PORCINE DERMATITIS I NEPHROPATHY SYNDROME (PDNS) U REGIJAMA GDE JE KLASIČNA KUGA SVINJA ENDEMIČNO PRISUTNA

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1 ВЕТЕРИНАРСКИ ЖУРНАП РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska 139 UDK 619:636.4: R. Došen 1, J. Prodanov, T. Petrović, I. Pušić PORCINE DERMATITIS I NEPHROPATHY SYNDROME (PDNS) U REGIJAMA GDE JE KLASIČNA KUGA SVINJA ENDEMIČNO PRISUTNA Kratak sadržaj Dermatitis nefritis sindrom svinja (PDNS) je oboljenje koje se javlja uglavnom kod zalučene prasadi i tovljenika. Prvi put je bolest opisana u Engleskoj godine, a ustanovljena je u gotovo svim zemljama sa razvijenom svinjarskom industrijom. Za dermatitis nefritis sindrom karakteristične su uglavnom promene na koži i bubrezima. lako ima malu prevalencu (>1), bolest je značajana pre svega sa diferencijalno-dijagnostičkog aspekta. U regionima gde je klasična kuga svinja (KKS) endemski prisutna, dijagnostički je teško razlikovati ove dve bolesti, pa mogu nastatiti značajne ekonomske štete. Cilj rada je bio da se ukaze na razlike u epidemiologiji, kliničkoj slici, patologiji ove dve bolesti, kao i značaj laboratorijskog ispitivanja u postavljanju pravovremene i tačne dijagnoze. Kao materijal za ispitivanja koristili smo obolele svinje iz seoskih domaćinstava u regijama gde je KKS bila endemično prisutna u periodu od do godine, a metode koje smo koristili su bile: analiza epizootioloških, kliničkih i obdukcijskih protokola, ELISA antigen za virus KKS, PCR tehnika. U radu je opisana epidemiologija, klinička slika, patologija, kao i ustanovljene razlike koje su vezane za ove dve bolesti. U ispitivanom periodu smo PDNS ustanovili u 15 naseljenih mesta kod ukupno 28 svinja. U 9 ispitanih slučajeva dijagnoza je postavljena na osnovu kliničke i patomorfološke slike, niske prevalence oboljenja i potvrde nakon laboratorijskog ispitivanja, a u 13 slučajeva je bilo neophodno, zbog epizootiološke situacije, laboratorijskim ispitivanjem isključiti i infekciju virusom KKS. Na osnovu rezultata istraživanja možemo zaključiti da istovremeno prisustvo PDNS i KKS virusa komplikuje pravovtemeno postavljanje tačne dijagnoze, te mogu nastati značajne ekonomske stete. Ključne reči: cirkovirus, PDNS, klasična kuga svinja, epidemiologija. R. Došen 1, J. Prodanov, T. Petrović, I. Pušić PORCINE DERMATITIS AND NEPHROPATHY SYNDROME (PDNS) IN AREA WITH ENDEMIC PRESENCE OF CLASSICAL SWINE FEVER (CSF) Summary ' Dermatitis nephritis swine syndrome (PDNS) is a disease that is usually found among the weaned piglets and fattening pigs. For the first time it was described in England in It was discovered in almost all the countries with developed pig production. Changes on skin and kidneys are characteristic for dermatitis nephropathy syndrome. Although its prevalence is low (>1), the disease is important, first of all for differential diagnostic aspect. In regions where CSF is endemically present, it is hard to differentiate these two diseases, so important economic losses may be expected. The aim of this research was to point on differences in epidemiology, clinical picture, pathology of these two diseases, and stress the importance of laboratory examination for Mr sc. vet. Radoslav Došen, istraživač saradnik; mr sc. vet. Jasna Prodanov, istraživač saradnik; dr sc. vet. Tamaš Petrović, naučni saradnik; mr sc. vet. Ivan Pušić, istraživač saradnik, svi iz: Naučni institut za veterinarstvo "Novi Sad", Rumenacki put 20, Novi Sad, Srbija M.Sc. Radoslav Došen; M.Sc. Jasna Prodanov; Ph.D. Tamaš Petrović; M.Sc. Ivan Pušić; Scientific Veterinary Institute "Novi Sad", Rumenacki put 20, Novi Sad, Serbia.

