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Topic:Vascular

The vascular system in horses encompasses a network of blood vessels responsible for the circulation of blood throughout the body. This system includes arteries, veins, and capillaries, which facilitate the transport of oxygen, nutrients, and waste products to and from tissues. The vascular health of horses is vital for maintaining overall physiological function and performance. Common areas of study within equine vascular research include the examination of blood flow dynamics, vascular diseases, and the impact of exercise on vascular function. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and clinical relevance of the vascular system in equine health.
Equine deep stromal abscesses (51 cases – 2004-2009)–Part 2: the histopathology and immunohistochemical aspect with attention to the histopathologic diagnosis, vascular response, and infectious agents.
Veterinary ophthalmology    October 17, 2013   Volume 17 Suppl 1 14-22 doi: 10.1111/vop.12102
de Linde Henriksen M, Andersen PH, Mietelka K, Farina L, Thomsen PD, Plummer CE, Mangan BG, Heegaard S, Coleman JK, Toft N, Brooks DE.To investigate histopathologic and immunohistochemical aspects of equine deep stromal abscesses (DSA) with a focus on the histopathologic diagnosis, presumptive etiology, and the immunohistochemical expression of three angiogenesis-related factors: vascular endothelial growth factor-A (VEGF-A), pigment epithelium-derived factor (PEDF), and interleukin-1 receptor antagonist (IL-1ra). Methods: Paraffin-embedded biopsy samples from 51 DSA. The biopsies were collected from full-thickness penetrating keratoplasty or split-thickness lamellar keratoplasty surgeries at the University of Florida Veteri...
Is the horse a reservoir or an indicator of Coxiella burnetii infection? Systematic review and biomolecular investigation.
Veterinary microbiology    October 1, 2013   Volume 167, Issue 3-4 662-669 doi: 10.1016/j.vetmic.2013.09.027
Marenzoni ML, Stefanetti V, Papa P, Casagrande Proietti P, Bietta A, Coletti M, Passamonti F, Henning K.The role of the horse in Coxiella burnetii infection has not been defined. Accordingly, a twofold approach was taken to further our knowledge on this topic: (1) conduct a systematic review of the literature to establish available evidence of C. burnetii infection in the horse; (2) undertake a biomolecular investigation of 122 cases of equine abortion, stillbirth and neonatal foal death, for the presence of C. burnetii using a PCR test targeting the IS1111 gene of C. burnetii. A review of the literature turned up seven studies that identified C. burnetii DNA in equine specimens, especially abor...
Role of equine herpesviruses as co-infecting agents in cases of abortion, placental disease and neonatal foal mortality.
Veterinary research communications    September 20, 2013   Volume 37, Issue 4 311-317 doi: 10.1007/s11259-013-9578-6
Marenzoni ML, Bietta A, Lepri E, Casagrande Proietti P, Cordioli P, Canelli E, Stefanetti V, Coletti M, Timoney PJ, Passamonti F.Herpesviral infections frequently occur in horses. The objective of this study was to investigate the possible association of equine herpesviruses (EHV-1, EHV-2, EHV-3, EHV-4, EHV-5) with other causes of abortion, neonatal mortality or placental disorder. Sixty-seven abortions, 22 stillbirths, 14 cases of neonatal foal mortality and 3 cases of placental disease were investigated for infectious and non-infectious causes. Type-specific nested PCR assays and virus isolation were performed to detect EHV infections. A cause of fetal loss or placental disease was reached in 68 out 116 (58.7%) cases....
Vasorelaxant effect of propentofylline in isolated equine digital veins.
European journal of pharmacology    September 17, 2013   Volume 718, Issue 1-3 124-130 doi: 10.1016/j.ejphar.2013.09.003
We evaluated the vasorelaxant effect of propentofylline (PPF), a methylxanthine derivative, and its mechanism of action in equine digital veins (EDVs). Cumulative concentration-response curves to PPF (1 nM-300 µM) were recorded in phenylephrine-precontracted EDV rings under different experimental conditions. PPF-induced relaxation was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (an adenosine receptor antagonist; 3 µM). PPF-induced relaxation was partially inhibited in the presence of L-NAME (a nitric oxide (NO) synthase inhibitor; 100 µM), ODQ (an inhibitor of...
