Veterinary Pathology最新文献

{"title":"<i>Helicosporidium</i> sp. infection in a California kingsnake (<i>Lampropeltis californiae</i>): Spillover of a pathogen of invertebrates to a vertebrate host.","authors":"Javier Asin, April L Childress, Eva Dervas, Michael M Garner, Francisco A Uzal, James F X Wellehan, Eileen E Henderson, Anibal G Armien","doi":"10.1177/03009858241259179","DOIUrl":"10.1177/03009858241259179","url":null,"abstract":"<p><p><i>Helicosporidium</i> is a genus of nonphotosynthetic, green algae in the family <i>Chlorellaceae</i>, closely related to <i>Prototheca</i>. It is a known pathogen of invertebrates, and its occurrence in vertebrates has not been documented. A captive, 10-month-old, male, albino California kingsnake (<i>Lampropeltis californiae</i>) was submitted for necropsy. Gross examination revealed hemorrhagic laryngitis and a red mottled liver. Histologically, intravascular, intramonocytic/macrophagic and extracellular, eukaryotic organisms were observed in all tissues. These organisms stained positive with Grocott-Gomori methenamine silver and periodic acid-Schiff and were variably acid-fast and gram-positive. Ultrastructural analysis revealed approximately 4 µm vegetative multiplication forms and cysts with 3 parallel ovoid cells and a helically coiled filamentous cell. A polymerase chain reaction with primers targeting <i>Prototheca</i>, amplicon sequencing, and Bayesian phylogenetic analysis confirmed it clustered within <i>Helicosporidium</i> sp. with 100% posterior probability. The genus <i>Helicosporidium</i> was found to nest within the genus <i>Prototheca</i>, forming a clade with <i>Prototheca wickerhamii</i> with 80% posterior probability.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"978-982"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel missense variant in the <i>RELN</i> gene in sheep with lissencephaly and cerebellar hypoplasia.","authors":"Leah K Manning, Emily Winkenwerder, Louise Baskind, Katie L M Eager, Cali E Willet, Ben Porebski, Brendon A O'Rourke, Imke Tammen, Marina Gimeno, Pedro Pinczowski","doi":"10.1177/03009858241283501","DOIUrl":"https://doi.org/10.1177/03009858241283501","url":null,"abstract":"<p><p>Lissencephaly and cerebellar hypoplasia (LCH) represents a spectrum of congenital developmental malformations of the cerebral cortex and cerebellum, mostly occurring as inherited conditions caused by variants in an increasingly recognized number of genes. LCH has been identified in three Dorset-cross lambs with congenital neurological signs in Australia. Lambs were unable to walk and had reduced vision, and one lamb developed a hypermetric gait and intention tremors. Grossly, the lambs had diffuse pachygyria with reduction in white matter, mild bilateral ventriculomegaly of the lateral ventricles, and a markedly hypoplastic cerebellum. Histologically, there was disorganization of neurons within the cerebral cortex and hippocampus. The cerebellar vermis had disorganized, thin, and hypocellular gray matter with frequent ectopic Purkinje cells, while identifiable folia were largely absent within the hemispheres. Luxol fast blue stain and glial fibrillary acidic protein, neuronal nuclear protein, synaptophysin, and neuron-specific enolase immunohistochemistry confirmed the thickened, disorganized cerebral cortical gray matter and reduced white matter. Within the cerebellum, immunohistochemistry demonstrated marked dysplasia. Whole-genome sequencing analysis and prediction of variant effects identified a missense variant of interest in the candidate gene <i>reelin</i> (<i>RELN</i>; NC_040255.1:g.50288685C>T; NM_001306121.1:c.7088G>A; NP_001293050.1:p.(R2363H)) with a deleterious Sorting Intolerant from Tolerant (SIFT) score. Sanger sequencing identified that the variant segregated with LCH disease in the 3 affected individuals, their sire, and 6 unaffected flock members. The NP_001293050.1: p.(R2363H) substitution is predicted to decrease the stability of the protein (ΔΔG = -1.55 kcal/mol). Pathological and genetic findings are consistent with previously described phenotypes of <i>RELN</i> variants in Churra sheep, dogs, and humans.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"3009858241283501"},"PeriodicalIF":2.