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Topic:Physiology

The physiology of horses encompasses the study of the biological functions and processes that occur within the equine body. This includes the examination of various systems such as the cardiovascular, respiratory, musculoskeletal, digestive, and nervous systems. Understanding equine physiology is essential for comprehending how horses adapt to different environmental conditions, perform physical activities, and respond to health challenges. Research in this field often focuses on the mechanisms of energy metabolism, thermoregulation, and muscle function during exercise, as well as the physiological responses to stress and disease. This page compiles peer-reviewed research studies and scholarly articles that explore the diverse aspects of equine physiology, providing insights into the biological processes that support the health and performance of horses.
Serum amyloid A in equine health and disease.
Equine veterinary journal    February 6, 2019   Volume 51, Issue 3 293-298 doi: 10.1111/evj.13062
Witkowska-Piłaszewicz OD, Żmigrodzka M, Winnicka A, Miśkiewicz A, Strzelec K, Cywińska A.Serum amyloid A (SAA) is the major acute phase protein in horses. It is produced during the acute phase response (APR), a nonspecific systemic reaction to any type of tissue injury. In the blood of healthy horses, SAA concentration is very low, but it increases dramatically with inflammation. Due to the short half-life of SAA, changes in its concentration in blood closely reflect the onset of inflammation and, therefore, measurement of SAA useful in the diagnosis and monitoring of disease and response to treatment. Increases in SAA concentration have been described in equine digestive, reprodu...
Differential Regulation of Gonadotropins in Response to Continuous Infusion of Native Gonadotropin-Releasing Hormone in the Winter Anovulatory Mare and Effects of Treatment With Estradiol-17β.
Journal of equine veterinary science    February 6, 2019   Volume 75 93-103 doi: 10.1016/j.jevs.2019.01.013
O'Neil MM, Korthanke CM, Scarpa JO, Welsh TH, Cardoso RC, Williams GL.We tested the hypotheses that in winter anovulatory mares (1) both chronic daily injections of estradiol-17β (E2) and subcutaneous E2 implants could enhance pituitary secretion of gonadotropins in response to continuous subcutaneous infusion of native gonadotropin-releasing hormone (GnRH); and (2) the secretory pattern of follicle-stimulating hormone (FSH) in response to continuous subcutaneous infusion of native GnRH is similar to that of luteinizing hormone (LH) but differs between mares that develop or fail to develop an estrogen-active, preovulatory follicle. In Experiment 1, 20 winter an...
Influence of Different Combinations of Permeable and Nonpermeable Cryoprotectants on the Freezing Capacity of Equine Sperm.
Journal of equine veterinary science    February 6, 2019   Volume 75 69-73 doi: 10.1016/j.jevs.2019.01.014
Vafaei F, Kohram H, Zareh-Shahne A, Ahmad E, Seifi-Jamadi A.This study was aimed to evaluate the effect of permeable cryoprotectants in combination with trehalose or sucrose on the freezing capacity of stallion sperm. For this purpose, the ejaculates (n = 24) were collected from four healthy mature Turkmen stallions. The ejaculates were pooled and diluted with one of the extenders containing a combination of 5% of permeating (dimethylacetamide [DMA]; dimethylformamide [DMF] or glycerol) and 50 mM of nonpermeating cryoprotectant agents (CPAs) (sucrose or trehalose) to a final concentration of 200 × 10 spermatozoa/mL. The extended samples were cryopr...
Using Estrous Behavior to Time Initiation of Oxytocin Administration to Prolong Luteal Function in Mares.
Journal of equine veterinary science    February 6, 2019   Volume 75 78-81 doi: 10.1016/j.jevs.2019.01.012
Manning HS, Runcan EE, Dias de Moraes CR, Coutinho da Silva MA.The objective of this study was to use estrous behavior alone to determine the appropriate time for beginning an oxytocin treatment protocol for estrus suppression. We hypothesized that administration of oxytocin beginning 8 days after the onset of estrus will prolong the luteal phase in mares. Twenty-three light breed mares (aged 4-20 years) were exposed to a stallion and observed for signs of sexual receptivity. Mares not displaying signs received 250 μg of cloprostenol intramuscularly (IM) and were teased again 3-4 days later. On the day that estrous behavior was observed (Day 0), mare...
