Analyze Diet

Topic:Animal Study

Animal studies involving horses encompass a wide range of research activities aimed at understanding various aspects of equine biology, behavior, health, and management. These studies can include investigations into equine physiology, nutrition, reproduction, and disease processes. Research often involves controlled experiments or observational studies to gather data on how horses respond to different interventions, environments, or management practices. This topic includes peer-reviewed research studies and scholarly articles that explore methodologies, findings, and implications of animal studies in equine science, contributing to the broader understanding of horse welfare and management.
Methylated tirilazad may mitigate oligofructose-induced laminitis in horses.
Frontiers in microbiology    September 25, 2024   Volume 15 1391892 doi: 10.3389/fmicb.2024.1391892
Tuniyazi M, Tang R, Hu X, Zhang N.Laminitis is a serious health condition that can cause severe pain and lameness in horses. Due to lack of understanding of laminitis, treatments often fail to achieve the desired results. In recent years, we have begun to recognize that laminitis may involve a complex interaction between local and systemic inflammation. Dysbiosis of the gut microbiota has been linked in the development of systemic inflammation, and our previous findings suggest that the development of laminitis is closely linked to the production of harmful metabolites of the gut microbiota. In addition, it was found that loca...
Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1.
Viruses    September 25, 2024   Volume 16, Issue 10 doi: 10.3390/v16101514
Holmes CM, Wagner B.Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4+ and CD8+ T cells were the major intranasal cell populations before infection and increased significantly by day six and fourteen post-infection, respectively. Nasal mucosal T cells were further characterized in healthy horses. Compared to peripheral blood mononuclear cells (PBMC), mucosal CD8+ T-cell percentages were elev...
Discovery of Biomarkers of a Recombinant Human Erythropoietin Administration to Thoroughbred Geldings by Label-Free Proteomics.
Drug testing and analysis    September 22, 2024   doi: 10.1002/dta.3810
Cheung HW, Wong KS, Tam JCL, Farrington AF, Bond AJ, Wan TSM, Ho ENM.Erythropoiesis-stimulating agents (ESAs) continue to be a significant threat to the integrity of human and equine sports. Besides conventional direct testing, monitoring the biomarkers associated with the effects of ESAs may provide a complementary approach via indirect detection to enhance doping control. In this study, we applied label-free proteomics to discover plasma protein biomarkers in Thoroughbred geldings after administration with a long-acting form of recombinant human erythropoietin (rhEPO), methoxy polyethylene glycol epoetin beta, Mircera. Increased haematocrit, haemoglobin and r...
Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares.
Drug testing and analysis    September 22, 2024   doi: 10.1002/dta.3796
Loy J, Cawley A, Sornalingam K, Scrivener CJ, Keledjian J, Noble GK.Altrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determ...
Electromyographic and behavioral analysis of horses submitted to medial patellar desmotomy.
Veterinary research communications    September 21, 2024   doi: 10.1007/s11259-024-10548-0
da Silva NV, Bernardino Júnior R, Nomelini QSS, Pereira GF, Delfiol DJZ, Nogueira GM.The passive stay apparatus works by blocking flexion of the knee and tarsus joints in the horse, preventing muscle fatigue. During ambulation, if this mechanism fails to release, the animal will present upward fixation of the patella, which in severe cases, can only be treated by medial patellar desmotomy (MPD). The objective of this study was to investigate the possible electromyographic and behavioral changes, after the impairment of the passive stay apparatus, in horses who have undergone MPD surgery. Five horses presenting dorsal fixation of the patella underwent electromyographic measurem...
Noseband type and tightness level affect pressure on the horse’s face at trot.