2 140 ВЕТЕРИНАРСКИ ЖУРНАЛ РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska giving timely and accurate diagnosis. Material used for this investigation were the pigs from farms in the regions where CSF was endemically present in period 2001 to 2006, and the following methods were used: analyses of epizootiological situation, clinical and post mortem protocols, ELISA antigen test for CSF virus, and PCR technique. In the work are described epidemiology, clinical picture, pathology and the differences between these two diseases. During the research PDNS was discovered in 15 settlements in 28 pigs. In 9 cases a diagnosis was given based on clinical and pathomorphologic picture, low prevalence and a confirmation after laboratory examination, while in 13 cases, due to epizootiologic situation, it was necessary to do laboratory examination and exclude the possibility of infection with CSF virus. Based on these results it may be concluded that simultaneous presence of PDNS and CSF makes it difficult to give timely and accurate diagnosis, what may cause significant economic losses. Key words: circovirus, PDNS, classical swine fever, epidemiology. UVOD Dermatitis i nefropatija sindrom svinja ustanov- Ijen je gotovo u svim zemljama sa razvijenom svinjarskoin industrijom (Drolet et al., 1999; Saoulidis et al., 2002; Segales, 2002; Segales et al. 1998; Thomson et al. 2002). Međutim, ovo oboljenje kod nas do sada nije dijagnostikovano niti opisano. lako je ovaj sindrom u literaturi opisan još godine, kao proliferanvni glomerulonefritis što bi moglo da predstavlja i najranije saopštenje, od tada je različito anvano od strane brojnih istraživača: "Porcine Dermatitis and Nephropathy Syndrome (PDNS)" (Drolet et al., 1999; Duran et al., 1997; Rosell et al., 2000; Segales et al., 1998; Smith et al., 1993; Van Halderen et al., 1995), "Dermatitis/Glomerulo-Nephropathy Syndrome" (Kavanagh, 1994), "Glomerulo- Nephiopathv Syndrome" (Higgins, 1993), spontani (prirodni, neposredni) glomerulonefritis (Bourgault and Drolet, 1995), sistemski nekrotični vaskulitis glomerulonefritis (Helie et al., 1995), "Porcine Immune Complex Glomerulonephritis Dermatitis Syndrome" (Sierra et al., 1997) i kao kutani sistemski nekrotizuajuci vaskulitis kod svinja (Thibault et al, 1998). Klinicka i patomorfoloska slika oboljenja može znacajno da varira, pri čemu su promenama najčešće zahvaceni koža i bubrezi. Smatra se da u osnovi ovog sindroma leži sistemski nekrotizirajući vaskulitis (Thomson et al., 1998). Tačna patogeneza nije razjašnjena ali ustanovljene lezije i imunopatološka zapažanja drugih autora ukazuju da III tip preoset- Ijivosti može imati odredenu ulogu u etiologiji oboljenja. U našoj zemlji bolest do sada nije dijagnostikovana niti opisana. lako je prevalenca bolesti veoma niska (>1%), oboljenje je posebno znacajno sa diferencijalno dijagnostičkog aspekta, pre svega kad je u pitanju klasična kuga svinja (KKS). Preliminarni izveštaj o patološkim nalazima je već objavljen u formi abstrakta na konferenciji epizootiologa u Srbiji (Došen et al., 2005). CILJ RADA U regionima gde je KKS endemski prisutna, diferencijalno dijagnostički je teško razlikovati ova dva oboljenja, i usled toga mogu nastatiti značajne ekonomske štete. Cilj rada je bio da se ukaze na postojeće razlike u epidemiologiji, kliničkoj slici, patologiji ove dve bolesti, kao i značaj laboratorijskog ispitivanja u postavljanju pravovremene i tačne dijagnoze. MATERIJAL I METODE Materijal za ispitivanja predstavljale su svinje poreklom iz seoskih domaćinstava u regijama gde je ustanovljeno da je KKS bila endemično prisutna u periodu od do godine. U cilju diferencijacije ova dva oboljenja primenjene su sledeće metode ispitivanja: analiza epizootioloških, kliničkih i obdukcijskih protokola, imunoenzimski test za ustanovljavanje prisustva virusa KKS u tkivu (ELISA

