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In the original article, there was a mistake in the legend for Figure 3 as published. The legend of Figure 3 (g-l) is incorrect. The correct legend appears below. FIGURE 3 | Photomicrographs of cryosections of canine cervical (C8) dorsal root ganglion showing cannabinoid receptor 2- (CB2), glial fibrillary acidic protein- (GFAP), and CD31-immunoreactivity. (a–c) Stars indicate NeuroTrace labeled (a) dorsal root ganglion sensory neurons which were CB2 receptor negative (b), as well as the satellite glial cells (white arrows). (d–f) Stars indicate sensory neurons encircled by satellite glial cells (white arrows) which were GFAP-immunoreactive (e) and CB2 receptor negative. CB2 receptor immunoreactivity was expressed by Schwann cells and neuronal nuclei (open arrow). (g–i) The empty arrow indicates one neuronal axon that bifurcates (T-junction) in its central and peripheral portions (large white arrows). The small arrows indicate the nuclei of Schwann cells. (j–l) Open arrows indicate smooth muscle cells (vessel on the left) and pericyte-like cells (elongated and thin blood vessel on the right) showing CB2 receptor immunoreactivity (j).White arrows indicate endothelial cells showing CD31 immunoreactivity (k). Bar: a–f, j–l = 50μm; g–i = 100 μm. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.

Due to a long life span and a high economical and emotional value koi carp (Cyprinus carpio koi) is considered as a pet worldwide [1]. In this species descriptions of gonadal tumors exist since years [2], however their occurrence only recently represents a regular finding [1]. Given the difficulty to fit into histological classification and to assess the incidence of these tumours in koi populations, the present work aims to describe and classify gonadal tumours by using an immunohistochemical tissue microarray (TMA) technique. Seventeen cases of koi gonadal tumors collected in Belgium by a veterinary practitioner from 2014 to 2015 were included. They were evaluated according to the veterinary WHO classification [3] and characterized with an antibody panel (vimentin, CD117, AE1/AE3 cytokeratin, E-cadherin, PLAP) by using TMA technique. The koi carps were held in private ponds, their age ranged between 3 and 12 years and they were mostly females. The affected fish exhibited abdominal enlargement, lethargy and anorexia. Grossly, the neoplasms were white-yellowish with soft cystic areas and multifocal haemorrhages. Twelve tumors were histologically diagnosed as sex cord-stromal tumors (SCST), three were mixed germ cell sex cord-stromal tumors (MGCSCST), two were germ cell tumors (GCT), and one was a carcinoma. AE1/AE3 cytokeratin strongly labelled the carcinoma and several SCST, but rarely GCT; E-cadherin strongly labelled almost all SCST, MGCSCST and GCT. Vimentin and CD117 were only expressed in one SCST and one MGCSCST, respectively. Our results indicate sex cord-stromal cells as the main cells of origin in accordance with a recent paper [1]. The diagnosis of gonadal tumours in fish as in mammals is still difficult due to the variety of histological patterns of SCST and the occurrence of GCT and SCST that mimic epithelial gonadal tumours [3,4]. Furthermore, none of the immunohistochemical markers can be considered specific for a tumor type and the use of a wide panel of antibodies is suggested [4,5]. Nonetheless, the antibodies here tested confirmed to be immunoreactive in fish tissues [6] and therefore useful for refining the histological diagnosis.

Hernias of intervertebral discs are a common canine disease that is usually treated surgically. Recently, a histological scoring system for surgically removed canine intervertebral herniated discs has been developed by scoring the lesions of both the anulus fibrosus (AF) and the nucleus pulposus (NP). Since the proportion of AF and NP in the surgical samples may vary, depending on the surgical approach, the aim of this study is to grade separately the lesions in AF and NP and to modify the previously described scoring system adding three parameters: inflammation, mineralization and neovascularization. Possible association of the modified grading system with clinical parameters were statistically assessed. Herniated disc material was collected from 27 dogs. AF was present in 10/27 cases and was classified as grade 2 in 4 cases, grade 3 in 5 cases and grade 4 in 1 case. The NP was present in all 27 cases and was classified as grade 2 in 1 case, grade 3 in 5 cases, grade 4 in 9 cases and grade 5 in 12 cases. A statistically significant association was evidenced between short pre-operative period and higher grade of both the NP and of the AF (P

