Persistent Interruption in Parvalbumin-Positive Inhibitory Interneurons: Biophysical and Mathematical Mechanisms.

Persistent activity in excitatory pyramidal cells (PYRs) is a putative mechanism for maintaining memory traces during working memory. We have recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon that could serve as a substrate for persistent activity in PYRs through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modeling and mathematical analysis showed that the slowly inactivating potassium current KV1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption of firing. Using a fast/slow separation of times scales approach with the KV1 inactivation variable as a bifurcation parameter shows that the initial inhibitory stimulus stops repetitive firing by moving the membrane potential trajectory onto a coexisting stable fixed point corresponding to a nonspiking quiescent state. As KV1 inactivation decays, the trajectory follows the branch of stable fixed points until it crosses a subcritical Hopf bifurcation (HB) and then spirals out into repetitive firing. In a model describing entorhinal cortical PV-INs without KV1, interruption of firing could be achieved by taking advantage of the bistability inherent in type 2 excitability based on a subcritical HB, but the interruption was not robust to noise. Persistent interruption of firing is therefore broadly applicable to PV-INs in different brain regions but is only made robust to noise in the presence of a slow variable, KV1 inactivation.

Persistent Interruption in Parvalbumin Positive Inhibitory Interneurons: Biophysical and Mathematical Mechanisms.

Persistent activity in principal cells is a putative mechanism for maintaining memory traces during working memory. We recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon which could serve as a substrate for persistent activity in principal cells through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modelling and mathematical analysis showed that the slowly inactivating potassium current Kv1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption of firing. Using a fast/slow separation of times scales approach with the Kv1 inactivation variable as a bifurcation parameter shows that the initial inhibitory stimulus stops repetitive firing by moving the membrane potential trajectory onto a co-existing stable fixed point corresponding to a non-spiking quiescent state. As Kv1 inactivation decays, the trajectory follows the branch of stable fixed points until it crosses a subcritical Hopf bifurcation then spirals out into repetitive firing. In a model describing entorhinal cortical PV-INs without Kv1, interruption of firing could be achieved by taking advantage of the bistability inherent in type 2 excitability based on a subcritical Hopf bifurcation, but the interruption was not robust to noise. Persistent interruption of firing is therefore broadly applicable to PV-INs in different brain regions but is only made robust to noise in the presence of a slow variable.

Accuracy of the fully integrated Insole3's estimates of spatiotemporal parameters during walking.

This study investigated the accuracy of the Insole3 wireless shoe device in estimating several clinically useful spatiotemporal parameters (STPs). Eleven subjects walked at slow (0.8-1.0 m/s) and moderate-paced (1.2-1.4 m/s) speeds. Data were simultaneously recorded using the Insole3 and an industry-standard, three-dimensional motion capture (MOCAP) system. An error analysis compared the resulting STP data from the two systems. The mean bias error (MBE) was generally lower for temporal variables, and somewhat higher, but acceptable, for spatial variables. The MBE for temporally-related cadence and cycle time were the lowest (less than ±0.45%), with 100% (110/110) of slow-paced walking trial values and 99.1% (109/110) of moderate-paced walking trial values within 5% of the MOCAP estimates. The MBE was highest for speed (3.23-4.91%) and stride length (3.68-4.63%), with between 52.7 and 69.1% of trial values falling within the 5% error range. Stance time and swing time ranged between -0.98 and 4.38% error for both walking conditions. The results of this study suggest that the Insole3 is a potential alternative to MOCAP for estimating several STPs, namely cadence, stance time, and cycle time, particularly for use outside of the laboratory setting.

Roles of each leg in impulse generation in professional baseball pitchers: preliminary findings uncover the contribution of the back leg towards whole-body rotation.

This study examined the roles of each leg in generating linear and angular impulses during baseball pitching. Professional pitchers (n = 4) pitched from a force plate instrumented mound, and 6-11 successful fastball pitches were used for analyses. We compared linear and angular impulses across the back and front legs. Linear and angular impulses were calculated from ground reaction force (GRF) and moment about each global axis passing through the centre of mass (COM), respectively. Additionally, we analysed measures that control the moment: (1) GRF magnitude, (2) magnitude of the position vector from COM to the centre of pressure and (3) the angle between (1) and (2). We found that the back leg generated forward linear impulse and the front leg generated backward linear impulse for all pitchers. Surprisingly, we found that the back leg generated significantly greater positive angular impulse about a global leftward axis (from the mound towards first base) than did the front leg in all four pitchers. Furthermore, the back leg's moment about the leftward axis became positive after the magnitude of forward GRF decreased from its maximum, suggesting that the back leg's role transitioned from generating forward linear momentum to angular momentum.

