Veronaea botryosa is a ubiquitous, dematiaceous mold capable of causing cutaneous and subcutaneous lesions in humans. In the last decade, V. botryosa has been associated with emergent systemic fungal infections in aquatic animals, including cultured sturgeon (Acipenser spp.), captive amphibians, and wild reptiles. Recently, repetitive extragenic palindromic PCR (rep-PCR) fingerprinting has demonstrated intraspecific variability among V. botryosa isolates from different clinically affected hosts and geographic regions. However, little is known regarding the pathogenic potential of the different genetic clades, and no mammalian model currently exists to investigate V. botryosa phaeohyphomycosis. In this study, we inoculated immunocompetent heterozygotic (nu/+) and immunodeficient homozygotic (nu/nu) Hsd:Athymic Nude-Fox1^nu mice subcutaneously or through orogastric gavage with 1 of 3 representative V. botryosa strains that had been recovered from white sturgeon (Acipenser transmontanus), green sea turtle (Chelonia mydas), and human hosts and typed by using rep-PCR analysis. Daily mortality and morbidity were recorded, and dissemination of the fungus was investigated through culture of splenic samples and histologic analysis of the injection site, regional lymph nodes, salivary gland, spleen, liver, mesenteric lymph node, and gastrointestinal tract. No differences in survival, fungal burden, or dissemination were observed between fungal strains, routes of inoculation, or host immune status. Fungal infection was observed after subcutaneous inoculation only, was localized to the inoculation site, and was identified in both nu/nu and nu/+ mice. Fungal strain variability was not associated with virulence in a murine model of infection, and this novel mouse model of V. botryosa phaeohyphomycosis recapitulates the human clinical condition.

Modeling chronic myelomonocytic leukemia (CMML) in immunodeficient NSGS mice relies on unique human CMML specimens and consistent murine engraftment. Only anecdotal comments have thus far supported the notion that research data may be altered by Corynebacterium bovis, an opportunistic cutaneous pathogen of immunodeficient mice. C. bovis disseminated by asymptomatic and clinically affected mice with hyperkeratotic dermatitis, resulting in resilient facility contamination and infectious recurrence. Herein we report that, compared with C. bovis PCR-negative counterparts, C. bovis PCR-positive NSGS mice developed periocular and facial hyperkeratosis and alopecia and had reduced metrics indicative of ineffective human CMML engraftment, including less thrombocytopenia, less splenomegaly, fewer CMML infiltrates in histopathologic sections of murine organs, and fewer human CD45₊ cells in samples from murine spleen, bone marrow, and peripheral blood that were analyzed by flow cytometry. All CMML model metrics of engraftment were significantly reduced in the C. bovis PCR-positive cohort compared with the - negative cohort. In addition, a survey of comprehensive cancer center practices revealed that most murine facilities do not routinely test for C. bovis or broadly decontaminate the facility or its equipment after a C. bovis outbreak, thus increasing the likelihood of recurrence of invalidated studies. Our findings document that CMML engraftment of NSGS mice is diminished—and the integrity of murine research data jeopardized—by C. bovis infection of immunodeficient mice. In addition, our results indicate that C. bovis should be excluded from and not tolerated in murine facilities housing immunodeficient strains.

Antimicrobial resistance is a growing problem in human medicine that extends to biomedical research. Compared with chemical-based therapies, light-based therapies present an alternative to traditional pharmaceuticals and are less vulnerable to acquired bacterial resistance. Due to immunologic privilege and relative tissue sensitivity to topical antibiotics, the brain poses a unique set of difficulties with regard to antimicrobial therapy. This study focused on 405-nm 'true violet' light—which has been shown to kill multiple clinically relevant bacterial species in vitro yet leave mammalian cells unscathed—and its effect on the murine brain. We built a 405-nm LED array, validated its power and efficacy against a clinical bacterial isolate in vitro, and then, at the time of craniotomy, treated mice with various doses of 405-nm light (36, 45, and 54 J/cm²). The selected doses caused no behavioral derangements postoperatively or any observable brain pathology as determined postmortem by histologic evaluation and immunofluorescence staining for caspase 3 and glial fibrillary acidic protein, markers of apoptosis and necrosis. True-violet light devices may present an inexpensive refinement to current practices for maintaining open craniotomy sites or reducing bacterial loads in contaminated surgical sites.

Known as devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT), transmissible cancer occurs in both Tasmanian devil and canine populations, respectively. Both malignancies show remarkable ability to be transmitted as allografts into subsequent hosts. How DFTD and CTVT avoid detection by immunocompetent hosts is of particular interest, given that these malignancies are rarely seen in other species in nature. Both of these transmissible cancers can downregulate the host immune system, enabling proliferation. DFTD is characterized by epigenetic modifications to the DNA promoter regions of β₂microglobulin, transporters associated with antigen processing 1 and 2, MHC I, and MHC II—crucial proteins required in the detection and surveillance of foreign material. Downregulation during DFTD may be achieved by altering the activity of histone deacetylases. DFTD has caused widespread destruction of devil populations, placing the species on the brink of extinction. CTVT demonstrates a proliferative phase, during which the tumor evades immune detection, allowing it to proliferate, and a regressive phase when hosts mount an effective immune response. Alteration of TGFβ signaling in CTVT likely impedes the antigen-processing capabilities of canine hosts in addition to hindering the ability of natural killer cells to detect immune system downregulation. Immunosuppressive cytokines such as CXCL7 may contribute to a favorable microenvironment that supports the proliferation of CTVT. When viewed from an evolutionary paradigm, both DFTD and CTVT may conform to a model of host–parasite coevolution. Furthermore, various genetic features, such as genetically active transposons in CTVT and chromosomal rearrangements in DFTD, play important roles in promoting the survival of these disease agents. Understanding the mode of transmission for these transmissible cancers may shed light on mechanisms for human malignancies and reveal opportunities for treatment in the future.

