4 Feb 2023, 11:11 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
This article argues the need for education and training of researchers carrying out animal studies on the fundamentals of experimental design (ED), as a key means of improving the reliability and reproducibility of preclinical results. The current landscape in ED education in Europe is presented, and we make the case for dedicated tutor-guided teaching of ED. With less than a day dedicated to it in many courses effective techniques for communicating key issues are needed. We have developed two approaches that transfer to experimental design teaching the case-study, problem-solving techniques known to be effective in other fields. They use realistic research scenarios to provoke discussion and engage learning. In one the scenario is for group discussion or informal or formal assessment with subsequent tutor-led discussion of key points. For this each scenario needs a clear statement of the purpose of the research study, simplified text outlining the comparisons and procedures, and a statement of the outcome measure. In the other approach, the scenario is used with freely-available software with a good graphical output to explore the sizing of experiments and the use of both sexes. Trainee feedback and informal assessment show that these approaches can make for interesting and memorable sessions and offer a useful contribution to improvement in experimental design teaching so that it produces meaningful learning that can translate into better practice.
3 Feb 2023, 2:25 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Culture of Care has been an integral part of Sanofi’s policy on animal protection for more than 15 years. Culture of Care goes beyond compliance with regulations and standards, since it relates to the attitudes of staff and to caring for research animals, as well as to the company’s commitment to an active animal protection policy. However, the concept of Culture of Care remains subjective. Via two anonymous and voluntary surveys conducted in 2018 and 2021, it was possible to understand the level of staff engagement and the perception of company efficiency. Based on key questions, it was possible to assess individual engagement (animal welfare knowledge, pride, engagement, recognition) and company commitments (oversight body efficiency, level of transparency, Sanofi policy on animal protection). The institutional scores were 7.7/10 and 7.9/10 obtained in 2018 and in 2021, respectively. The individual score obtained for 2018 was 6.7/10 compared to 6.9/10 obtained in 2021. The combination of these two criteria helps to determine a Culture of Care score and thus make it a performance indicator. The scores are CoC2018 (7.7; 6.7) and CoC2021 (7.9; 6.9). Being able to quantify this level of engagement and the perception that employees have of the company encourages the organisation of an improvement programme and helps measure the benefits.
3 Feb 2023, 2:24 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
Surgical embryo transfer in mice is a key technique in assisted reproduction and applied for different purposes in biomedical research. Due to its frequent application in rodent facilities across the world, further improvement of the procedure can substantially contribute to fulfil the principles of the 3Rs. Here, we investigated the effect of bilateral and unilateral left- or right-sided oviduct transfers on the success of embryo transfers. In total, we performed 223 embryo transfers (56 unilateral left, 56 unilateral right, 111 bilateral), in which we transferred 10–14 two-cell embryos each. We found that the type of transfer significantly influenced both the pregnancy rate of recipients and the survival rate of transferred embryos. Bilateral transfers yielded higher pregnancy and survival rates than left-sided unilateral transfers. Right-sided unilateral transfers yielded higher pregnancy rates than left-sided unilateral transfers and did not differ in embryo survival rates from bilateral transfers. We found no evidence that the number of transferred embryos affected the pregnancy rate. However, the number of born pups increased with the number of transferred embryos. In conclusion, unilateral embryo transfers into the right reproductive tract yield equally high pregnancy and embryo survival rates as bilateral transfers. Given that a second abdominal incision can be prevented and the time of surgery can be reduced, we recommend applying unilateral right-sided transfers, as this would reduce postoperative pain and lower the impact on recipients.
28 Jan 2023, 1:16 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
In the field of visual science study using rodents, several assessment methods have been developed for measuring visual function. However, methods such as electroretinograms tests, visual evoked potentials tests and maze tests have limitations in that they measure function of only a specific type of cells, are difficult to quantify or require sufficient training time. The method which uses an optokinetic reflex and optomotor response, a compensatory eye and head movement in response to changes in the visual scene, became the most widely used method. However, this method requires highly trained experimenters and is time consuming. We showed that measured visual acuity values are significantly different between beginner and expert. Here we suggest an automated optometry program, ‘SKY optomotry’, which automatically tracks rodents’ optomotor response to overcome subjectivity and the lengthy scoring procedure of the existing method. To evaluate the performance of SKY optomotry using 8–12-week-old C57BL/6 mice we compared the binomial decision of SKY optomotry with a skilled expert, and the area under the curve of SKY optomotry was 0.845. Comparing the final visual acuity, the intraclass correlation coefficient value between SKY optomotry and an expert was 0.860 (95% confidence interval (CI) 0.709–0.928), whereas that between an expert and a beginner was 0.642 (95% CI 0.292–0.811). SKY optomotry showed an excellent level of performance with good inter-rater agreements based on the visual acuity measured by an expert. With the use of our application, researchers will be able to test an experimental animal's eyesight more accurately while saving time on specialized training.
23 Jan 2023, 9:20 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Laboratory animal professionals (LAP) are faced with various situations and tasks influencing their mental well-being. A systematic review has been conducted to investigate whether there are specific stressors for LAP and which moderators are relevant for the development of psychological strain. A comprehensive search following PRISMA Guidelines was carried out in June 2021. Results include 12 studies and have been summarized qualitatively in narrative synthesis and tabular presentation. Available literature indicates that LAP are facing stressors but does not allow for conclusions on specific stressful job duties other than euthanasia.Signs of strain are present in LAP. Specifically, participants in qualitative studies reported acute symptoms, while chronic manifestations were in focus in quantitative studies. Although a wide variety of moderating factors have been investigated, only social support has been rated as relevant by multiple qualitative and quantitative studies without contrasting results.According to current data, there is a risk for psychological strain in LAP. However, there is limited understanding of specific stressors and data on moderators is diverse. Further studies that focus on domain-specific knowledge and clearly distinguish stressors from moderators are necessary to set up institutional programmes addressing psychological strain in LAP.
