Money, Mentorship, and Misinformation: Barriers and Facilitators to Veterinarians' Pursuit of Postdoctoral Training in Laboratory Animal Medicine.

Since 2015, it has become progressively more difficult for programs to recruit residents in laboratory animal medicine (LAM). Veterinarians are a necessary part of animal research, and having a shortage in veterinarians trained to work in this field has the potential to negatively impact research progress as well as animal welfare. With a goal to increase recruitment, we performed this study to better understand the barriers and facilitators that veterinarians experience when navigating the decision to pursue postdoctoral training in LAM. To do this, we recruited first-year LAM residents to participate in semistructured interviews, and performed thematic analysis on their responses. Key barriers included participants' awareness of perceived drawbacks of the field, inaccessibility of information about opportunities within the field, and misinformation about animal research both within the veterinary field and society at large. Key facilitators included participants' awareness of perceived benefits of the field, relationships with professionals involved in laboratory animal science, and formative predoctoral clinical experiences. Overall, we found evidence that information flow is particularly important in recruitment, suggesting that future recruitment strategies may want to target improved communication about LAM and animal research in general.

Suspected Anaphylactic Reaction to Ketamine in 3 Yucatan Swine (Sus scrofa).

This case series describes the clinical courses of 3 juvenile Yucatan miniature swine (Sus scrofa) that experienced a suspected anaphylactic reaction to ketamine hydrochloride during premedication for protocol-related surgery. All 3 swine rapidly developed diffuse erythema shortly after injection with ketamine-containing drug combinations. Clinical signs ranged from tachycardia and erythema alone to tachycardia and erythema followed by respiratory and cardiac arrest. Ketamine was considered the most likely cause of these reactions because it was the only agent in the premedication sedation combination that was used in all 3 swine. Subsequent intradermal skin testing confirmed this suspicion. With supportive care measures and standard medical interventions for anaphylaxis, all 3 animals recovered well and went on to be successful experimental subjects when an alternative anesthetic regimen that did not contain ketamine was used. To our knowledge, this report is the first description of a suspected adverse ketamine reaction of this type in swine despite the widespread use of the drug in this species. Ketamine anaphylaxis is rare in people, but the few cases described presented with symptoms similar to the clinical signs seen in the pigs in this report. In addition to highlighting a potential adverse drug reaction to ketamine in swine, this case series demonstrates the value of emergency preparedness for even the most routine of procedures.

Hydromorphone-induced Neurostimulation in a Yorkshire Swine (Sus scrofa) after Myocardial Infarction Surgery.

Opiates play an important role in the control of pain associated with thoracotomy in both people and animals. However, key side effects, including sedation and respiratory depression, could limit the use of opiates in animals that are lethargic due to cardiac disease. In addition, a rare side effect-neuroexcitation resulting in pathologic behavioral changes (seizures, mania, muscle fasciculation)-after the administration of morphine or hydromorphone is well-documented in many species. In pigs, however, these drugs have been shown to stimulate an increase in normal activity. In the case presented, we describe a Yorkshire-cross pig which, after myocardial infarction surgery, went from nonresponsive to alert, responsive, and eating within 30 min of an injection of hydromorphone. This pig was not demonstrating any signs associated with pain at this time, suggesting that the positive response was due to neural stimulation. This case report is the first to describe the use of hydromorphone-a potent, pure µ opiate agonist-for its neurostimulatory effect in pigs with experimentally-induced cardiac disease.

Postapproval Monitoring Practices at Biomedical Research Facilities.

Federal regulations and policies require institutions to establish procedures for ongoing IACUC oversight of approved animal care and use program activities including animal procedures. To fulfill these requirements, research institutions implement postapproval monitoring (PAM) programs designed to assure compliance in animal activities. Although several references commenting on the requirement to conduct PAM are available, few publications discuss actual best practices for accomplishing PAM. Here we use information collected through a survey of large academic research institutions to identify common practices for conducting PAM reviews. Many similarities and differences exist between institutions, which may or may not influence the overall quality of an institution's PAM program.

Pre-treatment with Meloxicam Prevents the Spinal Inflammation and Oxidative Stress in DRG Neurons that Accompany Painful Cervical Radiculopathy.

Painful neuropathic injuries are accompanied by robust inflammatory and oxidative stress responses that contribute to the development and maintenance of pain. After neural trauma the inflammatory enzyme cyclooxygenase-2 (COX-2) increases concurrent with pain onset. Although pre-treatment with the COX-2 inhibitor, meloxicam, before a painful nerve root compression prevents the development of pain, the pathophysiological mechanisms are unknown. This study evaluated if pre-treatment with meloxicam prior to painful root injury prevents pain by reducing spinal inflammation and peripheral oxidative stress. Glial activation and expression of the inflammatory mediator secreted phospholipase A2 (sPLA2) in the spinal cord were assessed at day 7 using immunohistochemistry. The extent of oxidative damage was measured using the oxidative stress marker, 8-hydroxyguanosine (8-OHG) and localization of 8-OHG with neurons, microglia and astrocytes in the spinal cord and peripherally in the dorsal root ganglion (DRG) at day 7. In addition to reducing pain, meloxicam reduced both spinal microglial and astrocytic activation at day 7 after nerve root compression. Spinal sPLA2 was also reduced with meloxicam treatment, with decreased production in neurons, microglia and astrocytes. Oxidative damage following nerve root compression was found predominantly in neurons rather than glial cells. The expression of 8-OHG in DRG neurons at day 7 was reduced with meloxicam. These findings suggest that meloxicam may prevent the onset of pain following nerve root compression by suppressing inflammation and oxidative stress both centrally in the spinal cord and peripherally in the DRG.

