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1.
Light microscopy was undertaken on sections from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold in 5 control horses, 5 horses with acute grass sickness (AGS), and 5 horses with chronic grass sickness (CGS). With the exception of the ileal submucous plexus of the CGS group, the AGS group had the lowest number of neurons as measured using a subjective scoring scheme. The proportion of abnormal neurons in the AGS group was similar in both plexuses and both regions, whereas the values for the CGS group were much higher in the duodenal region than in the ileal region. The motility of tissue adjacent to that used for histology was measured isometrically in vitro. The increase in the rate of contractions following exposure to physostigmine was greatest for the AGS group, both from the duodenal and from the ileal region. The latency was longest for the AGS group, suggesting that the material from this group had the least number of active cholinergic neurons. The studies with physostigmine thus indicated that the most severe functional damage occurred in cases of AGS. These findings confirm that extensive damage occurs in the enteric neurons in equine grass sickness. There was good correlation between the functional cholinergic responses and the extent of neuronal degeneration.  相似文献   

2.
REASONS FOR PERFORMING STUDY: There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. OBJECTIVES: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract of horses and to relate antibody levels to disease status. METHODS: Samples of tissue (n = 25: 6 duodenum, 7 jejunum and 12 ileum) were taken from acute grass sickness (AGS) cases and from control horses (n = 12; 4 samples from each site) at post mortem. They were extracted with the detergent saponin in the presence of protease inhibitors and assayed for total IgA, for specific IgA against botulinum neurotoxins types C and D (BoNT/C or BoNT/D), and against surface antigens of a BoNT/C negative strain of C. botulinum type C (SA) and of Clostridium tetani (TetSA), as a control. Specific IgA was expressed as percentage total IgA. RESULTS: Compared to controls, significantly higher levels of specific IgA against BoNT/C were detected in the jejunum (P = 0.04) and ileum (P = 0.02) of AGS cases. Similarly, higher specific levels against BoNT/D were demonstrated in duodenum (P = 0.01) and jejunum (P = 0.02). Significantly higher levels of IgA against SA were demonstrated only in duodenal samples (P = 0.01). CONCLUSIONS: Levels of IgA antibody to BoNTs in control horses were at near undetectable levels, suggesting no recent exposure to toxins. In AGS cases, significantly higher levels of specific IgA were detected predominantly in jejunum and ileum. POTENTIAL RELEVANCE: If specific IgA is protective then any successful vaccine for EGS should induce a mucosal response.  相似文献   

3.
The cause of grass sickness, an equine dysautonomia, is unknown. The disease usually results in death. Gastrointestinal (GI) dysfunction is a common clinical manifestation in all forms of the disease. It is generally thought that equine grass sickness (EGS) is caused by an ingested or enterically produced neurotoxin which is absorbed through the GI tract. Clostridium botulinum was first implicated as a causative agent when it was isolated from the GI tract of a horse with EGS in 1919. The aim of the present study was to investigate the hypothesis that EGS results from toxicoinfection with C. botulinum type C: growth of the bacterium in the GI tract with production of toxin (BoNT/C). Ileum contents and faeces from horses with EGS were investigated for BoNT/C, and indirectly for the presence of C. botulinum type C, and compared with control samples from horses without EGS. BoNT/C was detected directly by ELISA in the ileum of 45% (13/29) of horses with EGS compared to 4% (1/28) of controls, and in the faeces of 44% (20/45) of horses with EGS compared to 4% (3/77) of controls. Levels of up to 10 Mlg toxin/g wet weight of gut contents were observed. The one control horse with detectable toxin in the ileum had been clinically diagnosed as having acute EGS, but this was not confirmed by histopathology. The organism was detected indirectly by assaying for BoNT/C by ELISA after enrichment in culture medium. C. botulinum type C was shown to be present in 48% (14/29) of ileum samples and 44% (20/45) of faecal samples from horses with EGS, compared with 7% (2/27) of ileum samples and 8% (6/72) of faecal samples from controls. These results support the hypothesis that EGS results from a C. botulinum type C toxicoinfection.  相似文献   

