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Topic:Biopsy

Biopsy in horses involves the collection of tissue samples for diagnostic purposes, often to identify the presence of disease, evaluate tissue abnormalities, or monitor treatment responses. This procedure can be performed on various tissues, including skin, muscle, liver, and other organs, depending on the clinical indications. Biopsies are typically obtained using specialized instruments and techniques to ensure minimal discomfort and accurate sample collection. The analysis of biopsy samples can provide detailed histological information that aids in diagnosing conditions such as neoplasia, inflammatory diseases, and infectious processes. This page compiles peer-reviewed research studies and scholarly articles that explore the methodologies, applications, and outcomes of biopsy procedures in equine veterinary practice.
Histologic and micro-computed tomographic evaluation of the osseointegration of a nonresorbable bone substitute in alveoli of ponies after tooth extraction.
American journal of veterinary research    May 2, 2008   Volume 69, Issue 5 604-610 doi: 10.2460/ajvr.69.5.604
Vlaminck L, Cnudde V, Pieters K, Van Den Broeck W, Steenhaut M, Jacobs P, Gasthuys F.To evaluate the biological behavior of a nonresorbable bone substitute (NRBS) in the alveoli of ponies, compared with tissue quality in naturally healing alveoli, after cheek tooth extraction. Methods: 5 clinically normal ponies. Methods: In each pony, both maxillary fourth premolars (Triadan 108/208) were repulsed bilaterally during anesthesia. One randomly chosen alveolus was filled with NRBS and isolated from the oral cavity by use of dental impression material and a spring-wire retention device. The other alveolus was occluded in its occlusal third portion with dental impression material. ...
Polysaccharide storage myopathy in Cob Normand draft horses.
Veterinary pathology    April 22, 2008   Volume 45, Issue 2 154-158 doi: 10.1354/vp.45-2-154
Larcher T, Herszberg B, Molon-Noblot S, Guigand L, Chaffaux S, Guerin G, Cherel Y.Gluteus medius muscle was sampled from 53 Cob Normand horses for histologic evaluation. Twenty horses (38%) exhibited amylase-resistant material in myocytes consistent with polysaccharide storage myopathy. Diameter of affected type II fibers was increased (67.7 +/- 21.4 microm) compared with normal ones (57.3 +/- 19.7 microm). Two groups were distinguished by quantitative study. The first group (n = 14; 26%) was characterized by a low percentage of fibers (m = 0.98%) containing aggregates occurring singly or in perifascicular clusters without myopathic changes. The second group (n = 6; 11%) wa...
Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair.
Journal of dermatological science    April 22, 2008   Volume 51, Issue 2 103-112 doi: 10.1016/j.jdermsci.2008.03.008
Miragliotta V, Lefebvre-Lavoie J, Lussier JG, Theoret CL.Wounds on horse limbs can develop exuberant granulation tissue which resembles the human keloid. Clues gained from the study of over-scarring in horses might help control fibro-proliferative disorders. Objective: The aim of the present study was to clone full-length equine ANXA2 cDNA then to study spatio-temporal expression of ANXA2 and MMP1 mRNA and protein, potential contributors to remodeling, during repair of body (normal) and limb (fibro-proliferative) wounds in an established horse wound model. Methods: Cloning of ANXA2 was achieved by screening size-selected cDNA libraries. Expression w...
Evaluation of a thoracoscopic technique using ligating loops to obtain large lung biopsies in standing healthy and heaves-affected horses.
Veterinary surgery : VS    April 9, 2008   Volume 37, Issue 3 232-240 doi: 10.1111/j.1532-950X.2008.00371.x
Relave F, David F, Leclère M, Alexander K, Bussières G, Lavoie JP, Marcoux M.To evaluate use of pre-tied ligating loop to perform thoracoscopic, large lung biopsy in normal and heaves-affected horses. Methods: Prospective clinical study. Methods: Normal (n=5) and heaves-affected (n=6) horses. Methods: Lung biopsies, 1 from each hemithorax, were collected thoracoscopically using a pre-tied ligating loop. Horses were either normal (C) or heaves-affected with the latter being in remission (Ha) for the initial biopsy and in exacerbation (Hs) for the 2nd biopsy. Clinical variables, PaO(2), and PaCO(2) were used to determine the effect of surgical biopsy. Postoperative pneum...
