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Comparing United States and European Union academic animal programs: Organization, operation, and services offered.

The Yale Animal Resource Cost and Benchmarking survey©, conducted in US academic Animal Research/Resource Centers (ARC), was modified to capture similar thematic information in European Union (EU; including the non-EU countries Switzerland and the UK) academic ARCs, which are members of the League of European Research Universities (LERU). Participating institutions came from Denmark, England, Finland, France, Germany, Ireland, Italy, Netherlands, Scotland, Spain, and Switzerland. Survey data analysis suggests that: (a) in LERU programs, it is common to have more than one ARC under the umbrella of a single institution with organizational "lumping" of the financial, regulatory, and/or operational tasks under one administrative unit; (b) accreditation by an outside agency (e.g., the Association for the Assessment and Accreditation of Laboratory Animal Care) is more common in US than LERU ARCs; (c) LERU ARCs are responsible for murine breeding, which contrasts with US ARCs, where ∼40% of rodent breeding is managed by researchers; (d) cryopreservation is the most frequently requested fee-for-service offering among LERU participants (75% of participants) compared to 30% of US participants; (e) like US programs, almost all LERU programs have mice and rats, but fewer LERU programs have nonhuman primates (NHPs), and none have dogs on census; (f) LERU ARCs have about an equal amount of vivarium housing and procedure space, while US facilities have twice as much housing as procedure space; (g) a higher percentage of LERU colonies are free of Helicobacter and murine norovirus compared to US colonies; and (h) more LERU ARCs used environmental microbiologic monitoring of rodent colonies compared to US programs.

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Comparing United States and European Union academic animal programs: Finances.

The Yale Animal Resource Cost and Benchmarking survey, conducted in United States (US) academic animal research/resource centres (ARC), was modified to capture similar information in European Union (EU) (including the non-EU countries Switzerland and the United Kingdom) academic ARCs, who are members of the League of European Research Universities (LERU). Participating institutions came from Denmark, England, Finland, France, Germany, Ireland, Italy, Netherlands, Scotland, Spain and Switzerland. Survey data analysis suggests that (a) per diem rates have similar compositions in LERU and US programs, with >50% of the rates dedicated to recovering salary and fringe, followed by supplies (∼25%), facility costs (∼10%) and other expenses (∼15%); (b)  ∼60% of US and LERU programs under-recover mouse care costs; (c) on average, LERU programs have a small positive net-operating balance, while US programs average a large deficit; (d) in LERU programs <50% of institutions fund the animal program deficit, while in US programs almost 100% of such deficits are covered by the institution; and (e) when setting per diem rates, both US and LERU programs rank cost accounting as the most influential factor. Both US and LERU programs are reluctant to raise per diem rates to the extent required to recover costs and, thus, continue to under-recover costs, resulting in the animal program being 'caught in the middle' between the competing financial challenges of investigator 'affordability' and the animal program's fiduciary responsibility to the institution.

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Improving rat welfare through the development of a peribulbar anaesthesia technique for ophthalmic procedures: A preliminary study.

Rats are a commonly used animal model for the study of the pathogenesis and novel treatments of glaucoma, which is induced experimentally using invasive, painful procedures. Peribulbar anaesthesia (PBA) is frequently used in people and domestic animals prior to ophthalmic surgeries to provide excellent perioperative analgesia. Our goal was to develop a PBA technique adapted to rat anatomy, improving the welfare of animals used as a model for glaucoma. Eighteen rat cadavers (n = 36 eyes) were used to establish the optimal needle insertion location. Five injection techniques using 0.1 mL/100 g lidocaine 2% and a contrast agent (1:1 volume ratio) were compared via computed tomography (CT). CT images were scored for injectate distribution at four locations: extraconal, intraconal, around the optic nerve and at the orbital fissure (scale 0-8, where 0 = none and 8 = excellent). Median scores using the dorso-medial-75° (5; range 2-6) and medial-canthus (4.5; range 2-8) injection techniques were not different from the dorso-medial-45° (4; range 3-6) technique and were higher (better distribution) compared with mid-ventral (3; range 2-5) and ventro-lateral (2; range 1-3) techniques. The two superior techniques were used in two experimental rats (n = 4 eyes) to determine the volume of bupivacaine 0.5% necessary to affect corneal touch threshold (CTT) and periocular skin sensitivity (PSS). A volume of 0.05 mL/100 g decreased CTT and PSS for several hours, while a larger volume produced excessively long effects. Dorso-medial-75° or medial-canthus PBA using 0.05 mL/100 g bupivacaine are likely to provide ocular and periocular analgesia in rats, with minor transient adverse effects.

