Laryngeal and oropharyngeal adenocarcinoma with pulmonary metastases in a common raven (Corvus corax).

A captive 15-year-old male common raven (Corvus corax) was presented for post-mortem examination. It had been previously presented to a local veterinarian due to a 3-4 weeks long history of abnormal respiratory sounds. Upon admission, the bird demonstrated severe dyspnea and a massive amount of mucous in the oropharynx. After symptomatic treatment, dyspnea deteriorated dramatically, and euthanasia was elicited because of poor prognosis. The necropsy revealed a 2.65 x 2.15 x 2.18 cm expansile and poorly delineated cauliflower-shaped mass around the glottis and extending inside the tracheal lumen. Additionally, a dilated salivary gland in the adjacent tissue and multifocal reddish-fleshy areas in the lung parenchyma were detected. Histopathological examination identified the mass as moderately differentiated, tubular adenocarcinoma with invasive growth and moderate to marked cellular atypia and numerous mitoses. The presumptive origin of the neoplasia was one of the salivary glands. Multiple metastases were identified in the lung both macroscopically and histologically. Bacterial culture and molecular testing for West Nile and Usutu viruses were negative. To the authors' knowledge, this is the first report of metastatic laryngeal and oropharyngeal adenocarcinoma in a common raven.

A Novel Dipotassium Hydrogen Phosphate Phantom for Calibrating Computed Tomographic Bone Density Measurements in Birds.

The objective of this study was to construct a calibration phantom for bone mineral density (BMD) measurements adapted to avian anatomy by quantitative computed tomography. The determination of BMD is important to assess avian osteoporosis in poultry at production facilities and to study biological features in association with flight patterns in birds. Quantitative computed tomography measured in Hounsfield units is a well-established technique for BMD measurements. Translation of Hounsfield units into the International System of Units (mg/cm3) requires the use of a calibration phantom. Although calibration phantoms for routine use in humans are commercially available, phantoms suited to avian anatomy are not. A liquid dipotassium hydrogen phosphate calibration standard was constructed out of commercially available materials, easily allowing for variations in size, bone diameter, and adaptation to avian skeletal anatomy. Periodically, quantitative computed tomography scans were performed to monitor constant correlation to the calibration standard over 3 months and to monitor for the potential influence of gas bubbling and water evaporation in the rods on BMD measurements. Finally, the calibration phantom was tested for BMD measurements with carcasses from 2 bird species, including 3 peregrine falcons (Falco peregrinus; 2 juvenile males, 1 adult female with inactive reproductive status) and 4 Eurasian kestrels (Falco tinnunculus; 1 juvenile and 2 adult males, 1 adult female with inactive reproductive status). Results demonstrated stability of the calibration phantom without the need to refill or replace rods, plus a stable correlation line (R 2 = .99) over the 3-month evaluation period. It was possible to place the phantom directly on the bird carcasses, close to the measured bones, to improve BMD analysis. As evaluated, the phantom appeared to be adaptive to avian skeletal anatomy. Moreover, it was possible to build the phantom within 24 hours from commercially available materials.

Histopathological Findings in the Cardiovascular System of Psittacidae in Routine Diagnostics.

Samples of 363 Psittacidae were included in this study with a focus on cardiovascular diseases. These were identified in 28.9% of the animals, with pericarditis and/or epicarditis and myocarditis representing approximately half of all lesions and bacteria being the most common infectious cause. Cardiac lymphoma was only seen in 5 birds, whereas degenerative vascular lesions were diagnosed in 26.7% of the cases. Histopathology in the context of clinical findings and complementary examination results is the most useful tool for the evaluation of cardiac diseases.

Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial.

AIMS: To determine long-term safety and efficacy outcomes of a subretinal gene therapy for CNGA3-associated achromatopsia. We present data from an open-label, nonrandomised controlled trial (NCT02610582). METHODS: Details of the study design have been previously described. Briefly, nine patients were treated in three escalating dose groups with subretinal AAV8.CNGA3 gene therapy between November 2015 and October 2016. After the first year, patients were seen on a yearly basis. Safety assessment constituted the primary endpoint. On a secondary level, multiple functional tests were carried out to determine efficacy of the therapy. RESULTS: No adverse or serious adverse events deemed related to the study drug occurred after year 1. Safety of the therapy, as the primary endpoint of this trial, can, therefore, be confirmed. The functional benefits that were noted in the treated eye at year 1 were persistent throughout the following visits at years 2 and 3. While functional improvement in the treated eye reached statistical significance for some secondary endpoints, for most endpoints, this was not the case when the treated eye was compared with the untreated fellow eye. CONCLUSION: The results demonstrate a very good safety profile of the therapy even at the highest dose administered. The small sample size limits the statistical power of efficacy analyses. However, trial results inform on the most promising design and endpoints for future clinical trials. Such trials have to determine whether treatment of younger patients results in greater functional gains by avoiding amblyopia as a potential limiting factor.

