The boundary lubrication of chemically grafted and cross-linked hyaluronic acid in phosphate buffered saline and lipid solutions measured by the surface forces apparatus

High molecular weight hyaluronic acid (HA) is present in articular joints and synovial fluid at high concentrations; yet despite numerous studies, the role of HA in joint lubrication is still not clear. Free HA in solution does not appear to be a good lubricant, being negatively charged and therefore repelled from most biological, including cartilage, surfaces. Recent enzymatic experiments suggested that mechanically or physically (rather than chemically) trapped HA could function as an “adaptive” or “emergency” boundary lubricant to eliminate wear damage in shearing cartilage surfaces. In this work, HA was chemically grafted to a layer of self-assembled amino-propyl-triethoxy-silane (APTES) on mica and then cross-linked. The boundary lubrication behavior of APTES and of chemically grafted and cross-linked HA in both electrolyte and lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) solutions was tested with a surface forces apparatus (SFA). Despite the high coefficient of friction (COF) of μ ≈ 0.50, the chemically grafted HA gel significantly improved the lubrication behavior of HA, particularly the wear resistance, in comparison to free HA. Adding more DOPC lipid to the solution did not improve the lubrication of the chemically grafted and cross-linked HA layer. Damage of the underlying mica surface became visible at higher loads (pressure >2 MPa) after prolonged sliding times. It has generally been assumed that damage caused by or during sliding, also known as “abrasive friction”, which is the main biomedical/clinical/morphological manifestation of arthritis, is due to a high friction force and, therefore, a large COF, and that to prevent surface damage or wear (abrasion) one should therefore aim to reduce the COF, which has been the traditional focus of basic research in biolubrication, particularly in cartilage and joint lubrication. Here we combine our results with previous ones on grafted and cross-linked HA on lipid bilayers, and lubricin-mediated lubrication, and conclude that for cartilage surfaces, a high COF can be associated with good wear protection, while a low COF can have poor wear resistance. Both of these properties depend on how the lubricating molecules are attached to and organized at the surfaces, as well as the structure and mechanical, viscoelastic, elastic, and physical properties of the surfaces, but the two phenomena are not directly or simply related. We also conclude that to provide both the low COF and good wear protection of joints under physiological conditions, some or all of the four major components of joints—HA, lubricin, lipids, and the cartilage fibrils—must act synergistically in ways (physisorbed, chemisorbed, grafted and/or cross-linked) that are still to be determined.

Molecular aspects of boundary lubrication by human lubricin : effect of disulfide bonds and enzymatic digestion

Lubricin (LUB) is a glycoprotein of the synovial cavity of human articular joints, where it serves as an antiadhesive, boundary lubricant, and regulating factor for the cartilage surface. It has been proposed that these properties are related to the presence of a long, extended, heavily glycosylated and highly hydrated mucinous domain in the central part of the LUB molecule. In this work, we show that LUB has a contour length of 220 ± 30 nm and a persistence length of ≤10 nm. LUB molecules aggregate in oligomers where the protein extremities are linked by disulfide bonds. We have studied the effect of proteolytic digestion by chymotrypsin and removal of the disulfide bonds, both of which mainly affect the N− and C− terminals of the protein, on the adsorption, normal forces, friction (lubrication) forces, and wear of LUB layers adsorbed on smooth, negatively charged mica surfaces, where the protein naturally forms lubricating polymer brush-like layers. After in situ digestion, the surface coverage was drastically reduced, the normal forces were altered, and both the coefficient of friction and the wear were dramatically increased (the COF increased to μ = 1.1−1.9), indicating that the mucinous domain was removed from the surface. Removal of disulfide bonds did not change the surface coverage or the overall features of the normal forces; however, we find an increase in the friction coefficient from μ = 0.02−0.04 to μ = 0.13−1.17 in the pressure regime below 6 atm, which we attribute to a higher affinity of the protein terminals for the surface. The necessary condition for LUB to be a good lubricant is that the protein be adsorbed to the surface via its terminals, leaving the central mucin domain free to form a low-friction, surface-protecting layer. Our results suggest that this “end-anchoring” has to be strong enough to impart the layer a sufficient resistance to shear, but without excessively restricting the conformational freedom of the adsorbed proteins.