The equine endometrosis: new insights into the pathogenesis.
Animal reproduction science    March 30, 2008   Volume 111, Issue 2-4 261-278 doi: 10.1016/j.anireprosci.2008.03.019
Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA.This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season (n=509), on defined days during the estrous cycle (n=70) and before and after experimentally induced bacterial endometritis (n=200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical method...
Prevalence of equine polysaccharide storage myopathy and other myopathies in two equine populations in the United Kingdom.
Veterinary journal (London, England : 1997)    March 28, 2008   Volume 180, Issue 3 330-336 doi: 10.1016/j.tvjl.2008.01.008
McGowan CM, McGowan TW, Patterson-Kane JC.The aim of this study was to determine the prevalence of equine polysaccharide storage myopathy (EPSM) in two populations of horses in the UK. Biopsy specimens from 94 horses presented to an abattoir (population 1), and 46 horses with neuromuscular disorders presented to a university referral hospital (population 2) were obtained over a period of 4years. Histological sections were examined by a veterinary pathologist for lesions including abnormal polysaccharide inclusions in myofibres. In population 1, a diagnosis of EPSM was made in 8% and non-specific myopathy in 33% of horses. In populatio...
Effect of a novel solution for organ preservation on equine large colon in an isolated pulsatile perfusion system.
Equine veterinary journal    March 22, 2008   Volume 40, Issue 4 306-312 doi: 10.2746/042516408X295455
Polyak MM, Morton AJ, Grosche A, Matyjaszek S, Freeman DE.Several therapeutic agents have been tested in models of ischaemia and reperfusion injury (IRI) in equine jejunum, with mixed results. This study was based on the use of an organ perfusion solution (OPS) designed to protect human allografts from IRI. Objective: A modified OPS can preserve the integrity of equine large colon during 12 h of isolated pulsatile perfusion, in the absence of oxygen and blood. Methods: Segments of large colon were removed from anaesthetised horses, the contents removed and the mucosa rinsed with 0.9% saline. Experimental segments were perfused for 12 h with one litre...
Stereological characteristics of the equine accessory nerve.
Anatomia, histologia, embryologia    March 10, 2008   Volume 37, Issue 3 205-213 doi: 10.1111/j.1439-0264.2007.00830.x
Matiasek K, Gais P, Rodenacker K, Jütting U, Tanck JJ, Schmahl W.Stereological techniques have been increasingly employed for assessment and characterization of neuromuscular diseases in humans and animals. As an adjunct to histopathology, morphometrical algorithms provide quantitative evidence of the peripheral nerve composition, thereby shedding light on its fibre characteristics and basic electrophysiological properties. In the horse, stereological investigations already have focussed on the recurrent laryngeal, deep peroneal and lateral palmar nerves (LPN). Of these, only the latter is suitable for taking biopsies in clinical settings, however, it does ...
Evaluation of a laparoscopic technique for collection of serial full-thickness small intestinal biopsy specimens in standing sedated horses.
American journal of veterinary research    March 4, 2008   Volume 69, Issue 3 431-439 doi: 10.2460/ajvr.69.3.431
Bracamonte JL, Bouré LP, Geor RJ, Runciman JR, Nykamp SG, Cruz AM, Teeter MG, Waterfall HL.To assess a technique for laparoscopic collection of serial full-thickness small intestinal biopsy specimens in horses. Methods: 13 healthy adult horses. Methods: In the ex vivo portion of the study, sections of duodenum and jejunum obtained from 6 horses immediately after euthanasia were divided into 3 segments. Each segment was randomly assigned to the control group, the double-layer hand-sewn closure group, or the endoscopic linear stapler (ELS) group. Bursting strength and bursting wall tension were measured and compared among groups; luminal diameter reduction at the biopsy site was compa...
