293 research outputs found
Influence of seating styles on head and pelvic vertical movement symmetry in horses ridden at trot
Detailed knowledge of how a rider’s seating style and riding on a circle influences the movement symmetry of the horse’s head and pelvis may aid rider and trainer in an early recognition of low grade lameness. Such knowledge is also important during both subjective and objective lameness evaluations in the ridden horse in a clinical setting. In this study, inertial sensors were used to assess how different rider seating styles may influence head and pelvic movement symmetry in horses trotting in a straight line and on the circle in both directions. A total of 26 horses were subjected to 15 different conditions at trot: three unridden conditions and 12 ridden conditions where the rider performed three different seating styles (rising trot, sitting trot and two point seat). Rising trot induced systematic changes in movement symmetry of the horses. The most prominent effect was decreased pelvic rise that occurred as the rider was actively rising up in the stirrups, thus creating a downward momentum counteracting the horses push off. This mimics a push off lameness in the hindlimb that is in stance when the rider sits down in the saddle during the rising trot. On the circle, the asymmetries induced by rising trot on the correct diagonal counteracted the circle induced asymmetries, rendering the horse more symmetrical. This finding offers an explanation to the equestrian tradition of rising on the ‘correct diagonal.’ In horses with small pre-existing movement asymmetries, the asymmetry induced by rising trot, as well as the circular track, attenuated or reduced the horse’s baseline asymmetry, depending on the sitting diagonal and direction on the circle. A push off hindlimb lameness would be expected to increase when the rider sits during the lame hindlimb stance whereas an impact hindlimb lameness would be expected to decrease. These findings suggest that the rising trot may be useful for identifying the type of lameness during subjective lameness assessment of hindlimb lameness. This theory needs to be studied further in clinically lame horses
Effect of meloxicam treatment on movement asymmetry in riding horses in training
Quantitative gait analysis has revealed that a large proportion of horses in training, perceived as free from lameness by their owners, show movement asymmetries of equal magnitude to horses with mild clinical lameness. Whether these movement asymmetries are related to orthopaedic pain and/or pathology has yet to be further investigated. Therefore, the objective of this study was to determine whether movement asymmetries in riding horses in training are affected by anti-inflammatory treatment with meloxicam. In a crossover design, horses were treated with meloxicam or placebo for four days respectively, with a 14–16 day washout period between treatments. Objective movement analysis utilising body mounted accelerometers was performed on a hard and a soft surface before and on day four of each treatment. A trial mean was calculated for the differences between the two vertical displacement minima and maxima of head (HDmin, HDmax) and pelvis (PDmin, PDmax) per stride. Horses (n = 66) with trial mean asymmetries greater than 6 mm for HDmin or HDmax, or more than 3 mm for PDmin or PDmax, at baseline were included. The difference before and after each treatment in the measured movement asymmetry was assessed with linear mixed models. Treatment with meloxicam did not significantly affect the movement asymmetry in any of the models applied (all p>0.30). These results raise new questions: are the movement asymmetries in riding horses in training simply expressions of biological variation or are they related to pain/dysfunction that is non-responsive to meloxicam treatment
Epidemiology and economic burden of osteoporosis in Switzerland
Summary: This report describes the epidemiology, economic burden and treatment of osteoporosis in Switzerland. Introduction: Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased risks of fragility fractures which represent the main clinical consequence of the disease. Fragility fractures are associated with substantial pain and suffering, disability and even death for the affected patients and substantial costs to society. The aim of this report is to describe the epidemiology and economic burden of fragility fractures as a consequence of osteoporosis in Switzerland, as a detailed addition to the report for the European Union (EU27): "Osteoporosis in the European Union: Medical Management, Epidemiology and Economic Burden”. Methods: The literature on fracture incidence and costs of fractures in Switzerland was reviewed and incorporated into a model estimating the clinical and economic burden of osteoporotic fractures in 2010. Furthermore, data on sales of osteoporosis treatments and the population at high risk of fracture were used to estimate treatment uptake and treatment gap. Results: It was estimated that approximately 74,000 new fragility fractures were sustained in Switzerland in 2010, comprising 14,000 hip fractures, 11,000 vertebral fractures, 13,000 forearm fractures and 36,000 other fractures (i.e. fractures of the pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum and other femoral fractures). The economic burden of incident and previous fragility fractures was estimated at CHF 2,050 million for the same year. Incident fractures represented 76% of this cost, long-term fracture care 21% and pharmacological prevention 3%. Previous and incident fractures also accounted for 24,000 quality-adjusted life years (QALYs) lost during 2010. When accounting for the demographic projections for 2025, the number of incident fractures was estimated at 98,786 in 2025, representing an increase of 25,000 fractures. Hip, clinical vertebral (spine), forearm and other fractures were estimated to increase by 4,900, 3,200, 3,500 and 13,000, respectively. The burden of fractures in terms of costs (excluding value of QALYs lost) in Switzerland in 2025 was estimated to increase by 29% to CHF 2,642 million. Though the uptake of osteoporosis treatments increased from 2001, the proportion of patients aged 50 or above who received treatment remained at low levels in the past few years. The majority of women at high fracture risk do not receive active treatment. Conclusions: In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by an aging population, the use of pharmacological prevention of osteoporosis is significantly less than optimal, suggesting that a change in health care policy concerning the disease is warranted
PMS61 Health-Related Quality of Life After Vertebral Fracture: Differences Between the EQ-5D and Time-Trade-Off Instruments
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The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil
<p>Abstract</p> <p>Background</p> <p>Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H<sup>+</sup>-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-F1-ATPase/GAPDH), which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the <it>bioenergetic signature </it>of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP) and iodoacetate (IA), and the anti-metabolite, 5-fluorouracil (5-FU).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p
Cisplatin and Oxaliplatin Toxicity: Importance of Cochlear Kinetics as a Determinant for Ototoxicity
Background
Cisplatin is a commonly used platinum anti-cancer drug. Regrettably cisplatin
has dose-limiting ototoxic side effects, e.g. the drug can induce an irreversible
hearing loss. The ototoxic mechanisms of cisplatin have not been
elucidated in the human ear and no clinically useful oto-protectors are yet
available. Cisplatin is a necessary part of many treatment regimes. Its beneficial
therapeutic effects might be reduced if cisplatin was excluded from the
treatment in order to protect the hearing function. In this work the ototoxic
effects of cisplatin are studied with the aim to better understand the mechanisms
behind the irreversible hearing loss induced by this drug. Oxaliplatin is
a second generation platinum-derivative anti-cancer drug, free from ototoxic
side effects in clinical practice. The effects of oxaliplatin on the inner ear have
been studied in this work and the results are compared with cisplatin treatment.
