Can tibio-femoral kinematic and kinetic parameters reveal poor functionality and underlying deficits after total knee replacement? A systematic review.

BACKGROUND: Extensive efforts have been made to understand joint kinematics and kinetics in total knee arthroplasty (TKA) in subjects with satisfactory outcomes during daily functional activities and clinical tests, but it remains unclear whether such movement characteristics hold the potential to indicate the underlying aetiology of unsatisfactory or bad TKA outcomes. PURPOSE: To investigate which kinematic and kinetic parameters assessed during passive clinical tests and functional activities of daily living are associated with poor functionality and underlying deficits after total knee replacement. METHODS: We focused on studies characterizing the kinematic or kinetic parameters of the knee joint that are associated with poor clinical outcome after TKA. Seventeen articles were included for the review, and kinematic and kinetic data from 719 patients with minimal follow up of 6 months were extracted and analyzed. RESULTS: Passive posterior translation at 90°flexionexhibited good potential for differentiating stable and unstable TKAs. Anterior-posterior (A-P) translation of the medial condyle at 0-30° and 30-60° flexion, A-P translation of the lateral condyle at 60-90°during closed chain exercises, as well asknee extension moment during stair ascent and descent, knee abduction moment during stair descent, knee internal rotation moment and plantar flexion moment during walking, 2ndpeak ground reaction force during stair ascent and walkingshowed the greatest promise as functional biomarkers for a dissatisfied/poor outcome knee after TKA. CONCLUSION: In this study, we systematically reviewed the state-of-the-art knowledge of kinematics and kinetics associated with functional deficits, and found 11 biomechanical parameters that showed promise for supportingdecision making in TKA.

In Vivo Elongation Patterns of the Collateral Ligaments in Healthy Knees During Functional Activities.

BACKGROUND: Improved knowledge of in vivo function of the collateral ligaments is essential for enhancing rehabilitation and guiding surgical reconstruction as well as soft-tissue balancing in total knee arthroplasty. The aim of this study was to quantify in vivo elongation patterns of the collateral ligaments throughout complete cycles of functional activities. METHODS: Knee kinematics were measured using radiographic images captured with a mobile fluoroscope while healthy subjects performed level walking, downhill walking, and stair descent. The registered in vivo tibiofemoral kinematics were then used to drive subject-specific multibody knee models to track collateral ligament elongation. RESULTS: The elongation patterns of the medial collateral ligament varied distinctly among its bundles, ranging from lengthening of the anterior fibers to shortening of the posterior bundle with increases in the knee flexion angle. The elongation patterns of the lateral collateral ligament varied considerably among subjects. It showed an average 4% shortening with increasing flexion until 60% to 70% of the gait cycle, and then recovered during the terminal-swing phase until reaching its reference length (defined at heel strike). CONCLUSIONS: The observed nonuniform elongation of the medial collateral ligament bundles suggests that single-bundle reconstruction techniques may not fully restore healthy ligament function. Moreover, the observed ligament elongation patterns indicate greater varus than valgus laxity in the loaded knee. CLINICAL RELEVANCE: Through providing key knowledge about the in vivo elongation patterns of the collateral ligaments throughout complete cycles of functional activities, this study offers in vivo evidence for benchmarking ligament reconstruction and soft-tissue balancing in total knee arthroplasty.

Length-Change Patterns of the Collateral Ligaments During Functional Activities After Total Knee Arthroplasty.

This study aimed to quantify the elongation patterns of the collateral ligaments following TKA during functional activities of daily living. Using mobile video-fluoroscopy to capture radiographic images of the knee in a group of six patients, each with an ultra-congruent knee implant, tibiofemoral kinematics were reconstructed throughout complete cycles of level gait, downhill walking, stair descent, and squat activities. Kinematic data were then used to drive subject-specific multibody knee models to estimate length-change patterns of the LCL as well as three bundles of the MCL. In addition, a sensitivity analysis examined the role of the attachment site in the elongation patterns. Our data indicate a slackening of the LCL but non-uniform length-change patterns across the MCL bundles (ranging from lengthening of the anterior fibers to shortening of the posterior fibers) with increasing knee flexion angle. Near-isometric behavior of the intermediate fibers was observed throughout the entire cycle of the studied activities. These length-change patterns were found to be largely consistent across different activities. Importantly, length-change patterns were critically sensitive to the location of the femoral attachment points relative to the femoral component. Thus, in TKA with ultra-congruent implants, implantation of the femoral component may critically govern post-operative ligament function.

