Biomimetic knee design to improve joint torque and life for bipedal robotics

© Springer International Publishing AG, part of Springer Nature 2018. This paper details the design, construction, and performance analysis of a biologically inspired knee joint for use in bipedal robotics. The design copies the condylar surfaces of the distal end of the femur and utilizes the same crossed four-bar linkage design the human knee uses. The joint includes a changing center of rotation, a screw-home mechanism, and patella; these are characteristics of the knee that are desirable to copy for bipedal robotics. The design was calculated to have an average sliding to rolling ratio of 0.079, a maximum moment arm of 2.7 in and a range of motion of 151°. This should reduce wear and perform similar to the human knee. Prototypes of the joint have been created to test these predicted properties

Experimental validation of a new biphasic model of the contact mechanics of the porcine hip

Hip models that incorporate the biphasic behaviour of articular cartilage can improve understanding of the joint function, pathology of joint degeneration and effect of potential interventions. The aim of this study was to develop a specimen-specific biphasic finite element model of a porcine acetabulum incorporating a biphasic representation of the articular cartilage and to validate the model predictions against direct experimental measurements of the contact area in the same specimen. Additionally, the effect of using a different tension-compression behaviour for the solid phase of the articular cartilage was investigated. The model represented different radial clearances and load magnitudes. The comparison of the finite element predictions and the experimental measurement showed good agreement in the location, size and shape of the contact area, and a similar trend in the relationship between contact area and load was observed. There was, however, a deviation of over 30% in the magnitude of the contact area, which might be due to experimental limitations or to simplifications in the material constitutive relationships used. In comparison with the isotropic solid phase model, the tension-compression solid phase model had better agreement with the experimental observations. The findings provide some confidence that the new biphasic methodology for modelling the cartilage is able to predict the contact mechanics of the hip joint. The validation provides a foundation for future subject-specific studies of the human hip using a biphasic cartilage model

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

The effect of constitutive representations and structural constituents of ligaments on knee joint mechanics

Abstract Ligaments provide stability to the human knee joint and play an essential role in restraining motion during daily activities. Compression-tension nonlinearity is a well-known characteristic of ligaments. Moreover, simpler material representations without this feature might give reasonable results because ligaments are primarily in tension during loading. However, the biomechanical role of different constitutive representations and their fibril-reinforced poroelastic properties is unknown. A numerical knee model which considers geometric and material nonlinearities of meniscus and cartilages was applied. Five different constitutive models for the ligaments (spring, elastic, hyperelastic, porohyperelastic, and fibril-reinforced porohyperelastic (FRPHE)) were implemented. Knee joint forces for the models with elastic, hyperelastic and porohyperelastic properties showed similar behavior throughout the stance, while the model with FRPHE properties exhibited lower joint forces during the last 50% of the stance phase. The model with ligaments as springs produced the lowest joint forces at this same stance phase. The results also showed that the fibril network contributed substantially to the knee joint forces, while the nonfibrillar matrix and fluid had small effects. Our results indicate that simpler material models of ligaments with similar properties in compression and tension can be used when the loading is directed primarily along the ligament axis in tension

Workflow assessing the effect of gait alterations on stresses in the medial tibial cartilage - combined musculoskeletal modelling and finite element analysis

Abstract Knee osteoarthritis (KOA) is most common in the medial tibial compartment. We present a novel method to study the effect of gait modifications and lateral wedge insoles (LWIs) on the stresses in the medial tibial cartilage by combining musculoskeletal (MS) modelling with finite element (FE) analysis. Subject’s gait was recorded in a gait laboratory, walking normally, with 5° and 10° LWIs, toes inward (‘Toe in’), and toes outward (‘Toe out wide’). A full lower extremity MRI and a detailed knee MRI were taken. Bones and most soft tissues were segmented from images, and the generic bone architecture of the MS model was morphed into the segmented bones. The output forces from the MS model were then used as an input in the FE model of the subject’s knee. During stance, LWIs failed to reduce medial peak pressures apart from Insole 10° during the second peak. Toe in reduced peak pressures by −11% during the first peak but increased them by 12% during the second. Toe out wide reduced peak pressures by −15% during the first and increased them by 7% during the second. The results show that the work flow can assess the effect of interventions on an individual level. In the future, this method can be applied to patients with KOA

Cervicothoracic Multisegmental Transpinal Evoked Potentials in Humans

The objectives of this study were to establish the neurophysiological properties of the transpinal evoked potentials (TEPs) following transcutaneous electric stimulation of the spine (tsESS) over the cervicothoracic region, changes in the amplitude of the TEPs preceded by median nerve stimulation at group I threshold, and the effects of tsESS on the flexor carpi radialis (FCR) H-reflex in thirteen healthy human subjects while seated. Two re-usable self-adhering electrodes, connected to function as one electrode (cathode), were placed bilaterally on the clavicles. A re-usable electrode (anode) was placed on the cervicothoracic region covering from Cervical 4 – Thoracic 2 and held under constant pressure throughout the experiment. TEPs were recorded bilaterally from major arm muscles with subjects seated at stimulation frequencies of 1.0, 0.5, 0.33, 0.2, 0.125, and 0.1 Hz, and upon double tsESS pulses delivered at an inter-stimulus interval of 40 ms. TEPs from the arm muscles were also recorded following median nerve stimulation at the conditioning-test (C-T) intervals of 2, 3, 5, 8, and 10 ms. The FCR H-reflex was evoked and recorded according to conventional methods following double median nerve pulses at 40 ms, and was also conditioned by tsESS at C-T intervals that ranged from −10 to +50 ms. The arm TEPs amplitude was not decreased at low-stimulation frequencies and upon double tsESS pulses in all but one subject. Ipsilateral and contralateral arm TEPs were facilitated following ipsilateral median nerve stimulation, while the FCR H-reflex was depressed by double pulses and following tsESS at short and long C-T intervals. Non-invasive transpinal stimulation can be used as a therapeutic modality to decrease spinal reflex hyper-excitability in neurological disorders and when combined with peripheral nerve stimulation to potentiate spinal output