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Biomedical subjects

A E Goodship

Publications and source records attributed to A E Goodship.

At least 37 records · Page 2Linked to original sources

Are the material properties and matrix composition of equine flexor and extensor tendons determined by their functions?

REASONS FOR PERFORMING STUDY: Injury to the superficial digital flexor tendon (SDFT) is common in competition horses. The SDFT contributes to locomotory efficiency by storing energy; such tendons have low safety margins. Tendons which merely position the limb, including the opposing common digital extensor tendon (CDET), are rarely injured. The current failure of strategies to prevent or effectively treat injury to the SDFT indicates the importance of understanding how it differs from tendons which are not injury-prone. HYPOTHESIS: That the structural and material properties and matrix composition of the SDFT and CDET differ, reflecting their specific functional requirements in vivo. METHODS: Forelimb tendons were harvested from 26 mature horses and loaded to failure prior to matrix composition analysis of specimens. RESULTS: The SDFT had a significantly higher cross-sectional area, structural stiffness, failure load and failure strain and a lower elastic modulus than the CDET (P < 0.0001). CONCLUSIONS: The SDFT has conflicting requirements for strength and elasticity; although as a whole it is a stiffer structure than the CDET, differences in the matrix molecular composition including water and total sulphated glycosaminoglycan contents allow it to remain more elastic as a material. POTENTIAL RELEVANCE: Further information on how the two tendons attain these different properties may be of use in the development of prevention and treatment strategies for SDFT rupture.

Animals↗

The influence of ageing and exercise on tendon growth and degeneration--hypotheses for the initiation and prevention of strain-induced tendinopathies.

Strain-induced tendinopathy is a common injury in both human and equine athletes, with increasing incidence associated with greater involvement in sport and an increasingly aged population. This paper reviews our studies on the abundant non-collagenous protein, cartilage oligomeric matrix protein (COMP), in equine tendons. Its variation between tendon type and site, age and exercise has provided an insight into how age and exercise influence tendon growth and maturation. Tendons can be broadly divided into two types, reflecting their different matrix composition and function: the energy-storing tendons used for weight-bearing and locomotion, which suffer a high incidence of strain-induced tendinopathy, and positional tendons involved in limb placement or manipulative skills. It would appear that while energy-storing tendon can respond to the mechanical forces applied to it during growth, there is no evidence that it can do so after skeletal maturity. Instead, cumulative fatigue damage causes degeneration at the molecular level, potentially weakening it and increasing the risk of clinical injury. Appropriate exercise regimes early in life may help to improve the quality of growing tendon, thereby reducing the incidence of injury during ageing or subsequent athletic career.

Aging↗

Correlation of cartilage oligomeric matrix protein (COMP) levels in equine tendon with mechanical properties: a proposed role for COMP in determining function-specific mechanical characteristics of locomotor tendons.

Over-strain injury of the superficial digital flexor tendon (SDFT) is a common injury in the horse. Tendon appears to adapt to loads placed on it during development, but fatigue damage accumulates after skeletal maturity, which is inadequately repaired and predisposes to clinical tendinitis. In any population of horses, there is a wide variation in SDFT mechanical properties. A noncollagenous protein, cartilage oligomeric matrix protein (COMP), is particularly abundant during growth in the equine SDFT and has been proposed to have an organisational role in the formation of collagenous matrices. This study aimed to determine whether COMP levels were correlated to mechanical properties at skeletal maturity. Tendons from 2 groups of 12 horses were analysed: Group 1 horses with restricted age, 2 years +/- 2 months, showed a significant correlation between both ultimate tensile stress modulus of elasticity and stiffness and COMP, while Group 2 mature horses with varying age did not, because of age- and exercise-induced loss of COMP. These data supports the hypothesis that COMP is an important mediator in the growth of tendon. This data would suggest that the identification of low COMP levels in tendon during growth would indicate horses prone to tendon injury and methods of promoting COMP synthesis during growth would potentially improve tendon quality and reduce the risk of subsequent tendinitis.

Age Factors↗

Exercise-induced tendon hypertrophy: cross-sectional area changes during growth are influenced by exercise.