The Effect of Different Flushing Media Used to Aspirate Follicles on the Outcome of a Commercial Ovum Pickup-ICSI Program in Mares.
Journal of equine veterinary science    February 6, 2019   Volume 75 74-77 doi: 10.1016/j.jevs.2019.01.015
Cuervo-Arango J, Claes AN, Beitsma M, Stout TAE.The in vitro production of embryos by ovum pickup (OPU) and intracytoplasmic sperm injection (ICSI) is gaining popularity among horse breeders and veterinarians. Various collection media are available for flushing follicles during OPU. The objective of this study was to determine whether the type of flushing media used to aspirate follicles and collect oocytes influences the outcome of a commercial equine OPU-ICSI program. Two commercial embryo flushing media (EFM1 and EFM2) supplemented with heparin were compared with a flushing media designed specifically for the collection of oocytes (oocy...
Vitrification of Large Volumes of Stallion Sperm in Comparison With Spheres and Conventional Freezing: Effect of Warming Procedures and Sperm Selection.
Journal of equine veterinary science    February 6, 2019   Volume 83 102680 doi: 10.1016/j.jevs.2019.01.017
Consuegra C, Crespo F, Dorado J, Diaz-Jimenez M, Pereira B, Ortiz I, Arenas R, Morrell JM, Hidalgo M.Stallion sperm was vitrified using straws in comparison with spheres and conventional freezing. Vitrification was performed plunging 30 μL of sperm (spheres) or 0.5 mL straws into liquid nitrogen (LN) and conventional freezing using 0.5 mL straws frozen in LN vapors. Sperm vitrified in straws were submitted to different warming procedures (42°C/20 seconds; 60°C/15 seconds) and single-layer centrifugation (SLC). Total (TM, %) and progressive sperm motility (PM, %), plasma membrane (IMS, %) and acrosome integrity (AIS, %) were statistically compared between treatments (mean ± SEM). Signif...
Update on mammalian sperm capacitation: how much does the horse differ from other species?
Reproduction (Cambridge, England)    February 6, 2019   Volume 157, Issue 5 R181-R197 doi: 10.1530/REP-18-0541
Leemans B, Stout TAE, De Schauwer C, Heras S, Nelis H, Hoogewijs M, Van Soom A, Gadella BM.In contrast to various other mammalian species, conventional in vitro fertilization (IVF) with horse gametes is not reliably successful. In particular, stallion spermatozoa fails to penetrate the zona pellucida, most likely due to incomplete activation of stallion spermatozoa (capacitation) under in vitro conditions. In other mammalian species, specific capacitation triggers have been described; unfortunately, none of these is able to induce full capacitation in stallion spermatozoa. Nevertheless, knowledge of capacitation pathways and their molecular triggers might improve our understanding o...
Coding sequences of sarcoplasmic reticulum calcium ATPase regulatory peptides and expression of calcium regulatory genes in recurrent exertional rhabdomyolysis.
Journal of veterinary internal medicine    February 5, 2019   Volume 33, Issue 2 933-941 doi: 10.1111/jvim.15425
Valberg SJ, Soave K, Williams ZJ, Perumbakkam S, Schott M, Finno CJ, Petersen JL, Fenger C, Autry JM, Thomas DD.Sarcolipin (SLN), myoregulin (MRLN), and dwarf open reading frame (DWORF) are transmembrane regulators of the sarcoplasmic reticulum calcium transporting ATPase (SERCA) that we hypothesized played a role in recurrent exertional rhabdomyolysis (RER). Objective: Compare coding sequences of SLN, MRLN, DWORF across species and between RER and control horses. Compare expression of muscle Ca2+ regulatory genes between RER and control horses. Methods: Twenty Thoroughbreds (TB), 5 Standardbreds (STD), 6 Quarter Horses (QH) with RER and 39 breed-matched controls. Methods: Sanger sequencing of SERCA reg...
Comparison of the racing performance of Thoroughbreds with versus without osteochondral fragmentation of the accessory carpal bone identified on yearling sales repository radiographs.
