Laboratory animal ethics education improves medical students' awareness of laboratory animal ethics.

OBJECTIVE: In this study, we added laboratory animal ethics education into both didactic sessions and practical sessions the general surgery laboratory course, with the didactic sessions focus on teaching the fundamental principles of laboratory animal ethics, while the practical sessions emphasize the application of these principles in laboratory classes and have assessed the changes in medical students' perception of laboratory animal ethics following medical students exposure to such education. METHODS: One hundred and eighty-nine third-year medical students from Wuhan University's Second Clinical College completed a laboratory animal ethics awareness questionnaire and a laboratory animal ethics written examination before and after laboratory animal ethics education. RESULTS: After receiving laboratory animal ethics education, the percentage of students who supported euthanasia for the execution of animals and humane treatment of laboratory animals were 95.2% and 98.8%, respectively, which did not differ from the 94.9% and 96.4% observed before the education. Moreover, there was a notable increase in the proportion of students who knew about regulations related to laboratory animals (from 39.9% to 57.1%), welfare issues (from 31.9% to 50.0%), and the 3R principle (from 30.4% to 58.9%) post-education, all statistically significant at P < 0.05. Test scores also showed improvement, with students scoring (93.02 ± 11.65) after education compared to (67.83 ± 8.08) before, a statistically significant difference. CONCLUSIONS: This research helps to provide information for the good practices of laboratory animal ethics education. After receiving laboratory animal ethics education, students are better able to treat laboratory animals in a correct animal ethical manner. Laboratory animal ethics education helps improve students' knowledge of laboratory animal ethics. Students' perception towards how the laboratory animal ethics course should be delivered may vary. Still, new courses or better organized courses on laboratory animal ethics education are required in order to provide students an in-depth understanding.

La relevancia moral del dolor de animales de experimentación y de producción / The moral relevance of pain in experimental and production animals

RESUMEN: El aspecto emocional del dolor no solo es controvertido en aves, peces y roedores, sino también en los seres humanos autoconscientes. Cuando el dolor emocional, o la insatisfacción, es vista como un mal intrínseco, evitarla o, al menos, minimizarla es un deber moral directo. El objetivo de este artículo es mostrar que no solo los modelos animales mamíferos que se utilizan en experimentación -rata (Rattus norvegicus) y ratón (Mus musculus)- sienten dolor, como reconocen universalmente las instituciones que se ocupan del bienestar animal, sino también los peces de laboratorio (Danio rerio) y los de producción (Salmo salar), y que este hecho es moralmente relevante desde el punto de vista de todas las concepciones de la moral que suelen enfrentarse en los debates morales públicos y académicos. En consecuencia, también en el caso de los peces habría que tener en cuenta indicadores de bienestar animal.

SUMMARY: The emotional aspect of pain is not only controversial in fish and rodents, but also in self-conscious humans. When pain or dissatisfaction is seen as an intrinsic evil, avoiding it or at least minimizing it is a moral duty direct. The objective of this article is to refer to pain, stress and the most widely used indices of animal welfare both in laboratory fish (Danio rerio) and production fish (Salmo salar) as well as in rat experimental animal models (Rattus norvegicus) and mouse (Mus musculus).

Ethical considerations in animal research: the principle of 3r's

In the last century, progress in the knowledge of human diseases, their diagnosis and treatment have grown exponentially, due in large part to the introduction and use of laboratory animals. Along with this important progress, the need to provide training and guidance to the scientific community in all aspects related to the proper use of experimental animals has been indispensable. Animal research committees play a primary role in evaluating experimental research protocols, from their feasibility to the rational use of animals, but above all in seeking animal welfare. The Institutional Committee for the Care and Use of Animals (IACUC) has endeavored to share several relevant aspects in conducting research with laboratory animals. Here, we present and discuss the topics that we consider of utmost importance to take in the account during the design of any experimental research protocol, so we invite researchers, technicians, and undergraduate and graduate students to dive into the fascinating subject of proper animal care and use for experimentation. The main intention of these contributions is to sensitize users of laboratory animals for the proper and rational use of them in experimental research, as well as to disseminate the permitted and unpermitted procedures in laboratory animals. In the first part, the significance of experimental research, the main functions of IACUC, and the principle of the three R's (replacement, reduction, and refinement) are addressed.

Automated and Continuous Monitoring of Animal Welfare through Digital Alerting.