Adsorption, lubrication, and wear of lubricin on model surfaces : polymer brush-like behavior of a glycoprotein

Using a surface force apparatus, we have measured the normal and friction forces between layers of the human glycoprotein lubricin, the major boundary lubricant in articular joints, adsorbed from buffered saline solution on various hydrophilic and hydrophobic surfaces: i), negatively charged mica, ii), positively charged poly-lysine and aminothiol, and iii), hydrophobic alkanethiol monolayers. On all these surfaces lubricin forms dense adsorbed layers of thickness 60–100 nm. The normal force between two surfaces is always repulsive and resembles the steric entropic force measured between layers of end-grafted polymer brushes. This is the microscopic mechanism behind the antiadhesive properties showed by lubricin in clinical tests. For pressures up to ∼6 atm, lubricin lubricates hydrophilic surfaces, in particular negatively charged mica (friction coefficient μ = 0.02–0.04), much better than hydrophobic surfaces (μ > 0.3). At higher pressures, the friction coefficient is higher (μ > 0.2) for all surfaces considered and the lubricin layers rearrange under shear. However, the glycoprotein still protects the underlying substrate from damage up to much higher pressures. These results support recent suggestions that boundary lubrication and wear protection in articular joints are due to the presence of a biological polyelectrolyte on the cartilage surfaces.

Managing chondral lesions of the glenohumeral joint

With regard to the use of this technique in the shoulder there has been little published, and the paper by Snow on microfracture of chondral lesions of the glenohumeral joint in this edition of the IJSS aims to provide a little more data regarding outcomes. [4] PÎ ́ssler, in the German literature in 2000, described the use of microfracture in the shoulder in discussing 162 patients who were followed up following microfracture arthroplasty of a range of joints and reported overall good results, particularly for pain relief at 3-6 years.

Reliability maps and probabilistic guarantee of task motion for robotic manipulators

There are many applications for which reliable and safe robots are desired. For example, assistant robots for disabled or elderly people and surgical robots are required to be safe and reliable to prevent human injury and task failure. However, different levels of safety and reliability are required for different tasks so that understanding the reliability of robots is paramount. Currently, it is possible to guarantee the completion of a task when the robot is fault tolerant and the task remains in the fault-tolerant workspace (FTW). The traditional definition of FTW does not consider different reliabilities for the robotic manipulator's different joints. The aim of this paper is to extend the concept of a FTW to address the reliability of different joints. Such an extension can offer a wider FTW while maintaining the required level of reliability. This is achieved by associating a probability with every part of the workspace to extend the FTW. As a result, reliable fault-tolerant workspaces (RFTWs) are introduced by using the novel concept of conditional reliability maps. Such a RFTW can be used to improve the performance of assistant robots while providing the confidence that the robot remains reliable for completion of its assigned tasks. © 2012 Copyright Taylor & Francis and The Robotics Society of Japan.

Running in a minimalist and lightweight shoe is not the same as running barefoot : a biomechanical study

Aim The purpose of this study was to determine the changes in running mechanics that occur when highly trained runners run barefoot and in a minimalist shoe, and specifically if running in a minimalist shoe replicates barefoot running.

Methods Ground reaction force data and kinematics were collected from 22 highly trained runners during overground running while barefoot and in three shod conditions (minimalist shoe, racing flat and the athlete's regular shoe). Three-dimensional net joint moments and subsequent net powers and work were computed using Newton-Euler inverse dynamics. Joint kinematic and kinetic variables were statistically compared between barefoot and shod conditions using a multivariate analysis of variance for repeated measures and standardised mean differences calculated.