Repair of Retinal Degeneration following Ex Vivo Minicircle DNA Gene Therapy and Transplantation of Corrected Photoreceptor Progenitors.

The authors describe retinal reconstruction and restoration of visual function in heritably blind mice missing the rhodopsin gene using a novel method of ex vivo gene therapy and cell transplantation. Photoreceptor precursors with the same chromosomal genetic mutation were treated ex vivo using minicircle DNA, a non-viral technique that does not present the packaging limitations of adeno-associated virus (AAV) vectors. Following transplantation, genetically modified cells reconstructed a functional retina and supported vision in blind mice harboring the same founder gene mutation. Gene delivery by minicircles showed comparable long-term efficiency to AAV in delivering the missing gene, representing the first non-viral system for robust treatment of photoreceptors. This important proof-of-concept finding provides an innovative convergence of cell and gene therapies for the treatment of hereditary neurodegenerative disease and may be applied in future studies toward ex vivo correction of patient-specific cells to provide an autologous source of tissue to replace lost photoreceptors in inherited retinal blindness. This is the first report using minicircles in photoreceptor progenitors and the first to transplant corrected photoreceptor precursors to restore vision in blind animals.

[Surgical removal of a follicular carcinoma of the thyroid gland in a snakehead (Channa barca, HAMILTON, 1822)]. / Chirurgische Entfernung eines untypischen follikulären Schilddrüsenkarzinoms bei einem Schlangenkopffisch (Channa barca, HAMILTON, 1822).

Inflammatory processes, neoplastic growths or rare dysontogenetic malformations may cause mass formation in the gills of fish. In the present case, a follicular carcinoma of the thyroid gland in a Barca snakehead and its surgical removal are reported, and neoplasms in fish are discussed. Following clinical, radiological, cytological and sonographic examinations, the gill-associated partly cystic mass was incompletely removed surgically. The subsequent histological examination identified the mass partly as a follicular carcinoma of the thyroid gland. Because the main alterations of the surgical specimen were non-neoplastic, the development from a rare preexisting hamartoma is discussed. No bacteriological or mycological secondary infections were identified. This report is the first description of a follicular carcinoma and its surgical removal in a snakehead.

INVESTIGATIONS INTO CAUSES OF NEUROLOGIC SIGNS AND MORTALITY AND THE FIRST IDENTIFICATION OF SARCOCYSTIS CALCHASI IN FREE-RANGING WOODPECKERS IN GERMANY.

Between June and November 2015, 25 woodpeckers (Picidae) with neurologic signs or unknown cause of death were admitted to a veterinary clinic. Alive birds were clinically examined. Birds that were found dead or died despite intensive care treatment were forwarded to a pathologic examination. Necropsy and subsequent tests included screening for several infectious agents and toxins. Three birds tested positive for Sarcocystis calchasi. Toxoplasma gondii was detected in one bird demonstrating intracerebral cysts. Mycoplasma gypis was detected in one woodpecker in the absence of respiratory signs. Several microbial pathogens (eg, Aspergillus fumigatus, Clostridium perfringens, and Escherichia coli) were isolated from single individuals. However, there was no consistent finding in all birds that could explain nervous signs and mortality of the woodpeckers examined. To the authors' knowledge, M. gypis and S. calchasi were detected in a woodpecker for the first time in this study.

Single tracheal inoculation of Aspergillus fumigatus conidia induced aspergillosis in juvenile falcons (Falco spp.).

Aspergillosis is a common and life-threatening respiratory disease in raptors with acute and chronic courses. Among raptors, gyrfalcons (Falco rusticolus) and their hybrids are often declared to be highly susceptible with juvenile individuals being the most susceptible. However, species- and age-specific experimental studies are lacking and minimal infective doses (IDs) for Aspergillus spp. conidia are unknown.Therefore, 8-week-old, healthy gyr-hybrid falcons (F. rusticolus X F. cherrug) (N = 18) were experimentally infected with Aspergillus fumigatus using a single intratracheal inoculation with varying dosages of conidia (102 to 107 conidia). Over 28 days, clinical signs were monitored as well as haematological and serological parameters. Following euthanasia, necropsy, histopathology, bacteriology, and mycology were performed. Re-isolated fungi were compared to the inoculum using microsatellite length polymorphisms. During the trial, clinical signs and dyspnoea correlated significantly with the ID. Necropsy revealed fungal lesions in the upper and lower airways of 10/18 inoculated falcons, but not in the control birds. In 9/18 inoculated falcons, fungal granulomas were confirmed in histopathology and A. fumigatus was re-isolated from these granulomas. Except one nasal isolate all re-isolated fungal strains were identical to the inoculum strain. Based on mycology and histopathology a minimal ID of 50% was calculated to be MID50% (±S.E.) = 104.52±0.67 for a single tracheal inoculation of A. fumigatus conidia. This study demonstrates for the first time that a single exposure is able to cause acute aspergillosis in juvenile falcons.

