Journal of the American Association for Laboratory Animal Science : JAALAS最新文献

Advancements in laboratory animal training increasingly incorporate technological innovations aiming to better align training standards with the 3Rs (Replacement, Reduction, and Refinement). This trend is shifting away from traditional reliance on live animals and cadavers toward simulation-based methods. This study introduces and assesses the validity of a novel 3D-printed rodent surgical simulator designed for the practice and training of basic rodent surgical skills. To evaluate its potential to partially replace animal use, refine rodent surgical training, and reduce the number of animals needed, a multicenter validation study across 5 European and US research academic centers was conducted. The study assessed the simulator's face, content, and construct validity, involving participants inexperienced and experts in rodent surgery. The construct validity was evaluated through task completion times and blinded quality assessments across multiple training iterations. The results revealed that inexperienced participants demonstrated significant improvements in both speed and quality of surgical tasks with repeated simulator use, eventually reaching performance levels comparable to experts' initial attempts. Expert participants consistently outperformed the inexperienced group. Face and content validity were supported by postuse surveys, with high ratings from both groups regarding the simulator's anatomic realism and its perceived usefulness for the acquisition and development of fundamental surgical skills. Overall, the findings of this study support that this 3D-printed rodent surgical simulator offers a realistic, effective, and ethically sound alternative for basic rodent surgical skills training and competency assessment.

Professional identity formation (PIF) is the dynamic psychosocial process crucial to becoming enculturated into a profession. This nonlinear process starts with entrance into a training program and ideally results in the harmonization of norms, values, and aspirations of the person with those of the chosen field. PIF is most successful when trainees can reflect, have positive role models and mentors, and receive social validation. Those who experience lack of support or hardship during PIF are at risk of burnout and poor mental health during their careers. Medical education research indicates that residency training significantly impacts PIF. This occurs because residents' new patient care responsibilities force them to grapple with the differences between the ideal practice taught in medical school and the realities of their work lives. Emerging evidence in veterinary medical education research indicates that residents enrolled in laboratory animal medicine (LAM) residency programs experience similar tensions as they navigate relationships with stakeholders, encounter conditional valuation of their veterinary knowledge, and feel powerless to enact changes. To explore best practices for supporting PIF for developing LAM veterinarians, we performed a qualitative analysis of written comments from surveys completed by attendees at the 2022 American College of Laboratory Animal Medicine Forum meeting. Results were organized by 5 themes: (1) empowering residents to step into their authority and understand the limitations of their roles, (2) providing support for learning about the complexities of relationships within LAM, (3) serving as role models and mentors in building relationships, (4) creating opportunities to learn professional communication, and (5) advocating for the specialized and explicit value of the profession (LAM). From these results, we constructed a model that illustrates the PIF process for LAM veterinarians in training, with the goal of raising awareness of the connection between the quality of PIF and career wellness.

Campylobacter jejuni is a pathogenic bacterium commonly associated with enteritis and diarrhea in rhesus macaques (Macaca mulatta). The standard therapy at the California National Primate Research Center is oral azithromycin, a second-generation macrolide, given daily for 5 d. Oral treatment administration can be difficult with some animals. Poor oral compliance for antibiotics can result in treatment failure and potentially select for antibiotic resistance. Tulathromycin, a newer-generation macrolide, may offer an injectable alternative to azithromycin. The aim of the current study is to quantify the pharmacokinetics of tulathromycin in plasma in rhesus macaques. Six rhesus macaques were each given a single 2.5 mg/kg dose SC of tulathromycin, and serial blood samples were collected at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120, and 168 h, to quantify the concentration of tulathromycin in plasma over time. Results show that Cmax = 1,280 ± 395 ng/mL, Tmax = 1.25 ± 0.5 h, t1/2 = 77.2 ± 15.4 h, and AUC0-168 = 6,557.4 ± 875.4 h·ng/mL. There are no published Clinical and Laboratory Sciences Institute breakpoints for tulathromycin against C. jejuni, but based on an independently established minimum inhibitory concentration of 500 ng/mL, these data suggest that 2.5 mg/kg tulathromycin can be given subcutaneously to achieve potential therapeutic levels in rhesus macaques, possibly providing an alternative to oral azithromycin.

