Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. © 2013 Petersen et al.

Serum Metalloproteinases 2 and 9 as Predictors of Gait Status, Pressure Ulcer and Mortality after Hip Fracture

Introduction: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture. Methods: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded. Results: Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture. Conclusions: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture. © 2013 Gumieiro et al.

Mini Nutritional Assessment predicts gait status and mortality 6 months after hip fracture.

The aim of the present study was to evaluate the Mini Nutritional Assessment (MNA), the Nutritional Risk Screening (NRS) 2002 and the American Society of Anesthesiologists Physical Status Score (ASA) as predictors of gait status and mortality 6 months after hip fracture. A total of eighty-eight consecutive patients over the age of 65 years with hip fracture admitted to an orthopaedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, and the MNA, the NRS 2002 and the ASA were performed. Gait status and mortality were evaluated 6 months after hip fracture. Of the total patients, two were excluded because of pathological fractures. The remaining eighty-six patients (aged 80·2 (sd 7·3) years) were studied. Among these patients 76·7 % were female, 69·8 % walked with or without support and 12·8 % died 6 months after the fracture. In a multivariate analysis, only the MNA was associated with gait status 6 months after hip fracture (OR 0·773, 95 % CI 0·663, 0·901; P= 0·001). In the Cox regression model, only the MNA was associated with mortality 6 months after hip fracture (hazard ratio 0·869, 95 % CI 0·757, 0·998; P= 0·04). In conclusion, the MNA best predicts gait status and mortality 6 months after hip fracture. These results suggest that the MNA should be included in the clinical stratification of patients with hip fracture to identify and treat malnutrition in order to improve the outcomes.

Systematic review of the effects of fatigue on spatiotemporal gait parameters

PURPOSE: This systematic review aimed to assess changes on spatiotemporal gait parameters due to fatigue. MATERIAL AND METHOD: A search was carried out in literature published from 1950 to December 2010 and retrieved 771 articles using terms referring to walking and fatigue in the title, abstract or keywords. Two researchers assessed the selection and quality of each article independently. RESULTS: Seven studies were selected for this systematic review, two of which reported on the same data set. Several spatiotemporal parameters were reported to change with fatigue, but the few variables studied in multiple studies, gait speed and stride or step length and stride time, were affected only in single studies. Fatigue appears to modulate spatiotemporal gait parameters, but the effects of fatigue appear to be dependent on the muscles that were fatigued, and age that appears to be a moderator of the effects of fatigue on gait. © 2013 - IOS Press and the authors. All rights reserved.

Kinematic analysis of forelimb and hind limb joints in clinically healthy sheep

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Associations of vitamin D deficiency with postoperative gait and mortality among patients with fractures of the proximal femur

To assess whether serum vitamin D concentration is associated with gait status and mortality among patients with fractures of the proximal femur, six months after suffering the fracture. Consecutive patients aged ≥65 years with fractures of the proximal femur, who were admitted to the orthopedics and traumatology ward of our service between January and December 2011, were prospectively evaluated. Clinical, radiological, epidemiological and laboratory analyses were performed, including vitamin D. The patients underwent surgery and were followed up as outpatients, with return visits 15, 30, 60 and 180 days after discharge, at which the outcomes of gait and mortality were evaluated. Eighty-eight patients were evaluated. Two of them were excluded because they presented oncological fractures. Thus, 86 patients of mean age 80.2 ± 7.3 years were studied. In relation to serum vitamin D, the mean was 27.8 ± 14.5 ng/mL, and 33.7% of the patients presented deficiency of this vitamin. In relation to gait, univariate and multivariate logistic regression showed that vitamin D deficiency was not associated with gait recovery, even after adjustment for gender, age and type of fracture (OR: 1.463; 95% CI: 0.524-4.088; p = 0.469). Regarding mortality, Cox regression analysis showed that vitamin D deficiency was not related to its occurrence within six months, even in multivariate analysis (HR: 0.627; 95% CI: 0.180-2.191; p = 0.465). Serum vitamin D concentration was not related to gait status and/or mortality among patients with fractures of the proximal femur, six months after suffering the fracture.