Coagulation abnormalities and complications after percutaneous liver biopsy in horses.
Journal of veterinary internal medicine    February 22, 2008   Volume 22, Issue 1 185-189 doi: 10.1111/j.1939-1676.2007.0006.x
Johns IC, Sweeney RW.Liver biopsy is useful in the diagnosis of liver disease in horses. However, bleeding is the major complication. Liver dysfunction can result in abnormalities in coagulation, although there is no definitive association between risk of hemorrhage after biopsy and coagulopathy in humans. Frequency of coagulopathies in horses with liver disease and the nature and frequency of complications after liver biopsy are not reported. Objective: To determine whether there is an association between coagulopathy and hemorrhage after liver biopsy in horses. Methods: Horses with suspected liver disease from w...
Local and remote lesions in horses subjected to small colon distension and decompression. Faleiros RR, Macoris DG, Alves GE, Souza DG, Teixeira MM, Moore RM.The purpose of this study was to observe and characterize colonic and lung lesions in horses subjected to experimental distension and decompression of the small colon. Sixteen healthy adult horses were divided into 2 groups: 9 horses that were subjected to distension of the small colon by means of a latex balloon surgically implanted in the lumen and inflated to a pressure of 40 mm Hg for 4 h, and 7 horses in which the balloon was implanted but not inflated. Colonic biopsy specimens were collected before balloon implantation, at the end of the period of obstruction, and 1.5 and 12 h after deco...
Evaluation of equine laminar vein function: harvesting, dissection and the use of functional methods to distinguish between veins and arteries.
Journal of pharmacological and toxicological methods    January 19, 2008   Volume 57, Issue 2 92-99 doi: 10.1016/j.vascn.2007.10.005
Keen JA, Hillier C, McGorum BC, Bunton D, Nally JE.Pharmacological evaluation of the unique equine laminar microvasculature is crucial to understanding its role in health and in diseases such as laminitis. However, separating the distinctive characteristics of arterial versus venous components of this complex vascular network has previously proved to be extremely difficult. Encased in a hard hoof capsule, isolation of individual blood vessels presents a considerable challenge. Exacerbating this difficulty, the laminar venous network is adapted to sustain high intravascular pressures and consequently has thickened walls, making the normally str...
Lymphangiosarcoma in the nictitating membrane of a horse. Puff C, Herder V, Philipp A, Baumgärtner W.A 15-year-old Haflinger gelding presented with a mass in the left nictitating membrane. Two biopsies and the excised nictitating membrane were taken at different time points as a result of reoccurrence of the mass and submitted for histopathologic evaluation. The horse was euthanized as a result of poor prognosis following the reoccurrence of the mass after surgical removal. Histologically, the mass consisted of dilated, thin-walled vascular clefts and channels, lined by flattened to cuboidal endothelial cells with moderate cellular pleomorphism. There was up to 1 mitotic figure per high power...
Effects of hyperbaric oxygen on full-thickness meshed sheet skin grafts applied to fresh and granulating wounds in horses.
American journal of veterinary research    January 3, 2008   Volume 69, Issue 1 144-147 doi: 10.2460/ajvr.69.1.144
Holder TE, Schumacher J, Donnell RL, Rohrbach BW, Adair HS.To determine the effects of hyperbaric oxygen therapy (HBOT) on full-thickness skin grafts applied to fresh and granulating wounds of horses. Methods: 6 horses. Methods: On day 0, two 4-cm-diameter circular sections of full-thickness skin were removed from each of 2 randomly selected limbs of each horse, and two 4-cm-diameter circular skin grafts were harvested from the pectoral region. A skin graft was applied to 1 randomly selected wound on each limb, leaving the 2 nongrafted wounds to heal by second intention. On day 7, 2 grafts were harvested from the pectoral region and applied to the gra...
Partial divergence of cytokine mRNA expression in bronchial tissues compared to bronchoalveolar lavage cells in horses with recurrent airway obstruction.