Equine veterinary journal    September 21, 2024   doi: 10.1111/evj.14420
MacKechnie-Guire R, Murray R, Williams JM, Nixon J, Fisher M, Fisher D, Walker V, Clayton HM.Poor noseband adjustment could create high pressures that may risk pain or tissue damage. Objective: To quantify sub-noseband pressures dorsally over the nasal bone and ventrally over the mandibular rami for a Cavesson, Swedish (crank), Drop and Flash noseband at five tightness levels (2.0 to 0.0 finger equivalents). Methods: In vivo experiments. Methods: Eight high-level dressage horses were ridden at the trot in a straight line by their usual riders. Two small pressure mats, attached to the noseband over the nasal bone and the mandibular rami, collected force (N) and pressure (kPa) data from...
Fecal microbiome and functional prediction profiles of horses with and without crib-biting behavior: A comparative study.
Journal of equine veterinary science    September 20, 2024   Volume 142 105198 doi: 10.1016/j.jevs.2024.105198
Martínez-Aranzales JR, Córdoba-Agudelo M, Pérez-Jaramillo JE.Crib-biting is a stereotyped oral behavior with poorly understood etiology and pathophysiology. The relationship between the gut microbiome and brain function has been described in behavioral disorders such as schizophrenia, depression and anxiety in humans. In horses, studies of behavioral problems and the microbiome are very limited. This study aimed to characterize the fecal microbiome and the predicted functional profile of horses with and without aerophagia. Fecal samples were collected from 12 Colombian Creole Horses of both sexes, divided into two groups: group 1, composed of six horses...
Intra-arterial contrast enhanced computed tomography of the deep digital flexor tendon and palmar veins in the distal forelimb in Jeju horses: Evaluating contrast-enhancing factors.
Equine veterinary journal    September 19, 2024   doi: 10.1111/evj.14408
Lee S, Shin KY, Lee K, Seo JP.Few studies have investigated the adequate contrast enhancement (CE) evaluation depending on concentration, volume, and rate of administration of contrast media (CM) and the scan parameters in equine contrast enhanced computed tomography (CECT). Objective: To investigate CE of the deep digital flexor tendon (DDFT) and veins depending on the computed tomography (CT) voltage and concentration, volume, and rate of CM administration during intra-arterial CECT of equine distal forelimbs. Methods: In vivo experiments. Methods: Six horses underwent 54 CT scans. First, the CE of DDFT and veins was eva...
Effect of protein acetylation on capacitation of stallion sperm.
Journal of equine veterinary science    September 18, 2024   Volume 142 105195 doi: 10.1016/j.jevs.2024.105195
Aguiar LH, Pinto CRF.Sperm capacitation is considered the main factor limiting conventional in vitro fertilization (IVF) in horses. A recent scientific breakthrough in sperm processing for IVF in horses has resulted in embryos and foals being produced; however, various aspects of the IVF process remain to be fully elucidated. Lysine acetylation has been shown to play a role in sperm capacitation in several species and the objective of this study was to detect and evaluate this process in the horse. Ejaculates of two stallions were collected and incubated in different conditions with deacetylase inhibitors to induc...
A hybrid repair strategy for full-thickness cartilage defects: Long-term experimental study in eight horses. Fugazzola MC, De Ruijter M, Veraa S, Plomp S, van Buul W, Hermsen G, van Weeren R.The objective of this study was to evaluate a non-resorbable implant for the focal repair of chondral defects in eight adult horses with 12-month follow-up. The bi-layered construct composed of a polycarbonate-urethane-urea biomaterial which was printed in 3D fashion onto a bone anchor was implanted into surgically created osteochondral defects into the femoropatellar joints of eight horses. The analysis of post-mortem outcomes were compared to defects treated with microfracture in the same animal on the contralateral femoropatellar jointfemoropatellar joint. The overall macroscopic scoring af...
Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.
Frontiers in veterinary science    September 17, 2024   Volume 11 1461648 doi: 10.3389/fvets.2024.1461648
Knych HK, Steinmetz SJ, Traynham ML, McKemie DS, Kass PH.Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of sin...
Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’.