Cav1.3 calcium channels are full-range linear amplifiers of firing frequencies in lateral DA SN neurons.

The low-threshold L-type calcium channel Cav1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Cav1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Cav1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson's disease.

Validity and Reliability of the Insole3 Instrumented Shoe Insole for Ground Reaction Force Measurement during Walking and Running.

Pressure-detecting insoles such as the Insole3 have potential as a portable alternative for assessing vertical ground reaction force (vGRF) outside of specialized laboratories. This study evaluated whether the Insole3 is a valid and reliable alternative to force plates for measuring vGRF. Eleven healthy participants walked overground at slow and moderately paced speeds and ran at a moderate pace while collecting vGRF simultaneously from a force plate (3000 Hz) and Insole3 (100 Hz). Intraclass correlation coefficients (ICC) demonstrated excellent vGRF agreement between systems during both walking speeds for Peak 1, Peak 2, the valley between peaks, and the vGRF impulse (ICC > 0.941). There was excellent agreement during running for the single vGRF peak (ICC = 0.942) and impulse (ICC = 0.940). The insoles slightly underestimated vGRF peaks (−3.7% to 0.9% bias) and valleys (−2.2% to −1.8% bias), and slightly overestimated impulses (4.2% to 5.6% bias). Reliability between visits for all three activities was excellent (ICC > 0.970). The Insole3 is a valid and reliable alternative to traditional force plates for assessing vGRF during walking and running in healthy adults. The excellent ICC values during slow walking suggests that the Insole3 may be particularly suitable for older adults in clinical and home settings.

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.

Many hippocampal CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially tuned, temporally diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multicompartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared with somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in the closed state, which comprises the available pool. PKC activator phorbol-dibutyrate, known to reduce NaV long-term inactivation, removed spike amplitude attenuation in vitro more visibly in dendrites and greatly reduced adaptation, consistent with our hypothesized mechanism. Intracellular application of a peptide inducing long-term NaV inactivation elicited spike amplitude attenuation during spike trains in the soma and greatly enhanced adaptation. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is a key mechanism of adaptation in CA1 pyramidal cells.SIGNIFICANCE STATEMENT The hippocampus plays an important role in certain types of memory, in part through context-specific firing of "place cells"; these cells were first identified in rodents as being particularly active when an animal is in a specific location in an environment, called the place field of that neuron. In this in vitro/in silico study, we found that long-term inactivation of sodium channels causes adaptation in the firing rate that could potentially skew the firing of CA1 hippocampal pyramidal neurons earlier within a place field. A computational model of the sodium channel revealed differential regulation of spike frequency and amplitude by long-term inactivation, which may be a general mechanism for spike frequency adaptation in the CNS.

Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons.

Two subpopulations of midbrain dopamine (DA) neurons are known to have different dynamic firing ranges in vitro that correspond to distinct projection targets: the originally identified conventional DA neurons project to the dorsal striatum and the lateral shell of the nucleus accumbens, whereas an atypical DA population with higher maximum firing frequencies projects to prefrontal regions and other limbic regions including the medial shell of nucleus accumbens. Using a computational model, we show that previously identified differences in biophysical properties do not fully account for the larger dynamic range of the atypical population and predict that the major difference is that originally identified conventional cells have larger occupancy of voltage-gated sodium channels in a long-term inactivated state that recovers slowly; stronger sodium and potassium conductances during action potential firing are also predicted for the conventional compared to the atypical DA population. These differences in sodium channel gating imply that longer intervals between spikes are required in the conventional population for full recovery from long-term inactivation induced by the preceding spike, hence the lower maximum frequency. These same differences can also change the bifurcation structure to account for distinct modes of entry into depolarization block: abrupt versus gradual. The model predicted that in cells that have entered depolarization block, it is much more likely that an additional depolarization can evoke an action potential in conventional DA population. New experiments comparing lateral to medial shell projecting neurons confirmed this model prediction, with implications for differential synaptic integration in the two populations.

Scapular and humeral elevation coordination patterns used before vs. after Reverse Total Shoulder Arthroplasty.

