Effect of Speed and Surface Type on Individual Rein and Combined Left-Right Circle Movement Asymmetry in Horses on the Lunge

Differences in movement asymmetry between surfaces and with increasing speed increase the complexity of incorporating gait analysis measurements from lunging into clinical decision making. This observational study sets out to quantify by means of quantitative gait analysis the influence of surface and speed on individual-rein movement asymmetry measurements and their averages across reins (average-rein measurements). Head, withers, and pelvic movement asymmetry was quantified in 27 horses, identified previously as presenting with considerable movement asymmetries on the straight, during trot in hand and on the lunge on two surfaces at two speeds. Mixed linear models (p < 0.05) with horse as the random factor and surface and speed category (and direction) as fixed factors analyzed the effects on 11 individual-rein and average-rein asymmetry measures. Limits of agreement quantified differences between individual-rein and average-rein measurements. A higher number of individual-rein asymmetry variables-particularly when the limb that contributed to movement asymmetry on the straight was on the inside of the circle-were affected by speed (nine variables, all p <= 0.047) and surface (three variables, all p <= 0.037) compared with average-rein asymmetry variables (two for speed, all p <= 0.003; two for surface, all p <= 0.046). Six variables were significantly different between straight-line and average-rein assessments (all p <= 0.031), and asymmetry values were smaller for average-rein assessments. Limits of agreement bias varied between +0.4 and +4.0 mm with standard deviations between 3.2 and 12.9 mm. Fewer average-rein variables were affected by speed highlighting the benefit of comparing left and right rein measurements. Only one asymmetry variable showed a surface difference for individual-rein and average-rein data, emphasizing the benefit of assessing surface differences on each rein individually. Variability in straight-line vs. average-rein measurements across horses and exercise conditions highlight the potential for average-rein measurements during the diagnostic process; further studies after diagnostic analgesia are needed

Prevalence of vertical movement asymmetries at trot in Standardbred and Swedish Warmblood foals

Many horses, just before and during their athletic career, show vertical movement asymmetries, to the same degree as clinically lame horses. It is unknown whether these asymmetries are caused by pain or have alternative explanations, such as inherent biological variation. In the latter case, movement asymmetries would be expected to be present at a very young age. This study aimed to investigate the prevalence of movement asymmetries in foals. Motion analysis, using an inertial measurement unit-based system (Equinosis), was performed on 54 foals (31 Swedish Warmbloods, 23 Standardbreds) during straight-line trot. The foals were between 4–13 weeks old and considered sound by their owners. Differences between the vertical minimum and maximum values recorded for the head (HDmin, HDmax) and pelvis (PDmin, PDmax) between left and right stance were calculated for each stride and an average was computed for each trial. Thresholds for asymmetry were defined as absolute trial mean >6 mm for HDmin and HDmax, and >3 mm for PDmin and PDmax. These thresholds were exceeded for one or several parameters by 83% of Standardbred foals and 45% of Swedish Warmblood foals, demonstrating surprisingly high prevalence of asymmetries in young foals, although the risk of repetitive strain injuries and cumulative risk of trauma injuries was expected to be low in this age group. Standardbred foals showed similar prevalence of asymmetries to that reported previously for yearling Standardbred trotters, so relatively higher prevalence of movement asymmetries may be expected among trotters as a breed. In general, vertical head and pelvic movement asymmetries can be anticipated among foals considered sound by their owners. A better understanding of the aetiology of asymmetries is needed for correct interpretation of objective symmetry measurements in different populations of horses