Percutaneous implantation of the pulmonary valve through peripheral vascular access can be limited due to poor venous access, low patient weight, hemodynamic or rhythmic instability, and size constraints related to the valve. In such cases, hybrid procedures may provide alternatives. Because the most commonly used median sternotomy is unsuitable for chronic trials in large animals, we evaluated several hybrid approaches for pulmonary valve replacement in a swine model. We tested the feasibility of hybrid pulmonary valve implantation in pigs by using inhouse-generated valves containing bare-metal or nitinol stents. Valves consisted of bovine jugular veins, bovine pericardial valves, or sprayed polyurethane valves. Access was achieved through median sternotomy, lower partial sternotomy, transverse sternotomy, or right lateral thoracotomy. The delivery device was introduced in a transventricular manner. Implantation took place under fluoroscopic and epicardial echocardiographic guidance. We achieved implantation of the stented valve in 12 (92.3%) pigs, of which 5 (41.7%) of the implanted valves were in an optimal position. Paravalvular leakage occurred in 2 trials (16.7%). Lower partial sternotomy provided the best trade-off between feasibility and minimized trauma for long-term animal trials. Here we describe our experience with hybrid pulmonary valve implantation in an acute large-animal (swine) model. We demonstrate the feasibility of the procedure in terms of surgical technique and the perioperative management and preparation of the field for a chronic trial.

Most patients who undergo epidural anesthesia are pregnant and thus a protected population, which has limited investigations of the human epidural space. Among the several species studied as models for the human spine, the porcine spine has been used as a model for spine instrumentation. Although the spread of colored dye within the porcine epidural space has been investigated, no model has demonstrated in situ spread by using radiopaque contrast dye. To this end, we here used 10 Yorkshire swine cadavers through an approved tissue sharing agreement. Epidural catheters were placed by using a landmark-based loss-of-resistance technique; placement was confirmed through radiography. The catheters were connected to epidural infusion pumps to ensure consistent dosing, 2-mL boluses of contrast dye were injected into the space, and radiographs were taken and recorded after each bolus. The total spread of the contrast dye was analyzed. We demonstrated consistent and reliable spread of fluid in the epidural space among the animals used, with low variability between animals of different weights. Our results support the use of the epidural space of cadaveric swine as a model for the human epidural space. Furthermore, the technique for epidural administration by using the landmark-based loss-of-resistance demonstrated in this model was validated, thus supporting future investigations of medication delivery into the epidural space.

Methicillin-resistant Staphylococcus aureus (MRSA) carriage and infection are well documented in the human and veterinary literature; however only limited information is available regarding MRSA carriage and infection in laboratory NHP populations. The objective of this study was to characterize MRSA carriage in a representative research colony of rhesus and cynomolgus macaques through a cross-sectional analysis of 300 animals. MRSA carriage was determined by using nasal culture. Demographic characteristics of carriers and noncarriers were compared to determine factors linked to increased risk of carriage, and MRSA isolates were analyzed to determine antimicrobial susceptibility patterns, staphylococcal chromosome cassette mec (SCCmec) type, and multilocus sequence type (ST). Culture results demonstrated MRSA carriage in 6.3% of the study population. Animals with greater numbers of veterinary or experimental interventions including antibiotic administration, steroid administration, dental procedures, and surgery were more likely to carry MRSA. Susceptibility results indicated that MRSA isolates were resistant to β-lactams, and all isolates were resistant to between 1 and 4 non β-lactam antibiotics. In addition, 73.7% of MRSA isolates were identified as ST188-SCCmec IV, an isolate previously observed in an unrelated population of macaques and 15.8% were ST3268-SCCmec V, which has only been described in macaques. A single isolate had a novel sequence type, ST3478, and carried SCCmec V. These results suggest that NHP-adapted strains of MRSA exist and highlight the emergence of antimicrobial resistance in laboratory NHP populations.

Two healthy research cats involved in a randomized, blinded prospective pharmacodynamics study evaluating midazolam continuous-rate infusion as a means to decrease sevoflurane concentrations experienced unexpectedly prolonged recoveries. Midazolam loading doses, infusion rates, and the targeted plasma midazolam concentrations at steady-state were determined by pharmacokinetic modeling based on the results of a preliminary pharmacokinetic study using a single dose of midazolam. In the pharmacodynamics study, cats remained oversedated after recovery from anesthesia, and plasma concentrations of midazolam and its primary metabolite (1-hydroxymidazolam) remained elevated. The use of flumazenil was unsuccessful in timely treatment of oversedation. Administration of intravenous lipid emulsion was used in one of the cats to facilitate recovery and appeared to be effective in both reducing the depth of midazolam-induced oversedation and significantly reducing the plasma concentration of 1-hydroxymidazolam. The effects after the administration of both treatment modalities on clinical signs and plasma drug concentrations in cats are discussed. The observations suggest that cats may eliminate 1-hydroxymidazolam more slowly than expected; consequently dose adjustments may be required when continuous infusion of midazolam is intended. In addition, intravenous lipid emulsion may facilitate recovery from midazolam oversedation, particularly in cases unresponsive to traditional treatment modalities. However, further investigations are warranted to delineate the efficacy of this modality in the treatment of midazolam oversedation.