B-cell multicentric lymphoma as a probable cause of abortion in a Quarter horse broodmare.
The Canadian veterinary journal = La revue veterinaire canadienne    September 3, 2013   Volume 54, Issue 3 288-291 
Canisso IF, Pinn TL, Gerdin JA, Ollivett TL, Buckles EL, Schweizer CM, Ainsworth DM.A 5-year-old Quarter horse broodmare was evaluated for inappetence, depression, and diarrhea 13 days after aborting a 9-month gestation fetus. Clinical and laboratory examination ruled out uterine rupture and peritonitis. Ultrasonography of the uterus combined with cytological analysis of peritoneal fluid suggested the existence of diffuse lymphoma. A multicentric B-cell lymphoma involving the uterus and ovary was confirmed at necropsy and histopathological examination. Lymhome multicentrique à cellules B comme cause possible d’avortement chez une jument poulinière Quarter Horse. Une jumen...
The role of leptospirosis in reproductive disorders in horses.
Tropical animal health and production    August 30, 2013   Volume 46, Issue 1 1-10 doi: 10.1007/s11250-013-0459-3
Hamond C, Pinna A, Martins G, Lilenbaum W.Leptospirosis is a zoonotic disease of global importance and has a worldwide distribution. This infection displays clear seasonal nature in some regions of the tropics, where the rainy season is marked by high temperatures. Household and wild animals carry leptospires and contribute to their dissemination in nature. Transmission mainly occurs by contact with water contaminated with the urine of infected animals, and consequently, it is quite widespread especially in times of rain, since many areas are subject to flooding and have poor sanitation. Serological tests demonstrate that Leptospira s...
Equine herpesvirus 1 (EHV-1) nucleotide polymorphism determination using formalin fixed tissues in EHV-1 induced abortions and myelopathies with real-time PCR and pyrosequencing.
Journal of virological methods    July 11, 2013   Volume 193, Issue 2 371-373 doi: 10.1016/j.jviromet.2013.06.039
Tewari D, Del Piero F, Cieply S, Feria W, Acland H.Equine herpesvirus-1 (EHV-1) strains with a single point mutation at the 2254 nucleotide position with a G2254 constitution within the DNA polymerase gene are associated strongly with equine myeloencephalopathies. Infections with non-neuropathogenic EHV-1 strains without the G2254 nucleotide but with an A2254 nucleotide are associated less frequently with equine neurologic disease. A retrospective study utilizing DNA extracted from formalin fixed paraffin embedded tissues was conducted with real time PCR and pyrosequencing, to determine the infecting EHV-1 strains. Infection with EHV-1 A2254 a...
Low levels of naturally occurring regulatory T lymphocytes in blood of mares with early pregnancy loss.
Reproduction, fertility, and development    June 22, 2013   Volume 26, Issue 6 827-833 doi: 10.1071/RD13012
Aurich C, Weber J, Nagel C, Merkl M, Jude R, Wostmann S, Ollech D, Baron U, Olek S, Jansen T.Early pregnancy loss is a major reason for low reproductive efficiency in the horse. In humans and mice, low numbers of regulatory T cells (Treg cells) are linked to miscarriage. The percentage of Treg cells in oestrous mares at the start of the breeding season was evaluated in relation to the outcome of subsequent pregnancy. For identification and quantification of Treg cells, a highly sensitive and specific qPCR assay targeting the Treg-specific demethylated region in the equine forkhead box transcription factor (FOXP3) gene was established. In a total of 108 mares, pregnancy was followed un...
Influence of seroreactivity to leptospira and reproductive failures in recipient mares of equine embryo transfer programmes.
Reproduction in domestic animals = Zuchthygiene    April 13, 2013   Volume 48, Issue 4 e55-e57 doi: 10.1111/rda.12166
Pinna A, Martins G, Souza G, Lilenbaum W.The aim of this study was to demonstrate that seroreactivity against Leptospira is significantly associated to the reproductive efficiency of recipient mares of an embryo transfer (ET) programme. A serosurvey was conducted from August 2007 to March 2009 in five herds from Rio de Janeiro, Brazil, with high rates of reproductive failure, as early embryonic death (>12%), abortion (>12%) and perinatal death. Detailed information about the losses was obtained from practitioner. A total of 338 recipient mares were tested by microscopic agglutination test, and 226 (66.9%) were seroreactive, mainly ag...