Author Correction: Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

Total knee arthroplasty aims to mimic the natural knee kinematics by optimizing implant geometry, but it is not clear how loading relates to tibio-femoral anterior-posterior translation or internal-external pivoting. We hypothesised that the point of pivot in the transverse plane is governed by the location of the highest axial force. Tibio-femoral loading was measured using an instrumented tibial component in six total knee arthroplasty patients (aged 65-80y, 5-7y post-op) during 5-6 squat repetitions, while knee kinematics were captured using a mobile video-fluoroscope. In the range of congruent tibio-femoral contact the medial femoral condyle remained approximately static while the lateral condyle translated posteriorly by 4.1 mm (median). Beyond the congruent range, the medial and lateral condyle motions both abruptly changed to anterior sliding by 4.6 mm, and 2.6 mm respectively. On average, both the axial loading and pivot position were more medial near extension, and transferred to the lateral side in flexion. However, no consistent relationship between pivoting and load distribution was found across all patients throughout flexion, with R2 values ranging from 0.00 to 0.65. Tibio-femoral kinematics is not related to the load distribution alone: medial loading of the knee does not necessarily imply a medial pivot location.

Analysis of the role of GSK3 in the mitotic checkpoint.

The mitotic checkpoint ensures proper chromosome segregation; defects in this checkpoint can lead to aneuploidy, a hallmark of cancer. The mitotic checkpoint blocks progression through mitosis as long as chromosomes remain unattached to spindle microtubules. Unattached kinetochores induce the formation of a mitotic checkpoint complex (MCC) composed of Mad2, BubR1, Bub1 and Bub3 which inhibits anaphase onset. Spindle toxins induce prolonged mitotic arrest by creating persistently unattached kinetochores which trigger MCC formation. We find that the multifunctional ser/thr kinase, glycogen synthase kinase 3 (GSK3) is required for a strong mitotic checkpoint. Spindle toxin-induced mitotic arrest is relieved by GSK3 inhibitors SB 415286 (SB), RO 318220 (RO) and lithium chloride. Similarly, targeting GSK3ß with knockout or RNAi reduced mitotic arrest in the presence of Taxol. GSK3 was required for optimal localization of Mad2, BubR1, and Bub1 at kinetochores and for optimal assembly of the MCC in spindle toxin-arrested cells. The WNT- and PI3K/Akt signaling pathways negatively regulate GSK3ß activity. Inhibition of WNT and PI3K/Akt signaling, in the presence of Taxol, induced a longer mitotic arrest compared to Taxol alone. Our observations provide novel insight into the regulation of the mitotic checkpoint and its connection to growth-signaling pathways.

Revealing the quality of movement: A meta-analysis review to quantify the thresholds to pathological variability during standing and walking.

Neuromotor processes are inherently noisy, which results in variability during movement and fluctuations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysis of the literature investigates the thresholds between healthy and pathological task variability. After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy subjects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 for walking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upper thresholds of 2.6% and 265mm(2) discriminated pathological from asymptomatic performance, while 1.1% and 62mm(2) identified the lower thresholds for pathological variability. This window of healthy performance now provides science based evidence for the discrimination of both extremely low and extremely high levels of variability in the identification as well as standardised monitoring of functional status in neurological cases.

Increased unilateral tendon stiffness and its effect on gait 2-6 years after Achilles tendon rupture.

Achilles tendon rupture (ATR) alters tissue composition, which may affect long-term tendon mechanics and ankle function during movement. However, a relationship between Achilles tendon (AT) properties and ankle joint function during gait remains unclear. The primary hypotheses were that (a) post-ATR tendon stiffness and length differ from the noninjured contralateral side and that (b) intra-patient asymmetries in AT properties correlate to ankle function asymmetries during gait, determined by ankle angles and moments. Ultrasonography and dynamometry were used to assess AT tendon stiffness, strain, elongation, and rest length in both limbs of 20 ATR patients 2-6 years after repair. Three-dimensional ankle angles and moments were determined using gait analysis. Injured tendons exhibited increased stiffness, rest length, and altered kinematics, with higher dorsiflexion and eversion, and lower plantarflexion and inversion. Intra-patient tendon stiffness and tendon length ratios were negatively correlated to intra-patient ratios of the maximum plantarflexion moment and maximum dorsiflexion angle, respectively. These results suggest that after surgical ATR repair, higher AT stiffness, but not a longer AT, may contribute to deficits in plantarflexion moment generation. These data further support the claim that post-ATR tendon regeneration results in the production of a tissue that is functionally different than noninjured tendon.