Yorkshire piglets serve as valuable animal models in biomedical research, including partial heart transplantation research. This study characterizes the swine leukocyte antigen (SLA) diversity within a cohort of 16 Yorkshire piglets, including 5 genetically modified to express green fluorescent protein (GFP). Employing SLA typing, we identified 25 unique SLA class I alleles (9 SLA-1, 11 SLA-2, 5 SLA-3) and 17 unique SLA class II alleles (8 DRB1, 6 DQB1, 3 DQA). Notably, an allele of SLA-1*08:XX was detected in 75% of the piglets, while haplotypes Lr-7.26 and Lr-6.12b were most frequent, occurring at 18.75%. Comparative analysis with previous studies revealed consistent genetic trends, although differences in haplotype frequencies underscore the influence of breeding practices and sample size on SLA allele and haplotype distribution. Our findings highlight the significant polymorphism in the SLA complex of Yorkshire piglets, which is relevant for their utility as preclinical models for studying transplantation outcomes. The characterization of GFP piglets provides crucial genomic data for future research in cell tracking and graft integration. While the study's relatively small cohort may limit its generalizability, it represents the first baseline SLA typing of GFP Yorkshire piglets, offering foundational insights into their genetic diversity. This work emphasizes the importance of standardized genetic mapping to enhance the reproducibility and utility of laboratory swine in biomedical research.

Aged mice are becoming increasingly important models for human senescence. Many studies require anesthesia. Standard rodent ketamine/xylazine injectable regimens have been associated with increased incidences of death, unreliable surgical planes, and prolonged recoveries in geriatric mice. We hypothesized that the addition of atipamezole reversal and higher doses of ketamine or xylazine would result in a more reliable surgical plane of anesthesia and quicker recovery in geriatric mice without increasing mortality. Mice (n = 6 per group) were subjected to one of 3 anesthetic regimens: 100 mg/kg ketamine and 10 mg/kg xylazine without reversal (Standard); 150 mg/kg ketamine and 10 mg/kg xylazine with 1 mg/kg atipamezole reversal (High Ketamine); or 100 mg/kg ketamine and 15 mg/kg xylazine with 1 mg/kg atipamezole reversal (High Xylazine). While anesthetized, righting reflex, pedal withdrawal reflex, heart rate, respiratory rate, arterial oxygen saturation (SpO2), and temperature were recorded. While both experimental groups provided a more consistent surgical plane of anesthesia, the High Ketamine group had both the longest anesthetic period and the highest mortality (33.3%). The High Xylazine group had moderate mortality (16.6%) and a comparable anesthetic period to the Standard regimen, along with a superior SpO2 to both groups. Atipamezole reversal led to a faster return of righting reflex and an increase in SpO2 but did not affect the total length of recovery compared with the Standard group that did not include a reversal agent. Overall, the High Xylazine group provided a more reliable surgical plane to the Standard group in geriatric mice but increased mortality (16.6%), and the addition of atipamezole as a reversal agent did not significantly change the length of recovery. The information gained from this study can help guide decisions regarding the use of ketamine and xylazine in geriatric mice for surgical procedures or lengthy procedures for which redosing might be necessary.