Objectively measured movement asymmetry in yearling Standardbred trotters

Background Lameness evaluation of Standardbred trotters can be challenging due to discrepancies in observed movement asymmetry between in-hand and track exercise, and between different trotting speeds. There are few studies on objective measurement of movement in Standardbreds, and little knowledge regarding biological variation and clinical significance of measured movement asymmetry in this breed. Objectives To quantify the prevalence and magnitude of objectively measured movement asymmetry in young Standardbred trotters, and identify associations with trainer, sex, height, track type and in-hand measurement prior to or after track trials. Study design Cross-sectional, observational study. Methods A total of 114 Standardbred yearlings were evaluated with a wireless inertial sensor system during trot in-hand and when driven on a track. After exclusions relating to lameness or technical difficulties, 103 horses were included in the study; 77 were evaluated in-hand and on the track, 24 only in-hand and 2 only on the track. Results Front and/or hindlimb parameters were above asymmetry thresholds previously established for other breeds during in-hand trials for 94 (93%) horses and during track trials for 74 (94%) horses. Most horses showed mild asymmetry. A minority of horses (20%) switched side of the asymmetry for one or more parameters between in-hand and track trials. Mixed model analyses revealed no significant effects of trial mode (in-hand or track trial, in-hand trial pre- or post-track trial, straight or oval track), trainer or horse height. Females had a significant but small reduction in asymmetry in one front limb parameter (HDmax) compared with males (1.7 mm, 95% CI 0.18-3.28,P = .03). Main limitations High data variability, reflected in large trial standard deviations, relating mainly to a lack of horse compliance. Conclusions A high proportion of Standardbred yearlings showed movement asymmetries. There was no group-level effect between in-hand and track trials, however, considerable individual variation was observed

Adaptation strategies of the Icelandic horse with induced forelimb lameness at walk, trot and tölt

Background and objective Lameness assessment in the gaited Icelandic horse is complex. We aimed to describe their kinematic and temporal adaptation strategies in response to forelimb lameness at walk, trot and tolt.Study designIn vivo experiment.Methods Ten clinically non-lame Icelandic horses were measured before and after reversible forelimb lameness induction. Upper body and limb kinematics were measured using 11 inertial measurement units mounted on the poll, withers, pelvis (tubera sacrale) and all four limbs and hoofs (Equimoves (R), 500 Hz). Horses were measured on a straight line at walk and trot in-hand and at walk, trot and tolt while ridden. Linear mixed models were used to compare baseline and lame conditions (random factor = 'horse'), and results are presented as the difference in estimated marginal means or percentage of change.Results Lameness induction significantly (p < 0.05) increased head vertical movement asymmetry at walk (HDmin/HDmaxHAND: 18.8/5.7 mm, HDmin/HDmaxRIDDEN: 9.8/0.3 mm) and trot (HDmin/HDmaxHAND: 18.1/7.8 mm, HDmin/HDmaxRIDDEN: 24.0/9.3 mm). At the tolt, however, HDmin did not change significantly (1.1 mm), but HDmax increased by 11.2 mm (p < 0.05). Furthermore, pelvis vertical movement asymmetry (PDmax) increased by 4.9 mm, sound side dissociation decreased (-8.3%), and sound diagonal dissociation increased (6.5%). Other temporal stride variables were also affected, such as increased stance duration of both forelimbs at walk, tolt and in-hand trot.Main limitations Only one degree of lameness (mild) was induced with an acute lameness model.Conclusions Classical forelimb lameness metrics, such as vertical head and withers movement asymmetry, were less valuable at tolt compared to walk and trot, except for HDmax. Therefore, it is advised to primarily use the walk and trot to detect and quantify forelimb lameness in the Icelandic horse

Withers vertical movement symmetry is useful for locating the primary lame limb in naturally occurring lameness