Identification of functional parameters for the classification of older female fallers and prediction of 'first-time' fallers.

Falls remain a challenge for ageing societies. Strong evidence indicates that a previous fall is the strongest single screening indicator for a subsequent fall and the need for assessing fall risk without accounting for fall history is therefore imperative. Testing in three functional domains (using a total 92 measures) were completed in 84 older women (60-85 years of age), including muscular control, standing balance, and mean and variability of gait. Participants were retrospectively classified as fallers (n = 38) or non-fallers (n = 42) and additionally in a prospective manner to identify first-time fallers (FTFs) (n = 6) within a 12-month follow-up period. Principal component analysis revealed that seven components derived from the 92 functional measures are sufficient to depict the spectrum of functional performance. Inclusion of only three components, related to mean and temporal variability of walking, allowed classification of fallers and non-fallers with a sensitivity and specificity of 74% and 76%, respectively. Furthermore, the results indicate that FTFs show a tendency towards the performance of fallers, even before their first fall occurs. This study suggests that temporal variability and mean spatial parameters of gait are the only functional components among the 92 measures tested that differentiate fallers from non-fallers, and could therefore show efficacy in clinical screening programmes for assessing risk of first-time falling.

Towards understanding knee joint laxity: errors in non-invasive assessment of joint rotation can be corrected.

The in vivo quantification of rotational laxity of the knee joint is of importance for monitoring changes in joint stability or the outcome of therapies. While invasive assessments have been used to study rotational laxity, non-invasive methods are attractive particularly for assessing young cohorts. This study aimed to determine the conditions under which tibio-femoral rotational laxity can be assessed reliably and accurately in a non-invasive manner. The reliability and error of non-invasive examinations of rotational joint laxity were determined by comparing the artefact associated with surface mounted markers against simultaneous measurements using fluoroscopy in five knees including healthy and ACL deficient joints. The knees were examined at 0°, 30°, 60° and 90° flexion using a device that allows manual axial rotation of the joint. With a mean RMS error of 9.6°, the largest inaccuracy using non-invasive assessment was present at 0° knee flexion, whereas at 90° knee flexion, a smaller RMS error of 5.7° was found. A Bland and Altman assessment indicated that a proportional bias exists between the non-invasive and fluoroscopic approaches, with limits of agreement that exceeded 20°. Correction using average linear regression functions resulted in a reduction of the RMS error to below 1° and limits of agreement to less than ±1° across all knees and flexion angles. Given the excellent reliability and the fact that a correction of the surface mounted marker based rotation values can be achieved, non-invasive evaluation of tibio-femoral rotation could offer opportunities for simplified devices for use in clinical settings in cases where invasive assessments are not justified. Although surface mounted marker based measurements tend to overestimate joint rotation, and therefore joint laxity, our results indicate that it is possible to correct for this error.

Is gait variability reliable? An assessment of spatio-temporal parameters of gait variability during continuous overground walking.

The assessment of gait variability has become an important indicator for quantifying motor performance. However, the use of treadmills is known to influence the temporal rhythm of gait, while non-continuous (i.e. stop-start) overground walking alters gait variability, leading to erroneous results. Through establishing the "8-walk", an overground walking protocol that allows the collection of a high number of consecutive gait cycles, the aim of this study was to determine the conditions under which gait variability can be assessed reliably. Twelve healthy subjects performed continuous barefoot walking at their preferred speed in a path shaped as an "8". Kinematic data of the dominant foot was collected while subjects walked along the straight 10 m sections of the 8-walk during sessions on two different days. Mean spatio-temporal parameters of gait and gait variability were computed for 10, 20, 30, 40, 50 and 60 consecutive cycles. All mean parameters of gait showed excellent reliability (ICC: 0.88-0.98) with only 10 cycles included in the analysis. However, the reliability of spatial and temporal parameters of gait variability improved with increasing number of cycles (ICC: 0.60-0.90) but levelled-off after 50 consecutive cycles, revealing an inter-day test-retest variability of ≈ 13%. To reliably assess gait variability and evaluate human motor performance, we propose the collection of at least 50 cycles and the use of an 8-walk protocol, which avoids the limitations of treadmill and non-consecutive walking protocols.

Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND: Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. AIM: To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. METHODS: This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. RESULTS: IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. CONCLUSION: These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

BACKGROUND & OBJECTIVES: India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. METHODS: This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. RESULTS: A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported. INTERPRETATION & CONCLUSION: The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks.