3 ВЕТЕРИНАРСКИ ЖУРНАЛ РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska 141 antigen) i tehnika lančane reakcije polimeraze (PCR tehnika). U radu je opisana epidemioologija, klinička slika, patologija, kao i ustanovljene razlike koje su vezane za ove dve bolesti. REZULTATI ISPITIVANJA U epidemiologiji PDNS oboljenja treba istaći nekoliko činjenica koje su značajne u dijagnostici oboljenja. Bolest se javlja uglavnom kod zalučene prasadi i svinja u predtovu i tovu. Obično oboli samo jedna ili dve svinje u oboru ili dvorištu (niska prevalenca, >1%). Pored kjiničke slike i patomorfološkog nalaza, ovaj podatak je od izuzetnog značaja u diferencijalno4lijagnostickom postupku. Za razliku od KKS, u zapatu svinja koji nije vakcinisan, oboljenje se najčešće ustanovljava kod tovljenika, a da se pri tome ne prenosi na prasad na sisi ili zalucenu prasad u istom dvorištu. Pored toga, treba imati u vidu da od PDNS-a mogu oboljeti i svinje koje su vakcinisane protiv KKS (konvencionalna vakcina, Kina soj virusa). Klinička slika U okviru naših epizootioloških i kliničkih ispitivanja, kod oboljelih svinja ustanovljeni su sledeći klimcki simptomi: apatija, somnolentnost, svinje ne uzimaju hranu a ponekad i kašlju. Sporadično se kod svinja može ustanoviti redak izmet, žute boje, a u izmetu se mogu videti delovi nesvarene hrane. Posle nekoliko dana ustanovljava se egzantem na koži, pri čemu kašalj i proliv dobijaju na intenzitetu. Oboljele svinje mogu biti febrilne (40.0 do 42.0 C). Blaze oboljele svinje mogu pokazivati samo kožne lezije, pri čemu mogu biti afebrilne i živahne. Veći broj ovih svinja se na kraju oporavi bez terapijskog tretmana. U akutnoj fazi oboljenja ustanovljene su lezije na kozi koje su se karakterisale time sto su bile okiugle do nepravilne, crvene do tamno crvene (Ijubičaste) makule i papule, koje ponekad koalesciraju i formiraju velike, nepravilne pege, krugove. Vremenom, lezije su prekrivaju tamne kraste i postepeno se povlače ostavljajući ponekad i ožiljak. Ustanovili smo i slučajeve sa nekrozom promenjenih delova kože. Smatra se da distribucija kožnih lezija može u najvećem broju slučajeva biti tipična za ovu bolest, a promene se nalaze najčešće na koži u predelu perinealne regije, oko zadnjih ekstremiteta, ventralnih delova abdomena, toraksa, kao i na koži ušnih školjki. Obdukcioni nalaz Patomorfološkim pregledom uginulih jedinku pored spolja vidljivih promena na koži, ustanovljena su i podrucja sa subkutanim krvarenjima, sa sličnom distribucijom kao kod kožnih lezija. Čest nalaz je bio subkutani edem, koji je naročito zahvatao donje delove ekstremiteta i ventralne delove abdomena. Periferni limfni čvorovi su bili generalno uvećani (edem). Čest nalaz je bila i serozna ili serokrvava tečnost u abdominalnoj i pleuralnoj duplji, kao i u perikardu. Na sluzokoži želuca ponekad smo nalazili ulkuse u predelu fundusa. Ekimotična krvarenja su bila ponekad ustanovljena na seroznoj površini tankog creva, debelog creva i kapsuli slezine. Isto tako, u pojedinim slučajevima zabeleženo je uvećanje i kongestija mezenterijalnih limfnih čvorova. Najvažnije patomorfološke promene su ustanovljene na buburezima, što je u saglasnosti sa nalazima drugih autora. Bubrezi su bledi i nekoliko puta uvećani u poredenju sa zdravim. Na površini bubrega (ispod bubrežne kapsule), nalaze se multiple petehije, dok su na preseku krvarenja vidljiva najčešće u celom korteksu, te sam bubreg spolja liči na jaje ćurke. Rezultati laboratorijskog ispitivanja U ispitivanom periodu smo PDNS ustanovili u 15 naseljenih mesta, kod ukupno 28 svinja. U regiji u kojoj je istovremeno bila dijagnostikovana i infekcija svinja virusom KKS, organi poreklom od oboljelih jedinki su obavezno laboratory ski ispitivani i prisustvo antigena virusa KKS (ELISA test) i cirkovirus tip 2 (PCR tehnika). Pregledom organa i tkiva ni u jednom ispitivanom slučaju nije ustanov- Ijen antigen virusa KKS, dok je u 17 od ukupno 25 slučajeva ustanovljeno prisustvo cirkovirusa tipa 2 (PCV2). U organima poreklom od 8 svinja nije detektovano prisustvo ni jednog ispitivanog virusa (Tabela 1).