BackgroundDuring orthopaedic assessment of lame horses, a head nod is commonly present in both primary forelimb and hindlimb lame horses. Additional motion metrics that could assist clinicians in correctly differentiating between these two scenarios would be of great clinical value. ObjectivesThe primary objective of this study was to examine whether withers movement asymmetry can be used in a clinical setting to distinguish primary forelimb lameness from compensatory head movement asymmetry due to primary hindlimb lameness. Study designRetrospective, multicentre study. MethodsMovement asymmetry of head, withers and pelvis was measured using multi-camera optical motion capture, as part of routine lameness investigations at four European equine hospitals. Vertical movement asymmetry parameters from 317 horses trotting in a straight line were compared before and after successful diagnostic analgesia of a single limb. Descriptive statistics, t-tests and linear models were used to analyse the data. ResultsIn forelimb lame horses, 80%-81% showed head and withers asymmetry both indicating lameness in the same forelimb. In hindlimb lame horses, 69%-72% showed head asymmetry ipsilateral to the lame hindlimb and withers asymmetry diagonal to the lame hindlimb, thus, head and withers asymmetry indicated lameness in different forelimbs. A large (>15 mm) compensatory head nod was seen in 28%-31% of the hindlimb lame horses. In 89%-92% of these, head and withers asymmetry indicated lameness in different forelimbs. Withers asymmetry decreased linearly with reduced head or pelvic asymmetry for both forelimb and hindlimb lame horses. Main limitationsCompensatory strategies were evaluated on group level to identify common patterns, potentially ignoring uncommon individual strategies. ConclusionsWithers vertical movement asymmetry metrics can be useful in helping to locate the primary lame limb during quantitative lameness assessment. Head and withers movement asymmetry parameters generally indicate the same forelimb in forelimb lame horses, but different forelimbs in hindlimb lame horses

Timing of Vertical Head, Withers and Pelvis Movements Relative to the Footfalls in Different Equine Gaits and Breeds

Simple Summary Movement symmetry of the head and pelvis are used to measure lameness in horses in trot. Although head, pelvis and limb movements have been described, less is known about the temporal relationships between them. This information is needed to understand how the movements change with lameness. This is particularly relevant in gaited horses, such as the Icelandic horse that perform gaits such as tolt and pace, which are challenging to evaluate. This study used inertial measurement units to investigate head, withers and pelvis motion relative to limb movements in Icelandic, Warmblood and Iberian horses. Limb movements, together with vertical movements and lowest/highest positions of the head, withers and pelvis were calculated, and the relative timing of the events was compared across breeds. Additionally, data for tolt and pace were collected and evaluated in ridden Icelandic horses. For all gaits except walk and pace, the lowest/highest positions of the head/withers/pelvis were closely temporally related to midstance and hoof-off, respectively. Pelvic and withers total range of motion differed between all breeds. The Icelandic horses showed shorter stride duration and smaller movements of the upper body than the other breeds at trot, which may explain why lameness evaluation in this breed is challenging. Knowledge of vertical motion patterns of the axial body segments is a prerequisite for the development of algorithms used in automated detection of lameness. To date, the focus has been on the trot. This study investigates the temporal synchronization between vertical motion of the axial body segments with limb kinematic events in walk and trot across three popular types of sport horses (19 Warmbloods, 23 Iberians, 26 Icelandics) that are known to have different stride kinematics, and it presents novel data describing vertical motion of the axial body segments in tolting and pacing Icelandic horses. Inertial measurement unit sensors recorded limb kinematics, vertical motion of the axial body at all symmetrical gaits that the horse could perform (walk, trot, tolt, pace). Limb kinematics, vertical range of motion and lowest/highest positions of the head, withers and pelvis were calculated. For all gaits except walk and pace, lowest/highest positions of the pelvis and withers were found to be closely related temporally to midstance and start of suspension of the hind/fore quarter, respectively. There were differences in pelvic/withers range of motion between all breeds where the Icelandic horses showed the smallest motion, which may explain why lameness evaluation in this breed is challenging

Improving gait classification in horses by using inertial measurement unit (IMU) generated data and machine learning

For centuries humans have been fascinated by the natural beauty of horses in motion and their different gaits. Gait classification (GC) is commonly performed through visual assessment and reliable, automated methods for real-time objective GC in horses are warranted. In this study, we used a full body network of wireless, high sampling-rate sensors combined with machine learning to fully automatically classify gait. Using data from 120 horses of four different domestic breeds, equipped with seven motion sensors, we included 7576 strides from eight different gaits. GC was trained using several machine-learning approaches, both from feature-extracted data and from raw sensor data. Our best GC model achieved 97% accuracy. Our technique facilitated accurate, GC that enables in-depth biomechanical studies and allows for highly accurate phenotyping of gait for genetic research and breeding. Our approach lends itself for potential use in other quadrupedal species without the need for developing gait/animal specific algorithms