The purpose of this study was to compare scapulohumeral coordination used before and after Reverse Total Shoulder Arthroplasty (RTSA) during the ascent phase of scapular plane arm elevation tasks performed with varied shoulder rotations (neutral, external rotation, and internal rotation). We expected that after RTSA, participants would decrease scapulothoracic upward rotation angular displacement and increase the scapulohumeral rhythm (SHR) vs. before RTSA. 11 RTSA patients (12 shoulders) participated in this study before and after RTSA while optical motion capture measured kinematics of the humerus and scapula relative to the thorax. Angular kinematics were compared pre vs. post-RTSA within-participant using One Dimensional Statistical Parametric Mapping (SPM) t-tests (α = 0.05) and across-participants, using paired t-tests (α = 0.05) adjusted for multiple comparisons. As a group, during arm elevation with neutral rotation, the mean (SD) SHR pre-RTSA was 1.5 (0.5) and increased to 1.7 (0.3) post-RTSA, though, not significantly (p = 0.182). In contrast, during arm elevation with external rotation, the mean (SD) SHR pre-RTSA was 1.3 (0.4) and significantly increased (p = 0.018) post-RTSA to 1.7 (0.3). Likewise, during arm elevation with internal rotation, the mean (SD) SHR pre-RTSA was 1.2 (0.3) and significantly increased (p < 0.001) post-RTSA to 1.7 (0.2). In addition to these and other group trends, participant-specific patterns were uncovered through SPM analyses - with some participants significantly increasing and others significantly decreasing scapulothoracic angular displacements across humerothoracic elevation ranges. Both before and after RTSA, scapulohumeral rhythm ratios were within the range of those previously reported in post-RTSA patients and were smaller than those used by healthy populations.

Patient-specificity of scapular orientation measurements using an acromion marker cluster with multiple calibration poses.

The purpose of this study was to understand how each calibration pose affects scapular orientations measured by an Acromion Marker Cluster during scapular plane arm elevation performed by patients who had been pre-operatively indicated for Reverse Total Shoulder Arthroplasty. Eight pre-operative Reverse Total Shoulder Arthroplasty patients participated in this study while optical motion capture measured kinematics, specifically scapulothoracic angles and angular displacements, vs. humerothoracic elevation. The angle measurements were compared across the static calibration poses used to calculate them within-patient with One Dimensional Statistical Parametric Mapping paired t-tests and across-patients with a series of Sign Tests. The study uncovered patient-specificity in the effects of the Acromion Marker Cluster calibration pose on scapulothoracic angles and near linear offsets between the scapulothoracic upward rotation angles. The scapulothoracic upward rotation angular displacement measurements across calibration poses were within 5° of each other, suggesting nearly linear offsets between upward rotation angle measurements from each calibration pose. The Sign Tests revealed that using the Neutral calibration pose estimated significantly greater scapulothoracic protraction angles during arm elevation than did using the Hand to Back Pocket calibration pose (p = 0.02). Scapulothoracic protraction and posterior tilt measurements were near linear offsets between calibration poses only when humerothoracic elevation was less than 50°. Results encourage patient-specific and humerothoracic elevation-specific methods to combine calibration poses and the development of standards to report scapulothoracic orientations derived from using an Acromion Marker Cluster with multiple calibration poses.

Can a gait-dependent model predict wear on retrieved total knee arthroplasty components?

AIMS: A retrospective longitudinal study was conducted to compare directly volumetric wear of retrieved polyethylene inserts to predicted volumetric wear modelled from individual gait mechanics of total knee arthroplasty (TKA) patients. METHODS: In total, 11 retrieved polyethylene tibial inserts were matched with gait analysis testing performed on those patients. Volumetric wear on the articular surfaces was measured using a laser coordinate measure machine and autonomous reconstruction. Knee kinematics and kinetics from individual gait trials drove computational models to calculate medial and lateral tibiofemoral contact paths and forces. Sliding distance along the contact path, normal forces and implantation time were used as inputs to Archard's equation of wear to predict volumetric wear from gait mechanics. Measured and modelled wear were compared for each component. RESULTS: Volumetric wear rates on eight non-delaminated components measured 15.9 mm3/year (standard error (SE) ± 7.7) on the total part, 11.4 mm3/year (SE ± 6.4) on the medial side and 4.4 (SE ± 2.6) mm3/year on the lateral side. Volumetric wear rates modelled from patient gait mechanics predicted 16.4 mm3/year (SE 2.4) on the total part, 11.7 mm3/year (SE 2.1) on the medial side and 4.7 mm3/year (SE 0.4) on the lateral side. Measured and modelled wear volumes correlated significantly on the total part (p = 0.017) and the medial side (p = 0.012) but not on the lateral side (p = 0.154). CONCLUSION: In the absence of delamination, patient-specific knee mechanics during gait directly affect wear of the tibial component in TKA. Cite this article: Bone Joint J 2020;102-B(6 Supple A):129-137.