4 142 ВЕТЕРИНАРСКИ ЖУРНАЛ РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska Tabela 1. Rezultati laboratoryskog ispitivanja svinja kod kojih je ustanovljen PDNS i koje potiču iz regije u kojoj je istovremeno bio prisutan virus KKS aseljeno mesto br. Virus KKS Cirkovirus UKUPNO U regiji gde nije bila prisutna infekcija svinja sa (PCR tehnikom), na prisustvo cirkovirusa tipa 2, pri wrasom KKS, organe oboljelih svinja smo ispitali čemu su svi ispitani uzorci bili pozitivni (tabela br. 2). Tabela 2. Rezultati laboratoryskog ispitivanja svinja kod kojih je ustanovljen PDNS iz regije u kojoj nije bila prisutna infekcija sa virusom KKS Ispitivano naseljeno mesto Cirkovirus 1 A 1 2 B 1 3 c 3 4 D 1 5 E 1 6 F 1 7 G 1 8 H 1 9 I 1 UKUPNO 11 DISKUSIJA Britansko veterinarsko društvo (UK Pig Veterinary Society) je još godine upozorilo svoje članove da postoji ozbiljan problem u razlikovanju kliničke slike i patomorfoloških lezija koje se ustanovljavaju kod oboljelih od PDNS i KKS. Tom prilikom je istaknuto da je ovo naročito problem ukoliko se PDNS javlja kao oboljenje u epizootskoj (epidemicnqj) formi, koja je i dijagnostikovana kao problem u Velikoj Britaniji još od avgusta godine (Thomson et al., 2002). Na osnovu postignutih rezultata u našem istraživanju može se konstatovati da su epidemiologija, klinička slika i ustanovljene patomorfološke promene odgovarale opisima drugih autora (Drolet et al., 1999; Saoulidis et al., 2002; Segales, 2002). Medutim, za razliku od KKS, ovo oboljenje karakteriše niska prevalenca (>1%) (Segales, 2002). Jedan od važnih kliničkih znakova, naročito u akut-

5 ВЕТЕРИНАРСКИ ЖУРНАЛ РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska 143 noj fazi oboljenja jeste razvoj lezija na koži koje se karakterišu time što su okrugle do nepravilne, crvene do purpurne (tamno crvene, ljubicaste) makule i papule koje ponekad koalesciraju i formiraju velike, nepravilne pege i krugove (Segales et al., 1998; Saoulidis et al., 2002). Slučajevi u kojima je nastupio razvoj teških kožnih lezija, uglavnom su imali fatalni završetak. Smatra se da najveći broj ovih jedinki ugine u toku nekoliko dana nakon pojavljivanja kliničkih znakova (Drolet et al., 1999). Treba istaći da su u najvećem broju ispitanih slučajeva konstatovane patološke promene vezane za bubrege, koji su i nekoliko puta veći od zdravih. Thomson et al. (2002) je ustanovio da je kod oboljelih zalučenih svinja, svaki bubreg težio između 200 i 400g, u poređenju sa g kod većine bubrega poreklom od svinja istog uzrasta a koje nisu oboljele. U okviru naših istraživanja histopatološka ispitivanja nisu obavljena, ali su drugi autori pregledom delova promenjene kože ustanovili postojanje sistemskog nekrotizirajućeg vaskulitisa, većinom u krvnim sudovima malog dijametra, što je često bilo udruženo sa fokalnim dermalnim hemoragijama i nekrozom epiderma. U bubrežnom tkivu su ustanovljeni teški nekrotizirajući glomerulonefritis, glomerulama skleroza, intersticijalna inflamacija, fibroza i tubularna nekroza (Saoulidis et al., 2002). Postignuti rezultati laboratorijskog ispitivanja u okviru naših istraživanja ukazuju da je u najvećem broju slučajeva kod svinja oboljelih od virusa PDNS ustanovljeno prisustvo cirkovirusa