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Investigation of circulating infectious agents in experimental Beagle dogs of a production colony and three research facilities in China from June 2021 to May 2022.

To understand the epizootiologic characteristics of pathogens and opportunistic infections in one Beagle dog production colony and three research facilities, viruses and mycoplasma were detected in 1777 samples collected from Beagle dogs in China by polymerase chain reaction/reverse transcription polymerase chain reaction, and bacteria were isolated and identified by 16S rRNA sequence analysis. In addition, genotyping of the major circulating viruses was carried out by amplification of gene fragments and homology analysis. Canine coronavirus (CCoV), Escherichia coli, canine parvovirus (CPV), Bordetella bronchiseptica, Clostridium perfringens, Mycoplasma cynos, Klebsiella pneumoniae, Streptococcus canis, canine astrovirus (CaAstV), canine kobuvirus (CaKV), Pseudomonas aeruginosa, Proteus mirabilis, Macrococcus canis, Pasteurella canis, canine bocavirus (CBoV) and canine adenovirus (CAdV) were detected in the samples. Single, double, triple and quadruple infections accounted for 6.6%, 1.4%, 1.2% and 0.96% of samples, respectively. CCoV strains in 81 samples included three genotypes, CCoV-I, CCoV-IIa and CCoV-IIb, by analysis of S gene. The rate of single infection of CCoV-I, CCoV-IIa or CCoV-IIb was 19%, 38% or 7.4% respectively. The double and triple infection rates of CCoV were 32.8% and 2.5% respectively. All CPV strains in 36 samples belonged to CPV-2c. There were three amino acid differences in the Fiber protein of CAdV-positive sample QD2022, compared with the reference strain Toronto A26/61 and the vaccine strain YCA-18. These results suggest that CCoV and CPV are primary infectious agents, and that these two viruses were often identified in mixed infections, or coinfections alongside mycoplasma or other bacteria. These results will provide the basis for improvements in prevention and control of naturally occurring infectious diseases in Beagle dog production colonies and research facilities.

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Comparison of artery diameters in the Aachen minipig serving as a human intracranial in vivo model.

Minipigs are used as in vivo endovascular models, particularly in stroke and aneurysm research. However, detailed knowledge of the diameters of forelimb arteries that are commonly used as surrogates for human brain-supplying arteries are lacking. This study aimed to determine the diameters of forelimb and neck arteries in Aachen minipigs and to compare those to the diameters of human cerebral brain-supplying arteries in order to assess the validity of the Aachen minipig as a human intracranial in vivo model. We measured the diameters in the external carotid artery and eight different branches of the subclavian artery in 12 Aachen minipigs using angiographic imaging. Analysed arteries comprised the external carotid artery, axillary artery, brachial artery, subscapular artery first segment, subscapular artery second segment, external thoracic artery, caudal circumflex humeral artery, suprascapular artery and thoracodorsal artery. We compared these diameters to diameters of the following human brain-supplying arteries: terminal internal carotid artery (carotid-T and petrous segment), M1 segment of the middle cerebral artery, M2 segments of the middle cerebral artery, anterior cerebral artery, vertebral artery and basilar artery. Median diameters of porcine forelimb arteries ranged from 1.8 to 4.9 mm, and human brain supplying arteries ranged in diameter from 1.4 to 4.3 mm. Depending on the intended use, this allows porcine forelimb arteries to be selected which are statistically comparable to human brain-supplying vessels. In conclusion, we identified several equivalent arteries of the porcine subclavian branches that are comparable to human brain-supplying arteries. This may help to validate the minipig as a suitable in vivo model for neurovascular experiments.

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ERK1/2 modulation in the central nervous system of male and female thiamine-deficient mice with amprolium.