4.
REASONS FOR PERFORMING STUDY: The aetiopathogenesis of equine grass sickness (EGS) is unknown. The role of free radical-mediated neuronal damage has not previously been investigated in this condition. OBJECTIVES: To investigate the potential contribution of oxidative damage and antioxidant status to neurodegeneration in EGS. METHODS: Systemic levels of surrogate biomarkers were determined in 10 horses with acute EGS and in 2 control populations; 10 healthy horses co-grazing with the 10 EGS horses at the onset of clinical disease, and 10 healthy mares grazing where EGS has not been reported. RESULTS: EGS horses had alterations in levels of several antioxidants, consistent with oxidative stress, the acute phase response and/or the secondary metabolic complications of EGS. EGS horses had elevated plasma dihydroxyphenylalanine (DOPA) levels. CONCLUSIONS: The elevated DOPA levels probably reflected a generalised disturbance of catecholamine metabolism rather than increased DOPA production via free radical-mediated oxidation of tyrosine. However, there was no evidence of systemic macromolecular oxidative damage. POTENTIAL CLINICAL RELEVANCE: Further work is required to determine whether macromolecular oxidative damage occurring at the neuronal level contributes to EGS.  相似文献   

5.
REASONS FOR PERFORMING THE STUDY: Clinical evidence of motor neuron involvement in equine grass sickness (EGS) has not been reported. HYPOTHESIS: Quantitative electromyography (EMG) analysis can elucidate subtle changes of the lower motor neuron system present in horses with EGS, performed ante mortem. METHODS: Fourteen horses diagnosed clinically with acute, subacute or chronic EGS were examined and quantitative EMG performed. Previously published data on healthy horses and horses with proven lower motor neuron disease (LMND) were used as controls. In 8 horses post mortem examination was performed, and in 7 muscle biopsies of the lateral vastus muscle underwent histopathology and morphometry. RESULTS: Clinical electrophysiological evidence of neuropathy was present in 12 horses. Analysis of data from the first 4 horses resulted in 95% confidence intervals (CI) of nontransformed data for motor unit action potential (MUP) duration in subclavian, triceps and lateral vastus muscle of 11.0-13.7, 14.8-20.3 and 12.2-17.2 msecs, respectively, and for MUP amplitude 291-453, 1026-1892 and 957-1736 microV, respectively. For number of phases the 95% CI was 3.6-4.4, 2.9-3.6 and 2.9-3.4, respectively, and for number of turns 5.0-6.5, 4.3-5.3 and 3.7-4.6, respectively. No changes in duration of insertional activity were measured. Pathological spontaneous activity was observed in all horses. EGS as evidenced by degenerative changes in the autonomic ganglia in combination with minor degenerative changes of the spinal lower motor neurons was observed on post mortem examination in all 8 available autopsies. In muscle biopsies of 4 out of 7 horses changes consistent with slight neurogenic atrophy were found. CONCLUSIONS AND POTENTIAL RELEVANCE: EMG results demonstrated the presence of a neuropathy of skeletal muscles in all horses suspected to have EGS. The combination of clinical and electrophysiological evidence may aid differential diagnosis of neurogenic disease in cases of weight loss and colic.  相似文献   

6.
Reasons for performing study: While previous studies have demonstrated an association between equine grass sickness (EGS) and the presence of Clostridium botulinum within ileal contents and faeces, no such associations with other intestinal‐derived anaerobic bacteria have been extensively investigated. Hypothesis: The prevalence of C. perfringens in the ileal contents and faeces of EGS horses is greater than control horses; the detection of C. perfringens in faeces by ELISA could be diagnostically beneficial in a clinical setting. Methods: The prevalence of C. perfringens in faeces from EGS horses and healthy grazing control horses was determined by both selective culture and ELISA to permit both validation of the ELISA and inter‐group comparisons. Additionally, the prevalence of C. perfringens (ELISA) in ileal contents from EGS horses was compared with that for control horses with nongastrointestinal disease. Finally, the prevalence of C. perfringens (ELISA) in faeces from EGS cases was compared with that from both horses with which they shared pasture at the time of disease onset and non‐EGS colic horses. Results: When compared with culture, the ELISA had a sensitivity and specificity of 86 and 98%, respectively. The prevalence of C. perfringens in faeces as determined by both culture and ELISA was significantly higher (P<0.001) for EGS horses (7/9 and 15/37, respectively) than for healthy grazing controls (0/60 and 1/74, respectively). The prevalence of C. perfringens in ileal contents from EGS horses (5/10) was greater than that for horses with nongastrointestinal disease (1/12) at a level that approached significance (P = 0.056). EGS cases had a significantly greater prevalence of C. perfringens in faeces (15/37) than co‐grazing horses (1/18) and colic (1/16) horses. The specificity (93%) and PPV (94%) of the detection of C. perfringens by ELISA on faecal samples in relation to disease status (EGS compared with colic horses) was good. Sensitivity (41%) and NPV (39%) were poor. Conclusions and potential relevance: The use of a commercial ELISA to detect faecal C. perfringens may be diagnostically beneficial when differentiating EGS cases from colic cases, although further work is required to fully evaluate its potential.  相似文献   