Establishing a screening method for rodent pathogens is an integral component of an institution's rodent health surveillance program. Most rodent quarantine programs use direct colony sampling (DCS) from live animals for pathogen PCR testing. DCS may elicit undue stress to the animal and be time consuming, contingent on the number of quarantined animals. Sentinel-free soiled bedding (SFSB) sampling has previously been used to monitor the pathogen status of research rodents. A pilot study was conducted to determine the feasibility of an SFSB-based quarantine by comparing it to DCS for the evaluation of pet shop mice of different age ranges. Enhanced detection by SFSB for the 6- to 10-wk age range supported further investigation. The subsequent main study evaluated whether SFSB sampling is as effective as traditional DCS for detecting rodent pathogens. We hypothesized that SFSB contact media sampling is either equivalent to or more effective than DCS for detecting pathogens in quarantined mice. The study included mice imported from various institutions between October 2023 and August 2024. The DCS and exposed contact media were tested using PCR analyses. The total number of positive agent assay detections by DCS was 157, compared with 173 with the SFSB method. These results suggest that contact media sampling provides equivalent or superior detection of rodent pathogens compared with the DCS method. Although not statistically significant, it was observed that delaying sample submission decreased detection rates for 2 RNA viruses: 80% for murine astrovirus-1 (MuAstV1; 4 out of 5 samples) and 67% for genogroup V norovirus (MNV; 4 out of 6 samples). Immediate submission restored the detection rate to 100% for MuAstV1 and 91% for MNV. To conclude, SFSB rapid submission during quarantine provides a reliable and effective alternative to the traditional DCS method for the detection of rodent pathogens. This nonintrusive methodology mitigates stress during sampling while enhancing the effectiveness and sensitivity of pathogen detection.

Pharmaceutical-grade medium-chain triglycerides (MCTs) are common excipients for in vivo pharmacological studies in laboratory animals and as an experimental therapeutic in certain metabolic and neurologic disorders. In this study, we examined the tolerability of repeated administration of a pharmaceutical-grade formulation of 3 MCTs-caprylic, capric, and lauric acid-in mice via the oral and intraperitoneal routes. We administered either 8 or 4 µL of 100% MCTs or saline/gram of body weight (∼7.56 or 3.78 g/kg, respectively) twice daily for 7 d. During administration, and for 7 d after, we monitored weight change and clinical presentation. On day 14, or upon meeting euthanasia criteria, animals were sacrificed for gross necropsy, histology, and CBC. We observed significant weight loss, clinical decline, and 100% mortality in animals receiving 8 µL/g MCTs via the intraperitoneal route of administration. Gross necropsy revealed serosanguinous fluid in the thoracic cavity, dark red mottled lungs, and adhesions in the abdominal cavity. Histology confirmed inflammation of the lungs, mediastinum, and peritoneum. Mild pathology and initial weight loss (through day 3) were also present in mice receiving 4 µL/g MCTs IP. However, these animals regained weight by day 7 and exhibited no clinical decline or mortality. These adverse effects were not seen in animals receiving either 8 µL/g MCTs PO or 8 µL/g saline IP. These findings suggest that repeated intraperitoneal administration of MCTs may cause dose-dependent toxicity and mortality at high doses, but it confers no adverse effects when administered via the oral route.

Peripheral venous access in rabbits can be difficult to obtain. When failure occurs, there is a dire need for alternative vascular access routes to be available. The AVMA categorizes intrarenal injection of pentobarbital as acceptable with conditions for euthanasia. Animals must be in an unconscious state, and only minimal studies using intrarenal administration have been reported. A total of 53 rabbits were used to conduct 3 separate analyses to assess and measure the efficacy, efficiency, and validity of the intrarenal route for euthanasia in New Zealand White rabbits by assessing the time to cardiopulmonary arrest (TCPA). Animals were sedated with 40 mg/kg ketamine and 50 μg/kg dexmedetomidine intramuscularly into the lumbar muscles, and timing started at the beginning of the injection and ended when cardiac and respiratory arrest were observed. Cardiac and respiratory arrest following intravenous injection of pentobarbital was significantly quicker (cardiac, 6 to 24 s, median 9 s; respiratory, 6 to 19 s, median 9 s; P < 0.001) than for the intrarenal route (cardiac, 40 to 900 s, median 411 s; respiratory, 23 to 900 s, median 120 s; P < 0.001), with no negative animal reactions observed during euthanasia injection performance. Four animals did not achieve TCPA within 15 min after administration. Although TCPA was longer with intrarenal compared with intravenous euthanasia (P < 0.001), this study demonstrates that the intrarenal approach under anesthesia is a feasible alternative to the intravenous approach, as it can be reliably performed without observed animal distress or alterations in organ pathology. The overall information from this study can help guide both laboratory and practicing clinicians considering this technique. Still, factors such as variable times to cardiopulmonary arrest and technical skill should be considered.