A primary goal in preclinical animal research is respectful and responsible care aimed toward minimizing stress and discomfort while enhancing collection of accurate and reproducible scientific data. Researchers use hands-on clinical observations and measurements as part of routine husbandry procedures or study protocols to monitor animal welfare. Although frequent assessments ensure the timely identification of animals with declining health, increased handling can result in additional stress on the animal and increased study variability. We investigated whether automated alerting regarding changes in behavior and physiology can complement existing welfare assessments to improve the identification of animals in pain or distress. Using historical data collected from a diverse range of therapeutic models, we developed algorithms that detect changes in motion and breathing rate frequently associated with sick animals but rare in healthy controls. To avoid introducing selec- tion bias, we evaluated the performance of these algorithms by using retrospective analysis of all studies occurring over a 31-d period in our vivarium. Analyses revealed that the majority of the automated alerts occurred prior to or simultaneously with technicians' observations of declining health in animals. Additional analyses performed across the entire duration of 2 studies (animal models of rapid aging and lung metastasis) demonstrated the sensitivity, accuracy, and utility of automated alerting for detecting unhealthy subjects and those eligible for humane endpoints. The percentage of alerts per total subject days ranged between 0% and 24%, depending on the animal model. Automated alerting effectively complements standard clinical observations to enhance animal welfare and promote responsible scientific advancement.

Ethics and Policy for Bioprinting.

3D bioprinting involves engineering live cells into a 3D structure, using a 3D printer to print cells, often together with a compatible 3D scaffold. 3D-printed cells and tissues may be used for a range of purposes including medical research, in vitro drug testing, and in vivo transplantation. The inclusion of living cells and biomaterials in the 3D printing process raises ethical, policy, and regulatory issues at each stage of the bioprinting process that include the source of cells and materials, stability and biocompatibility of cells and materials, disposal of 3D-printed materials, intended use, and long-term effects. This chapter focuses on the ethical issues that arise from 3D bioprinting in the lab-from consideration of the source of cells and materials, ensuring their quality and safety, through to testing of bioprinted materials in animal and human trials. It also provides guidance on where to seek information concerning appropriate regulatory frameworks and guidelines, including on classification and patenting of 3D-bioprinted materials, and identifies regulatory gaps that deserve attention.

The current state of animal models in research: A review.

Animal models have provided invaluable information in the pursuit of medical knowledge and alleviation of human suffering. The foundations of our basic understanding of disease pathophysiology and human anatomy can largely be attributed to preclinical investigations using various animal models. Recently, however, the scientific community, citing concerns about animal welfare as well as the validity and applicability of outcomes, has called the use of animals in research into question. In this review, we seek to summarize the current state of the use of animal models in research.

Humane endpoint in mice by Brazilian researchers in the vaccine sector / Ponto final humanitário em camundongos aplicado por pesquisadores brasileiros da área de vacinas

The application of a humane endpoint (HE) for mice in vaccine trials and further challenging tasks with lethal samples is necessary to reduce or prevent pain and suffering in these animals, and is a refinement of the 3R policy enforced for animal testing in both national and international scenarios. In order to investigate the application of HE in Brazil, researchers from the vaccine sector have answered a questionnaire about their research profile, their usage of HE and their knowledge of its defining criteria, monitoring of animals, staff training, and euthanasia methods employed. The main results revealed that researchers failed to recognise the very concept of HE as well as when to apply it. In addition, the Institutional Animal Care and Use Committees (IACUCs) failed upon giving their approval to the trials. HE is an important refinament of animal testing policy, and these results highlight the need for a clear pre-established definition of when and how it should be implemented in order to ensure more effective application. Furthermore, it is important to clarify the ethics involved and the commitment of both the research teams and IACUCs to animal welfare.(AU)

A aplicação de um ponto final humanitário (PFH) em experimentos com vacinação e posterior desafio com amostras letais em camundongos é necessária para diminuir ou impedir a dor e o sofrimento desses animais, constituindo refinamento de acordo com a política dos 3Rs, vigente em âmbito nacional e internacional, no cenário da experimentação animal. A fim de investigar a aplicação de PFH no Brasil, foi enviado um questionário para pesquisadores da área de vacinas, com perguntas sobre perfil do pesquisador, aplicação de PFH e critérios para sua definição, monitoramento dos animais, treinamento da equipe e métodos de eutanásia empregados. Os principais resultados revelaram que há falhas tanto em reconhecer o conceito quanto em aplicar o PFH, por parte dos pesquisadores, e que as CEUAs também falharam ao aprovar tais experimentos. Chama-se atenção para o fato de que o PFH é um importante refinamento e para a necessidade de definição prévia de PFH e sua aplicação, assim como para a importância do esclarecimento da questão ética envolvida e do necessário compromisso das equipes de pesquisa e das CEUAs com o bem-estar animal.(AU)