Journal of the American Veterinary Medical Association    February 5, 2019   Volume 254, Issue 4 501-507 doi: 10.2460/javma.254.4.501
Davern AJ, Peloso JG, Hawkins JF, Moore GE, Morehead JP.OBJECTIVE To evaluate 2- and 3-year-old and career race performance of Thoroughbred racehorse prospects with and without osteochondral fragmentation of the accessory carpal bone (ACB) identified on yearling presale radiographs. DESIGN Retrospective, matched cohort study. ANIMALS 47 nonlame Thoroughbreds with (exposed cohort) and 94 nonlame Thoroughbreds without (unexposed cohort) osteochondral fragmentation of ACB facture identified on yearling sales repository radiographs. PROCEDURES Repository radiographic interpretation reports for September yearling sales of a large Kentucky auction house ...
Balance control during stance – A comparison between horseback riding athletes and non-athletes.
PloS one    February 5, 2019   Volume 14, Issue 2 e0211834 doi: 10.1371/journal.pone.0211834
Olivier A, Viseu JP, Vignais N, Vuillerme N.Horseback riding requires the ability to adapt to changes in balance conditions, to maintain equilibrium on the horse and to prevent falls. Postural adaptation involves specific sensorimotor processes integrating visual information and somesthesic information. The objective of this study was to examine this multisensorial integration on postural control, especially the use of visual and plantar information in static (stable) and dynamic (unstable) postures, among a group of expert horse rider women (n = 10) and a group of non-athlete women (n = 12). Postural control was evaluated through the c...
External stress increases sympathoadrenal activity and prolongs the expulsive phase of foaling in pony mares.
Theriogenology    February 4, 2019   Volume 128 110-115 doi: 10.1016/j.theriogenology.2019.02.006
Melchert M, Aurich C, Aurich J, Gautier C, Nagel C.Mares usually give birth when they perceive their environment as safe and therefore disturbance at foaling may inhibit labor. In this study, foaling mares were transferred to an unfamiliar environment at rupture of the allantochorion (stress, n = 6) or were left undisturbed (control, n = 5). The progress of foaling, heart rate, heart rate variability (HRV) and plasma catecholamine, oxytocin and cortisol concentration were determined. In stressed mares, time from rupture of the allantochorion to appearance of the fetal feet (5.3 ± 1.1 vs. 1.6 ± 0.4 min) and total length of f...
Exploring the genetics of trotting racing ability in horses using a unique Nordic horse model.
BMC genomics    February 4, 2019   Volume 20, Issue 1 104 doi: 10.1186/s12864-019-5484-9
Velie BD, Lillie M, Fegraeus KJ, Rosengren MK, Solé M, Wiklund M, Ihler CF, Strand E, Lindgren G.Horses have been strongly selected for speed, strength, and endurance-exercise traits since the onset of domestication. As a result, highly specialized horse breeds have developed with many modern horse breeds often representing closed populations with high phenotypic and genetic uniformity. However, a great deal of variation still exists between breeds, making the horse particularly well suited for genetic studies of athleticism. To identify genomic regions associated with athleticism as it pertains to trotting racing ability in the horse, the current study applies a pooled sequence analysis ...
Dietary-induced modulation of the hindgut microbiota is related to behavioral responses during stressful events in horses.
Physiology & behavior    February 3, 2019   Volume 202 94-100 doi: 10.1016/j.physbeh.2019.02.003
Destrez A, Grimm P, Julliand V.The bidirectional communication between the central and the enteric nervous system named the gut-brain axis has been widely recognized. The gut microbiota has been implicated in a variety of stress-related conditions including anxiety, depression and irritable bowel syndrome based on rodent studies or correlative analysis in human patients. The aim of the present study was to investigate to what extent changes in behavior during stressful events and in the microbial composition of the colonic ecosystem were associated in horses. The microbiota alterations were induced by a change from a high-f...
Altered gene expression in embryos and endometrium collected on day 8 of induced aluteal cycles in mares.
Theriogenology    February 2, 2019   Volume 128 81-90 doi: 10.1016/j.theriogenology.2019.01.028
Leisinger CA, Klein C, Markle ML, Premanandan C, Sones JL, Pinto CRF, Paccamonti DL.Aluteal cycles were induced in the mare to evaluate the effects of progesterone deprivation on the gene expression of embryos and endometrium collected eight days after ovulation. We hypothesized that the transcript expression would be altered during induced aluteal (AL) cycles (low progesterone <1 ng/mL) when compared with control cycles during diestrus (high progesterone; > 4 ng/mL) for 1) the embryonic expression of progesterone-mediated transcripts and those related to normal embryo growth and development and 2) the endometrial expression of progesterone-mediated transcripts and those ...