Balance and ankle muscle strength predict spatiotemporal gait parameters in individuals with diabetic peripheral neuropathy

The aims of this study were to evaluate aspects of balance, ankle muscle strength and spatiotemporal gait parameters in individuals with diabetic peripheral neuropathy (DPN) and verify whether deficits in spatiotemporal gait parameters were associated with ankle muscle strength and balance performance. Thirty individuals with DPN and 30 control individuals have participated. Spatiotemporal gait parameters were evaluated by measuring the time to walk a set distance during self-selected and maximal walking speeds. Functional mobility and balance performance were assessed using the Functional Reach and the Time Up and Go tests. Ankle isometric muscle strength was assessed with a handheld digital dynamometer. Analyses of variance were employed to verify possible differences between groups and conditions. Multiple linear regression analysis was employed to uncover possible predictors of gait deficits. Gait spatiotemporal, functional mobility, balance performance and ankle muscle strength were affected in individuals with DPN. The Time Up and Go test performance and ankle muscle isometric strength were associated to spatiotemporal gait changes, especially during maximal walking speed condition. Functional mobility and balance performance are damaged in DPN and balance performance and ankle muscle strength can be used to predict spatiotemporal gait parameters in individuals with DPN.

Analysis of human body kinematics using a hybrid markerless video acquisition and processing

A main objective of the human movement analysis is the quantitative description of joint kinematics and kinetics. This information may have great possibility to address clinical problems both in orthopaedics and motor rehabilitation. Previous studies have shown that the assessment of kinematics and kinetics from stereophotogrammetric data necessitates a setup phase, special equipment and expertise to operate. Besides, this procedure may cause feeling of uneasiness on the subjects and may hinder with their walking. The general aim of this thesis is the implementation and evaluation of new 2D markerless techniques, in order to contribute to the development of an alternative technique to the traditional stereophotogrammetric techniques. At first, the focus of the study has been the estimation of the ankle-foot complex kinematics during stance phase of the gait. Two particular cases were considered: subjects barefoot and subjects wearing ankle socks. The use of socks was investigated in view of the development of the hybrid method proposed in this work. Different algorithms were analyzed, evaluated and implemented in order to have a 2D markerless solution to estimate the kinematics for both cases. The validation of the proposed technique was done with a traditional stereophotogrammetric system. The implementation of the technique leads towards an easy to configure (and more comfortable for the subject) alternative to the traditional stereophotogrammetric system. Then, the abovementioned technique has been improved so that the measurement of knee flexion/extension could be done with a 2D markerless technique. The main changes on the implementation were on occlusion handling and background segmentation. With the additional constraints, the proposed technique was applied to the estimation of knee flexion/extension and compared with a traditional stereophotogrammetric system. Results showed that the knee flexion/extension estimation from traditional stereophotogrammetric system and the proposed markerless system were highly comparable, making the latter a potential alternative for clinical use. A contribution has also been given in the estimation of lower limb kinematics of the children with cerebral palsy (CP). For this purpose, a hybrid technique, which uses high-cut underwear and ankle socks as “segmental markers” in combination with a markerless methodology, was proposed. The proposed hybrid technique is different than the abovementioned markerless technique in terms of the algorithm chosen. Results showed that the proposed hybrid technique can become a simple and low-cost alternative to the traditional stereophotogrammetric systems.

"Influence of lower-limb joint models on subject-specific musculoskeletal model predictions during gait" ( "modelli muscoloscheletrici personalizzati dell'arto inferiore: Analisi dell'effetto della modellazione dei giunti sulla predizione dei carichi agenti sul sistema scheletrico durante il cammino").