Thiamine deficiency experimental models focus on using the pyrithiamine analog in male rodents, making the thiamine deficiency effects in females and the use of other thiamine antagonists, such as amprolium, unknown. We investigated the impact of thiamine deficiency with amprolium in the cerebral cortex and thalamus of male and female mice by evaluating the modulation of ERK1/2 phosphorylation. The animals were exposed for 20 days to thiamine-deficient chow with different doses of amprolium (20, 40, 60 and 80 mg/kg) and at different treatment periods (five, 10, 15 or 20 days) at a dose of 60 mg/kg. After treatments, ERK1/2 phosphorylation was analyzed by western blot. In male mice, we observed a progressive increase in ERK1/2 phosphorylation in both the cerebral cortex and thalamus in response to the dose of amprolium. In females, ERK1/2 phosphorylation did not progressively increase in response to the amprolium dosage. However, an increase in phosphorylation at the higher doses of 60 and 80 mg/kg was observed. We observed a more intense increase in ERK1/2 phosphorylation in males' cerebral cortex and thalamus from 10 days onwards. In females, the ERK1/2 modulation profiles were similar. The results show that thiamine deficiency induction with amprolium is efficient, compatible with other recognized models that use pyrithiamine, showing changes in cell signaling in the nervous system. The study showed differences in response to thiamine deficiency with amprolium between male and female mice in relation to ERK1/2 phosphorylation and demonstrated that females respond positively to the method and can also be used as model animals.

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Evaluating rearing behaviour as a model-specific pain indicator in mouse osteotomy models.

To assess pain in mouse models of bone fractures, currently applied assessment batteries use combinations of clinical signs with spontaneous behaviours and model-specific behaviours, including walking and weight-bearing behaviour. Rearing behaviour - an upright position on the hindlimbs - has a motivational and an ambulatory component. Thus, rearing behaviour might have the potential to be an indicator for model-specific pain in mouse fracture models. To date, the assessment of rearing behaviour in bone fracture models using mice is only scarcely described. In this study, we aimed to determine whether the duration of rearing behaviour is affected by osteotomy of the femur in male and female C57BL/6N mice with external fixation (rigid vs. flexible) and could be an additional sign for model-specific pain, such as the presence of limping. Rearing duration was significantly decreased after osteotomy in male and female mice at 24 h, 48 h and 72 h, but was not affected by anaesthesia/analgesia alone. In male mice, the relative rearing duration increased over 72 h (both fixations) and at 10 days in the rigid fixation group but remained significantly lower in the flexible fixation group. In contrast, in female mice, no increase in rearing duration was observed within 72 h and at 10 days post-osteotomy, independent of the fixation. We did not identify any association between relative rearing time and presence or absence of limping. In summary, our results do not provide sufficient evidence that altered rearing behaviour might be an indicative sign for pain in this model.

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Perceived professional quality of life and mental well-being among animal facility personnel in Spain.

Animal facility personnel provide the husbandry and care of laboratory animals. We aimed to investigate their work-related quality of life, empathy and mental well-being. Participants living in Spain were contacted by email and asked to complete an anonymous online questionnaire, in which they answered the Professional Quality of Life scale, the Cognitive and affective empathy test, the Warwick-Edinburgh Mental Well-Being Scale, and their perceived human-animal interaction. Participants were asked whether they were receiving psychological therapy or were taking anxiolytics, hypnotics or antidepressant medication. The study comprised 80 participants. No differences were observed related to personal or professional variables. Participants working with small carnivores reported higher total empathy, and those working with non-human primates reported higher emotional comprehension. Higher human-animal interaction was reported by participants working with small carnivores, farm animals and non-human primates. More than half of the participants reported high levels of mental well-being, positively correlated with emotional comprehension, emphatic joy and compassion satisfaction. Participants working with farm animals reported higher levels of secondary traumatic stress that was positively correlated with human-animal interaction and negatively with mental well-being. Most participants reported low-average levels of burnout, which was negatively correlated with mental well-being. The percentage of animal facility personnel in psychotherapy was higher than in the general population, and the consumption of anxiolytics was a little lower and antidepressants higher. Overall, our results indicate that animal-facility personnel who felt stress or worse mental well-being were in therapy and took medication to improve their condition.

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