Veterinary immunology and immunopathology    December 24, 2007   Volume 122, Issue 3-4 256-264 doi: 10.1016/j.vetimm.2007.12.001
Riihimäki M, Raine A, Art T, Lekeux P, Couëtil L, Pringle J.The aim of this study was to investigate mRNA levels of cytokines in bronchial epithelium in horses with recurrent airway obstruction (RAO) during acute crisis and remission. Additionally, cytokine mRNA levels in endobronchial biopsies and bronchoalveolar lavage (BAL) cells were compared. Seven RAO horses were examined while in respiratory crisis following provocation and again while in remission after 2 months on pasture, during which time six healthy horses on pasture were also examined. Quantitative real-time PCR (RT-PCR) was used to assess mRNA expression for cytokines IL-5, IL-6, IL-8, IL...
An epidemiological study of myopathies in Warmblood horses.
Equine veterinary journal    December 20, 2007   Volume 40, Issue 2 171-177 doi: 10.2746/042516408X244262
Hunt LM, Valberg SJ, Steffenhagen K, McCue ME.There are few detailed reports describing muscular disorders in Warmblood horses. Objective: To determine the types of muscular disorders that occur in Warmblood horses, along with presenting clinical signs, associated risk factors and response to diet and exercise recommendations, and to compare these characteristics between horses diagnosed with polysaccharide storage myopathy (PSSM), those diagnosed with a neuromuscular disorder other than PSSM (non-PSSM) and control horses. Methods: Subject details, muscle biopsy diagnosis and clinical history were compiled for Warmblood horses identified ...
Endometrial gland surface density and hyperaemia of the endometrium during early pregnancy in the mare.
Equine veterinary journal    December 11, 2007   Volume 39, Issue 6 511-515 doi: 10.2746/042516407X235821
Lefranc A-, Allen WR.The morphology and surface density of endometrial glands responsible for the nutrition of the placenta requires further study employing computer assisted morphometric analysis. Objective: To analyse changes in the morphology and surface density of endometrial glands situated adjacent to, and remote from, the conceptus during the first 30 days of gestation. Methods: Endometrial biopsies were recovered, under videoendoscopic control, from both nonpregnant and pregnant mares 12 days after ovulation, as well as from pregnant mares on Days 16, 20, 25 and 30 of gestation. One biopsy was taken at the...
Modeling trophoblast differentiation using equine chorionic girdle vesicles.
Placenta    December 3, 2007   Volume 29, Issue 2 158-169 doi: 10.1016/j.placenta.2007.10.005
de Mestre AM, Bacon SJ, Costa CC, Leadbeater JC, Noronha LE, Stewart F, Antczak DF.The chorionic girdle of the equine conceptus is comprised of specialized trophoblast cells which, at day 36-38 of equine pregnancy, gain an invasive phenotype and invade the endometrium to form endometrial cups. Studies of equine endometrial cups remain difficult to perform because of the invasive techniques required to obtain cup tissue and because sampling requires termination of the pregnancy. In this study we developed a system to model trophoblast differentiation and trophoblast-immune interactions in vitro and in vivo. We utilized a method of culturing chorionic girdle pieces in serum-fr...
High prevalence of bovine papillomaviral DNA in the normal skin of equine sarcoid-affected and healthy horses.
Veterinary microbiology    November 19, 2007   Volume 129, Issue 1-2 58-68 doi: 10.1016/j.vetmic.2007.11.008
Bogaert L, Martens A, Van Poucke M, Ducatelle R, De Cock H, Dewulf J, De Baere C, Peelman L, Gasthuys F.Bovine papillomavirus (BPV), the causative agent of papillomas in cattle, has been shown to play a major role in the pathogenesis of equine sarcoids in horses. BPV has also been detected occasionally in normal equine skin. In this study, presence and activity of BPV in normal skin and peripheral blood of 4 groups of horses were evaluated: sarcoid-affected horses, horses living in contact with sarcoid-affected horses, horses living in contact with papilloma-affected cattle and control horses. From each horse, 3 samples on 4 locations were collected: a swab of the intact skin surface and both a ...