Molecular human reproduction    September 17, 2024   Volume 30, Issue 9 gaae033 doi: 10.1093/molehr/gaae033
Walter J, Colleoni S, Lazzari G, Fortes C, Grossmann J, Roschitzki B, Laczko E, Naegeli H, Bleul U, Galli C.Assisted reproductive technologies are an emerging field in equine reproduction, with species-dependent peculiarities, such as the low success rate of conventional IVF. Here, the 'cumulome' was related to the developmental capacity of its corresponding oocyte. Cumulus-oocyte complexes collected from slaughterhouse ovaries were individually matured, fertilized by ICSI, and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS)-based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total o...
Survey of ocular abnormalities in a population of Turkmen horses.
Veterinary ophthalmology    September 16, 2024   Volume 28, Issue 4 741-746 doi: 10.1111/vop.13276
Faghihi H, Gharibi A, Ansari Mood M, Rajaei SM, Alavi SM.The aim of this study was to detect and describe ocular abnormalities in a population of Turkmen horses. Methods: A total of 55 Turkmen horses (33 mares and 22 stallions) from one herd were evaluated in this study. Methods: Demographic data (Age, Sex, Coat color) were recorded. All animals underwent complete ophthalmic examination. The Schirmer tear test -I (STT-I) was performed for all horses prior to other diagnostic tests. Neuro-ophthalmic examinations (menace response, dazzle reflex, pupillary light reflex, maze test, and visual tracking) were carried out in different lighting situations (...
Pharmacokinetics of Ethyl Glucuronide and Ethyl Sulfate and Pharmacodynamic Effects Following Intravenous and Oral Administration of Ethanol to Exercised Horses.
Drug testing and analysis    September 15, 2024   doi: 10.1002/dta.3803
Knych HK, Blea J, Scollay M, Kass PH, McKemie DS.Ethanol, a central nervous system depressant and banned substance in horseracing, has reportedly been administered to horses prior to competition to "calm a horse's nerves." In this study, the pharmacokinetics of two metabolites of ethanol were studied to better understand the behavior of this compound in the horse and provide a scientific basis for regulation of its administration. Six horses received a single intravenous (30 mL; 1200 mg) and oral (90 mL; 3600 mg) administration of ethanol (vodka, 40% ABV) in a balanced cross-over design. Blood and urine samples were collected at vari...
Horseshoe effects on equine gait-A systematic scoping review.
Veterinary surgery : VS    September 15, 2024   Volume 54, Issue 1 31-51 doi: 10.1111/vsu.14162
Aoun R, Takawira C, Lopez MJ.To provide an overview of available research about effects of horseshoes on equine kinetics and kinematics. Methods: The terms, "horse/equine," "hoof," "shoes/horseshoes," "kinetics," and "kinematics" were searched in PubMed, Web of Science, Center for Agriculture and Bioscience International, and United States Department of Agriculture National Agricultural Library for manuscripts from first availability to 2024. Independent reviewers used preferred reporting items for systematic reviews and meta-analyses guidelines to map and extract evidence-based data from sources. Metrics included partici...
Heart rate variability in horses with and without severe equine asthma.
Equine veterinary journal    September 14, 2024   doi: 10.1111/evj.14414
Nyerges-Bohák Z, Kovács L, Povázsai Á, Hamar E, Póti P, Ladányi M.Equine asthma in severe form (severe equine asthma [sEA]) shares remarkable similarities with human asthma. Human studies detected changes in the autonomic nervous system function in asthmatic patients based on heart rate variability (HRV) analysis. Methods: Observational study. Objective: To investigate the relationship between sEA and HRV in horses. Methods: Twenty horses diagnosed with sEA and 20 asymptomatic (non-sEA) horses were investigated. SEA horses showed clinical signs. The RR intervals of the ECG were recorded for 1 h at rest between 9 AM and 11 AM using a heart rate (HR) mon...
Detection of levamisole and its metabolites in horses after oral levamisole administration over seven days.
