intervertebral joint moments at each vertebral level were found by summing the moments of each of the torso segment masses above the required joint. Results The patients’ mean age was 15.3 years (SD 2.3; range 11.9 – 22.3 years); mean thoracic major Cobb angle 52° (SD 5.9°; range 42°-63°) and mean weight 57.5 kg (SD 11.5 kg; range 41 – 84.7 kg). Joint moments of up to 7 Nm were estimated at the apical level. No significant correlation was found between the patients’ major Cobb angles and apical joint moments. Conclusions Patients with larger Cobb angles do not necessarily have higher joint moments, and curve shape is an important determinant of joint moment distribution. These findings may help to explain the variations in progression between individual patients. This study suggests that substantial corrective forces are required of either internal instrumentation or orthoses to effectively counter the gravity-induced moments acting to deform the spinal joints of idiopathic scoliosis patients.