Results There were significant differences between barefoot and shod conditions for kinematic and kinetic variables at the knee and ankle, with no differences between shod conditions. Barefoot running demonstrated less knee flexion during midstance, an 11% decrease in the peak internal knee extension and abduction moments and a 24% decrease in negative work done at the knee compared with shod conditions. The ankle demonstrated less dorsiflexion at initial contact, a 14% increase in peak power generation and a 19% increase in the positive work done during barefoot running compared with shod conditions.

Conclusions Barefoot running was different to all shod conditions. Barefoot running changes the amount of work done at the knee and ankle joints and this may have therapeutic and performance implications for runners.

Combined joint fusion for index and middle carpometacarpal instability in elite boxers

Isolated instability of the index and middle finger carpometacarpal joints is uncommon. An unpublished injury pattern in a consecutive series of 13 elite boxers is described, with mid-term radiological and functional results of two novel surgical treatments. All the boxers (from Australia and the UK) were unable to compete owing to pain and weakness. Four boxers were managed initially by open reduction and temporary K-wire fixation. Nine boxers underwent primary carpometacarpal arthrodesis. All were able to return to their previous level of competition. One boxer who had undergone a soft tissue reconstruction competed at international level but required an arthrodesis because of recurrent symptoms. In elite boxers, simple reduction and wiring may be appropriate for an acute injury causing index or middle finger carpometacarpal joint instability, however, arthrodesis is the treatment of choice when instability and degenerative changes are present.

Forward kinematics analysis of offset 6-RRCRR parallel manipulators

A methodology for the numerical solution of the forward kinematics problem of 6-RRCRR parallel manipulators with orthogonal non-intersecting RR-joint configuration is presented in this article. The inverse and forward kinematics solutions of such robots compared with that of parallel robots with orthogonal intersecting RR-joint or universal joint configurations are much more complicated due to the existence of dependent joint variables. The constraints of RR-joints are analysed and the numerical algorithm for the forward kinematics solution is assessed. Numerical results for the solution of the forward kinematics of 6-RRCRR parallel robot under study are provided to confirm the accuracy and efficiency of the procedure.

Inverse kinematics analysis of 6-RRCRR parallel manipulators

This paper presents a solution to the inverse kinematics of 6-RRCRR parallel manipulators with orthogonal non-intersecting RR-joint configuration. The inverse kinematics solution of such parallel robots compared with that of parallel robots with orthogonal intersecting RR-joint or universal joint configuration is more complex due to the existence of RR-joint variables. A novel methodology is established to define 6 independent variables of the actuators and 12 dependent RR-joint variables using the pose of the mobile platform with respect to the base frame. The constraint of RR-joints are analysed and the numerical algorithm to obtain joint variables is assessed. The forward kinematics of a 6- RRCRR parallel manipulator is modelled and computational analysis is performed in order to numerically verify the accuracy and effectiveness of the proposed methodology for the inverse kinematics analysis. Numerical results of a trajectory tracking simulation are provided. The results verify high accuracy for the proposed inverse kinematics solution of this special family of parallel micromanipulators.

The DSM-5: hyperbole, hope or hypothesis?

The furore preceding the release of the new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is in contrast to the incremental changes to several diagnostic categories, which are derived from new research since its predecessor’s birth in 1990. While many of these changes are indeed controversial, they do reflect the intrinsic ambiguity of the extant literature. Additionally, this may be a mirror of the frustration of the field’s limited progress, especially given the false hopes at the dawn of the “decade of the brain”. In the absence of a coherent pathophysiology, the DSM remains no more than a set of consensus based operationalized adjectives, albeit with some degree of reliability. It does not cleave nature at its joints, nor does it aim to, but neither does alternate systems. The largest problem with the DSM system is how it’s used; sometimes too loosely by clinicians, and too rigidly by regulators, insurers, lawyers and at times researchers, who afford it reference and deference disproportionate to its overt acknowledged limitations.