Vertebral Osteomyelitis and Septic Arthritis Associated With Staphylococcus hyicus in a Juvenile Peregrine Falcon ( Falco peregrinus ).

A 6-week-old, parent-reared peregrine falcon ( Falco peregrinus ) was presented with spastic hypertonus of its hind limbs of unknown origin and duration. Radiologic examination revealed smooth periosteal reactions ventrally at thoracic vertebrae 5 to 7. Contrast-enhanced computed tomography identified the swelling as inflammation; antibiotic, antimycotic, anti-inflammatory, and analgesic treatments were initiated, and vitamins and minerals were supplemented. Because the bird's condition did not improve after 10 days, it was euthanatized and submitted for postmortem examination. On histopathologic examination, chronic, active osteomyelitis was diagnosed in thoracic vertebrae 5 to 7, and chronic, active arthritis was present in both the right shoulder and left elbow joints. Staphylococcus hyicus was isolated from these 3 locations, as well as from lungs and liver, indicating a chronic septic staphylococcosis. Although infections with Staphylococcus species are occasional causes of vertebral osteomyelitis in juvenile poultry with active growth plates, it is only sporadically reported in raptors and companion birds. This case report is the first description of the clinical features and diagnostic and pathologic findings in a juvenile peregrine falcon with hematogenous osteomyelitis and arthritis associated with septicemia caused by S hyicus.

DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly, via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.).

As West Nile virus (WNV) can cause lethal diseases in raptors, a vaccination prophylaxis of free-living and captive populations is desirable. In the absence of vaccines approved for birds, equine vaccines have been used in falcons, but full protection against WNV infection was not achieved. Therefore, two DNA vaccines encoding the ectodomain of the envelope protein of WNV lineages 1 and 2, respectively, were evaluated in 28 large falcons. Four different vaccination protocols were used, including electroporation and booster-injections of recombinant WNV domain III protein, before challenge with the live WNV lineage 1 strain NY99. Drug safety, plasmid shedding and antibody production were monitored during the vaccination period. Serological, virological, histological, immunohistochemical and molecular biological investigations were performed during the challenge trials. Antibody response following vaccination was low overall and lasted for a maximum of three weeks. Plasmid shedding was not detected at any time. Viremia, mortality and levels, but not duration, of oral virus shedding were reduced in all of the groups during the challenge trial compared to the non-vaccinated control group. Likewise, clinical scoring, levels of cloacal virus shedding and viral load in organs were significantly reduced in three vaccination groups. Histopathological findings associated with WNV infections (meningo-encephalitis, myocarditis, and arteritis) were present in all groups, but immunohistochemical detection of the viral antigen was reduced. In conclusion, the vaccines can be used safely in falcons to reduce mortality and clinical signs and to lower the risk of virus transmission due to decreased levels of virus shedding and viremia, but full protection was not achieved in all groups.

Transcorneal electrical stimulation shows neuroprotective effects in retinas of light-exposed rats.

PURPOSE: To examine the effects of transcorneal electrical stimulation (TES) on retinal degeneration of light-exposed rats. METHODS: Thirty-three Sprague Dawley albino rats were divided into three groups: STIM (n = 15) received 60 minutes of TES, whereas SHAM (n = 15) received identical sham stimulation 2 hours before exposure to bright light with 16,000 lux; healthy animals (n = 3) served as controls for histology. At baseline and weekly for 3 consecutive weeks, dark- and light-adapted electroretinography was used to assess retinal function. Analysis of the response versus luminance function retrieved the parameters Vmax (saturation amplitude) and k (luminance to reach ½Vmax). Retinal morphology was assessed by histology (hematoxylin-eosin [HE] staining; TUNEL assay) and immunohistochemistry (rhodopsin staining). RESULTS: Vmax was higher in the STIM group compared with SHAM 1 week after light damage (mean intra-individual difference between groups 116.06 µV; P = 0.046). The b-wave implicit time for the rod response (0.01 cd.s/m²) was lower in the STIM group compared with the SHAM group 2 weeks after light damage (mean intra-individual difference between groups 5.78 ms; P = 0.023); no other significant differences were found. Histological analyses showed photoreceptor cell death (TUNEL and HE) in SHAM, most pronounced in the superior hemiretina. STIM showed complete outer nuclear layer thickness preservation, reduced photoreceptor cell death, and preserved outer segment length compared with SHAM (HE and rhodopsin). CONCLUSIONS: This sham-controlled study shows that TES can protect retinal cells against mild light-induced degeneration in Sprague Dawley rats. These findings could help to establish TES as a treatment in human forms of retinal degenerative disease.