Calcium dynamics control K-ATP channel-mediated bursting in substantia nigra dopamine neurons: a combined experimental and modeling study.

Burst firing in medial substantia nigra (mSN) dopamine (DA) neurons has been selectively linked to novelty-induced exploration behavior in mice. Burst firing in mSN DA neurons, in contrast to lateral SN DA neurons, requires functional ATP-sensitive potassium (K-ATP) channels both in vitro and in vivo. However, the precise role of K-ATP channels in promoting burst firing is unknown. We show experimentally that L-type calcium channel activity in mSN DA neurons enhances open probability of K-ATP channels. We then generate a mathematical model to study the role of Ca2+ dynamics driving K-ATP channel function in mSN DA neurons during bursting. In our model, Ca2+ influx leads to local accumulation of ADP due to Ca-ATPase activity, which in turn activates K-ATP channels. If K-ATP channel activation reaches levels sufficient to terminate spiking, rhythmic bursting occurs. The model explains the experimental observation that, in vitro, coapplication of NMDA and a selective K-ATP channel opener, NN414, is required to elicit bursting as follows. Simulated NMDA receptor activation increases the firing rate and the rate of Ca2+ influx, which increases the activation of K-ATP. The model suggests that additional sources of hyperpolarization, such as GABAergic synaptic input, are recruited in vivo for burst termination or rebound burst discharge. The model predicts that NN414 increases the sensitivity of the K-ATP channel to ADP, promoting burst firing in vitro, and that that high levels of Ca2+ buffering, as might be expected in the calbindin-positive SN DA neuron subpopulation, promote rhythmic bursting pattern, consistent with experimental observations in vivo. NEW & NOTEWORTHY Recently identified distinct subpopulations of midbrain dopamine neurons exhibit differences in their two primary activity patterns in vivo: tonic (single spike) firing and phasic bursting. This study elucidates the biophysical basis of bursts specific to dopamine neurons in the medial substantia nigra, enabled by ATP-sensitive K+ channels and necessary for novelty-induced exploration. A better understanding of how dopaminergic signaling differs between subpopulations may lead to therapeutic strategies selectively targeted to specific subpopulations.

Are Instrumented Knee Forces Representative of a Larger Population of Cruciate-Retaining Total Knee Arthroplasties?

BACKGROUND: It is not known if the loads and motions reported for instrumented knees are generalizable to a larger population of total knee arthroplasty (TKA) patients. The purpose of this study is to (1) report axial implant force data for chair and stair activities for a population of cruciate-retaining TKA patients and (2) compare the population forces to those measured with instrumented TKAs. METHODS: Twenty-three subjects with a cruciate-retaining TKA underwent motion analysis during stair ascending, stair descending, chair sitting, and chair rising activities after informed consent in this institutional review board approved study. Axial TKA forces were calculated using a previously validated computational model. Differences between the mean and variability of population instrumented TKA peak forces and force impulses were tested using t tests and Levene test. RESULTS: Peak axial forces were 3.06, 2.74, 2.65, and 2.60 kN for stair ascent, stair descent, chair rising, and chair sitting, respectively. Force impulses were 123.3, 123.4, 153.5, and 154.0 kN*% activity cycle for stair ascent, stair descent, chair sitting, and chair rising, respectively. Population TKA and instrumented TKA peak forces were different for stair ascent (P = .03) and stair descent (P = .03) in the second half of the activity cycles. The variability of the peak forces and impulses were not different (P = .106 to P = .99). CONCLUSION: The forces and motions presented in this study represent cruciate-retaining TKA patients and could be used for displacement-driven knee wear testing. The forces are similar to those in the literature from instrumented prostheses of an ultracongruent cruciate-sacrificing TKA.

Relationship of surface damage appearance and volumetric wear in retrieved TKR polyethylene liners.

Recently developed techniques have enabled volume loss measurements on surgically retrieved total knee replacements (TKR). However, it is not well understood how volume loss relates to polyethylene surface damage appearance. Sixty-four fixed bearing cruciate retaining components retrieved from revision and postmortem surgeries were analyzed for penetration and volume loss on the topside articular surface. An autonomous reconstruction method was used to approximate the original unworn surfaces. Surface damage patterns were also mapped using a video microscope, and each pattern's contribution to volume loss was calculated. With consideration for creep, a total wear rate of 12.9 ± 5.97 mm3 /year was found for the population. The penetration rate was 0.035 ± 0.017 mm/year medially and 0.034 ± 0.011 mm/year laterally, of which the location on the plateau varied greatly. Although striated patterns contributed to most to volume loss, damage patterns generally were only moderate predictors of material volume loss. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2053-2059, 2017.