Bacteria isolated from field cases of equine amnionitis and fetal loss.
Australian veterinary journal    March 26, 2013   Volume 91, Issue 4 138-142 doi: 10.1111/avj.12022
Todhunter KH, Muscatello G, Blishen AJ, Chicken C, Perkins NR, Gilkerson JR, Begg AP.A series of unusual abortions occurred in Thoroughbred and Quarterhorse mares in the Hunter Valley region of New South Wales from mid-March to November 2004. The initial link between early cases was the microbiological culture of atypical environmental coryneforms from the stomach contents and/or lungs of fetuses aborted on different properties. Methods: The unique pathologic lesions were described with a case definition and the term 'equine amnionitis and fetal loss' (EAFL) was established. Results: The causal factor was the ingestion of the processionary caterpillar (Ochrogaster lunifer). Ba...
Clinical observations and management of a severe equine herpesvirus type 1 outbreak with abortion and encephalomyelitis.
Acta veterinaria Scandinavica    March 5, 2013   Volume 55, Issue 1 19 doi: 10.1186/1751-0147-55-19
Walter J, Seeh C, Fey K, Bleul U, Osterrieder N.Latent equine herpesvirus type 1 (EHV-1) infection is common in horse populations worldwide and estimated to reach a prevalence nearing 90% in some areas. The virus causes acute outbreaks of disease that are characterized by abortion and sporadic cases of myeloencephalopathy (EHM), both severe threats to equine facilities. Different strains vary in their abortigenic and neuropathogenic potential and the simultaneous occurrence of EHM and abortion is rare. In this report, we present clinical observations collected during an EHV-1 outbreak caused by a so-called "neuropathogenic" EHV-1 G(2254)/D(...
Exposure of mares to processionary caterpillars (Ochrogaster lunifer) in early pregnancy: an additional dimension to equine amnionitis and fetal loss.
Equine veterinary journal    March 4, 2013   Volume 45, Issue 6 755-760 doi: 10.1111/evj.12044
Cawdell-Smith AJ, Todhunter KH, Perkins NR, Bryden WL.Equine amnionitis and fetal loss (EAFL) is an unusual form of abortion in mid- to late-gestation mares, first identified in Australia in 2004. It has been shown that both whole processionary caterpillars (Ochrogaster lunifer) and their shed exoskeletons can induce abortion in mares during midgestation. These abortions exhibited gross pathology and bacteriology results consistent with field cases of EAFL. Objective: To determine whether exposure of mares to the shed exoskeletons of processionary caterpillars can induce abortion in the preplacentation (<35 days' gestation) and early plac...
Serum amyloid A concentration in healthy periparturient mares and mares with ascending placentitis.
Equine veterinary journal    February 22, 2013   Volume 45, Issue 5 619-624 doi: 10.1111/evj.12034
Coutinho da Silva MA, Canisso IF, MacPherson ML, Johnson AE, Divers TJ.Placentitis is a prevalent cause of abortion, premature delivery and neonatal death in mares. Early diagnosis is paramount for the survival of the fetus and delivery of a live foal. Objective: To determine: 1) Serum amyloid A (SAA) profile in healthy mares during late gestation; 2) if placentitis affects SAA concentrations and 3) the effects of therapy on SAA concentrations and pregnancy outcome in mares with placentitis. Methods: In Experiment I, 15 healthy pregnant mares were evaluated from 280 days of gestation to 60 h post partum. In Experiment II, pregnant mares were inoculated intra-cerv...
A case of umbilical cord teratoma in an aborted foal. Binanti D, Livini M, Riccaboni P, Sironi G.A 16-year-old primiparous mare aborted an apparently normal fetus at 240 days of gestation. A large, oval mass, measuring approximately 20 cm × 30 cm × 20 cm, was detected attached to the umbilical cord of the fetus. On the cut surface, the mass showed multifocal cystic structures, foci of mineralization, and diffuse hemorrhages. Histological examination of the mass revealed haphazardly arranged cartilage, bone, mesenchymal stroma, adipose tissue, vascular structures, smooth muscle, ciliated epithelium, squamous cornifying epithelium, and undifferentiated germ cells with areas of necrosis an...