7.
Equine grass sickness (EGS) is a neurodegenerative disease affecting grazing equids of which a single case of the chronic clinical presentation has previously been reported in a Przewalski's horse (Equus ferus [caballus] przewalskii). A group of 8 Przewalski's horses were moved to a new enclosure, recently vacated by a group of 4 Eastern kiang (Equus kiang holdereri) that showed no evidence of disease. After 23 days the first Przewalski's horse showed clinical signs of acute EGS including flank sweating, belly kicking, rapid loss of body condition, cessation of faecal passage, nasogastric reflux and mouthing water. It was subjected to euthanasia within 48 h due to lack of therapeutic response. Within 24 h of this first case developing clinical signs, a further 5 Przewalski's horses showed similar clinical signs of acute EGS and were subjected to euthanasia. Post mortem examinations confirmed acute EGS, with all animals demonstrating typical chromatolysis, cytoplasmic hypereosinophilia, cellular swelling, vacuolation, pyknosis and loss of nuclei in approximately 90% of neurones in the cranial cervical and cranial mesenteric ganglia and myenteric and submucosal plexi of the ileum. Two Przewalski's horses within the group showed no clinical signs of disease. No single pathogen was identified as the causal agent, but the epidemiological pattern of the outbreak was typical for that previously reported for acute EGS in domestic equids. All affected animals and the 2 surviving Przewalski's horses had low antibody titres to Clostridium botulinum type C. This is the first report of acute EGS in a herd of Przewalski's horses.  相似文献   

8.
To determine whether urinalysis can aid the diagnosis of equine grass sickness, samples of urine from 15 horses with acute grass sickness, eight horses with subacute grass sickness, 17 co-grazing horses and 17 stabled control horses were analysed. The samples from all of the horses with grass sickness had a significantly higher specific gravity, higher protein and creatinine concentrations and a significantly lower pH; the samples from the horses with acute grass sickness also had significantly higher glucose concentrations. These differences may support a diagnosis of grass sickness but they are not pathognomonic for the disease.  相似文献   

9.
Small intestine was taken from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold of 25 horses, 9 with acute grass sickness (AGS), 12 with subacute grass sickness (SAGS) and 12 with chronic grass sickness (CGS). The motility in the samples was measured isometrically either within 1 h of death or after storage for 24 h at 4°C.In control tissue, noradrenaline produced contractions of muscle strips which did not involve a muscarinic cholinergic mechanism and which were unaffected by the 1 antagonist prazosin but were blocked by the 2 antagonist yohimbine. Pretreatment with the antagonist phentolamine prevented the contractile response to noradrenaline and the background contractions either continued at a reduced rate and amplitude or were abolished after a few minutes. Thus, following blockade, noradrenaline reduced the background contraction rate by an effect on inhibitory adrenoceptors. The rate of background contractions in duodenal preparations was significantly greater than that in control ileal preparations.Although cold storage for 24 h caused a reduction in the background contraction rates of the control preparations, there was no effect on the contractile responses to noradrenaline, the associated pharmacology being similar to that of fresh tissue. This suggests that noradrenaline-evoked contraction was not dependent on enteric neural elements.The response to noradrenaline by grass sickness-affected tissue was generally similar to that of tissue from control horses, with an immediate contraction which was 2 sensitive. The contractile response to noradrenaline after propranolol was significantly reduced in the CGS group and there were significant differences between the AGS, CGS and control groups. There was a significant difference between the ileal preparations from the control and SAGS groups in their response to noradrenaline following pretreatment with propranolol.  相似文献   