OBJECTIVES: Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks. METHODS: We conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥ 2. RESULTS: Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥ 2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P=0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P=0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos. CONCLUSIONS: Oseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks.

Effective marker placement for functional identification of the centre of rotation at the hip.

The accuracy and precision of quantifying musculoskeletal kinematics, and particularly determining the centre of rotation (CoR) at the hip joint, using skin marker based motion analysis is limited by soft tissue artefact (STA). We posed the question of whether the contribution of individual markers towards improving the precision of the functional joint centre using marker based methods could be assessed, and then utilised to allow effective marker placement for determination of the CoR at the hip. Sixty-three retro-reflective skin markers were placed to encompass the thighs of seven healthy subjects, together with a set of sixteen markers on the pelvis. The weighted optimal common shape technique (wOCST) was then applied to determine the weighting, or importance, of each marker for identifying the centre of rotation at the hip. The markers with the highest weightings over all subjects and measurements were determined that identified the HJC with the highest precision. The use of six markers in selected regions (two anterior, two lateral and two posterior) allowed the HJC to be determined with a similar precision to the complete set of 63 markers, with the determined regions predominantly distant from the hip joint, excluding areas associated with the bellies of large muscles and therefore large motion artefact from muscle activity. The novel approach presented here allows an understanding of each marker's contribution towards a precise joint determination, and therefore enables the targeted placement of markers for reliable assessment of musculoskeletal kinematics.

Evolutionary inaccuracy of pairwise structural alignments.

MOTIVATION: Structural alignment methods are widely used to generate gold standard alignments for improving multiple sequence alignments and transferring functional annotations, as well as for assigning structural distances between proteins. However, the correctness of the alignments generated by these methods is difficult to assess objectively since little is known about the exact evolutionary history of most proteins. Since homology is an equivalence relation, an upper bound on alignment quality can be found by assessing the consistency of alignments. Measuring the consistency of current methods of structure alignment and determining the causes of inconsistencies can, therefore, provide information on the quality of current methods and suggest possibilities for further improvement. RESULTS: We analyze the self-consistency of seven widely-used structural alignment methods (SAP, TM-align, Fr-TM-align, MAMMOTH, DALI, CE and FATCAT) on a diverse, non-redundant set of 1863 domains from the SCOP database and demonstrate that even for relatively similar proteins the degree of inconsistency of the alignments on a residue level is high (30%). We further show that levels of consistency vary substantially between methods, with two methods (SAP and Fr-TM-align) producing more consistent alignments than the rest. Inconsistency is found to be higher near gaps and for proteins of low structural complexity, as well as for helices. The ability of the methods to identify good structural alignments is also assessed using geometric measures, for which FATCAT (flexible mode) is found to be the best performer despite being highly inconsistent. We conclude that there is substantial scope for improving the consistency of structural alignment methods. CONTACT: msadows@nimr.mrc.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The quality of bone surfaces may govern the use of model based fluoroscopy in the determination of joint laxity.

The assessment of knee joint laxity is clinically important but its quantification remains elusive. Calibrated, low dosage fluoroscopy, combined with registered surfaces and controlled external loading may offer possible solutions for quantifying relative tibio-femoral motion without soft tissue artefact, even in native joints. The aim of this study was to determine the accuracy of registration using CT and MRI derived 3D bone models, as well as metallic implants, to 2D single-plane fluoroscopic datasets, to assess their suitability for examining knee joint laxity. Four cadaveric knees and one knee implant were positioned using a micromanipulator. After fluoroscopy, the accuracy of registering each surface to the 2D fluoroscopic images was determined by comparison against known translations from the micromanipulator measurements. Dynamic measurements were also performed to assess the relative tibio-femoral error. For CT and MRI derived 3D femur and tibia models during static testing, the in-plane error was 0.4 mm and 0.9 mm, and out-of-plane error 2.6 mm and 9.3 mm respectively. For metallic implants, the in-plane error was 0.2 mm and out-of-plane error 1.5 mm. The relative tibio-femoral error during dynamic measurements was 0.9 mm, 1.2 mm and 0.7 mm in-plane, and 3.9 mm, 10.4 mm and 2.5 mm out-of-plane for CT and MRI based models and metallic implants respectively. The rotational errors ranged from 0.5° to 1.9° for CT, 0.5-4.3° for MRI and 0.1-0.8° for metallic implants. The results of this study indicate that single-plane fluoroscopic analysis can provide accurate information in the investigation of knee joint laxity, but should be limited to static or quasi-static evaluations when assessing native bones, where possible. With this knowledge of registration accuracy, targeted approaches for the determination of tibio-femoral laxity could now determine objective in vivo measures for the identification of ligament reconstruction candidates as well as improve our understanding of the consequences of knee joint instability in TKA.