Use of the Rat Grimace Scale to Evaluate Neuropathic Pain in a Model of Cervical Radiculopathy.

Although neck and low-back pain are common sources of neuropathic pain with high societal costs, the pathophysiology of neuropathic pain is not well-defined. Traditionally, most rodent pain studies rely on evoked reflex-based testing to measure pain. However, these testing methods do not reveal spontaneous pain, particularly early after injury. The rat grimace scale (RGS) for quantifying spontaneous pain has been validated after visceral, incisional, orthopedic, and inflammatory insults but not neuropathic pain. The current study used a rat model of radiculopathy to investigate the time course of RGS, the effect of the NSAID meloxicam on RGS, and the reliability and consistency of RGS across testers. RGS values at baseline and at 3, 6, 24, and 48 h after cervical nerve root compression (NRC) that induced robust evoked pain responses were compared with those obtained after sham surgery. The RGS was also evaluated at 6 h after NRC in another set of rats that had received meloxicam treatment prior to surgery. At 6 h, NRC induced higher RGS scores (1.27 ± 0.18) than did sham surgery (0.93 ± 0.20), and scores remained above baseline for as long as 48 h. Treatment with meloxicam before NRC reduced RGS at 6 h to sham levels, which were lower than those of injury without treatment. The RGS was associated with very good interobserver reliability (intraclass correlation coefficient, 0.91) and excellent internal consistency (Cronbach α, 0.87). These findings suggest that RGS is a useful approach to identifying and monitoring acute neuropathic pain in rats.

Collagenoma in an African Clawed Frog (Xenopus laevis).

A 3-y-old female Xenopus laevis was reported for a gray mass on the abdomen. The frog was used for egg collection and was otherwise experimentally naïve. On physical exam, the frog was bright and active and had a firm, gray, lobulated mass (1.5 cm × 0.5 cm × 0.5 cm) in the cutaneous tissue of the left lateral abdomen. An excisional biopsy was performed under anesthesia, and the entire mass was removed and processed for histopathology. Microscopically, the dermis was greatly expanded by connective tissue with a marked decrease in the number of glands, and occasional degenerative glands were present. When stained with Masson trichrome, the excessive connective tissue stained blue, indicating that it was composed of collagen. With Verhoeff-van Gieson staining, the connective tissue stained bright red with an absence of black-staining material, demonstrating the presence of collagen and ruling out elastic fibers. In light of the morphology of the mass and the results of the special stains, the mass was diagnosed as a collagenoma. To our knowledge, this report is the first description of a collagenoma in X. laevis.

Evaluation of Presurgical Skin Preparation Agents in African Clawed Frogs (Xenopus laevis).

Despite the routine collection of oocytes from African clawed frogs (Xenopus laevis) for use in research, few studies have evaluated methods for preparing their skin for surgery. We evaluated 3 skin preparatory agents by examining their antibacterial efficacy and the gross and microscopic appearance of Xenopus skin after exposure. Frogs (n = 14) were sedated and treated (contact time, 10 min) with 0.9% sterile NaCl on one-half of the ventrum and with 0.5% povidone-iodine or 0.75% chlorhexidine on the other half. Bacterial cultures were obtained before and after skin treatment; bacteria were identified by mass spectrometry. To assess inflammation and degenerative changes, the incision sites were photographed and biopsied at 0, 1, and 7 d after surgery. We isolated at least 22 genera of bacteria from the skin of our frog population (mean ± SE, 5.21 ± 0.82 genera per frog). Iodine (2.00 ± 0.44 genera) and chlorhexidine (0.29 ± 0.76 genera) both had greater antimicrobial activity than did saline. Skin erythema did not correlate with treatment group. Histologic evidence of epidermal degeneration and necrosis was greater on days 1 and 7 after chlorhexidine treatment than after iodine or saline. In addition, frogs treated with chlorhexidine had a higher incidence of clinical illness associated with the exposure site. In summary, although chlorhexidine has adequate antimicrobial activity against organisms on X. laevis skin, it leads to skin damage and subsequent clinical complications. We therefore do not recommend chlorhexidine as a preoperative preparation agent in Xenopus.

Developmental differences in elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during Xenopus laevis development.

Although 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates, several frog species are insensitive to TCDD, especially during early life stages. Previous experiments with ranid frogs suggest that TCDD insensitivity results largely from rapid elimination. Recent studies in the African clawed frog (Xenopus laevis; family Pipidae) link low TCDD toxicity with the low binding affinity of aryl hydrocarbon receptors, which mediate the toxic effects of dioxin-like compounds. The present study sought to examine TCDD elimination in X. laevis embryos and tadpoles, enabling an integrated assessment of the relative roles of TCDD elimination and AHR-related mechanisms in TCDD insensitivity within a single frog species. Using tadpoles (stage 52-55; approximately 1 month old) exposed to [3H]TCDD, we observed that TCDD has a relatively short half life of 102.6 h, consistent with other frogs and much faster than reported clearance rates in developing fish. In contrast, TCDD elimination is much slower during early development. Embryos exposed during primary organogenesis (from stage 31-41, beginning approximately 36 h after fertilization) exhibited little TCDD elimination during the subsequent 96 h. Enhanced TCDD clearance in later developmental stages may follow the appearance of a functional digestive tract and the onset of feeding. These results suggest that rapid elimination is unlikely to contribute mechanistically to TCDD insensitivity during development of the cardiovascular system, which is significantly perturbed by TCDD in fish embryos.