10.
This study compares quantitatively the microbiota of the gastrointestinal tract of healthy horses with that of horses with equine grass sickness (EGS). Faecal and ileal samples were cultured quantitatively on selective and non-selective media. Confirmed anaerobes were identified to species level.Overall faecal counts gave a ratio of aerobes:anaerobes of approximately 1:1. However, the mean counts in healthy horses of 4.4x10(8) aerobes:3.7x10(8) anaerobes per gram wet weight were different from counts in EGS (means were 10-100-fold higher), with statistically significant differences for the anaerobes (p=0.04). There were 10-100-fold more anaerobic cocci in EGS samples compared to healthy controls. Most of the seven species of anaerobic cocci were found in both healthy horses and EGS. Differences in clostridia isolated between health and disease were notable: fourteen species were isolated from EGS cases, compared to only one (C. bifermentans) in controls. The mean faecal clostridial counts in chronic disease were higher than in controls (10-fold) and in acute EGS (100-fold). In contrast, mean counts for ileal samples from acute cases, showed a 10-fold increase for clostridia compared to 1000-fold reduction in chronic cases (compared to faecal counts). Results indicate an increase in the bacterial numbers in the GI tract of animals with EGS compared to the controls and clostridia are prominent in EGS. Whether the increase in clostridia is the cause of GI stasis or a consequence remains uncertain.  相似文献   

11.
To test the hypothesis that equine grass sickness may be associated with the ingestion of cyanogenic glycosides from white clover (Trifolium repens), the concentrations of whole blood cyanide, and plasma and urinary thiocyanate, the main metabolite of cyanide, were measured in 12 horses with acute grass sickness and 10 horses with subacute grass sickness, and in 43 control horses, of which 21 were co-grazing with cases of acute grass sickness, 12 grazed pastures where grass sickness had not been reported, and 10 were stabled horses. The healthy horses which grazed with cases of acute grass sickness had higher concentrations of blood cyanide, and plasma and urinary thiocyanate than the other control horses, consistent with an increased exposure to cyanogens. The horses with grass sickness had no evidence of a recent intake of cyanogens, but may have been exposed to increased levels of cyanogens before they became anorexic.  相似文献   

12.
Equine grass sickness (EGS; equine dysautonomia) is a polyneuronopathy affecting both the central and the peripheral nervous systems of horses. As the name implies, EGS almost exclusively affects grazing horses, resulting in the development of a characteristic array of clinical signs, most of which can be attributed to neuronal degeneration in the autonomic and enteric nervous systems. Varying disease severities occur, largely determined by the extent of neuronal degeneration in the myenteric and submucous plexuses of the enteric nervous system. Extensive neuronal degeneration, as seen in acute and subacute forms of EGS, results in intestinal dysmotility, the severity of which is incompatible with survival. In comparison, a proportion of chronic forms of EGS, characterised by less severe neuronal degeneration, will survive. Despite extensive research efforts since EGS was first reported over 100 years ago, the precise aetiology remains elusive. This article reviews much of the scientific literature on EGS, covering epidemiology, pathology, diagnosis, treatment and aetiological hypotheses.  相似文献   

13.
This report concerns 2 horses that suffered typical clinical signs of atypical myopathy (AM) and equine grass sickness (EGS) concurrently. Clinical details and pathological lesions of the cases are described. EGS and AM are relatively rare diseases and the concurrency of the diseases in the same animals is therefore considered unlikely to be a coincidence. However, it is not suggested that the evidence shows a common aetiology but rather the existence of common predisposing causes.  相似文献   