A predictive model for reproductive performance following abortion in Thoroughbred mares.
The Veterinary record    October 31, 2012   Volume 172, Issue 2 44 doi: 10.1136/vr.100670
Schulman ML, Kass PH, Becker A, Van der Merwe B.Pregnancy losses include early embryonic death (EED) and later (postimplantation) abortion. Abortions, particularly Equid herpesvirus (EHV-1) abortion epizootics, cause severe economic and production losses. The long-term effects of EHV-1 and other abortions on subsequent reproductive performance in broodmare populations, however, remain undefined. This study described the relationships of EED and abortion with the following reproductive outcomes in Thoroughbred systems: breeding efficiency, month of last breeding, subsequent pregnancy and live foal rates. A prospective cohort study in broodma...
Strain impact on equine herpesvirus type 1 (EHV-1) abortion models: viral loads in fetal and placental tissues and foals.
Vaccine    August 31, 2012   Volume 30, Issue 46 6564-6572 doi: 10.1016/j.vaccine.2012.08.046
Gardiner DW, Lunn DP, Goehring LS, Chiang YW, Cook C, Osterrieder N, McCue P, Del Piero F, Hussey SB, Hussey GS.Equine herpesvirus-1 (EHV-1) continues to cause both sporadic and epidemic abortions despite extensive vaccination. Lack of progress in the development of protective vaccines may be hindered by the lack of equine abortion models that employ contemporary EHV-1 strains. The objective of our experiments was to compare a contemporary EHV-1 strain with a previously described challenge strain, and to quantify EHV-1 loads in various maternal and fetal tissues. Infection experiments were performed in two groups of 7 pregnant pony mares at 270-290 days of gestation with a contemporary EHV-1 strain (Uni...
Analysis of several factors of variation of gestation loss in breeding mares.
Animal : an international journal of animal bioscience    August 9, 2012   Volume 6, Issue 12 1925-1930 doi: 10.1017/S1751731112001164
Langlois B, Blouin C, Chaffaux S.The files for ultrasound diagnosis of gestating mares belonging to the French equine herd recorded for 3 consecutive years were joined with the files for foal birth of these same mares, allowing the statistical analysis of factors of pregnancy loss. For 28 872 positive diagnoses of gestation, 2898 losses were recorded, that is, a global rate of gestation interruption of 9.12%. The etiology of these interruptions is mainly extrinsic: the year and month of insemination, as well as region for climatic reasons. The intrinsic causes that are implicated are breed of the father (heavy breeds except t...
Equine luteal function regulation may depend on the interaction between cytokines and vascular endothelial growth factor: an in vitro study.
Biology of reproduction    June 22, 2012   Volume 86, Issue 6 187 doi: 10.1095/biolreprod.111.097147
Galvão A, Henriques S, Pestka D, Lukasik K, Skarzynski D, Mateus LM, Ferreira-Dias GM.We hypothesized that cytokines influence luteal angiogenesis in mares, while angiogenic factors themselves can also regulate luteal secretory capacity. Therefore, the purpose of this study was to evaluate the role of cytokines--tumor necrosis factor alpha (TNF), interferon gamma (IFNG) and Fas ligand (FASL)--on in vitro modulation of angiogenic activity and mRNA level of vascular endothelial growth factor A (VEGF), its receptor VEGFR2, thrombospondin 1 (TSP1), and its receptor CD36 in equine corpus luteum (CL) throughout the luteal phase. After treatment, VEGF protein expression was determined...
Rapid and efficient diagnosis of leptospirosis in an aborted foal by PCR of gastric juice.
Veterinary microbiology    May 29, 2012   Volume 160, Issue 1-2 274-275 doi: 10.1016/j.vetmic.2012.05.030
Hamond C, Martins G, Lilenbaum W, Medeiros MA.No abstract available
Increased hypoxia-inducible factor 1α expression in lung cells of horses with recurrent airway obstruction.