The aim of the present thesis was to investigate the influence of lower-limb joint models on musculoskeletal model predictions during gait. We started our analysis by using a baseline model, i.e., the state-of-the-art lower-limb model (spherical joint at the hip and hinge joints at the knee and ankle) created from MRI of a healthy subject in the Medical Technology Laboratory of the Rizzoli Orthopaedic Institute. We varied the models of knee and ankle joints, including: knee- and ankle joints with mean instantaneous axis of rotation, universal joint at the ankle, scaled-generic-derived planar knee, subject-specific planar knee model, subject-specific planar ankle model, spherical knee, spherical ankle. The joint model combinations corresponding to 10 musculoskeletal models were implemented into a typical inverse dynamics problem, including inverse kinematics, inverse dynamics, static optimization and joint reaction analysis algorithms solved using the OpenSim software to calculate joint angles, joint moments, muscle forces and activations, joint reaction forces during 5 walking trials. The predicted muscle activations were qualitatively compared to experimental EMG, to evaluate the accuracy of model predictions. Planar joint at the knee, universal joint at the ankle and spherical joints at the knee and at the ankle produced appreciable variations in model predictions during gait trials. The planar knee joint model reduced the discrepancy between the predicted activation of the Rectus Femoris and the EMG (with respect to the baseline model), and the reduced peak knee reaction force was considered more accurate. The use of the universal joint, with the introduction of the subtalar joint, worsened the muscle activation agreement with the EMG, and increased ankle and knee reaction forces were predicted. The spherical joints, in particular at the knee, worsened the muscle activation agreement with the EMG. A substantial increase of joint reaction forces at all joints was predicted despite of the good agreement in joint kinematics with those of the baseline model. The introduction of the universal joint had a negative effect on the model predictions. The cause of this discrepancy is likely to be found in the definition of the subtalar joint and thus, in the particular subject’s anthropometry, used to create the model and define the joint pose. We concluded that the implementation of complex joint models do not have marked effects on the joint reaction forces during gait. Computed results were similar in magnitude and in pattern to those reported in literature. Nonetheless, the introduction of planar joint model at the knee had positive effect upon the predictions, while the use of spherical joint at the knee and/or at the ankle is absolutely unadvisable, because it predicted unrealistic joint reaction forces.

The Effect of Metronome Pacing on Gait in Healthy Subjects

The complex process of gait is rendered partially automatic by central pattern generators (CPGs). To further our understanding of their role in gait control in healthy subjects, we applied a paradigm of anti-phase, or syncopated, movement to gait. To provide a context for our results, we reviewed the literature on in-phase, or synchronized, gait. The review results are as follows. Auditory cueing increased step/stride rate for older subjects, but not younger. Stride rate variability decreased for younger subjects, perhaps because the metronome’s cue acted as a temporal ‘anchor point’ for each step. Step width increased in half of the treadmill studies, but none of the overground ones, suggesting a cumulative effect of the attentional demands of synchronizing gait while on a treadmill. Time series analysis revealed that the α exponent was the most sensitive parameter reported, decreasing toward anti-persistence in almost all cued-gait studies. This project compares in-phase (IN) and anti-phase gait (ANTI) in young and old healthy subjects. We expected gait to be less disrupted during ANTI trials at preferred speed, when the facilitating effect of CPGs would be strongest. The measures step time variability, jerk index, and harmonic ratio quantified gait perturbation: none indicated that ANTI was easiest at preferred walking speed. Surprisingly, the gait of older subjects was no more perturbed than that of younger subjects. When they successfully matched the pace of the beat, they unwittingly synchronized to it. The temporal relationship of their steps to the beat was the same in the IN and ANTI conditions. Younger subjects, visibly struggling during ANTI trials, were able to walk in syncopation. This result suggests that cognitive resources available only to the younger group are required to resist synchronizing to the beat.

Assessment of gait spatio-temporal parameters in neurological disorders using wearable inertial sensors

Movement analysis carried out in laboratory settings is a powerful, but costly solution since it requires dedicated instrumentation, space and personnel. Recently, new technologies such as the magnetic and inertial measurement units (MIMU) are becoming widely accepted as tools for the assessment of human motion in clinical and research settings. They are relatively easy-to-use and potentially suitable for estimating gait kinematic features, including spatio-temporal parameters. The objective of this thesis regards the development and testing in clinical contexts of robust MIMUs based methods for assessing gait spatio-temporal parameters applicable across a number of different pathological gait patterns. First, considering the need of a solution the least obtrusive as possible, the validity of the single unit based approach was explored. A comparative evaluation of the performance of various methods reported in the literature for estimating gait temporal parameters using a single unit attached to the trunk first in normal gait and then in different pathological gait conditions was performed. Then, the second part of the research headed towards the development of new methods for estimating gait spatio-temporal parameters using shank worn MIMUs on different pathological subjects groups. In addition to the conventional gait parameters, new methods for estimating the changes of the direction of progression were explored. Finally, a new hardware solution and relevant methodology for estimating inter-feet distance during walking was proposed. Results of the technical validation of the proposed methods at different walking speeds and along different paths against a gold standard were reported and showed that the use of two MIMUs attached to the lower limbs associated with a robust method guarantee a much higher accuracy in determining gait spatio-temporal parameters. In conclusion, the proposed methods could be reliably applied to various abnormal gaits obtaining in some cases a comparable level of accuracy with respect to normal gait.