Journal of the American Veterinary Medical Association    September 13, 2024   Volume 262, Issue 12 1632-1638 doi: 10.2460/javma.23.06.0340
Adam E, Scollay M, Howard B, Taormina J, Hartmann P, Knych H.Levamisole is a regulated substance sometimes administered to racehorses to treat equine protozoal myelitis. Metabolites include compound II, aminorex, and pemoline. Aminorex and pemoline are Horseracing Integrity and Safety Authority-banned substances. Previous studies have examined single doses of the drug. This study examined the disposition of levamisole after 7 days of dosing. Methods: 6 healthy Thoroughbred geldings. Methods: Horses were treated with 500 mg (approx 0.91 to 1 mg/kg) of compounded levamisole hydrochloride paste PO every 12 hours for a total of 13 doses over 7 days. Serum a...
Evaluation of the feasibility of equine in-vivo ultrasound technique for the medial branch of the dorsal ramus of the cervical spinal nerves.
The veterinary quarterly    September 13, 2024   Volume 44, Issue 1 1-5 doi: 10.1080/01652176.2024.2403456
Nocera I, Di Franco C, Sorvillo B, Aliboni B, Bucchioni E, Sgorbini M, Sala G, Citi S.Ultrasound-guided local anaesthesia is commonly used in veterinary orthopaedics for horses. This study aimed to assess an ultrasound technique for the medial branch of the dorsal branch of the cervical spinal nerves (MB-DBCSNs) in horses and compare the performance of clinicians with different experience levels. Ten healthy, skeletally mature horses were examined using radiographic and ultrasound (US) techniques in the cervical area (C3-C7). Four operators with varying experience conducted US examinations using a 10 MHz linear and 6 MHz curvilinear transducer over ten training sessions. T...
Effect of repetitive transcranial magnetic stimulation on trigeminal-mediated headshaking in 17 horses.
Journal of veterinary internal medicine    September 12, 2024   Volume 38, Issue 5 2758-2765 doi: 10.1111/jvim.17194
Franzen V, Gruber NA, Klußmann S, Schoster A, May A.Trigeminal-mediated headshaking is a neuropathic facial pain condition in horses. No treatment has been entirely successful. Repetitive transcranial magnetic stimulation (rTMS) is used in human medicine as a treatment for various neuropathic pain conditions, and good results have been achieved in cases of trigeminal neuralgia. Objective: Apply rTMS to horses with trigeminal-mediated headshaking (TMHS) and to evaluate tolerability, application of the setting, and success rate. Methods: Seventeen horses with nonseasonal signs of TMHS. Methods: Other underlying causes of headshaking were ruled ou...
EFFECTS OF DIFFERENT SHOEING CONDITIONS ON EQUINE CERVICAL AND BACK KINEMATICS DURING WALKING AND TROTTING ON A SOFT SURFACE.
Journal of equine veterinary science    September 12, 2024   105194 doi: 10.1016/j.jevs.2024.105194
Caure S, Dendauw P, Thesee L, Villedey E, Malinvaud A, Cousty M, Prie V, Horan K, Weller R.There is a paucity of scientific data on the effect of shoeing on equine neck and back kinematics during locomotion over commonly used sand training surfaces. A better appreciation of how alterations at hoof-ground interface influence equine upper body movements is relevant for improving horse's health and performance. Our objectives were to determine the effects of different shoeing conditions on equine neck and back kinematics at walk and trot in straight line over sand. Two-dimensional kinematic video analysis was performed under seven shoeing conditions: front feet shod with aluminum shoes...
Effects of maternal dietary supplementation with antioxidants on clinical status of mares and their foal.
BMC veterinary research    September 11, 2024   Volume 20, Issue 1 404 doi: 10.1186/s12917-024-04252-z
Del Prete C, Vastolo A, Pasolini MP, Cocchia N, Montano C, Cutrignelli MI.The peripartum period constitutes a delicate physiological moment in mares showing a transient state of oxidative stress. Diet supplementation with antioxidants during pregnancy in women appears to have a beneficial effect on mother and neonate health. The aim of this work was to evaluate the effects of diet supplementation with a commercial product containing a mix of antioxidants (Oxyliver®, Candioli) on the length of gestation, weight, and haemato-biochemical parameters in Italian Salernitano mares and their newborn foals. Eight late-term pregnant mares were randomly divided into two group...