Effects of age on serum glucose and insulin concentrations and glucose/insulin ratios in neonatal foals and their dams during the first 2 weeks postpartum.
Veterinary journal (London, England : 1997)    February 1, 2019   Volume 246 1-6 doi: 10.1016/j.tvjl.2019.01.013
Berryhill EH, Magdesian KG, Tadros EM, Edman JE.Maintaining serum glucose concentrations is critical in neonatal foals and is often dysregulated in illness; however, few studies have assessed the effects of age, or variation of glucose and insulin, in neonates and their postpartum dams. This study aimed to serially evaluate serum glucose and insulin concentrations and glucose/insulin (G/I) ratios in seven healthy foals and their dams immediately postpartum and at 1-2 and 10-12days of age. The hypotheses were that: (1) there would be wide temporal variation in hourly glucose and insulin measurements among foals; and (2) measured parameters i...
The Identification of Novel Single-Nucleotide Polymorphisms of Equine Beta-Lactoglobulin and Lactotransferrin Genes.
Journal of equine veterinary science    February 1, 2019   Volume 75 60-64 doi: 10.1016/j.jevs.2019.01.005
Işık R.Lactoferrin (LTF), also called lactotransferrin, is an iron-binding protein and member of transferrin family, whereas β-LG is an important milk protein and belongs to the ligand-binding protein family of lipocalins and binds retinol. Beta-lactoglobulin (β-LG) is a major whey protein and it is a member of lipocalins family. β-LG is also known as a major allergen reason of cow milk protein allergy. Yet, no information has been reported about β-LG and LTF genes in donkeys. In this study, the genetic variation of β-LG and LTF genes were analyzed via DNA sequencing in 77 donkeys, which were in...
Fecal coagulase-negative staphylococci from horses, their species variability, and biofilm formation.
Folia microbiologica    January 31, 2019   Volume 64, Issue 6 719-726 doi: 10.1007/s12223-019-00684-5
Bino E, Lauková A, Ščerbová J, Kubašová I, Kandričáková A, Strompfová V, Miltko R, Belzecki G.The intestinal microbiota has enormous impact on the health and performance of horses. Staphylococci belong in the phylum Firmicutes, and their occurrence, especially of methicillin-resistant strains and species, has been reported in horses previously. Moreover, biofilm formation is one of the virulence factors; it has been not completely studied in fecal coagulase-negative staphylococci (CoNS) from horses. Therefore, this study was focused on biofilm formation by various species of fecal CoNS from horses because it has been never reported before. In addition, their antibiotic profile was test...
Thyroid Hormone and Thyrotropin Concentrations and Responses to Thyrotropin-Stimulating Hormone in Horses with PPID Compared with Age-Matched Normal Horses.
Journal of equine veterinary science    January 30, 2019   Volume 75 35-40 doi: 10.1016/j.jevs.2019.01.008
Breuhaus BA.Glucocorticoids are known to exert inhibitory action on the hypothalamic-pituitary-thyroid axis. With recent evidence that free plasma cortisol and urinary excretion of cortisol metabolites may be increased in horses with pituitary pars intermedia dysfunction (PPID), it is important to further examine thyroid function in horses with PPID. To test the hypothesis that serum thyrotropin (TSH) concentrations are decreased in horses with PPID, baseline serum thyroid hormone and TSH concentrations, and responses to TSH-releasing hormone (TRH), were compared between 12 horses diagnosed as having PPID...
Test of four hypotheses to explain the function of overmarking in foals of four equid species.
Animal cognition    January 30, 2019   Volume 22, Issue 2 231-241 doi: 10.1007/s10071-019-01239-4
Pluháček J, Tučková V, King SRB, Šárová R.Overmarking occurs when one individual places its scent mark directly on top of the scent mark of another individual. Although it is almost ubiquitous among terrestrial mammals, we know little about the function of overmarking. In addition, almost all studies on mammalian overmarking behaviour dealt with adult individuals. Reports on this behaviour in juveniles are extremely rare, yet may elucidate the function of this behaviour. We tested four mutually non-exclusive hypotheses which might explain this behaviour in juveniles: (1) conceal the individual's scent identity, (2) announcement of ass...