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized bone marrow assessment, risk variables, and survival in dogs with myelodysplastic syndrome and acute myeloid leukemia","authors":"Anna M. Meredith, Janet Beeler-Marfisi, Olaf Berke, Anthony J. Mutsaers, Dorothee Bienzle","doi":"10.1177/03009858241277982","DOIUrl":"https://doi.org/10.1177/03009858241277982","url":null,"abstract":"Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are heterogeneous neoplasms of hematopoietic stem cells that are challenging to diagnose, differentiate, and prognosticate. Cytogenetic and mutational analyses are useful in humans but unavailable for dogs, where diagnosis and classification still rely largely on hematologic and morphologic assessment. The objectives of this study were to apply a classification scheme to myeloid neoplasms and to assess outcome in relation to predictor variables. Keyword search of a laboratory database, application of sequential exclusion criteria, and consensus from 3 reviewers yielded 70 cases of myeloid neoplasia with hematology results, and cytologic (11), histologic (14), or both (45) types of marrow specimens. Based on blast percentage and morphology, 42 cases were classified as MDS and 28 as AML. Dogs with MDS had significantly lower body weights, hemoglobin concentrations and blood blasts, and higher red blood cell size variability and platelet numbers than dogs with AML. Estimates of median survival using Kaplan-Meier curves for dogs with MDS and AML were 384 and 6 days, respectively ( P &lt; .001). The instantaneous risk of death for dogs with MDS was approximately 5× lower than that of dogs with AML. Significant predictor variables of survival were body weight, white blood cell count, platelet count, and percent blood blasts ( P &lt; .05). Hazard ratios (HRs) derived from best-fitting Cox regression models were 1.043, 0.998, and 1.061 for increased neutrophils, decreased platelets, and increased blood blasts, respectively. Findings from this study suggest that hematologic and morphologic variables are useful to predict outcomes in myeloid neoplasia.","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"32 1","pages":"3009858241277982"},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal pathology in goats challenged with Clostridium perfringens type D strain CN1020 wild-type and its genetically modified derivatives","authors":"Eleonora L. Morrell, Mauricio A. Navarro, Jorge P. Garcia, Juliann Beingesser, Francisco A. Uzal","doi":"10.1177/03009858241273122","DOIUrl":"https://doi.org/10.1177/03009858241273122","url":null,"abstract":"Clostridium perfringens type D is the causative agent of enterotoxemia in sheep, goats, and cattle. Although in sheep and cattle, the disease is mainly characterized by neurological clinical signs and lesions, goats with type D enterotoxemia frequently have alterations of the alimentary system. Epsilon toxin (ETX) is the main virulence factor of C. perfringens type D, although the role of ETX in intestinal lesions in goats with type D enterotoxemia has not been fully characterized. We evaluated the contribution of ETX to C. perfringens type D enteric pathogenicity using an intraduodenal challenge model in young goats, with the virulent C. perfringens type D wild-type strain CN1020; its isogenic etx null mutant; an etx-complemented strain; and sterile, non-toxic culture medium. The intestinal tract of each animal was evaluated grossly, microscopically, and immunohistochemically for activated caspase-3. Both ETX-producing strains induced extensive enterocolitis characterized by severe mucosal necrosis, apoptosis, and diffuse suppurative infiltrates. No significant gross or microscopic lesions were observed in goats inoculated with the non–ETX-containing inocula. These results confirm that ETX is essential for the production of intestinal lesions in goats with type D disease. Also, our results suggest that the intestinal pathology of type D enterotoxemia in goats is, at least in part, associated with apoptosis.","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":"106 1","pages":"3009858241273122"},"PeriodicalIF":2.