Anesthesia is commonly performed with mice in the research setting. Standard doses of anesthetic drugs are typically recommended, without customization to strain, substrain, or sex. The purpose of this study was to evaluate C57BL/6 substrain and sex differences in response to isoflurane and ketamine/xylazine/acepromazine (KXA) injectable anesthesia. Female and male C57BL/6NTac, C57BL/6J, C57BL6/6NHsd, and C57BL/6NCrl mice were sourced from 4 different vendors. Isoflurane anesthesia trials were performed with a subset of the mice (n = 24) to determine the minimum alveolar concentration (MAC). Loss of righting reflex, total loss of righting time, time to loss of pedal withdrawal reflex, and total time at surgical plane were evaluated for mice (n = 64) administered 100 mg/kg ketamine, 10 mg/kg xylazine, and 1 mg/kg acepromazine by intraperitoneal injection. Heart rate, respiratory rate, and hemoglobin oxygen saturation (SpO2) were monitored throughout each anesthetic event. Isoflurane MAC was not affected by sex or substrain. In the KXA trials, male mice exhibited a longer duration of loss of righting reflex and remained at a surgical plane of anesthesia significantly longer than the female mice. No significant differences in substrain were detected in the depth or duration of anesthesia. Evaluation of physiologic parameters revealed differences in heart rate between substrains, with C57BL/6NHsd mice exhibiting significantly lower heart rates than the other 3 substrains during both isoflurane and KXA anesthesia. C57BL/6J mice had the highest heart rates during KXA anesthesia. These heart rate differences can impact clinical monitoring practices and are important to consider when selecting strains for study models, especially for cardiovascular studies. In conclusion, the male C57BL/6 mice exhibited a longer duration of anesthesia in response to KXA, while no substrain differences were detected for anesthetic depth or duration of either isoflurane or KXA anesthesia.

In this study we investigated the sedative, anesthetic, and pulmonary histopathologic effects of dexmedetomidine/morphine (DM) and xylazine/morphine (XM) in sheep. We hypothesized that DM would provide profound sedation and better maintain physiologic parameters under anesthesia than XM in sheep undergoing laparoscopic surgery. Nineteen male sheep were premedicated with either DM (dexmedetomidine [0.006 mg/kg] and morphine [0.3 mg/kg]) or XM (xylazine [0.1 mg/kg] and morphine [0.3 mg/kg]). After DM or XM administration, 3 blinded veterinarians evaluated sedation scores (0 [no sedation], 1 [mild], 2 [moderate], 3 [severe]). Sheep were induced with intravenous tiletamine/zolazepam, intubated, and maintained with isoflurane in 100% oxygen. Anesthetic parameters were monitored for 60 min, including heart rate, respiratory rate, indirect blood pressure, oxygen saturation, end-tidal carbon dioxide, body temperature, arterial blood gas analysis, and isoflurane requirement. At the end of the procedure, the sheep were euthanized, and lung pathology (pulmonary edema) was assessed. The results showed that the sedation scores did not differ between DM (0.8 [0.4 to 1.0]) and XM (1.0 [1.0 to 1.0]). In addition, the anesthetic parameters were comparable between the groups, but the DM group exhibited a higher heart rate than the XM group. Finally, marked pulmonary changes, consistent with pulmonary edema, were observed in the XM group. In conclusion, DM and XM provided similar sedation and physiologic stability under isoflurane anesthesia, but DM may help minimize bradycardia and was associated with less evidence of pulmonary edema.