Aspergillosis is an airborne fungal disease caused by Aspergillus spp., a group of ubiquitous molds. This disease causes high morbidity and mortality in both humans and animals. The growing importance of this infection over recent decades has created a need for practical and reproducible models of aspergillosis. The use of laboratory animals provides a platform to understand fungal virulence and pathophysiology, assess diagnostic tools, and evaluate new antifungal drugs. In this review, we describe the fungus, various Aspergillus-related diseases in humans and animals and various experimental animal models. Overall, we highlight the advantages and limitations of the animal models, the experimental variables that can affect the course of the disease and the reproducibility of infection, and the critical need for standardization of the species, immunosuppressive drugs, route of infection, and diagnostic criteria to use.

Antimicrobial resistance (AMR) presents serious threats to human and animal health. Although AMR of pathogens is often evaluated independently between humans and animals, comparative analysis of AMR between humans and animals is necessary for zoonotic pathogens. Major surveillance systems monitor AMR of zoonotic pathogens in humans and food animals, but comprehensive AMR data in veterinary medicine is not diligently monitored for most animal species with which humans commonly contact, including NHP. The objective of this review is to provide a complete report of the prevalences of AMR among zoonotic bacteria that present the greatest threats to NHP, occupational, and public health. High prevalences of AMR exist among Shigella, Campylobacter, and Yersinia, including resistance to antimicrobials important to public health, such as macrolides. Despite improvements in regulations, standards, policies, practices, and zoonotic awareness, occupational exposures to and illnesses due to zoonotic pathogens continue to be reported and, given the documented prevalences of AMR, constitute an occupational and public health risk. However, published literature is sparse, thus indicating the need for veterinarians to proactively monitor AMR in dangerous zoonotic bacteria, to enable veterinarians to make more informed decisions to maximize antimicrobial therapy and minimize occupational risk.

Spaceflight results in bone loss like that associated with osteoporosis or decreased weight-bearing (for example, high-energy trauma such as explosive injuries and automobile accidents). Thus, the unique spaceflight laboratory on the International Space Station presents the opportunity to test bone healing agents during weightlessness. We are collaborating with NASA and the US Army to study bone healing in spaceflight. Given the unique constraints of spaceflight, study design optimization was required. Male mice were selected primarily because their femur is larger than females', allowing for more reproducible surgical outcomes. However, concern was raised regarding male mouse aggression. In addition, the original spaceflight study design included cohousing nonoperated control mice with mice that had undergone surgery to create a segmental bone defect. This strategy prompted the concern that nonoperated mice would exhibit aggressive behavior toward vulnerable operated mice. We hypothesized that operated and nonoperated male mice could be cohoused successfully when they were cagemates since birth and underwent identical anesthetic, analgesic, preoperative, and postoperative conditions. Using quantitative behavioral scoring, body weight, and organ weight analyses (Student t test and ANOVA), we found that nonoperated and operated C57BL/6 male mice could successfully be housed together. The male mice did not exhibit aggressive behavior toward cagemates, whether operated or nonoperated, and the mice did not show evidence of stress, as indicated by veterinary assessment, or change in body or proportional organ weights. These findings allowed our mission to proceed (launched February 2017) and may inform future surgical study designs, potentially increasing housing flexibility.

The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague–Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.

Enhancer of zeste homolog 2 (EZH2) shows upregulated expression in tumors and is an important driver of tumor development and progression. However, the mechanism underlying the mediation of tumor aggressiveness by EZH2 remains unclear. We here investigated the levels of EZH2 in various normal and tumorous dog tissues and compared these patterns with those of the corresponding human tissues. Immunohistochemical analysis showed positive staining for EZH2 in 76 of 82 cases of canine tumors, whereas low or negligible staining occurred in normal tissues and other canine tumors, including hepatocellular adenoma and lipoma. In particular, canine lymphoma, melanoma, basal cell tumors, squamous cell carcinoma, and prostate cancer all show EZH2 overexpression, as do their human counterparts. Given the similarities of spontaneous canine tumors to human cancers, we believe that these canine tumors can be used as animal models in future research and clinical trials in the development of EZH2 inhibitors.

Congestive heart failure (CHF) is characterized by reduced heart rate variability. Although various methods to achieve parasympathetic withdrawal and sympathetic activation have been documented, stimulation of the vagal nerve (that is, vagal maneuvers) has not often been used to assess the autonomic impairment associated with disease progression in veterinary species. In this study, we investigated cardiac autonomic control in a naturally occurring canine model of mitral insufficiency by means of individual responses to oculocardiac reflex. Indices of heart rate variability were calculated from 5-min ECG tracings obtained before and after ocular compression. After compression, significant increases in the standard deviation of RR intervals, root mean square of the successive differences in RR intervals, and vasovagal tonus index were documented in healthy control animals. In addition, these indices were increased in asymptomatic dogs with remodeled hearts, but no variation occurred in symptomatic animals. Although only the percentage change in vasovagal tonus index differed significantly between controls and diseased dogs, all other parameters showed a tendency to behave the opposite way in the symptomatic group as in the control and asymptomatic groups. Our results document CHF-dependent autonomic dysfunction in a canine model of valve insufficiency.