14.
REASONS FOR PERFORMING STUDY: Equine grass sickness is a dysautonomia characterised by widespread destruction of autonomic ganglia, resulting in the clinical signs of dysphagia, constipation, profuse sweating, tachycardia, rhinitis sicca and high mortality rate. Rhinitis sicca is a common finding in horses with the chronic form and we have postulated that alterations in autonomic innervation of the nasal mucosa might underlie this clinical presentation. OBJECTIVES: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal marker protein gene-product 9.5 (PGP 9.5; ubiquitin) and the intermediate neurofilaments (PAN-N; neurorfilaments L, M and H) in the nasal mucosa of normal horses (n = 10) and horses with EGS (n = 18; acute n = 8, subacute n = 3, chronic n = 7) was assessed. METHODS: Innervation density and distribution was investigated in the different groups using standard immunohistochemical techniques. RESULTS: Significant differences were noted when comparing the density and distribution of nerve fibres immunoreactive for PGP 95 and PAN-N, with PGP 95 consistently giving better staining in all groups and at all sites in the nasal mucosa. An apparent increase in the density of innervation was noted for acute vs. normal cases. A significant reduction in the density of innervation was noted only with PAN-N when comparing normal horses and acute cases with the chronic group (P < 0.05). CGRP and SP immunoreactive nerve fibres were typically most abundant in the epithelial and subepithelial layers, but the quality of staining and nerve fibre density was greater for SP, achieving significant difference in several comparisons. The density of innervation for SP was significantly reduced in the chronic group compared to the normal and acute groups (P < 0.01). A significant decrease was noted for CGRP only for the acute and chronic groups (P<0.05). CONCLUSIONS: These results demonstrate a reduction in the expression of the sensory neuropeptides in nasal mucosal innervation as a consequence of equine dysautonomia, and may underlie the clinical presentation of rhinitis sicca noted with this disease. POTENTIAL RELEVANCE: Nasal biopsy may be of use in antemortem diagnosis of grass sickness and identification of mucosal denervation; and might also be useful in the treatment of rhinitis in EGS cases.  相似文献   

15.
The aetiology of equine grass sickness (EGS) is still unknown. There is increasing evidence that toxicoinfection with Clostridium botulinum type C is involved. Epidemiological evidence shows that resistance to EGS can occur in older horses and those that have been on a particular pasture for longer or have been in prior contact with the disease. This resistance may be in the form of an immune response to the aetiological agent. Levels of systemic antibodies to the surface antigens of C. botulinum type C (using the closely related and safe C. novyi type A as a phenotypic marker) and to the botulinum type C neurotoxin (BoNT/C) were investigated in horses with and without EGS. Horses with grass sickness were found to have significantly lower levels of systemic IgG to both surface antigens and BoNT/C. Horses with low levels of systemic immunity to these antigens may be more susceptible to developing EGS. There were no significant differences in antibody levels between the different categories of EGS, suggesting systemic immunity to C. botulinum type C does not play a significant role in influencing the severity of the disease. However, horses that had been in contact with EGS or that were grazing land where it had occurred frequently in the past had significantly higher antibody levels to these antigens. These horses may have been exposed to subclinical doses of C. botulinum type C and BoNT/C, resulting in the production of a protective immune response against the putative aetiological agent. This finding is of potential significance for the prospect of prevention of EGS by vaccination against C. botulinum type C.  相似文献   

16.
Equine grass sickness (EGS) occurs mainly in Great Britain, but has once been reported in Hungary. The stud which was affected by EGS in 2001 had no new cases until 2009/10, when 11 of 60 and five of 12 one- to three-year-old colts died or were euthanased due to EGS. Following a few hours in the high-risk field during the winter of 2010/11 further four cases of acute EGS were noted among these horses. The affected horses showed somewhat different clinical signs compared with the cases reported in Great Britain. Histopathological findings in these horses were consistent with EGS. In most examined cases carbofuran, a carbamate was found in the liver by toxicological examination, and it is postulated that carbofuran may influence the immune system and therefore predispose the horses to develop EGS. Carbamates are thought to cause a delayed neurotoxicity in human beings. Further studies are needed to clarify the potential role of carbamates in EGS.  相似文献   