Effect of exercise on development of capillary supply and oxidative capacity in skeletal muscle of horses.
American journal of veterinary research    November 3, 2007   Volume 68, Issue 11 1226-1231 doi: 10.2460/ajvr.68.11.1226
Rietbroek NJ, Dingboom EG, Schuurman SO, Hengeveld-van der Wiel E, Eizema K, Everts ME.To determine whether postnatal development of oxidative capacity and capillary supply of skeletal muscle is affected by various movement regimens in horses. Methods: 35 foals. Methods: Dutch Warmblood foals were allocated into 3 groups (box stall rest, box stall rest with training, and free pasture exercise). Training comprised an increasing number of gallop sprints from 1 week after birth to 22 weeks of age. From 22 to 48 weeks, the 3 groups were combined and allowed to exercise freely. Capillary supply (diffusion index [ie, area supplied by 1 capillary]), citrate synthase (CS) activity, and ...
Mechanisms behind intrauterine device-induced luteal persistence in mares.
Animal reproduction science    June 14, 2007   Volume 107, Issue 1-2 94-106 doi: 10.1016/j.anireprosci.2007.06.010
Rivera Del Alamo MM, Reilas T, Kindahl H, Katila T.Intrauterine glass balls are used to prevent oestrous signs in sports mares, but the mechanism of action is unknown. It has been suggested that the glass ball can mimic an embryo or act via an induced chronic uterine inflammation and absent or continuous low-grade prostaglandin (PG) release. The purpose of this study was to induce prolonged luteal function in mares using a small intrauterine device (IUD) and to study the mechanisms behind prolonged IUD-induced luteal function. A uterine swab and a biopsy specimen were obtained in early oestrus. A water-filled plastic ball, diameter 20mm and we...
Equine endometrial biopsy: enhancement of clinical value by more extensive histopathology and application of new diagnostic techniques?
Theriogenology    June 8, 2007   Volume 68, Issue 3 413-422 doi: 10.1016/j.theriogenology.2007.04.040
Schlafer DH.During the 1960s and 1970s, the clinical value of equine endometrial histopathology was firmly established after it was shown that fertility outcome was correlated with the presence and severity of specific microscopic lesions. The objective of this paper is to summarize reports from the veterinary literature published after the mid 1980s that describe new diagnostic methods of assessing equine uterine health using material collected by endometrial biopsy.
Use of a low-volume uterine flush for diagnosing endometritis in chronically infertile mares.
Theriogenology    May 31, 2007   Volume 68, Issue 3 403-412 doi: 10.1016/j.theriogenology.2007.04.038
LeBlanc MM, Magsig J, Stromberg AJ.Low-volume uterine flush (n=401) was performed in 308 infertile mares to diagnose endometritis. Mares evaluated were either barren after three or more breedings or had two or more unsuccessful embryo recovery attempts during consecutive cycles. Culture results were compared with cytological and histological findings, efflux clarity and pH to substantiate that the micro-organisms recovered were truly pathogens. Cytological specimens were evaluated for presence of epithelial and inflammatory cells, bacteria, yeast and debris. Endometrial biopsies (n=110) were examined for the presence of neutrop...
Muscle characteristics of dutch warmblood foals with different genetic background at ages 6 and 12 months.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 326-329 doi: 10.1111/j.2042-3306.2006.tb05562.x
Rietbroek NJ, Dingboom EG, Everts ME.REASONS OF PERFORMING STUDY: To obtain broader insight into the muscle of foals with different genetic background, muscle fibre composition, its post natal development and citrate synthase (CS) activity of the gluteus medius were investigated. Objective: Because muscle properties are influenced genetically and related directly to performace ability, muscle characteristics should be affected by selection and correspond with the requirement of ths sports selected for. Methods: The foals were divided into Group A, (n = 16), considered an average of the population, and Group B (n = 36), selected f...