Due esemplari di salmerino (Salvelinus fontinalis) adulti, provenienti da allevamenti siti in Friuli Venezia Giulia, presentavano rispettivamente una neoformazione sottocutanea dorsale a livello dell’apertura opercolare e una neoformazione cutanea nella regione della mascella inferiore. Campioni di entrambe le neoformazioni sono stati fissati in formalina tamponata al 10% e processati secondo la metodica istologica di routine. La massa nella regione dorsale si presentava non demarcata, non capsulata, di 7,5 x 4,5 cm, non ulcerata, di consistenza parenchimatosa; in sezione si mostrava bianca lucida con multifocali aree emorragiche a margini irregolari. All'esame istologico si osservava una proliferazione neoplastica non incapsulata, non demarcata, infiltrante ed altamente cellulare, costituita da foglietti monomorfi di cellule rotonde densamente stipate e sostenute da esili setti fibrovascolari. Le cellule erano di forma rotonda, di dimensioni di circa 15 µm, con limiti citoplasmatici ben definiti, scarso citoplasma eosinofilo, elevato rapporto nucleo/citoplasma, nucleo rotondo centrale o eccentrico con cromatina da finemente reticolare a irregolarmente distribuita e nucleolo magenta ben evidente, singolo e di forma bizzarra; talvolta si osservavano numerose cellule multinucleate neoplastiche con nuclei in fila e citoplasma eosinofilo fibrillare (strap cell) e cellule con abbondante citoplasma intensamente eosinofilo anche esse con contenuto fibrillare che presentava bandeggiatura simile a quella delle miofibrille dei sarcomeri delle cellule muscolari striate. Anisocitosi e anisocariosi erano marcate, le mitosi, frequentemente atipiche, erano fino a 15 per campo ad ingrandimento 400x. Si riscontravano numerose apoptosi. Multifocalmente, si osservavano aree emorragiche e una estesa infiltrazione dei tessuti circostanti. Il quadro istologico era suggestivo di rabdomiosarcoma. La neoformazione cutanea della regione mascellare si presentava demarcata, non capsulata esofitica, a cavolfiore, di dimensioni 2,4 x 2,6 x 5,7 cm, di colore rossastro e consistenza spugnosa; in sezione il tessuto fissato appariva di colore brunastro, multilacunare e con multifocali aree biancastre di necrosi. All’esame istologico si osservava una neoplasia esofitica di pertinenza sottocutanea, non capsulata, scarsamente demarcata, infiltrante il muscolo scheletrico, moderatamente cellulare, costituita da cellule di aspetto mesenchimale disposte a formare lacune ematiche irregolari e di dimensioni variabili, sostenute da un abbondante stroma edematoso. Le cellule neoplastiche di 15-20 µm erano fusate, con limiti citoplasmatici non ben definiti, moderato citoplasma eosinofilo granulare, rapporto nucleo/citoplasma intermedio, nucleo ovale centrale con cromatina a zolle e nucleoli multipli, color magenta ben evidenti; anisocitosi e anisocariosi erano da moderate a marcate, le mitosi erano rare ad ingrandimento 400x. Si osservavano occasionali cellule neoplastiche binucleate. Multifocalmente vi erano vaste aree di necrosi colliquativa intratumorale e un abbondante infiltrato infiammatorio costituito da neutrofili e piccoli linfociti. Il muscolo scheletrico era marcatamente infiltrato dalla proliferazione neoplastica. Il quadro istologico era compatibile con sarcoma di probabile origine endoteliale.

The utility of using portfolios of solvers for constraint satisfaction problems is well reported. We show that when runtimes are properly clustered, simple classification techniques can be used to predict the class of runtime as, for example, short, medium, long, time-out, etc. Based on runtime classifiers we demonstrate a dispatching approach to solving a set of problem instances in order to minimise the average completion time of each instance. We show that this approach significantly out-performs a well-known CSP solver and performs well against an oracle implementation of a solver portfolio.