17.
REASONS FOR PERFORMING STUDY: The reasons why equine grass sickness (EGS) recurs on premises are unknown and, consequently, practical methods for reducing the risk of recurrence are not available. OBJECTIVES: To identify risk factors associated with recurrence of EGS on premises and to gain possible insights into the pathogenesis of the disease. METHODS: Data on disease history and risk factors were collected by postal questionnaire from premises with EGS cases between 1st January 1997 and 31st December 2001. Data on variation in rates of recurrence of EGS for different risk factors were analysed using Poisson regression analysis. RESULTS: Of 509 premises contacted, 305 (60%) returned useable questionnaires and 100 of these (33%) were classified as 'recurrent' premises. An overall median incidence rate for EGS of 2.1 EGS incidents/100 horses/premises/year was recorded. There was an increased rate of recurrence with higher numbers of horses, presence of younger animals, stud farms and livery/riding establishments, loam and sand soils, rearing of domestic birds and mechanical droppings removal. The rate of recurrence decreased with chalk soil, cograzing ruminants, grass cutting on pastures and removal of droppings by hand. Several statistically significant interactions were identified. CONCLUSIONS: Many of the findings are consistent with the theory that EGS is a toxico-infectious form of botulism. Several of the significant factors identified may directly or indirectly relate to soil disturbance and consequent soil contamination of grass, thereby increasing the rate of exposure of grazing horses to Clostridium botulinum, which resides in soil. Potential relevance: Identification of potentially modifiable risk factors may, ideally following validation in appropriately designed, controlled and randomised intervention studies, lead to practical measures to reduce the incidence of EGS on previously affected premises.  相似文献   

18.
In an attempt to compare the equine grass sickness as reported in Europe with that described in the Republic of Colombia, sera from horses experiencing grass sickness in Scotland were used in neutralisation tests with Clostridium perfringens type A enterotoxin. The sera, from acute and chronic cases of the disease, failed to neutralise either crude or partially-purified enterotoxin. Neither were precipitin lines formed when the sera were treated against the toxin in immunoelectrophoresis. These results suggest that grass sickness in Europe and the equine disease in Colombia have a different aetiology.  相似文献   

19.
Serum total lipids, lipoprotein fractions, triglycerides, cholesterol, phospholipids and free fatty acids were measured in horses with acute, subacute and chronic grass sickness (equine dysautonomia) and in colic cases. The values were compared with those of normal grazing and stabled horses. A marked individual variation occurred, but total lipids, triglycerides and free fatty acids were significantly higher than normal in grass sickness and colic cases with cholesterol was significantly higher than normal in grass sickness cases only. Pre-beta lipoprotein was significantly increased in colic and subacute grass sickness although all abnormal groups showed this fraction which was absent from normal horses. The percentage of alpha 2b lipoprotein was significantly higher in colic and grass sickness. The changes described are typical of those occurring in fat mobilisation in the horse and are considered to be due to a number of factors including decreased food intake, cortisol and catecholamine release and insulin resistance.  相似文献   

20.
REASONS FOR PERFORMING STUDY: The gastrointestinal pacemaker cells, the interstitial cells of Cajal (ICC), have been implicated in several human gastrointestinal dysmotility syndromes. Recently, the involvement of these cells in equine gastrointestinal diseases has been investigated in cases of equine grass sickness where a significant reduction in ICC density was observed. OBJECTIVE: To investigate ICC density in equine obstructive gastrointestinal disorders using immunohistochemical labelling methods. METHODS: Intestinal samples were analysed from 44 horses undergoing exploratory surgery for colic and from 11 control animals subjected to euthanasia for conditions not related to the gastrointestinal tract. Immunohistochemical labelling of ICC was carried out using an anti-c-Kit antibody. Two independent observers assessed ICC density using a semiquantitative grading system. RESULTS: There was a significant reduction in ICC density in horses with large colon disorders compared to the controls (P<0.01). Horses with strangulating lesions of the small intestine showed no difference when compared to the controls. CONCLUSIONS: There was a reduction in ICC density in horses with large intestinal disorders. POTENTIAL RELEVANCE: The reduction in ICC density may be associated with the clinical findings as well as recurrent colic episodes observed in a number of these cases. This immunohistochemical study provides a basis for future functional electrophysiological investigations to determine the precise effect of ICC reduction on equine intestinal motility.  相似文献   

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