Most skeletal tissues are thought to adapt to the mechanical environment they experience. While this has been demonstrated for muscle and bone, previous studies in the mature horse have failed to demonstrate adaptation in the superficial digital flexor tendon (SDFT), which suffers a high frequency of injury. This study tested the hypothesis that imposed exercise during growth would result in an increase in SDFT cross-sectional area (CSA). Fourteen Thoroughbred foals were divided into 2 sex-matched groups. A control group received 4 h pasture exercise and an exercise group had the same amount of pasture exercise with an additional short period of treadmill exercise daily from age 2-15 months. Activity at pasture was assessed objectively using a visual system. There was no significant difference in pasture activity between groups, although males were more active than females. The exercise programme resulted in a significantly larger tendon CSA in the exercise group at several, but not all, timepoints, which may be attributed to levels of variance. However, there was a significantly greater rate of increase in tendon CSA as a function of time in the exercised compared to the control group. This is the first evidence to suggest that tendon development can be modulated by exercise during growth in the horse, potentially increasing the ability of tendon to withstand the rigours of later athletic activity.

Adaptation, Physiological↗

Do regional variations in flexor tendons predispose to site-specific injuries?

Partial rupture occurs most often to the superficial digital flexor tendon (SDFT) of the forelimb at the mid-metacarpal level. In this study, we tested the hypothesis that the mid-metacarpal region of the SDFT has the smallest cross sectional area (CSA) and a similar collagen content to other regions and, therefore, represents a weak point in the tendon. The SDFT was collected from the forelimbs of 9 horses. Each tendon was marked at 7 different levels from the origin of the accessory ligament to the phalangeal region. The CSA, water content and collagen content was measured at each level. The mid-metacarpal level had a significantly smaller CSA than the most proximal and distal levels measured and a significantly higher dry matter content than proximal levels. However, the total amount of collagen present in the mid-metacarpal section was not significantly less than other regions except for the most distal sections. The results of this study suggest that the mid-metacarpal region of the SDFT, although smaller in CSA, is not significantly weaker than the proximal end and manica flexoria region of the tendon. Therefore, other factors such as hypoxia and/or hyperthermia may be responsible for site-specific tendon lesions in the SDFT.

Animals↗

The effect of intra-articular methylprednisolone acetate and exercise on equine carpal subchondral and cancellous bone microhardness.

Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. Intra-articular corticosteroid treatment is used commonly to manage exercise-associated articular pain, but its use remains highly controversial in the equine athlete. This project, therefore, aimed to compare the mechanical properties of intra-articular MPA and diluent-treated middle carpal subchondral and cancellous bone in horses undergoing a short-term treadmill exercise programme. It was hypothesised that subchondral and cancellous bone mechanical properties are influenced by intra-articular administration of methylprednisolone acetate (MPA). Eight 2-year-old female horses had MPA or diluent administered into contralateral middle carpal joints at 14 day intervals, for a total of 4 treatments per horse. Horses underwent a standard treadmill exercise protocol until euthanasia (Day 70). Standard sites were located on the dorsal aspect of third, radial and intermediate carpal bones. Osteochondral samples from each test site were divided into subchondral bone and cancellous bone portions. These were dried, resin-embedded and gold-coated. Microhardness measurements were obtained at each test site. No significant effect of intra-articular treatment was detected. At each site, cancellous bone trabecular struts had an 18-19% higher microhardness value than the overlying subchondral bone. These findings indicate that intra-articular administration of MPA at this dose has no effect on subchondral or cancellous bone adaptation to short-term exercise and, therefore, on the propensity of carpal bones to injury. Further investigation into the calcified cartilage layer, effect of different corticosteroid preparations and diffusion of medication are required.

Animals↗

Asymmetric densitometric and mechanical adaptation of the left fifth metacarpal bone in racing greyhounds.

The densitometric and mechanical structural properties of the left and right fifth metacarpal bones of 10 racing greyhounds with a fracture of the central tarsal bone and 10 without a fracture were investigated by dual energy x-ray absorptiometry and a servo-hydraulic materials testing machine. In all the greyhounds the bone mineral density of the left fifth metacarpal bone was significantly greater than that of the right (P<0.001), but there was no significant difference between the degree of asymmetry in bone mineral density in the two groups. The ultimate torque and energy-to-failure of the left fifth metacarpal bone of the greyhounds with a fracture of the right central tarsal bone were significantly higher than in the right fifth metacarpal bone and higher than in both the left and right fifth metacarpal bones of the greyhounds with no fracture (P<0.05). The ultimate torque and energy-to-failure were significantly related to bone mineral density (P<0.005), and 22 per cent of the variation in these structural properties could be explained by variations in bone mineral density. Fifth metacarpal remodelling in response to asymmetric cyclic loading is bone-specific, and structural properties are enhanced in the left fifth metacarpal of greyhounds with a fracture of the right central tarsal bone.