The role of starburst amacrine cells in visual signal processing.

Starburst amacrine cells (SBACs) within the adult mammalian retina provide the critical inhibition that underlies the receptive field properties of direction-selective ganglion cells (DSGCs). The SBACs generate direction-selective output of GABA that differentially inhibits the DSGCs. We review the biophysical mechanisms that produce directional GABA release from SBACs and test a network model that predicts the effects of reciprocal inhibition between adjacent SBACs. The results of the model simulations suggest that reciprocal inhibitory connections between closely spaced SBACs should be spatially selective, while connections between more widely spaced cells could be indiscriminate. SBACs were initially identified as cholinergic neurons and were subsequently shown to contain release both acetylcholine and GABA. While the role of the GABAergic transmission is well established, the role of the cholinergic transmission remains unclear.

Carbonic anhydrase-related protein VIII is expressed in rod bipolar cells and alters signaling at the rod bipolar to AII-amacrine cell synapse in the mammalian retina.

Mutation of the gene encoding carbonic anhydrase-related protein VIII (CAVIII) results in motor coordination deficits in mice and humans, due to loss of this protein in Purkinje cells of the cerebellum. Recent studies have indicated that the CAVIII gene, Car8, is also expressed in rod bipolar cells (RBCs), a critical glutamatergic neuron for scotopic vision. We investigated the localization of CAVIII in the mouse and macaque retina, and utilized the wdl mouse, which has a null mutation in the Car8 gene, to determine how the loss of CAVIII affects retinal signaling. CAVIII immunoreactivity was observed in RBCs, with particularly high staining intensity in the axon terminals. In addition, weaker staining was observed in a subset of cone bipolar cells and γ-aminobutyric acid (GABA)ergic amacrine cells. Light-evoked current and voltage responses of RBCs were not altered in the wdl mutant. However, light-evoked current responses from the AII-amacrine cell, a postsynaptic partner at the RBC ribbon synapse, were significantly larger, and more prolonged than in control mice. These changes could not be attributed to alterations in calcium current activation or inactivation, or to changes in the density of RBCs. Furthermore, no gross synaptic alterations were evident in the wdl mutant at the light or ultrastructural level. These data provide evidence that the CAVIII protein, which is highly conserved in vertebrates, is selectively expressed within neural circuits, and may be important for modulating retinal neurotransmission.

Kinematic measures for assessing gait stability in elderly individuals: a systematic review.

Falls not only present a considerable health threat, but the resulting treatment and loss of working days also place a heavy economic burden on society. Gait instability is a major fall risk factor, particularly in geriatric patients, and walking is one of the most frequent dynamic activities of daily living. To allow preventive strategies to become effective, it is therefore imperative to identify individuals with an unstable gait. Assessment of dynamic stability and gait variability via biomechanical measures of foot kinematics provides a viable option for quantitative evaluation of gait stability, but the ability of these methods to predict falls has generally not been assessed. Although various methods for assessing gait stability exist, their sensitivity and applicability in a clinical setting, as well as their cost-effectiveness, need verification. The objective of this systematic review was therefore to evaluate the sensitivity of biomechanical measures that quantify gait stability among elderly individuals and to evaluate the cost of measurement instrumentation required for application in a clinical setting. To assess gait stability, a comparative effect size (Cohen's d) analysis of variability and dynamic stability of foot trajectories during level walking was performed on 29 of an initial yield of 9889 articles from four electronic databases. The results of this survey demonstrate that linear variability of temporal measures of swing and stance was most capable of distinguishing between fallers and non-fallers, whereas step width and stride velocity prove more capable of discriminating between old versus young (OY) adults. In addition, while orbital stability measures (Floquet multipliers) applied to gait have been shown to distinguish between both elderly fallers and non-fallers as well as between young and old adults, local stability measures (λs) have been able to distinguish between young and old adults. Both linear and nonlinear measures of foot time series during gait seem to hold predictive ability in distinguishing healthy from fall-prone elderly adults. In conclusion, biomechanical measurements offer promise for identifying individuals at risk of falling and can be obtained with relatively low-cost tools. Incorporation of the most promising measures in combined retrospective and prospective studies for understanding fall risk and designing preventive strategies is warranted.