Cyclooxygenase (COX, also called prostaglandin H synthase), is a bifunctional enzyme that catalyzes the conversion of arachidonic acid into prostaglandins. Currently, three COX isoenzymes are known: the COX-1 isoform is expressed constitutively, and is mainly associated with the production of prostaglandins involved in important physiological processes such as the cytoprotection of the gastric mucosa and renal blood flow; COX-3 is a splice variant of COX-1; the COX-2 isoform is inducible and is expressed in normal cells, such as macrophages, in response to pro-inflammatory stimuli and in multiple types of cancer cells, where it may mediate several oncogenic functions, including stimulation of proliferation and angiogenesis, inhibition of apoptosis, and immune suppression. Recent studies have demonstrated COX-2 expression in a variety of canine and feline tumors, including squamous-cell carcinoma, transitional-cell carcinoma, mammary gland carcinoma, melanoma, and osteosarcoma. Furthermore, strong COX-2 expression has been identified as a negative prognostic factor in several human neoplasms, as well as in canine and feline mammary tumors and in canine osteosarcoma. In human neurology, COX-2 is frequently expressed in the brain during different pathologic conditions. Numerous data show the presence of COX-2 in the glioma-affected brain and indicate the therapeutic effectiveness of COX inhibitors in the gliomas. COX-2 overexpression has been observed also in the majority of meningiomas, although the increasing immunohistochemical COX-2 expression was not constantly associated to malignancy grade. Furthermore, an association of COX-2 up-regulation to edema index, as revealed by CT scan, has been reported, suggesting a role of COX-2 also in the development of the brain edema associated to meningioma. Recently, COX-2 expression has been found also in 21 out of 24 canine intracranial meningiomas, with no significant association to tumor grade. Conversely, COX-2 expression has not been investigated yet in feline meningiomas. The aim of this study was to evaluate by immunohistochemistry the expression of COX-2 in a series of 35 intracranial feline meningiomas (20 biopsy and 15 post mortem samples) classified histologically according to the WHO system. Nineteen were transitional, seven fibroblastic, four psammomatous, four malignant, one meningothelial. The histological grade was I in 24 and II in 11 cases. Eight cases were also investigated with MRI, and moderate peritumoral edema was evident in only one of them (transitional histotype, grade I). COX-2 immunohistochemistry was carried out using a rabbit polyclonal antibody (Cayman Chemical) and prompted immunopositivity in 15 out of 35 feline meningiomas (43%). The immunoreactivity was cytoplasmic with occasional perinuclear reinforcement, and spread multifocally throughout the sections in meningothelial nests and small cellular aggregates. COX-2 immunopositivity was marked in only three cases, one grade I and two grade II meningiomas, and mild to moderate in the other cases. COX-2 was expressed also by intratumoral inflammatory cells in only one case (malignant histotype, grade II); the endothelial cells of peritumoral vessels and the adjacent normal brain tissue did not express COX-2. Pearson’s chi-square test did not show any correlation between COX-2 expression, tumor histotype and tumor grade. These findings suggest that COX-2 is expressed in feline meningiomas at low levels, if compared to COX-2 expression in canine and human meningiomas, suggesting a basic species disparity. Further investigations are required to support these preliminary results and to elucidate the actual role of COX-2 in the biological behavior of feline meningioma and the possible perspectives of COX-2 inhibitory treatment strategies.

A 13 yr old castrated male vizsla was referred to the authors’ institute because of polyuria, polydipsia, polyphagia, and weight loss. Pituitary-dependent hypercortisolism (PDH) was diagnosed by hormone testing and adrenal and pituitary imaging. Computed tomography (CT) revealed a pituitary mass measuring 21 mm in width. Medical therapy was initiated with trilostane. Despite adequate control of the hypercortisolemia, the polyuria and polydipsia persisted and the dog developed neurologic signs due to the pituitary mass effect. Pituitary transsphenoidal debulking surgery was performed and immunocytochemistry confirmed a corticotroph adenoma. The dog survived for 13 mo after surgery. Postmortem examination revealed an empty fossa without pituitary remnants and the presence of a malignant pheochromocytoma in the right adrenal gland. This case report demonstrates, for the first time, that a large pituitary adenoma in the dog may be treated successfully by pituitary surgery.