BMC veterinary research    May 23, 2012   Volume 8 64 doi: 10.1186/1746-6148-8-64
Toussaint M, Fievez L, Desmet CJ, Pirottin D, Farnir F, Bureau F, Lekeux P.Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-α in myeloid cells in ho...
Uterine haemodynamics in young and aged pregnant mares measured using Doppler ultrasonography.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 15-21 doi: 10.1111/j.2042-3306.2011.00446.x
Ousey JC, Kölling M, Newton R, Wright M, Allen WR.Aged mares with endometrosis suffer higher rates of pregnancy loss than young mares, due to poor placental development. Reduced uterine blood supply may be one contributory factor. Objective: To measure uterine artery (UA) blood flow and other Doppler indices throughout pregnancy and compare placental and foal development in young mares and aged mares. Methods: Thoroughbred mares were grouped according to age and endometrial biopsy score: 1) 6 young mares (mean age 7.3 years, Category ); 2) 6 aged mares (mean age 18.3 years, Category II). Vascular pathology was nil or mild except in one aged m...
Infection of an equine placenta with a novel mycobacterial species leading to abortion. Johnson AK, Roberts JF, Hagan A, Wilborn RR, Dujovne G, Sells SF, Donahue JM.A 25-year-old pregnant American Quarter Horse mare presented with a 1-week history of progressively worsening vaginal discharge. Transrectal ultrasound revealed increased thickness of the combined uterus and placenta with evidence of chorioallantoic edema but no placental separation. A thickened amnion was visible on transabdominal ultrasound. Abortion occurred 2 days after presentation despite medical treatment. At necropsy, the chorioallantois had variable but diffuse thickening with focally extensive browning of the chorionic surface in the right horn and adjacent body. There were fluid-fil...
Serological responses and clinical outcome after vaccination of mares and foals with equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) vaccines.
Veterinary microbiology    May 8, 2012   Volume 160, Issue 1-2 9-16 doi: 10.1016/j.vetmic.2012.04.042
Bresgen C, Lämmer M, Wagner B, Osterrieder N, Damiani AM.Equine herpesvirus type 1 and type 4 (EHV-1 and EHV-4) cause infections of horses worldwide. While both EHV-1 and EHV-4 cause respiratory disease, abortion and myeloencephalopathy are observed after infection with EHV-1 in the vast majority of cases. Disease control is achieved by hygiene measures that include immunization with either inactivated or modified live virus (MLV) vaccine preparations. We here compared the efficacy of commercially available vaccines, an EHV-1/EHV-4 inactivated combination and an MLV vaccine, with respect to induction of humoral responses and protection of clinical d...
Plasma protein changes in horse after prolonged physical exercise: a proteomic study.
Journal of proteomics    April 24, 2012   Volume 75, Issue 14 4494-4504 doi: 10.1016/j.jprot.2012.04.014
Scoppetta F, Tartaglia M, Renzone G, Avellini L, Gaiti A, Scaloni A, Chiaradia E.Physical exercise induces various stress responses and metabolic adaptations that have not yet been completely elucidated. Novel biomarkers are needed in sport veterinary medicine to monitor training levels and to detect subclinical conditions that can develop into exercise-related diseases. In this study, protein modifications in horse plasma induced by prolonged, aerobic physical exercise were investigated by using a proteomic approach based on 2-DE and combined mass spectrometry procedures. Thirty-eight protein spots, associated with expression products of 13 genes, showed significant quant...
Hydrallantois in the mare–a report of five cases.
Reproduction in domestic animals = Zuchthygiene    March 27, 2012   Volume 48, Issue 1 e1-e6 doi: 10.1111/j.1439-0531.2012.02013.x
Govaere JL, De Schauwer C, Hoogewijs MK, Chiers K, Lefère L, Catry B, Roels K, van Heerden M, Broeckx S, de Kruif A.Hydrallantois in the mare is a very rare condition, and clinical reports help to gather information to elucidate its pathogenesis, treatment options and prognosis. Five different cases of hydrallantois in the mare are reported in this article, all with the involvement of placentitis. The five mares were presented because of acute distention of the abdomen, dyspnoea, stiff gait and a lack of appetite. After a gradual release of the excessive amount of allantoic fluid, an abortion was induced in all five mares. The foals were either born dead or euthanized. The mares recovered quickly. One mare ...