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitotic activity: A systematic literature review of the assessment methodology and prognostic value in feline tumors.","authors":"Christof A Bertram, Taryn A Donovan, Alexander Bartel","doi":"10.1177/03009858241239566","DOIUrl":"10.1177/03009858241239566","url":null,"abstract":"<p><p>Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"743-751"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology of \"double scale\" skin defect in farmed American alligators (<i>Alligator mississippiensis</i>) and the possible association with hepatic fibrosis.","authors":"Ilaria M Piras, Annemarie Bezuidenhout, Josué Díaz-Delgado, Deirdre Slawski, Pamela A Kelly","doi":"10.1177/03009858241238685","DOIUrl":"10.1177/03009858241238685","url":null,"abstract":"<p><p>\"Double scale\" is a poorly characterized skin defect of crocodilians that drastically reduces the economic value of crocodilian skin. This study investigated the morphology and pathogenesis of double scale in a ranching farm of American alligators (<i>Alligator mississippiensis</i>). We compared the histopathology of skin and selected organs (liver, lung, kidney, heart, spleen, intestine, and brain) of alligators with double scale against healthy control animals, together with serum and liver vitamin and mineral levels. Skin affected with double scale had statistically significant hyperkeratosis, epidermal atrophy, and increased basal cell degeneration compared with control alligators (<i>P</i> < .0001). Interestingly, all alligators with double scale had varying degrees of hepatic fibrosis. Feed analysis showed that alligators that had double scale and hepatic fibrosis had prolonged dietary exposure to high levels of vitamin A, iron, and copper. Serum analysis indicated that levels of zinc (<i>p</i> < .0001), copper (<i>P</i> < .05), and vitamin E (<i>P</i> < .002) were significantly lower in alligators with hepatic fibrosis and double scale compared with controls. Finally, immunohistochemical analysis of skin with double scale showed a marked reduction in immunolabeling with the zinc-binding protein metallothionein. These results suggest that zinc deficiency, in combination with other micronutrient anomalies, may play a role in the pathogenesis of double scale in alligators with liver fibrosis.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"815-828"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal alterations in cats (<i>Felis catus</i>) housed in shelters and affected by systemic AA-amyloidosis: Clinicopathological data, histopathology, and ultrastructural features.","authors":"Filippo Ferri, Silvia Ferro, Silvia Lucia Benali, Luca Aresu, Lorenza Muscardin, Federico Porporato, Francesco Rossi, Chiara Guglielmetti, Enrico Gallo, Carlo Palizzotto, Carolina Callegari, Stefano Ricagno, Maria Mazza, Luigi Michele Coppola, Gabriele Gerardi, Francesca Lavatelli, Serena Caminito, Giulia Mazzini, Giovanni Palladini, Giampaolo Merlini, Eric Zini","doi":"10.1177/03009858241257903","DOIUrl":"10.1177/03009858241257903","url":null,"abstract":"<p><p>AA-amyloidosis is frequent in shelter cats, and chronic kidney disease is the foremost cause of death. The aims were to describe kidney laboratory and microscopic findings in shelter cats with AA-amyloidosis. Cats were included if kidney specimens were collected post-mortem and laboratory data were available within 6 months before death. Renal lesions were evaluated with optical and electron microscopy. Mass spectrometry was used to characterize amyloid. Nine domestic short-hair cats were included; 4 females and 5 males with a median age of 8 years (range = 2-13). All cats had blood analyses and urinalyses available. Serum creatinine concentrations were increased in 6 cats and symmetric dimethylarginine was increased in all of the cats. All of the cats had proteinuria. Eight of 9 cats had amyloid in the medulla, and 9 had amyloid in the cortex (glomeruli). All cats had amyloid in the interstitium. Six cats had concurrent interstitial nephritis and 1 had membranoproliferative glomerulonephritis. All cats had extrarenal amyloid deposits. Amyloid was AA in each case. In conclusion, renal deposition of amyloid occurs in both cortex and medulla in shelter cats and is associated with azotemia and proteinuria. Renal involvement of systemic AA-amyloidosis should be considered in shelter cats with chronic kidney disease. The cat represents a natural model of renal AA-amyloidosis.