Absorptiometry, Photon↗

Subchondral bone thickness, hardness and remodelling are influenced by short-term exercise in a site-specific manner.

It was hypothesised that subchondral bone thickness, hardness and remodelling are influenced by exercise intensity, and by location within a joint. Dorsal carpal osteochondral injury is a major cause of lameness in horses undergoing high intensity training. This project aimed to determine the subchondral bone thickness, formation, resorption and hardness at sites with high and low incidence of pathology in 2 year-old horses undergoing 19 weeks high intensity treadmill training or low intensity exercise, and to compare these factors between exercise groups. Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Adjacent osteochondral samples from each test site underwent histomorphometric analysis (for subchondral bone thickness, osteoid perimeter, osteoid seam width, eroded cavity area and eroded cement line surface length) and microhardness testing. Bone from horses undergoing high intensity training was thicker with a greater osteoid perimeter, and at individual sites had a smaller osteoid seam width and eroded cavity. Exercise-related differences were most marked at dorsal locations. Maximal differences in bone formation indices were observed at dorsal radial and medial third carpal locations. Overall subchondral bone from dorsal sites was thicker with a greater osteoid perimeter. Subchondral bone from dorsal sites was approximately 35% harder than bone from palmar sites. These results show topographical variations in subchondral bone structure, formation, resorption and material properties and a site-specific response to exercise. The maximal response to exercise was at high load sites with a clinical predisposition to injury. These findings indicate that the combined effect of exercise and local load variations within a joint may lead to maximal adaptive responses or overload of these responses at sites predisposed to injury.

Animals↗

Biochemical composition of equine carpal articular cartilage is influenced by short-term exercise in a site-specific manner.

UNLABELLED: It was hypothesized that cartilage macro-molecular characteristics are influenced by exercise intensity and by location within a joint. OBJECTIVE: To determine the macromolecular characteristics of carpal articular cartilage at common and uncommon sites of pathology in horses undergoing high or low intensity exercise, and to compare this composition between exercise groups. DESIGN: Twelve horses (19.3+/-0.9 years) were assigned to exercise groups. Each group underwent 19 weeks high-intensity treadmill training (N=6) or low-intensity exercise (N=6). Dorsal and palmar test sites were identified on radial, intermediate and third carpal articular surfaces after euthanasia. Cartilage was collected from each site, freeze-dried and assessed for water content. Hydroxyproline, glycosaminoglycan and DNA analyses were performed on cartilage from each test site. Adjacent cartilage underwent histological preparation and assessment for chondrocyte numerical density at each site and proteoglycan distribution through the depth of cartilage. RESULTS: Dorsal cartilage had a higher collagen content, DNA content, and chondrocyte numerical density, but lower glycosaminoglycan content than palmar cartilage. Cartilage from horses undergoing high-intensity training had a significantly higher glycosaminoglycan content than cartilage from horses undergoing low-intensity exercise, with maximal difference being observed in cartilage from dorsal radial and dorsal intermediate carpal articular surfaces. Overall no effect of exercise on collagen was observed, but at sites predisposed to clinical lesions cartilage from horses undergoing high-intensity training contained significantly less collagen than from horses undergoing low-intensity exercise. Distribution of proteoglycan was non-uniform in 52% of the sections examined, with superficial loss of toluidine blue staining primarily at dorsal sites and in the high-intensity exercise group. CONCLUSIONS: These results indicate that topographical and exercise related differences exist in carpal cartilage composition, and that the effect of exercise on overall composition and distribution within the cartilage was maximal at sites predisposed to clinical lesions. These findings could indicate that the combined effect of exercise and local load variations within a joint may lead to a risk of exceeding the physiologic threshold at high load sites that are predisposed to clinical injury.