How Does Wear Rate Compare in Well-functioning Total Hip and Knee Replacements? A Postmortem Polyethylene Liner Study.

BACKGROUND: The longevity of total hip (THR) and knee replacements (TKR) that used historical bearing materials of gamma-in-air sterilized UHMWPE was affected more by osteolysis in THRs than in TKRs, although osteolysis remains a concern in TKRs. Therefore, the study of polyethylene wear is still of interest for the knee, particularly because few studies have investigated volumetric material loss in tibial knee inserts. For this study, a unique collection of autopsy-retrieved TKR and THR components that were well-functioning at the time of retrieval was used to compare volumetric wear differences between hip and knee polyethylene components made from identical material. QUESTIONS/PURPOSES: The following questions were addressed: (1) How much did the hip liners wear and what wear patterns did they exhibit? (2) How much did the knee inserts wear and what wear patterns did they exhibit? (3) What is the ratio between TKR and THR wear after controlling for implantation time and patient age? METHODS: We compared 23 THR components (Harris-Galante [HG] and HG II) and 20 TKR components (Miller-Galante [MG II]) that were retrieved postmortem. The components were made from the same polyethylene formulation and with similar manufacturing and sterilization (gamma-in-air) processes. Twenty-one patients (12 males, nine females) had THRs and 16 (four males, 12 females) had TKRs. Patients who had TKRs had an older (p = 0.001) average age than patients who had THRs (age, 75 years; SD, 10, versus 66 years; SD, 12, respectively). Only well-functioning components were included in this study. Therefore, implants retrieved postmortem from physically active patients and implanted for at least 2 years were considered. In addition, only normally wearing TKR components were considered, ie, those with fatigue wear (delamination) were excluded. The wear volume of each component was measured using metrology. For the tibial inserts an autonomous mathematic reconstruction method was used for quantification. RESULTS: The acetabular liners of the THR group had a wear rate of 38 mm(3) per year (95% CI, 29-47 mm(3)/year). Excluding patients with low-activity, the wear rate was 47 mm(3) per year (95% CI, 37-56 mm(3)/year). The wear rate of normally wearing tibial inserts was 17 mm(3) per year (95% CI, -6 to 40 mm(3)/year). After controlling for the relevant confounding variable of age, we found a TKR/THR wear rate ratio of 0.5 (95% CI, 0.29-0.77) at 70 years of age with a slightly increasing difference with increasing age. CONCLUSIONS: Excluding delamination, TKRs exhibited lower articular wear rates than THRs for historical polyethylene in these two unique cohorts of postmortem retrievals. CLINICAL RELEVANCE: The lower TKR wear rate is in line with the lower incidence of osteolysis in TKRs compared with THRs.

Methods for locating the tibio-femoral contact pathway in total knee replacements using marker-based gait analysis and standard radiography.

INTRODUCTION: The purpose of this study was to develop and test techniques for tracking the path of contact between the tibial and femoral total knee replacement components during level over-ground walking. The tibio-femoral path of contact could be an indicator of the in vivo performance of a total knee replacement as an estimator of areas of contact between the implant components. A longer contact path, indicative of more sliding between the implant components during walking, could indicate an implant at risk for increased wear. In addition, the tibio-femoral contact path determines the position and length of the muscle and ligament lever arms about the knee, and can subsequently influence knee contact force calculations. METHODS: Two methods were developed to predict the tibio-femoral contact pathways for total knee replacement devices. Both methods used patient-specific knee kinematics obtained during gait analysis, standard radiographs obtained during clinical follow-ups, and point-clouds of the tibial and femoral bearing surfaces. The validity of the techniques was evaluated with knee wear simulator tests and comparisons to wear scars on postmortem retrieved tibial components. RESULTS: The average total anterior-posterior distance covered by the contact path for ten patients implanted with a total knee replacement was 29.01 mm on the lateral side, and 21.80 mm on the medial side. Both methods for predicting the tibiofemoral contact pathways yielded similar results, and fell within the wear scars of simulator-tested and postmortem retrieved implants. CONCLUSIONS: The methods for predicting the tibio-femoral contact pathway using marker-based gait analysis and standard clinical radiographs are computationally simple, and reliably predict contact path characteristics as evaluated against wear scars from knee wear simulator tests and postmortem retrieved implants.