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"771-782"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short beak and dwarfism syndrome among Pekin ducks: First detection, full genome sequencing, and immunohistochemical signals of novel goose parvovirus in tongue tissue.","authors":"Amal A M Eid, Mohamed A Lebdah, Sarah S Helal, Mohamed G Seadawy, Abdelgalil El-Gohary, Mohamed R Mousa, Ayman H El-Deeb, Fakry F Mohamed, Reham M ElBakrey","doi":"10.1177/03009858241249108","DOIUrl":"10.1177/03009858241249108","url":null,"abstract":"<p><p>Novel goose parvovirus (NGPV) is continuously threatening the global duck industry, as it causes short beak and dwarfism syndrome among different duck breeds. In this study, we investigated the viral pathogenesis in the tongue of affected ducks, as a new approach for deeper understanding of the syndrome. Seventy-three, 14- to 60-day-old commercial Pekin ducks were clinically examined. Thirty tissue pools of intestine and tongue (15 per tissue) were submitted for molecular identification. Clinical signs in the examined ducks were suggestive of parvovirus infection. All examined ducks had short beaks. Necrotic, swollen, and congested protruding tongues were recorded in adult ducks (37/73, 51%). Tongue protrusion without any marked congestion or swelling was observed in 20-day-old ducklings (13/73, 18%), and no tongue protrusion was observed in 15-day-old ducklings (23/73, 32%). Microscopically, the protruding tongues of adult ducks showed necrosis of the superficial epithelial layer with vacuolar degeneration. Glossitis was present in the nonprotruding tongues of young ducks, which was characterized by multifocal lymphoplasmacytic aggregates and edema in the propria submucosa. Immunohistochemical examination displayed parvovirus immunolabeling, mainly in the tongue propria submucosa. Based on polymerase chain reaction, goose parvovirus was detected in 9 out of 15 tongue sample pools (60%). Next-generation sequencing confirmed the presence of a variant goose parvovirus that is globally named NGPV and closely related to Chinese NGPV isolates. Novel insights are being gained from the study of NGPV pathogenesis in the tongue based on molecular and immunohistochemical identification.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"829-838"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage polarization in lymph node granulomas from cattle and pigs naturally infected with <i>Mycobacterium tuberculosis</i> complex.","authors":"Fernanda Larenas-Muñoz, Mohamed G Hamed, Inés Ruedas-Torres, José María Sánchez-Carvajal, Javier Domínguez, Francisco José Pallarés, Librado Carrasco, Irene M Rodríguez-Gómez, Jaime Gómez-Laguna","doi":"10.1177/03009858241231606","DOIUrl":"10.1177/03009858241231606","url":null,"abstract":"<p><p>Tuberculosis in animals is caused by members of the <i>Mycobacterium tuberculosis</i> complex (MTC), with the tuberculous granuloma being the main characteristic lesion. The macrophage is the main cell type involved in the development of the granuloma and presents a wide plasticity ranging from polarization to classically activated or pro-inflammatory macrophages (M1) or to alternatively activated or anti-inflammatory macrophages (M2). Thus, this study aimed to analyze macrophage polarization in granulomas from cattle and pig lymph nodes naturally infected with MTC. Tuberculous granulomas were microscopically categorized into four stages and a panel of myeloid cells (CD172a/calprotectin), M1 macrophage polarization (iNOS/CD68/CD107a), and M2 macrophage polarization (Arg1/CD163) markers were analyzed by immunohistochemistry. CD172a and calprotectin followed the same kinetics, having greater expression in late-stage granulomas in pigs. iNOS and CD68 had higher expression in cattle compared with pigs, and the expression was higher in early-stage granulomas. CD107a immunolabeling was only observed in porcine granulomas, with a higher expression in stage I granulomas. Arg1+ cells were significantly higher in pigs than in cattle, particularly in late-stage granulomas. Quantitative analysis of CD163+ cells showed similar kinetics in both species with a consistent frequency of immunolabeled cells throughout the different stages of the granuloma. Our results indicate that M1 macrophage polarization prevails in cattle during early-stage granulomas (stages I and II), whereas M2 phenotype is observed in later stages. Contrary, and mainly due to the expression of Arg1, M2 macrophage polarization is predominant in pigs in all granuloma stages.</p>","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"792-802"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139997565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brief history of the American College of Veterinary Pathologists (2009-2024).","authors":"Krista M D La Perle","doi":"10.1177/03009858241265038","DOIUrl":"10.1177/03009858241265038","url":null,"abstract":"","PeriodicalId":23513,"journal":{"name":"Veterinary Pathology","volume":" ","pages":"699-703"},"PeriodicalIF":2.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}