Three-dimensional CT observation of position and movability of the scapula in the horse using carcasses of Falabella.
Anatomia, histologia, embryologia    January 29, 2019   Volume 48, Issue 3 250-255 doi: 10.1111/ahe.12430
Endo H, Nguyen ST, Yoshida M, Kudo K.The three-dimensionally real position and movement of the scapula in the lateral side of the ribcage could not be clarified in the horse, since the body size of the horse is too large to apply the CT scanning and image analysis methods. In this study, therefore, we examined the position and the movability of scapula using a carcass of the Falabella which is one of the smallest breeds of the horse. The whole skeletal system in thoracic part of the Falabella could be three-dimensionally observed by CT scanning method. The three-dimensional images show that the scapula cranially slides and the ve...
Post-thaw Addition of Caffeine and/or Pentoxifylline Affect Differently Motility of Horse and Donkey-Cryopreserved Spermatozoa.
Journal of equine veterinary science    January 29, 2019   Volume 75 41-47 doi: 10.1016/j.jevs.2019.01.003
Rota A, Sabatini C, Przybył A, Ciaramelli A, Panzani D, Camillo F.To increase sperm motility, several molecules have been tested in mammals. Methylxanthines have shown effects on sperm motility, capacitation, and on in vitro fertilization processes. The aim of the study was to evaluate if the post-thaw addition of caffeine and/or pentoxifylline changes motility parameters of cryopreserved stallion and donkey spermatozoa. Straws derived from 14 horses and 7 donkeys were thawed and diluted in a milk-based extender to obtain the following final concentrations: CTR (control, no additives), CAF 5 (5 mM caffeine), CAF 10 (10 mM caffeine), PTX 5 (5 mM pentoxify...
Evaluation of a Proprietary Slow-Release Oxytocin Formulation on Corpus Luteum Function in Mares.
Journal of equine veterinary science    January 29, 2019   Volume 77 28-30 doi: 10.1016/j.jevs.2019.01.004
Sarnecky BA, Vanderwall DK, Mason HM, Kirschner SM, Ambrose B, Parker TL.Prolonging function of the corpus luteum (CL) is a method of suppressing estrus that relies on continued secretion of endogenous progesterone to keep mares out of heat naturally. The use of oxytocin treatment to prolong CL function is gaining increasing use, and the most common treatment protocol involves administration of 60 units of oxytocin intramuscularly (IM) once daily on days 7-14 after ovulation (eight daily treatments). Although that protocol induces prolonged CL function in ≥70% of treated mares, the need for daily administration is a drawback to its use. Therefore, the objective o...
Effect of Topical 1% Cyclopentolate Hydrochloride on Tear Production, Intraocular Pressure, and Pupil Size in Healthy Turkman Horses.
Journal of equine veterinary science    January 29, 2019   Volume 75 25-29 doi: 10.1016/j.jevs.2019.01.002
Ansari Mood M, Rajaei SM, Faghihi H, Ghiadi A.This study was performed to evaluate the effect of topical 1% cyclopentolate hydrochloride on tear production (STT), intraocular pressure (IOP), and vertical pupil diameter (VPD) in healthy Turkman horses. Forty eyes of 20 clinically normal horses were used for this study, which were randomly assigned to two groups. Before instillation of 1% cyclopentolate, the baseline STT, IOP, and VPD of each group were recorded. Then, one drop of cyclopentolate was instilled randomly into one eye of each animal, and the contralateral eye served as control. Measurements were repeated at 20 minutes, 60 min...
Development of the central nervous system in equine twin fetuses derived by somatic cell nuclear transfer.
Reproduction, fertility, and development    January 29, 2019   Volume 31, Issue 5 941-952 doi: 10.1071/RD18215
Rigoglio NN, Smith OE, Matias GSS, Miglino MA, Smith LC.Because of the growing importance of horses in leisure and several sports, somatic cell nuclear transfer (SCNT) is being used more frequently for cloning animals for performance and reproductive purposes. However, because of the need to perforate the zona pellucida during microsurgical reconstruction of the oocyte, it is possible that SCNT-derived embryos undergo premature hatching, resulting in embryo bisection and twinning. Therefore, because equine twin pregnancies often lead to abnormal embryo development and pregnancy failure, we performed a detailed comparative assessment of equine twin ...
Exosomes isolation and identification from equine mesenchymal stem cells.