Formulation and simulation of a 3D mechanical model of embryos for microinjection

The understanding of cell manipulation, for example in microinjection, requires an accurate model of the cells. Motivated by this important requirement, a 3D particlebased mechanical model is derived for simulating the deformation of the fish egg membrane and the corresponding cellular forces during microrobotic cell injection. The model is formulated based on the kinematic and dynamic of spring- damper configuration with multi-particle joints considering the visco-elastic fluidic properties. It simulates the indentation force feedback as well as cell visual deformation during microinjection. A preliminary simulation study is conducted with different parameter configurations. The results indicate that the proposed particle-based model is able to provide similar deformation profiles as observed from a real microinjection experiment of the zebrafish embryo published in the literature. As a generic modelling approach is adopted, the proposed model also has the potential in applications with different types of manipulation such as micropipette cell aspiration.

Rheumatoid arthritis and incident fracture in women: a case-control study

Background:
To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia.

Methods:
Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994–2001 were eligible for inclusion as cases (n =1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age- adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann–Whitney U-test to examine age-differences.

Results:
Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p= 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p< 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p= 0.22).

Conclusion:
Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.

Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis

Arthritis is a multifactorial disease for which current therapeutic intervention with high efficacy remains challenging. Arthritis predominately affects articular joints, and cartilage deterioration and inflammation are key characteristics. Current therapeutics targeting inflammatory responses often cause severe side effects in patients because of the systemic inhibition of cytokines or other global immunosuppressive activities. Furthermore, a lack of primary response or failure to sustain a response to treatment through acquired drug resistance is an ongoing concern. Nevertheless, treatments such as disease-modifying anti-rheumatic drugs, biological agents, and corticosteroids have revealed promising outcomes by decreasing pain and inflammation in patients and in some cases reducing radiographic progression of the disease. Emerging and anecdotal therapeutics with anti-inflammatory activity, alongside specific inhibitors of the A Disintegrin-like And Metalloproteinase domain with Thrombospondin-1 repeats (ADAMTS) cartilage-degrading aggrecanases, provide promising additions to current arthritis treatment strategies. Thus, it is paramount that treatment strategies be optimized to increase efficacy, reduce debilitating side effects, and improve the quality of life of patients with arthritis. Here, we review the current strategies that attempt to slow or halt the progression of osteoarthritis and rheumatoid arthritis, providing an up-to-date summary of pharmaceutical treatment strategies and side effects. Importantly, we highlight their potential to indirectly regulate ADAMTS aggrecanase activity through their targeting of inflammatory mediators, thus providing insight into a mechanism by which they might inhibit cartilage destruction to slow or halt radiographic progression of the disease. We also contrast these with anecdotal or experimental administration of statins that could equally regulate ADAMTS aggrecanase activity and are available to arthritis sufferers worldwide. Finally, we review the current literature regarding the development of synthetic inhibitors directed toward the aggrecanases ADAMTS4 and ADAMTS5, a strategy that might directly inhibit cartilage destruction and restore joint function in both rheumatoid arthritis and osteoarthritis.

A method for extending planar axis-symmetric parallel manipulators to spatial mechanisms

This paper investigates axis-symmetric parallel manipulators, composed of a central base column and an arm system able to rotate around this column. The arm system includes several actuated upper arms, each connected to a manipulated platform by one or more lower arm linkages. Such manipulators feature an extensive positional workspace in relation to the manipulator footprint and equal manipulator properties in all radial half-planes defined by the common rotation-axis of the upper arms. The similarities between planar manipulators exclusively employing 2-degrees-of-freedom (2-DOF) lower arm linkages and lower mobility spatial manipulators only utilising 5-DOF lower arm linkages are analysed. The 2-DOF linkages are composed of a link with a 1-DOF hinge on both ends whilst the 5-DOF linkages utilise 3-DOF spherical joints and 2-DOF universal joints. By employing a proposed linkage substitution scheme, it is shown how a wide range of spatial axis-symmetric parallel manipulators can be derived from a limited range of planar manipulators of the same type.