The two drugs differ regarding both anti-cancer effects and side effects,
which could be attributed to differences in pharmacokinetic factors, cellular
uptake and apoptotic mechanisms. The thioredoxin redox system with the
enzyme thioredoxin reductase (TrxR) was studied in cochleae due to a suggested
DNA-independent apoptotic mechanism of the hair cells. The cochlear
pharmacokinetics of cisplatin was assessed and the transport protein organic
cation transporter 2 (OCT2) was studied in relation to the ototoxic effect of
cisplatin.
Material and methods
Cultured human colon carcinoma cells and cell cultures of rat organ of Corti
were used for apoptosis studies in vitro following exposure to cisplatin and
oxaliplatin. Cisplatin and oxaliplatin were administered i.v. to guinea pigs,
followed by in vivo sampling of blood, cerebrospinal fluid (CSF) and scala
tympani (ST) perilymph. Liquid chromatography with post-column derivatization
was used to determine the concentration of parent drug in the samples.
Electrophysiological hearing thresholds and the loss of hair cells were assessed
to evaluate their ototoxic effects. Phenformin, a potential blocker of
OCT2 was administered and the ototoxic side effect of cisplatin was evaluated.
For immunohistochemical studies, cochlea from rat, guinea pig and pig
were used, where TrxR and OCT2 were evaluated in the cochlea. TrxR-assays
were used to measure the TrxR activity in cochlear tissue, both in vivo and in
vitro.
Results
The results from the in vitro studies showed that addition of either cisplatin
or oxaliplatin to the culture medium in organ of Corti cell cultures caused a
similar amount of outer hair cell loss and inhibition of TrxR activity. Cisplatin
exposure to cultured human colon carcinoma cells also reduced the activity
of TrxR. The results from the in vivo studies showed that a considerable concentration
of cisplatin was present in ST perilymph as compared with weak
concentrations of oxaliplatin after high dose oxaliplatin i.v. Ten minutes after
cisplatin administration, its concentration in ST perilymph was 4-fold higher
in the basal turn of the cochlea as compared to the apex. Cisplatin could be
analysed in ST perilymph for up to 120 min. Phenformin i.v. did not reduce
the ototoxic side-effect of cisplatin. Positive immunoreactivity to TrxR was
evident in both hair cells and spiral ganglion cells. Futhermore, OCT2 was
expressed in the supporting cells of organ of Corti and in the spiral ganglion
cells.
Conclusion
The transport of cisplatin to the vulnerable cells of hearing seems to be of major
importance for the ototoxic effects. An early high concentration of cisplatin
in the base of the cochlea and delayed elimination of cisplatin from ST perilymph
may be related to the cisplatin-induced loss of outer hair cells in the
basal turn of the cochlea. Cisplatin and oxaliplatin both cause similar ototoxic
effects when the organ of Corti is directly exposed in vitro. The thioredoxin
redox system with the TrxR enzyme may well play a critical role in cisplatininduced
ototoxicity. The presence of OCT2 in the supporting cells indicates
that this transport protein is primarily not involved in the uptake of cisplatin
from the systemic circulation but rather from the deeper compartments of
the cochlea. The knowledge elicited in this work will hopefully suggest objectives
for further studies in order to develop oto-protective treatments to
preserve the hearing of cisplatin treated patients
Comparing subjective and objective evaluation of show jumping competition and warm-up arena surfaces
The development of safety and quality standards for equestrian surfaces needs to be based on objective, repeatable measurements which allow comparisons between surfaces. These measurements should incorporate the assessment of surface performance by riders. This study provides data from objective and subjective assessment of functional properties of high-level show jumping competition and warm-up arenas. Twenty-five arenas in nine international show jumping events were evaluated by mechanical insitu testing with a surface tester, rider assessments using visual analogue scales (198 riders provided 749 arena evaluations), descriptions of arena constructions and by laboratory tests of surface material. Mixed models were used to present subjective evaluation of rider perception of the functional properties for each arena while controlling for rider and event. The association between objective and subjective assessments were also explored creating mixed models, controlling for rider and event. Mechanical measurements of impact firmness, and to a lesser extent cushioning and grip, had a significant positive association with the riders’ perception. Responsiveness as assessed by the Orono biomechanical surface tester (OBST) was negatively associated with the riders’ perceptions, which suggests riders and the OBST had different concepts of this functional property and that further developments of the OBST might be necessary. Objectively measured uniformity showed no useful association with riders’ perception. Even though arena assessments were made by top level riders, a substantial inter-rider variation was demonstrated
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
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