The neurodegeneration associated with Huntington disease (HD) leads to the onset of motor and cognitive impairment and their advancement with increased age in humans. In children at risk for HD, body measurement growth abnormalities include a reduction in BMI, weight, height, and head circumference. The transgenic HD NHP model was first reported in 2008, and progressive decline in cognitive behaviors and motor impairment have been reported. This study focuses on longitudinal body measurements in HD macaques from infancy through adulthood. The growth of HD macaques was assessed through head circumference, sagittal and transverse head, and crown-to-rump ('height') measurements and BMI. The animals were measured monthly from 0 to 72 mo of age and every 3 mo from 72 mo of age onward. A mixed-effect model was used to assess subject-specific effects in our nonlinear serial data. Compared with WT controls, HD macaques displayed different developmental trajectories characterized by increased BMI, head circumference, and sagittal head measurements beginning around 40 mo of age. The physiologic comparability between NHP and humans underscores the translational utility of our HD macaques to evaluate growth and developmental patterns associated with HD.

Providing social housing for adult male macaques can be challenging. One successful strategy for long-term social housing of adult male macaques is to pair them with adult females; however, unwanted breeding must be prevented by sterilization of the male or female. Vasectomy is a simple, highly effective, and minimally invasive method of contraception that is used at our institution to facilitate social housing. We performed a retrospective review to analyze the surgical outcomes and rate of postoperative complications after vasectomy of adult rhesus macaques at our research facility. In addition, we evaluated the success rate of pairing vasectomized macaques with female partners. Over 10 y, 16 macaques were vasectomized, of which 5 developed postoperative complications such as orchitis, epididymitis, or surgical site infection. These complications resolved completely and without incident after antibiotic and analgesic therapy; an additional male had postoperative incisional swelling that resolved quickly after NSAID treatment. This complication rate is consistent with that in humans by surgeons who perform open vasectomies relatively infrequently. In addition, 5 of the vasectomized macaques (31%) developed sperm granulomas, which are a common and generally benign complication in humans and have been reported to develop in 40% of macaques after vasectomy. Successful pair housing with a female partner was achieved for 13 of 16 (81%) of the vasectomized macaques. We conclude that surgical vasectomy is a safe and simple procedure that can be used as a highly effective method to facilitate social housing of adult male rhesus macaques in research facilities.

Here we present a 32-y-old rhesus macaque (Macaca mulatta) with a large recurrent ventral incisional hernia. The initial surgery included midline celiotomy for treatment of endometriosis, in which the animal developed a hernia that was repaired with interposition of mesh. Hernia recurrence at 1 y resulted in a defect measuring 7 × 13 cm, with loss of abdominal domain. Skin breakdown was noted with areas of exposed mesh through the skin with associated acute on chronic infection. Clinically, the animal was lethargic, not eating, and failing to thrive. The present surgical treatment included midline celiotomy, removal of mesh, and attempted primary fascial closure. Due to the large defect and high tension, the fascia could not be closed. To facilitate closure, abdominal component separation technique was used and consisted of skin and subcutaneous dissection, external oblique muscle release, and dissection between the external and internal oblique musculature. This technique allowed for primary fascial closure and resection of excess diseased skin. A piece of polypropylene mesh was placed in a sublay fashion to reinforce the primary fascial closure. The animal tolerated the procedure well and has demonstrated steady weight gain, with no recurrence at 12 mo. Large ventral abdominal hernia defects in after surgery or trauma in NHP can present reconstructive challenges to veterinary surgeons. Failure to achieve a dynamic, low-tension closure can result in hernia recurrence, necessitating additional operations. Abdominal component separation is not commonly used in veterinary surgery and may be a helpful tool in cases of difficult abdominal reconstructions.

A male rhesus macaque with a cephalic chamber implant for neurophysiology recording presented with hemiparesis affecting the left thoracic and pelvic limbs at approximately 5 wk after craniotomy surgery. MRI indicated a 1×2-cm ovoid cerebrocortical cystic lesion immediately subjacent to the right hemisphere craniotomy and recording chamber. Transdural aspiration of sterile transudate and resultant decompression resolved the hemiparesis, and follow-up MRI at 1 mo indicated resolution of the lesion. Subsequently, necropsy at study end revealed a cerebrocortical foreign body composed of silicon. The atypically slow cure rate of the lot of silicon used and the unique recording chamber configuration were underlying factors that contributed to the formation of this foreign body. To our knowledge, this report is the first description of iatrogenic intracerebral foreign body in a macaque.