Scopo del lavoro è quello di indagare l’espressione dell’attività metalloproteinasica (MMP2 e MMP9) nei meningiomi del cane e del gatto,mettendola in relazione con l’espressione dell’attività telomerasica (h-TERT) e dei recettori per il progesterone (PR88), al fine di individuare parametri significativi nella valutazione prognostica di tali tumori. Sebbene le MMP siano state indagate in molte neoplasie del cane e del gatto, nulla emerge ancora riguardo alla loro specifica espressione nel meningioma di queste specie.

Sono descritte le caratteristiche clinico-patologiche di un caso di prototecosi coinvolgente il SNC in un cane da Pastore Maremmano-Abruzzese maschio di 3 anni che era stato presentato con una anamnesi di depressione, movimenti in circolo e tetraparesi che progredirono fino a decubito laterale con pleurototono. All’esame macroscopico del SNC erano evidenti focolai necrotizzanti multifocali a livello del talamo e del tronco encefalico. Le lesioni istopatologiche erano caratterizzate da meningoencefalite granulomatosa multifocale con presenza di numerosi macrofagi, linfociti, plasmacellule e rari eosinofili. I granulomi erano presenti soprattutto a livello di talamo, ippocampo e tronco encefalico caudale, coinvolgevano la sostanza bianca, la sostanza grigia e le meningi ed erano associati a demielinizzazione, degenerazione assonale, gliosi e malacia. A livello dei nervi ottici era evidente neurite periassiale ed assiale multifocale associata ad atrofia segmentale e fibrosi. Nei focolai granulomatosi dell’encefalo e a livello delle meningi erano evidenti numerosi organismi ovali-rotondeggianti non pigmentati, di circa 6 x 15 μm con una spessa parete PAS e GMS positiva, compatibili con alghe del genere Prototheca spp. (famiglia Chlorellaceae). Erano evidenti anche organismi sporulanti con 2-4 endospore. Tramite esame ultrastrutturale numerosi organismi singoli e multipli erano presenti soprattutto all’interno dei macrofagi. Questi organismi apparivano degenerati con perdita del nucleo, dei granuli di amido, dei corpi densi e con una membrana plasmatica irregolare. In letteratura sono descritti casi sporadici di prototecosi a carico del SNC nel cane, ma questa infezione dovrebbe essere considerata nella diagnostica differenziale in caso di sindrome neurologica multifocale anche in Italia.

Telomerase is a ribonucleoprotein complex that prevents the erosion of chromosomal extremities (telomeres) in eukaryotic cells. The role of telomerase in the process of tumoural transformation is currently undergoing intense scrutiny, as its activation is considered a fundamental step in “immortalization” of neoplastic cells, and has been suggested to play a key role in the progression of several tumours, including human intracranial meningiomas. This study aimed to evaluate in 25 cases of archived meningiomas (14 canine and 11 feline) the presence of telomerase, determined by immunohistochemistry (IHC) with an anti-h-TERT monoclonal antibody (clone 44F12, Novocastra), which detects the enzymatic catalytic subunit. The positive reaction, identified by the evidence of scattered nuclear and/or nucleolar staining, was computed with an automated image analysis system ("Lucia 32G/Mutech", Nikon) and expressed as percentage of positive tumoural cells. According to WHO International Classification of Tumors of the Nervous System of Domestic Animals, meningiomas were grouped into the following histotypes: meningothelial (6 canine), transitional/mixed (1 canine, 6 feline), psammomatous (1 canine, 2 feline), fibrous/fibroblastic (1 canine, 1 feline), anaplastic/malignant (5 canine, 2 feline). In 15 out of 25 meningiomas (6 canine, 9 feline) h-TERT protein was localized in the nuclei, notably nucleoli and occasionally in the cytoplasm (two cases) of the cells, with mild to strong staining intensity. Even the percentage of positive cells was variable, ranging from 5 to 80%, regardless of the histological type. Although the number of telomerase-negative meningiomas may depend upon overfixation, the heterogeneous h-TERT expression suggests the existence of alternative mechanisms to telomerase involved in the tumoural transformation and prompts the necessity to correlate h-TERT expression with proliferative activity and biologic behaviour.