Does the Uterine Ozone Therapy Alter the Transcript Profile of Anti- and Proinflammatory Genes in Mares With Endometritis?
Reproduction in domestic animals = Zuchthygiene    September 10, 2024   Volume 59, Issue 9 e14718 doi: 10.1111/rda.14718
Botelho JHV, Pessoa GO, Caixeta ES, Sales G, de Oliveira KR, Nascimento Neto JDP, Ferreira RD, Palhão MP.This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti-inflammatory (IL-1RA and IL-10), proinflammatory (IL-R1B3i and TNFα) and pleiotropic (IL-6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 μg/mL ozone insufflation), resulting in four groups: N...
Transdermal carbon dioxide may accelerate hoof growth in healthy, sound horses in a short-term, randomized, controlled clinical trial.
American journal of veterinary research    September 10, 2024   Volume 85, Issue 11 doi: 10.2460/ajvr.24.06.0161
Rudnick MJ, Stewart HL, Burleson MD, Levine DG.Slow hoof growth poses a clinical challenge when hoof wear exceeds natural growth. Many treatment options have been reported without controlled prospective trials. The objective of this study was to evaluate the effect of transdermal CO2 on the rate of growth in treated hooves. Methods: A prospective, randomized, blinded, crossover study of 14 Warmblood mares. Horses were randomly assigned a number and allocated for treatment of the front feet with room air or CO2 for 30 minutes 3 times per week, and groups were switched after 5 weeks. Hoof growth was measured on the dorsal midline and the qua...
Bioreactance noninvasive cardiac output monitoring in euvolemic adult horses subjected with 7.2% saline and 6% hydroxyethyl starch (130/0.4) solution infusions.
Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)    September 10, 2024   doi: 10.1111/vec.13418
Long AE, Hurcombe S, Hopster K.To compare the ability of bioreactance noninvasive cardiac output (BR-NICO) with thermodilution cardiac output (TDCO) for the measurement of cardiac output (CO) in healthy adult horses receiving 2 different IV volume replacement solutions. Methods: Prospective randomized crossover study from September to November 2021. Methods: University teaching hospital. Methods: Six university-owned adult horses. Methods: Horses were randomly assigned to receive 7.2% hypertonic saline solution (HSS) or 6% hydroxyethyl starch (130/0.4) solution (HETA). BR-NICO and TDCO were measured simultaneously at baseli...
Cortisol levels, heart rate, and autonomic responses in horses during repeated road transport with differently conditioned trucks in a tropical environment.
PloS one    September 6, 2024   Volume 19, Issue 9 e0301885 doi: 10.1371/journal.pone.0301885
Lertratanachai S, Poochipakorn C, Sanigavatee K, Huangsaksri O, Wonghanchao T, Charoenchanikran P, Lawsirirat C, Chanda M.Horse's stress responses have been reported during road transport in temperate but not tropical environments. Therefore, this study measured cortisol levels, heart rate (HR), and heart rate variability (HRV) in horses during medium-distance road transport with different truck conditions in a tropical environment. Six horses were repeatedly transported in either air-conditioned trucks with full (ATF) or space (ATS) loads or non-air-conditioned trucks with full (N-ATF) and space (N-ATS) loads. Blood cortisol was determined beforehand and 5, 30, and 90 minutes post-transport. HR and HRV were asse...
The Effect of Different Storage Temperatures over Time on the pH of Mammary Gland Secretions in Periparturient Mares.