tipa 2. Literatumi podaci ukazuju da su još od godine, brojna izbijanja PDNS virusa bila udružena sa multisistemskim sindromom slabljenja i kržljanja prasadi (Postweaning Multisystemic Wasting syndrome, PMWS), zajedno sa učešćem svinjskog cirkovirusa tipa 2 (Rosell et al., 2000). U slučajevima kada je bio izvršen pregled velikog broja svinja, PCV2 je bio ustanovljen primenom metode imunohistohemije u velikom procentu svinja oboljelih sa znakovima PDNS. Dalje, ustanovljeno je da je PDNS bio udružen sa PCV2 u Španiji, Francuskoj, Belgiji, Velikoj Britaniji, Holandiji, Argentini, Juznoj Koreji, Kanadi i Severnoj Americi. Antigen virusa, nukleinska kiselina PCV2 ili oba zajedno su dokazani u malom broju ispitanih svinja koje su imale PDNS znake (upoređujući to sa nalazima kod PMWS) (Segales, 2002). Diferencijalno dijagnostički druga oboljenja i stanja koja su udružena sa crvenim diskoloracijama kože uključuju KKS, afričku kugu svinja, crveni vetar, septikemičnu salmonelozu, infekciju sa Actinibacillus suis, stres sindrom, prolazni eritemi različite etiologije i drugi slučajevi koji su povezani sa bakterijskom septikemijom. Pored toga, oboljenja kao što su KKS, afrička kuga svinja i septikemična salmoneloza mogu uticati na razvoj nastanka promena na bubrezima koje su slične onima koje se ustanovljavaju kod PDNS oboljenja. Kao rezultat toga, PDNS se mora primarno diferencirati od KKS u Evropi i od septikemične salmoneloze u Severnoj Americi (Segales, 2002). U okviru naših istrazivanja u ispitivanom periodu PDNS je ustanovljen u 15 naseljenih mesta, kod ukupno 28 svinja. Neophodno je naglasiti da je u svim ispitivanim slučajevima dokazano i prisustvo cirkovirusa tipa 2 (PCV2). U ukupno 9 slučajeva dijagnozu je postavljena na osnovu kliničke i patomorfološke slike, niske prevalence i potvrde nakon laboratorijskog ispitivanja, dok je u 13 ispitanih slučajeva bilo neophodno, zbog epizootiološke situacije, laboratorijskim ispitivanjem isključiti i infekciju virusom KKS. Pri tome, u svim ispitivanim slučajevima nije ustanovljeno prisustvo antigen virusa KKS u uzorcima tkiva i organa. Konačno, u uzorcima organa i tkiva poreklom od 8 svinja laboratorijskim ispitivanjem nije ustanovljeno prisustvo ni jednog ispitivanog virusa, iako su klinička slika i patomorfološki nalaz ukazivali na PDNS. S obzirom na to da se, naročito u akutnoj fazi PDNS oboljenja, razvijaju lezije na koži, zatim, ekimotična i tačkasta krvarenja po serozi tankih i debelih creva i bubrezima, ovo oboljenje se može diferencijalno dijagnostički zameniti sa KKS oboljenjem. ZAKLJUČAK Na osnovu postignutih rezultata istrazivanja može se zaključiti da istovremeno prisustvo dva oboljenja (PDNS i KKS) u velikoj meri komplikuje pravovremeno postavljanje tačne dijagnoze usled čega mogu nastati značajne ekonomske štete. Zbog toga je neophodno u svim sumnjivim slučajevima laboratorijskim ispitivanjima isključiti infekciju virusom KKS. Za pravovremeno postavljanje tačne