BMC veterinary research    January 28, 2019   Volume 15, Issue 1 42 doi: 10.1186/s12917-019-1789-9
Klymiuk MC, Balz N, Elashry MI, Heimann M, Wenisch S, Arnhold S.Mesenchymal stem cells are used for different therapeutic approaches, e.g. for osteoarthritis, lesions of the tendon as well as for bone defects. Current research on the mechanism of stem cells on the repair of damaged tissue suggest an important role of a cell-to-cell communication through secreted extracellular vesicles, mainly represented by exosomes. To enhance the scarce knowledge on the functional role of exosomes we compared as a first step different techniques to isolate and identify exosomes from the supernatant of equine adipose derived mesenchymal stem cells for further characteriza...
Two-dimensional echocardiographic measurements of the right coronary artery in healthy horses – a pilot study.
BMC veterinary research    January 28, 2019   Volume 15, Issue 1 43 doi: 10.1186/s12917-019-1792-1
Siwinska N, Michalek M, Zak A, Slowikowska M, Noszczyk-Nowak A, Niedzwiedz A, Paslawska U.Precise understanding of the dimensions of the vascular lumina is essential for accurate interpretation of cardiac vessels imaging. To the authors' best knowledge, this is the first study focusing on the ultrasound measurement of the right coronary artery (RCA) in the horse. The aim of this study was to determine both the ultrasonographic range of the normal diameter and lumen area of the RCA in horses and the influence of gender, age and level of training on the RCA dimensions. An additional aim of the study was to assess intra- and inter-observer repeatability of the collected measurements. ...
Effects of dofetilide and ranolazine on atrial fibrillatory rate in a horse model of acutely induced atrial fibrillation.
Journal of cardiovascular electrophysiology    January 28, 2019   Volume 30, Issue 4 596-606 doi: 10.1111/jce.13849
Carstensen H, Hesselkilde EZ, Haugaard MM, Flethøj M, Carlson J, Pehrson S, Jespersen T, Platonov PG, Buhl R.The atrial fibrillatory rate is a potential biomarker in the study of antiarrhythmic drug effects on atrial fibrillation (AF). The purpose of this study was to evaluate whether dose-dependent changes in the atrial fibrillatory rate can be monitored on surface electrocardiography (ECG) following treatment with dofetilide, ranolazine, and a combination of the two in an acute model of AF in horses. Eight horses were subjected to pacing-induced AF on 4 separate days. Saline (control), dofetilide, ranolazine, or a combination of dofetilide and ranolazine was administered in four incremental doses. ...
Assessing pain in horses.
The Veterinary record    January 27, 2019   Volume 184, Issue 4 124 doi: 10.1136/vr.l385
Gleerup KB.No abstract available
Intraovarian spatial and vascular harmony between follicles and corpus luteum in monovulatory heifers, mares, and women.
Theriogenology    January 25, 2019   Volume 128 31-39 doi: 10.1016/j.theriogenology.2019.01.019
Ginther OJ.Heifers have two or three major follicular waves per interovulatory interval (IOI). In mares and women, the ovulatory wave is the only major wave in most (75%) IOI. The beginning of diameter deviation during follicle selection of the future dominant follicle (DF) is followed by continued growth of DF and decreasing growth of the future subordinate follicles. Diameter deviation in Bos taurus heifers, mares, and women begins when the future DF is a mean of 8.5, 22.5, and 10.5 mm, respectively. Selection of the ovulatory follicle occurs more frequently from right ovary (RO) in heifers and women...
The Effect of Core Abdominal Muscle Rehabilitation Exercises on Return to Training and Performance in Horses After Colic Surgery.
Journal of equine veterinary science    January 25, 2019   Volume 75 14-18 doi: 10.1016/j.jevs.2019.01.001
Holcombe SJ, Shearer TR, Valberg SJ.We conducted a retrospective cohort study to test the hypothesis that performing 4 weeks of core abdominal rehabilitation exercises (CARE) postoperatively would be safe and associated with faster return to training and improved performance after colic surgery. Performance horses that recovered from colic surgery performed by the same surgeon and survived ≥ 1 year from 2008 to 2017 were included. Data were obtained from a review of medical records. Information about the horses' rehabilitation and performance was obtained from owners/trainers. Data from horses that completed a 4-week CARE pr...
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