Association between single nucleotide polymorphisms in p53 and abortion in Thoroughbred mares.
Veterinary journal (London, England : 1997)    March 11, 2012   Volume 193, Issue 2 573-575 doi: 10.1016/j.tvjl.2012.02.003
Leon PM, Campos VF, Thurow HS, Hartwig FP, Selau LP, Dellagostin OA, Neto JB, Deschamps JC, Seixas FK, Collares T.Single nucleotide polymorphisms (SNPs) in the p53 gene have been studied extensively in humans. The aims of this study were to determine the frequency of the Arg/Pro SNP in p53 in Thoroughbred mares on one stud in Brazil and to correlate p53 genotypes with reproductive performance. SNPs were detected by PCR-restriction fragment length polymorphism in blood samples from 105 horses and confirmed by sequencing. The allele frequency in Thoroughbred mares at codon 72 in exon 4 was 73.3% Arg/Pro, 17.1% Arg/Arg and 9.6% Pro/Pro. The presence of Arg/Pro was significantly associated with abortion (P=0....
Relationship between the timing of prostaglandin-induced luteolysis and effects on the conceptus during early pregnancy in mares.
Reproduction, fertility, and development    March 10, 2012   Volume 24, Issue 3 411-424 doi: 10.1071/RD11132
Betteridge KJ, Waelchli RO, Christie HL, Raeside JI, Quinn BA, Hayes MA.To advance the understanding of early pregnancy and pregnancy failure in horses, this study determined how luteolysis induced by cloprostenol (an analogue of prostaglandin F2α) affects conceptus development. Mares were injected on Days 12, 14, 16 or 18 of pregnancy with either cloprostenol (treatment groups, total n=83 pregnancies) or saline (controls, n=81), and growth of the conceptuses was monitored and compared by daily ultrasonography until they were collected transcervically on Days 15-22, 1-4 days after the injections. The comparisons were extended in the recovered conceptuses by count...
Molecular and pathological investigations of EHV-1 and EHV-4 infections in horses in Turkey.
Research in veterinary science    March 7, 2012   Volume 93, Issue 3 1504-1507 doi: 10.1016/j.rvsc.2012.01.019
Turan N, Yildirim F, Altan E, Sennazli G, Gurel A, Diallo I, Yilmaz H.The aim of the present study was to investigate abortion storms that occurred in the Marmara region of Turkey in 2008-2009 using a real-time PCR. Two aborted foetuses were necropsied and histo-pathological findings reported herein. Ten lungs, 3 brains and one nasal swab from 10 aborted foetuses, 6 nasal swabs and 3 vaginal swabs from aborting mares were included in this study. EHV-1 was isolated from the lung, liver and brain of 1 aborted foetus. EHV-1 DNA was detected in the lungs, livers and spleens of 2 necropsied foetuses and in 3 lungs from 10 foetuses submitted for diagnosis. A brain fro...
Molecular characterisation of the ORF68 region of equine herpesvirus-1 strains isolated from aborted fetuses in Hungary between 1977 and 2008.
Acta veterinaria Hungarica    March 1, 2012   Volume 60, Issue 1 175-187 doi: 10.1556/AVet.2012.015
Malik P, Bálint A, Dán A, Pálfi V.Equine herpesvirus-1 (EHV-1) can be classified into distinct groups by single nucleotide polymorphisms (SNPs) in their genomes. Only a few of these can be associated with a special attribute of the virus. Differences in the ORF30 region can determine the neuropathogenic potential, while by substitutions in the ORF68 region several strain groups can be made. In previous studies no connection was found between the neuropathogenic potential and the SNPs in ORF68, but the occurrence of members of distinct groups in different outbreaks can facilitate epidemiological investigations because the geogr...
Causes of equine abortion, stillbirth and neonatal death in central Italy.
The Veterinary record    February 24, 2012   Volume 170, Issue 10 262 doi: 10.1136/vr.100551
Marenzoni ML, Lepri E, Casagrande Proietti P, Bietta A, Coletti M, Timoney PJ, Passamonti F.No abstract available
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