Animals↗

Hind-limb/hind-quarter vascular resistance and blood flow changes: possible intrinsic renin--angiotensin system involvement.

For many years there was a general belief that the enzyme renin, having been secreted into the circulation by the kidney in response to appropriate stimuli, initially generates the inactive decapeptide angiotensin I in the bloodstream. This is then converted to the biologically active octapeptide angiotensin II by angiotensin converting enzyme on or near, vascular surface receptors both in the lungs and in the organs supplied by the systemic circulation. The results of various investigations have, however, latterly led to the conclusion that the overall system is widely distributed throughout the vasculature with the local intracellular formation of angiotensin II. In this review the reckoned intrinsic renin-angiotensin activity in hind-limb/hind-quarter is discussed with particular regard to the widespread use of radioimmunoassay, together with a consideration of other factors, more especially ACE inhibition, affecting the relevant regional vascular resistance and blood flow.

Animals↗

Fractographic examination of racing greyhound central (navicular) tarsal bone failure surfaces using scanning electron microscopy.

The greyhound is a fatigue fracture model of a short distance running athlete. Greyhounds have a high incidence of central (navicular) tarsal bone (CTB) fractures, which are not associated with overt trauma. We wished to determine whether these fractures occur because of accumulation of fatigue microdamage. We hypothesized that bone from racing dogs would show site-specific microdamage accumulation, causing predisposition to structural failure. We performed a fractographic examination of failure surfaces from fractured bones using scanning electron microscopy and assessed microcracking observed at the failure surface using a visual analog scale. Branching arrays of microcracks were seen in failure surfaces of CTB and adjacent tarsal bones, suggestive of compressive fatigue failure. Branching arrays of microcracks were particularly prevalent in remodeled trabecular bone that had become compact. CTB fractures showed increased microdamage when compared with other in vivo fractures (adjacent tarsal bone and long bone fractures), and ex vivo tarsal fractures induced by monotonic loading (P < 0.02). It was concluded that greyhound racing and training often results in CTB structural failure, because of accumulation and coalescence of branching arrays of fatigue microcracks, the formation of which appears to be predisposed to adapted bone.

Adaptation, Physiological↗

Is high-dose estrogen-induced osteogenesis in the mouse mediated by an estrogen receptor?

Although estrogen is known to induce new bone formation in the long bones of female mice, this response is only thought to occur following administration of high doses, suggesting that it may not be mediated by a conventional estrogen receptor. To address this question further, we first examined the stereospecificity of this response by comparing the potency of 17beta-estradiol (E(2)) in stimulating cancellous bone formation at the proximal tibial metaphysis of intact female mice with that of the relatively inactive stereoisomer, 17alpha-estradiol (alphaE(2)). We found that E(2) was significantly more potent than alphaE(2), as assessed by histomorphometry. To provide further evidence for an estrogen-receptor-mediated process, we examined whether E(2)-induced osteogenesis in intact female mice could be inhibited by the estrogen receptor antagonist, ICI 182,780 (ICI). Although ICI itself had no effect on histomorphometric indices of the proximal tibial metaphysis when given alone, it significantly inhibited the osteogenic response to E(2). Finally, we examined the dose dependency of E(2)-induced osteogenesis at the proximal tibial metaphysis in intact mice. We found that E(2) stimulated cancellous bone formation in a dose-dependent manner over a wide dose range (i. e., 1-4000 microg/kg per day), with significant increases observed at doses of 4 microg/kg per day and beyond. Our results raise the possibility that estrogen-induced osteogenesis in the mouse represents an estrogen-receptor-mediated response that is not confined solely to supraphysiological estrogen levels.

Animals↗

Dual-energy X-ray absorptiometry measurement of bone-mineral density in the distal aspect of the limbs in racing Greyhounds.