Myosin heavy chain fibre type composition in foals: analyses at the mRNA and protein level.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 316-321 doi: 10.1111/j.2042-3306.2006.tb05560.x
Eizema K, van der Wal DE, van den Burg MM, Dingboom EG, Everts ME.An optimal developed musculoskeletal system is vital for the performance of the horse. Previously, we showed that in the m. gluteus medius from adult untrained horses, identical mRNA and protein expression patterns were found in the majority of fibres. However, co-expression of IIa and IId/x myosin heavy chain (MyHC) was substantially more common at the protein than at the mRNA level, suggesting a transcriptionally controlled fine-tuning of these 2 genes. Objective: To analyse the MyHC transcripts and proteins (including the cardiac alpha isoform) in the same muscle during post natal developme...
Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society    April 4, 2007   Volume 25, Issue 7 913-925 doi: 10.1002/jor.20382
Wilke MM, Nydam DV, Nixon AJ.Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 month...
Prevalence of polysaccharide storage myopathy in horses with neuromuscular disorders.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 340-344 doi: 10.1111/j.2042-3306.2006.tb05565.x
McCue ME, Ribeiro WP, Valberg SJ.Controversy exists as to the prevalence of polysaccharide storage myopathy (PSSM) in breeds of horses and its impact on performance. Objective: To determine 1) the prevalence of PSSM in horses that presented with a neuromuscular disorder, as well as breed, sex and age distributions and clinical signs 2) effect of diagnostic criteria on prevalence, breed distribution and age of horses diagnosed with PSSM. Methods: Fresh frozen biopsies (n = 1426) submitted to the Neuromuscular Diagnostic Laboratory at the University of Minnesota were searched to identify horses diagnosed with PSSM. Horses with ...
Recruitment pattern of muscle fibre type during flat and sloped treadmill running in thoroughbred horses.
Equine veterinary journal. Supplement    April 4, 2007   Issue 36 349-353 doi: 10.1111/j.2042-3306.2006.tb05567.x
Eto D, Yamano S, Hiraga A, Miyata H.There is little information about the muscle fibre recruitment pattern during sloped and flat track running in Thoroughbred horses. Objective: To examine the glycogen depletion pattern of each muscle fibre type during running on a flat and sloped treadmill. Methods: Thirteen Thoroughbred horses (3-9 years old) were used. They were initially subjected to incremental exercise tests on a treadmill at 10 and 0% inclines in each horse to determine running speed at 90 and 60% VO2max. Needle biopsy samples were obtained from the middle gluteal muscle immediately after the running at 90% VO2max for 4 ...
Effects of intensity and duration of exercise on muscular responses to training of thoroughbred racehorses.
Journal of applied physiology (Bethesda, Md. : 1985)    January 25, 2007   Volume 102, Issue 5 1871-1882 doi: 10.1152/japplphysiol.01093.2006
Rivero JL, Ruz A, Martí-Korff S, Estepa JC, Aguilera-Tejero E, Werkman J, Sobotta M, Lindner A.This study examined the effects of the intensity and duration of exercise on the nature and magnitude of training adaptations in muscle of adolescent (2-3 yr old) racehorses. Six thoroughbreds that had been pretrained for 2 mo performed six consecutive conditioning programs of varying lactate-guided intensities [velocities eliciting blood lactate concentrations of 2.5 mmol/l (v2.5) and 4 mmol/l (v4), respectively] and durations (5, 15, 25 min). Pre- and posttraining gluteus muscle biopsies were analyzed for myosin heavy chain content, fiber-type composition, fiber size, capillarization, and fi...
Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses–a preliminary report.
Veterinary journal (London, England : 1997)    December 14, 2006   Volume 174, Issue 3 565-569 doi: 10.1016/j.tvjl.2006.10.022
Manso Filho HC, McKeever KH, Gordon ME, Costa HE, Watford M.One of the hallmarks of insulin resistance is a reduction in glucose transporter-4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However, while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it has not been demonstrated in adipose tissue. The initial objectives of the present study were: (1) to test the hypothesis that Glut-4 expression would vary between selected key skeletal muscles; (2) to test the hypothesis that it would also vary between representative adipose tissue depots, and (3) to see whether expression would be greater in adipose tissue c...
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