16 Jan 2023, 11:53 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Virtual education isn’t new. Teaching has been delivered remotely for many years, although it came to prominence with the enforced move to online learning during the COVID-19 pandemic. Technologies provide tools that are integral to our everyday lives, and training and assessment are no different. Stepping back from the obligatory remote delivery of practical skills training, now we have the opportunity to review and evaluate our own learning (as educators) about the value of resources for training delivery. Combining sound educational principles with the available technologies, we can use remotely delivered learning to enhance our teaching and to increase access to learning, without hindrance because of distance or the type of facility. Remote connections allow expertise and best practice to become suddenly available to a wider cohort of researchers, rapidly spreading new ideas about refinement of in vivo procedures and supporting colleagues to learn and develop. We currently use only a few of the technological tools available, and there is much to learn from other disciplines where virtual and augmented reality are assisting surgeons, aircraft pilots and others daily. By harnessing remote and assisted technologies in teaching, we can also develop the mindset and ability of the biomedical community to use them to augment, or even to replace, animal studies in future and to democratise training globally.
16 Jan 2023, 11:50 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
Pemphigus is a severe autoimmune bullous disease of the skin and/or mucous membranes caused by autoantibodies that mainly target the adhesion proteins desmoglein (Dsg) 3 and/or Dsg1. Clinically, pemphigus is characterized by flaccid blistering, leading to severe water and electrolyte loss. Before the introduction of corticosteroid treatment, the disease turned out to be fatal in many cases. Despite recent therapeutic improvements, treatment of pemphigus patients is centred on prolonged systemic immunosuppression and remains challenging. Current drug development for pemphigus has a strong focus on disease-causing B cells and autoantibodies and, more recently, also on modulating autoantibody-induced tissue pathology and keratinocyte signalling. This drug development requires reliable pre-clinical model systems replicating the pathogenesis of the human disease. Among those are neonatal and adult mouse models based on the transfer of Dsg3, Dsg1/3 or Dsg1-specific autoantibodies. To reduce the number of animal experiments, we recently established a standardized human skin organ culture (HSOC) model for pemphigus. This model reproduces the clinical phenotype of autoantibody-induced tissue pathology in pemphigus vulgaris. For induction of blistering, a recombinant single-chain variable fragment (scFv) targeting both Dsg1 and 3 is injected into pieces of human skin (obtained from plastic surgeries). Further characterization of the HSOC model demonstrated that key morphologic, molecular and immunologic features of pemphigus are being replicated. Thus, the pemphigus HSOC model is an excellent alternative to pemphigus animal model systems that are based on the transfer of (auto)antibodies.
16 Jan 2023, 1:12 am
Laboratory Animals
Laboratory Animals, Ahead of Print.
12 Jan 2023, 11:48 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
In this observational retrospective study, an outbreak of Staphylococcus aureus abscesses was correlated with the presence of sharp edges in damaged plastic environmental enrichment within the cages. In 2010, Lawson reported cases of S. aureus mandibulofacial and maxillofacial abscess in mice and proposed excessive barbering or grooming, leading to the mastication and fragmentation of hair, as an aetiopathogenesis of S. aureus abscesses. In contrast, in this study, the presence of hair was not found in any of the histopathology, and abscesses were present in the periorbital area. S. aureus colonises the skin, nasopharynx and intestines, and may cause pyogenic infections if a breach in local defences promotes staphylococcal invasion. Whole genome sequencing and analysis supported the hypothesis that this outbreak resulted from clonal expansion of S. aureus infected C57BL6/J mice imported into the area and infection transmission from humans to mice was ruled out. An additional aetiopathogenesis is proposed for S. aureus abscesses with the sharp edges of damaged plastic environmental enrichment items leading to oral mucosal injury allowing S. aureus entrance into tissues, its carriage into the submucosa, followed by abscess formation.
11 Jan 2023, 10:13 pm
Laboratory Animals
Laboratory Animals, Ahead of Print.
In experimental procedures inevitably leading to the sacrifice of animals, suitable measures should be taken to minimise their pain and suffering as much as possible, as well as to prevent any modification or masking in the experimental results obtained. An overdose of anaesthetic is the method of euthanasia most employed in fish, since it is effective and easy to apply. Our objectives were to compare the efficacy of eugenol and of tricaine methanesulfonate (MS-222) as euthanasia agents in zebrafish, and to make a histological evaluation of the possible effects derived from their application. The concentrations established for eugenol were 0.25 and 0.35 mg/mL, and those for MS-222 were 0.25 and 0.50 mg/mL, for both the buffered solution and the non-buffered one. Eugenol turned out to be a stronger euthanasia agent than MS-222 in zebrafish, presenting with significantly shorter euthanasia times. However, the exposure of the fish to euthanasia doses of eugenol triggered branchial alterations, in addition to serious lesions and changes in their nerve tissue. The results obtained with MS-222 also revealed a marked branchial alteration derived from its use. In this respect, the addition of a buffer to the MS-222 solution enhanced the effectiveness of the drug, with significantly shorter euthanasia times being achieved than with the non-buffered solution, and diminished the severity of the lesions described. We therefore determined that the buffered MS-222 solution is the most effective, reliable and safest method of euthanasia for use in research on zebrafish.