OBJECTIVE: To determine those bones in the distal aspect of the limbs of Greyhounds with fatigue fractures that have the greatest left-to-right differences in bone-mineral density (BMD). SAMPLE POPULATION: Limbs obtained from 20 Greyhounds. PROCEDURE: Dual-energy x-ray absorptiometry (DXA) of the distal aspect of each limb and isolated bones from 10 dogs with a fracture of the central tarsal bone (CTB) of the right pelvic limb was performed. High-resolution scanning was performed on excised bones, and BMD measurements of CTB also were obtained from limbs of dogs without a CTB fracture. RESULTS: The BMD of the accessory carpal bone and calcaneus was not significantly different from the BMD of those bones in the contralateral limb. Although BMD of the CTB of the entire right pelvic limb and isolated bones from dogs with a CTB fracture was lower, compared with values for the entire left pelvic limb, values for isolated CTB from dogs without a CTB fracture were not significantly different. Metacarpal or metatarsal and thoracic or pelvic limb significantly affected BMD for measurements of the entire limb and isolated bones. Left-to-right differences in BMD were greatest for metacarpal 5. CONCLUSIONS AND CLINICAL RELEVANCE: Asymmetric adaptive remodeling of metacarpal 5 can be detected by DXA. The potentially confounding effects of CTB fracture and unknown racing history made it difficult to interpret BMD changes in the CTB of these specimens. Densitometry could be developed as an in vivo assessment for risk of fractures in racing Greyhounds.

Absorptiometry, Photon↗

Exercise affects the mechanical properties and histological appearance of equine articular cartilage.

Dorsal carpal osteochondral injury is a major cause of reduced performance in horses undergoing high-intensity training. It was hypothesised that the mechanical behaviour and histology of cartilage are influenced by the intensity of exercise and by location within a joint. Relationships between histology and mechanical behaviour were identified in 2-year-old horses undergoing 19 weeks of high-intensity treadmill training or low-intensity exercise and then compared between groups. Dorsal and palmar test sites were identified on radial, intermediate, and third carpal articular surfaces after euthanasia. The mechanical properties of cartilage were determined with an automated creep indentation apparatus as previously described for equine cartilage. Cartilage morphology was assessed with use of sections stained with haematoxylin and eosin and toluidine blue. Dorsal cartilage was less permeable, thinner, and had a loss of chondrocyte alignment compared with palmar cartilage. Cartilage from strenuously trained horses showed more fibrillation and chondrocyte clusters than did cartilage from gently exercised animals. Dorsal radial carpal cartilage and third carpal cartilage of strenuously trained animals were significantly less stiff than that from gently exercised animals, and the former had reduced superficial toluidine blue staining compared with that from the gently exercised group. These results indicate that topographical and exercise-related differences exist in the morphology and mechanical properties of carpal cartilage and suggest that strenuous training may lead to deterioration of cartilage at sites with a high clinical incidence of lesions.

Animals↗

Galloping exercise induces regional changes in bone density within the third and radial carpal bones of Thoroughbred horses.

This study was performed to test the hypothesis that a localised bone hypertrophy could occur within the subchondral cancellous architecture of the third and radial carpal bones. Using 2 levels of controlled and defined exercise, it was observed that a high intensity treadmill exercise protocol resulted in functional adaptation of the carpal bones. The increase in trabecular thickening and density was seen to be localised to those regions underlying common sites of cartilage degradation, the interface of the thickened trabeculae with the normal architecture in the third carpal bone was coincident with a common site of clinical fractures. The bone changes were determined both qualitatively on examination of slab radiographs and quantified by dual energy x-ray absorptiometry. The findings from this study are relevant to mechanical factors involved in the pathophysiology of joint degeneration. The potential clinical implications of this study are in relation to changes in the type and duration of exercise regimens used in training of equine athletes. The rapid response of bone to mechanical stimulation has implications in the longer term for localised cartilage degradation. Imaging techniques could be developed to monitor these early bone changes in the specific areas identified in this study and thus allow appropriate changes in training intensity to minimise subsequent damage to the articular surface.

Absorptiometry, Photon↗

Age-related changes to the molecular and cellular components of equine flexor tendons.