Fine tuning total knee replacement contact force prediction algorithms using blinded model validation.

The purpose of this study was to perform a blinded comparison of model predictions of total knee replacement contact forces to in vivo forces from an instrumented prosthesis during normal walking and medial thrust gait by participating in the "Third Grand Challenge Competition to Predict in vivo Knee Loads." We also evaluated model assumptions that were critical for accurate force predictions. Medial, lateral, and total axial forces through the knee were calculated using a previously developed and validated parametric numerical model. The model uses equilibrium equations between internal and external moments and forces to obtain knee joint contact forces and calculates a range of forces at instances during the gait cycle through parametric variation of muscle activity levels. For 100 instances during a normal over-ground gait cycle, model root mean square differences from eTibia data were 292, 248, and 281 for medial, lateral, and total contact forces, respectively. For 100 instances during a medial thrust gait cycle, model root mean square differences from eTibia data were 332, 234, and 470 for medial, lateral, and total contact forces, respectively. The percent difference between measured and predicted peak total axial force was 2.89% at the first peak and 9.36% at the second peak contact force for normal walking and 3.94% at the first peak and 14.86% at the second peak contact force for medial thrust gait. After unblinding, changes to model assumptions improved medial and lateral force predictions for both gait styles but did not improve total force predictions. Axial forces computed with the model compared well to the eTibia data under blinded and unblinded conditions. Knowledge of detailed knee kinematics, namely anterior-posterior translation, appears to be critical in obtaining accurate force predictions.

An autonomous mathematical reconstruction to effectively measure volume loss on retrieved polyethylene tibial inserts.

Wear of the polyethylene tibial component is a major factor in the success of total knee replacements. However, sampling resolution and the challenges of estimating original surfaces with relatively complex articulating geometries have limited the accuracy of volumetric measurements of wear on surgically retrieved inserts. A mathematical model analyzed volume error due to sampling resolution and found that 100 × 100 µm(2) point spacing reduced error below 1 mm(3). Small volumes of material were progressively removed from the topside of three unworn tibial inserts, after which each component was weighed and digitized with a laser coordinate measuring machine. Six inserts worn in knee simulator tests and nine surgically retrieved inserts visually scored for damage were also digitized. For these tests, the original surface of an insert was mathematically reconstructed from unworn regions of the same component, and volume loss and its spatial distribution were calculated. Volume loss estimated by autonomous reconstruction correlated strongly to mass removed manually (R(2) = 0.954, slope = 1.02 ± 0.04), mass lost during simulator testing (R(2) = 0.935, slope = 1.01 ± 0.07) and visual damage scores separated by size (R(2)large = 0.9824, R(2)small = 0.9728). These results suggest that an autonomous mathematical reconstruction can be used to effectively measure volume loss in retrieved tibial inserts.

Effect of europium(II) stearate on the mechanical properties and the oxidation resistance of UHMWPE.

The objective of this pilot study is to investigate the effect of europium(II) stearate additive on the mechanical properties and oxidation resistance of an ultra-high molecular weight polyethylene (UHMWPE), which has been used as an articulating surface in prosthetic devices for many years. It is hypothesized in this study that combining the UHMWPE with lanthanide stearates could enhance oxidation resistance, leading to better preservation of the material's mechanical integrity. Compression molded UHMWPE was doped at 0, 375 and 750 ppm of europium(II) stearate, γ-irradiated to 35 kGy in a nitrogen atmosphere, and accelerated aged in accordance with the ASTM standard F2003-02. Non-irradiated and nonaged samples were used as controls. Miniature samples were comparatively tested for mechanical properties using the small punch test. Oxidation indices (OIs) were obtained through the FTIR spectroscopy on thin film sections of all irradiated samples. The UHMWPE doped with the europium(II) stearate had the same small punch test curve shape as the conventional UHMWPE control; the ultimate displacement remained unchanged (approximately 4.33±0.02 mm), while the ultimate load and work-to-failure exhibited only small changes (<7.5% and <5.0%, respectively). The doped material was more resistant to oxidation than the control material, retaining 83% of its as-irradiated work-to-failure after irradiation and accelerated aging, versus only 53% for the control. Accelerated aging changed the average oxidation index of the control group from 0.07 to 0.40; whereas the average oxidation indices changed from 0.03 to 0.15 and from 0.05 to 0.13 for the 375 ppm and the 750 ppm doped condition, respectively.