Animals : an open access journal from MDPI    September 6, 2024   Volume 14, Issue 17 doi: 10.3390/ani14172598
Canisso IF, Amorim GBAG, Magalhaes HB.The objectives of this study were (i) to determine pH and electrolyte concentrations in MGS collected prepartum and at parturition, (ii) to characterize mare milk pH during the first week postpartum, and (iii) to evaluate pre-foaling MGS pH at three storage temperatures. This study outlined two hypotheses: (i) all mares exhibit acidic pH, increased calcium, magnesium, and potassium, and reduced sodium concentrations regardless of prepartum pH and electrolytes; (ii) pre-foaling MGS pH varies with storage temperature and time in an initial value-dependent manner. Twenty-three multiparous mares w...
Metabolic Pathway of Osilodrostat in Equine Urine Established through High-resolution Mass Spectrometric Characterization for Doping Control.
Current drug metabolism    September 5, 2024   doi: 10.2174/0113892002325954240903062440
Ishii H, Shigematsu R, Takemoto S, Ishikawa Y, Mizobe F, Nomura M, Arima D, Kunii H, Yuasa R, Yamanaka T, Tanabe S, Nagata SI, Yamada M, Leung GN.Osilodrostat, used to treat Cushing's disease, exhibits an anabolic effect, leading to its classification as a prohibited substance in horseracing and equestrian sports. This study reports the characterization of osilodrostat metabolites in horse urine and elucidates its metabolic pathways for the first time for doping control purposes. Methods: Osilodrostat was administered nasoesophageally to four thoroughbreds (one gelding and three mares) at a dose of 50 mg each. Potential metabolites were extensively screened via our developed generic approach employing differential analysis to identify m...
The impact of short-term transportation stress on insulin and oral sugar responses in insulin dysregulated and non-insulin dysregulated horses.
Equine veterinary journal    September 4, 2024   doi: 10.1111/evj.14403
Jacquay ET, Harris PA, Adams AA.It is unknown whether short-term transportation affects endocrine responses similarly in horses with and without insulin dysregulation (ID). Objective: To characterise the effect of short-term transportation on stress parameters and insulin responses to an oral sugar test (OST) in horses with and without ID. Methods: Longitudinal cohort study. Methods: Fourteen adult non-pregnant, non-PPID mares of mixed light breeds were grouped as either ID (n = 7) or non-ID (n = 7) based on endocrine testing. Over 2 weeks, horses were transported once, in groups of 3-4 in a horse trailer on a roun...
Straight from the horse’s mouth: The effect of different feedstuffs on oral pH in horses and ponies.
Journal of equine veterinary science    September 4, 2024   Volume 142 105181 doi: 10.1016/j.jevs.2024.105181
Daniels SP, Whiteside EJ, Martin S, Moore-Colyer MJS, Harris P.Feedstuffs, especially ensiled forage, may be detrimental to equid oral health by exposing the oral cavity to low pH. This study aimed to identify if salivary pH was altered by 1) a range of different feedstuffs and (2) specifically by feeding haylages with differing nutrient profiles. Two studies were conducted. The first measured oral pH following five feedstuffs, (hay, haylage, unmolassed sugarbeet pulp, unmolassed alfalfa chaff and rolled oats), tested individually over five days. Saliva (≥1 ml) was collected in triplicate, prior to feeding, directly after ingesting 500 g of each feedstu...
Increased packed cell volume alters point of care viscoelastic clotting parameters in horses.
Equine veterinary journal    September 3, 2024   doi: 10.1111/evj.14413
Bishop RC, Jonk KM, Migliorisi A, Austin SM, Mullins EC, Wilkins PA.Polycythaemia and coagulopathy are identified risk factors for non-survival in critically ill horses. Assessment of coagulation is recommended for critical care monitoring but may be affected by concurrent polycythaemia. Objective: To evaluate the effects of induced polycythaemia on coagulation parameters as measured by a point-of-care viscoelastic coagulation device (VCM Vet™). Methods: Prospective interventional study. Methods: Healthy adult horses (n = 7) were given 6 mcg/kg of phenylephrine IV over 15 min to induce transient polycythaemia. Samples for packed cell volume (PCV), to...
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