Specific tendons show a high incidence of partial central core rupture which is preceded by degeneration. In the performance horse, the superficial digital flexor tendon (SDFT) is most often affected. We have described previously the molecular changes that are associated with degeneration in the central core region of the equine SDFT. The pathophysiological mechanism leading to change in synthetic activity of central zone cells in degenerated tendons is not known. In this study, we test the hypothesis that ageing results in matrix composition changes within the central zone of the SDFT. Extracellular matrix composition and cellularity were analysed in equine SDFTs collected from Thoroughbred horses and compared with a flexor tendon which rarely shows degenerative change and subsequent injury (deep digital flexor tendon, DDFT). Data were examined for age-related changes to central and peripheral zone tissue of the SDFT and DDFT. Ageing in both tendons (SDFT and DDFT) resulted in a significant increase in collagen-linked fluorescence and a decrease in cellularity in the DDFT but not the SDFT. The central zone tissue from the SDFT had a significantly higher proportion of type III collagen than the peripheral zone of the tendon. The highest level of type III collagen was found in the central zone tissue of the SDFT from the older group of horses and this may represent the early stages of a degenerative change. Collagen content did not differ between the 2 flexor tendons; however, there were differences in collagen type and organisation. The SDFT had a higher type III collagen content, higher levels of the mature trifunctional collagen crosslink hydroxylysylpyridinoline, lower total chondroitin sulphate equivalent glycosaminoglycan content, smaller diameter collagen fibrils and a higher cellularity than the DDFT. In conclusion, differences in macromolecular composition exist between the flexor tendons and ageing contributes to a tendon specific change in composition.

Aging↗

Should equine athletes commence training during skeletal development?: changes in tendon matrix associated with development, ageing, function and exercise.

In human athletes, conditioning, training and competition are commenced before skeletal maturity. Yet in equine athletics, racing of young (age 2 years) horses remains contentious. Tendon injury persists as major causes of wastage in equine athletes. Minimising injury and associated welfare issues could involve a radical approach to the timing and implementation of conditioning and training. Tendons were examined from Thoroughbreds, Dutch Warmblood foals, working horses and also a group of wild horses to evaluate effects of age, function and exercise. Gross mechanical properties did not differ significantly with age or exercise, but showed a high variance within each group. Mechanical properties of tendon tissue showed significant differences as a function of age and location. The collagen fibril crimp angle and length showed a regional reduction in the central core with exercise and age, with a synergistic effect. Regional differences in collagen fibril diameter were seen in long-term exercised older horses, but not in short-term exercised, or younger, horses. The higher proportion of small fibrils in the central region of the long-term exercised horses did not correlate with new collagen formation and therefore appear to result from disassembly of the larger diameter fibrils. Fibril diameter distributions were influenced by exercise regimens in the growing foal. Changes in molecular composition occurred in longer-term exercise and older horses, in the centre of the tendon, with higher levels of type III collagen and changes in glycosaminoglycan (GAG) content. Cartilage Oligomeric Matrix Protein (COMP) levels also appear to be modulated by age, function and superimposition of exercise. These changes were all exacerbated with age and exercise, suggesting appropriate exercise in young horses may lead to a lower incidence of injury than in older horses. An hypothesis is advanced that immature tendon can respond to exercise while mature tendon has limited, if any, ability to do so. These findings support potentially controversial earlier conditioning and racing of younger, rather than older, equine athletes.

Aging↗

Treadmill exercise-induced tendon hypertrophy: assessment of tendons with different mechanical functions.

The equine superficial digital flexor tendon (SDFT) functions as an energy store during high-speed gaits reducing the energetic cost of locomotion. To enable the SDFT to function effectively, the appropriate mechanical properties are essential. We tested the hypothesis that the SDFT does not undergo gross hypertrophy in response to high-intensity exercise whereas tendons not involved in energy storage undergo adaptive hypertrophy. Two groups (n = 6) of Thoroughbred fillies were trained at high-intensity on a high-speed equine treadmill for 5 months (short-term study) or 18 months (long-term study). Age-matched groups (n = 6) of horses undertook low-intensity exercise only for the same time period. Throughout the short-term study the SDFT and deep digital flexor tendon (DDFT) were ultrasonograpically scanned at mid-metacarpal level and cross-sectional area (CSA) calculated. At the end of the short-term study (horse age = 2 years) and long-term study (horse age = 3 years) the left SDFT, DDFT, suspensory ligament (SL) and common digital extensor tendon (CDET) were harvested and CSA calculated. Comparison of the DDFT from 2- and 3-year-old horses revealed an age-related increase in CSA which was confirmed by ultrasonographs. Post mortem analysis showed a significant hypertrophy of the CDET with high-intensity training in the short-term study (younger horses). CSA did not differ significantly between training groups for any of the structures following long-term training. These results suggest a structure specific hypertrophic response to the imposed training regime.

Animals↗