6 144 ВЕТЕРИНАРСКИ ЖУРНАЛ РЕПУБЛИКЕ СРПСКЕ - Veterinary Journal of Republic of Srpska dijagnoze važno je imati u vidu određene karakteristike PDNS oboljenja: niska prevalenca oboljenja u zahvećenom zapatu, oboljevaju samo starije kategorije svinja, iako je u istom zapatu prisutna i prasad na sisi, i da se simptomi koji su slični KKS mogu javiri kod svinja kod kqjih je obavljena vakcinacija. U ovom poslednjem slučaju ne treba izgubiti iz vida da postoji opasnost da se bez saznanja proriv KKS vakcinišu i oboljele svinje, u penodu inkubacije, kao i jedinke koje su perzistentno inficirane KKS virusom. LITERATURA 1. Bourgault A. and Drolet R. (1995): Spon taneous glomerulonephritis in swine. J. Vet. Diagn. Invest. 7, Došen R., Ličina J., Petrović T., Polaček V. (2005): Dijagnostički značaj "porcine derma titis and nephropaty syndrome" (PDNS) u regionima gde je klasična kuga svinja (KKS) endemično prisutna. Zbornik referata i kratkih sadržaja, Jagodina, str Drolet R., Thibault S., D allaire S., Thomson J., Done S. (1999): Porcine dermatitis and nephropathy syndrome (PDNS): an overview of the disease. Swine Health Prod. 7(6): Duran C.O., Ramos-Vara J. A. and Render J.A. (1997): Porcine dermatitis and nephro pathy syndrome: a new condition to include in the differential diagnosis list for skin discolo uration in swine. Swine Health Prod. 5, Helie P., Drolet R., Germain M. C., Bourgault A. (1995): Systemic necrotising vasculitis and glomerulonephritis in grower pigs in south eastern Quebec. Can. Vet. J. 36, Higgins R. J. (1993): Glomerulo-nephropathy syndrome. Pig Vet J. 31, Kavanagh N. T. (1994): Dermatitis/glomemlonephropathy. Vet. Rec., 134, Rosell C. et al. (2000): Identification of porcine circovirus in tissues of pigs with porcine dermatitis and nephropathy syndrome. Vet. Rec. 146, Saoulidis K., Kyriakis S.C., Kennedy S., Lekkas S., Miliotis Ch. C., Allan G., Balkamos G. C. and Papoutsis P. A. (2002): First Report of Post-Weaning Multisystemic Was ting Syndrome and Porcine Dermatitis and Nephropathy Syndrome in Pigs in Greece. J. Vet. Med. B 49, Segales J. (2002): Update on postweaning multisystemic wasting syndrome and porcine dermatitis and naphropathy syndrome diagno stics. J Swine Health and Prod. 10(6): Segales J., Piella J., Marco E., Mateu De Antonio M., Espuna E. and Domingo M. (1998): Porcine Dermatitis and nephropathy syndrome in Spain. Veterinary Record 142, 483^ Sierra M. A., de la Mulas J. M., Molenbeek R. P., van Maanen J, Vos J. H., Quezada M. and Grays E. (1997): Porcine immune complex glomerulonephritis dermatitis (PIGD) syndro me. E.J.V.P. 3, Smith W. J., Thomson J. R. and Done S. (1993): Dermatitis/nephropathy syndrome of pigs. Vet Rec. 132, Thibault S., Drolet R, Germain M.C., D Allarie S., Larochelle R. and Magar R. (1998): Cutaneus andsystemic necrotizing vasculitis in swine.vet Pathol., 35, Thomson J. R., Higgins R. J., Smith W. J. and Done S. H. (1998): A review of the major pathological features of porcine immune complex glomerulonephritis and dermatitis syndrome in the United Kingdom. Proc IPVS Cong., Birmingham, UK, 15 (3): Thomson J. R., Higgins R. J., Smith W. J., and Done S. H. (2002): Porcine Dermatitis and Nephropathy syndrome. Clinical and Pathologiacl Features of Cases in the United Kingdom ( ). J. Vet. Med. A 49, Van Halderen A., Backer S.K., Wessels J.C., der Lugt J. J. (1995): Dermatitis/nephropathy syndrome of pigs. J S. Afr. Vet. Med. Assoc. 66,

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