Genome-wide analysis reveals selection for important traits in domestic horse breeds.

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

Do executive dysfunction and freezing of gait in Parkinson's disease share the same neuroanatomical correlates?

Current hypotheses postulate a relationship between executive dysfunction and freezing of gait (FOG) in Parkinson's disease (PD). Hitherto, most evidence comes from entirely clinical approaches, while knowledge about this relationship on the morphological level is sparse. The aim of this study was therefore to assess the overlap of gray matter atrophy associated with FOG and executive dysfunction in PD. We included 18 PD patients with FOG and 20 without FOG in our analysis. A voxel-based morphometry approach was used to reveal voxel clusters in the gray matter which were associated with FOG and executive dysfunction as measured by the Frontal Assessment Battery, respectively. Conjunction analysis was applied to detect overlaps of the associated patterns. FOG correlated with different cortical clusters in the frontal and parietal lobes, whereas those associated with the FAB scores were, although widespread, widely confined to the frontal lobe. Conjunction analysis revealed a significant cluster of gray matter loss in the right dorsolateral prefrontal cortex. We could show that the patterns of neurodegeneration associated with FOG and executive dysfunction (as measured by the FAB) share atrophic changes in the same cortical areas. However, there is also a considerable number of cortical areas where neurodegenerative changes are only unique for either sign. Particularly, the involvement of parietal lobe areas seems to be more specific for FOG.

Human Motion Analysis Based on Sequential Modeling of Radar Signal and Stereo Image Features

Falls are one of the greatest threats to elderly health in their daily living routines and activities. Therefore, it is very important to detect falls of an elderly in a timely and accurate manner, so that immediate response and proper care can be provided, by sending fall alarms to caregivers. Radar is an effective non-intrusive sensing modality which is well suited for this purpose, which can detect human motions in all types of environments, penetrate walls and fabrics, preserve privacy, and is insensitive to lighting conditions. Micro-Doppler features are utilized in radar signal corresponding to human body motions and gait to detect falls using a narrowband pulse-Doppler radar. Human motions cause time-varying Doppler signatures, which are analyzed using time-frequency representations and matching pursuit decomposition (MPD) for feature extraction and fall detection. The extracted features include MPD features and the principal components of the time-frequency signal representations. To analyze the sequential characteristics of typical falls, the extracted features are used for training and testing hidden Markov models (HMM) in different falling scenarios. Experimental results demonstrate that the proposed algorithm and method achieve fast and accurate fall detections. The risk of falls increases sharply when the elderly or patients try to exit beds. Thus, if a bed exit can be detected at an early stage of this motion, the related injuries can be prevented with a high probability. To detect bed exit for fall prevention, the trajectory of head movements is used for recognize such human motion. A head detector is trained using the histogram of oriented gradient (HOG) features of the head and shoulder areas from recorded bed exit images. A data association algorithm is applied on the head detection results to eliminate head detection false alarms. Then the three dimensional (3D) head trajectories are constructed by matching scale-invariant feature transform (SIFT) keypoints in the detected head areas from both the left and right stereo images. The extracted 3D head trajectories are used for training and testing an HMM based classifier for recognizing bed exit activities. The results of the classifier are presented and discussed in the thesis, which demonstrates the effectiveness of the proposed stereo vision based bed exit detection approach.

Three-Dimensional kinetic adaptations of gait throughout pregnancy and postpartum

Biomechanical adaptations that occur during pregnancy can lead to changes on gait pattern. Nevertheless, these adaptations of gait are still not fully understood. The purpose was to determine the effect of pregnancy on the biomechanical pattern of walking, regarding the kinetic parameters. A three-dimensional analysis was performed in eleven participants. The kinetic parameters in the joints of the lower limb during gait were compared at the end of the first, second, and third trimesters of pregnancy and in the postpartum period, in healthy pregnant women. The main results showed a reduction in the normalized vertical reaction forces, throughout pregnancy, particularly the third peak. Pregnant women showed, during most of the stance phase, medial reaction forces as a motor response to promote the body stability. Bilateral changes were observed in hip joint, with a decrease in the participation of the hip extensors and in the eccentric contraction of hip flexors. In ankle joint a decrease in the participation of ankle plantar flexors was found. In conclusion, the overall results point to biomechanical adjustments that showed a decrease of the mechanical load of women throughout pregnancy, with exception for few unilateral changes of hip joint moments.