Timing of Vertical Head, Withers and Pelvis Movements Relative to the Footfalls in Different Equine Gaits and Breeds

Knowledge of vertical motion patterns of the axial body segments is a prerequisite for the development of algorithms used in automated detection of lameness. To date, the focus has been on the trot. This study investigates the temporal synchronization between vertical motion of the axial body segments with limb kinematic events in walk and trot across three popular types of sport horses (19 Warmbloods, 23 Iberians, 26 Icelandics) that are known to have different stride kinematics, and it presents novel data describing vertical motion of the axial body segments in tölting and pacing Icelandic horses. Inertial measurement unit sensors recorded limb kinematics, vertical motion of the axial body at all symmetrical gaits that the horse could perform (walk, trot, tölt, pace). Limb kinematics, vertical range of motion and lowest/highest positions of the head, withers and pelvis were calculated. For all gaits except walk and pace, lowest/highest positions of the pelvis and withers were found to be closely related temporally to midstance and start of suspension of the hind/fore quarter, respectively. There were differences in pelvic/withers range of motion between all breeds where the Icelandic horses showed the smallest motion, which may explain why lameness evaluation in this breed is challenging

Mitochondria and cellular energy metabolism in platinum chemotherapy

Chemotherapy is a major strategy in the treatment of cancer. Unfortunately, treatment of advanced cancers often fails due to tumor resistance to chemotherapeutic drugs. Studies of cell death signaling induced by chemotherapeutic agents are of importance to develop strategies for improved therapy, either by development of new drugs or by potentiation of existing drugs. Discovery of markers for prediction of therapeutic outcome is also of great importance for identification of responsive patients and thereby improved treatment. This thesis presents results on apoptotic stress-signaling induced by the platinum chemotherapeutic drug cisplatin, and on combining chemotherapeutic drugs with inhibitors of cell metabolism as a potentiation strategy. MEKK1, a kinase in the MAPK-signaling pathway, was shown to be responsible for cisplatin induced activation of the mitochondrial proapoptotic protein Bak, as seen by conformational change of this protein. However, activation of Bak was not sufficient to induce apoptosis unless signaling from another protein of the MAPK pathway, JNK, was present. Gel filtration experiments revealed Bak complexes of sizes between 80 to 170 kDa in cells with cisplatin-induced onset of apoptosis. By chemical inhibition and gene knock-out, JNK was shown to be crucial for the formation of these complexes. p53 is involved in responses to platinum drugs. Here, a novel mechanism for negative regulation of p53 translocation to mitochondria is presented. Induction of iNOS after cisplatin treatment was shown to inhibit mitochondrial translocation of p53 as evaluated by chemical inhibition of iNOS. There was no upregulation of iNOS after treatment with oxaliplatin; however, addition of exogenous nitric oxide abrogated mitochondrial translocation of p53 after treatment with this drug. Seventeen clinical and experimental drugs were screened for potentiation of apoptosis together with glycolysis inhibitor 2-deoxyglucose (DG) and inhibitor of fatty acid beta-oxidation etomoxir in HCT116 colon carcinoma cells. DG was more potent than etomoxir in this respect. Cytotoxic responses to combination treatment varied and included apoptosis, necrosis and growth arrest. The combination of cisplatin and DG showed substantial increase in apoptotic response compared to cisplatin alone. Because treatment of ovarian cancer involves platinum drugs, this combination was further studied in two ovarian carcinoma cell lines and primary ovarian carcinoma cells purified from ascites. In the cell lines, higher use of glucose was coupled to increased resistance to cisplatin and carboplatin. In the primary tumor cells, low expression of mitochondrial beta-F1-ATPase correlated with reduced cisplatin IC50 in the presence of DG