A non-living, effective model for microvascular training

Abstract Purpose: To introduce a nonliving microvascular training model based on vessels diameter and feasibility. Methods: We dissected ten oxen tongues, and divided the pedicles into three-thirds: proximal, middle and distal. We measured the external vessels diameter in all regions. We performed a descriptive statistical analysis. Three students (two beginner level and one intermediate level) performed this training. We evaluated the confidence, according Likert scale. Results: We dissected all oxen tongues, each tongue showed two parallel pedicles. Each pedicle was located at 1.5 - 2.0 cm from the midline. Proximal median artery and vein diameter were 3.9 ± 0.7, and 5.04 ± 1.44mm, respectively. In the middle third, the mean artery diameter was 3.3 ± 0.4mm, and the vein diameter was 3.5 ± 0.9mm. The distal third showed a mean artery diameter of 2.0 ± 0.42mm, and a vein diameter of 2.4 ± 0.82mm. The students performed ten anastomoses. This study showed a higher confidence level (CL) (p=0.03) than the pre training CL assessment. Conclusion: This study suggested a feasible non-animal model for microsurgical training process for beginners and intermediate trainees.

Separate the Sheep from the Goats: Use and Limitations of Large Animal Models in Intervertebral Disc Research.

Approximately 5,168 large animals (pigs, sheep, goats, and cattle) were used for intervertebral disc research in identified studies published between 1985 and 2016. Most of the reviewed studies revealed a low scientific impact, a lack of sound justifications for the animal models, and a number of deficiencies in the documentation of the animal experimentation. The scientific community should take suitable measures to investigate the presumption that animal models have translational value in intervertebral disc research. Recommendations for future investigations are provided to improve the quality, validity, and usefulness of animal studies for intervertebral disc research. More in vivo studies are warranted to comprehensively evaluate the suitability of animal models in various applications and help place animal models as an integral, complementary part of intervertebral disc research.

Animal ethics and welfare education in wet-lab training can foster residents' ethical values toward life.

Live animals are used in surgical skills training in wet lab, which has undeniable effectiveness for the development of future surgeons. However, where such training is provided, animal welfare is a major consideration. Increasingly, institutions that offer wet-lab training are incorporating animal ethics and welfare-related content into their training courses, but the effectiveness of such animal ethics education has yet to be evaluated quantitatively. We investigated whether the animal ethics content of a training course affected trainees by measuring increase in ethical awareness using visual analog scale questionnaires before and after training. Our results demonstrated a significant and positive increase in awareness of animal ethics (significance level of 5%; 0.0380≤P≤0.0016).

Human tissues in a dish: The research and ethical implications of organoid technology.

The ability to generate human tissues in vitro from stem cells has raised enormous expectations among the biomedical research community, patients, and the general public. These organoids enable studies of normal development and disease and allow the testing of compounds directly on human tissue. Organoids hold the promise to influence the entire innovation cycle in biomedical research. They affect fields that have been subjects of intense ethical debate, ranging from animal experiments and the use of embryonic or fetal human tissues to precision medicine, organoid transplantation, and gene therapy. However, organoid research also raises additional ethical questions that require reexamination and potential recalibration of ethical and legal policies. In this Review, we describe the current state of research and discuss the ethical implications of organoid technology.

Microsurgical Training with the Three-Step Approach.

Background Microsurgery is very challenging, requiring a high degree of dexterity and manual skills that should be fully trained outside of the operating room. Common microsurgery courses usually follow a stepwise training approach beginning practice on nonliving models and proceeding with live rats. However, training on live rats raises certain issues, including ethical concerns as well as the associated costs. As such, there is an increasing drive toward alternative models. The current article describes a three-step training approach (latex glove-endovascular prosthesis-human placenta), which aims to prepare trainees for the clinical direct application. Also, to validate it, this approach was compared with microsurgical training on rats. Methods Overall, 20 residents were randomly assigned to two different microsurgical training courses, each based on one of the aforementioned approaches. Residents were evaluated in terms of correct handling of the instruments, correct use of the microscope, adventectomy, triangulation technique, posterior wall technique, success of the end-to-end anastomosis, and ability in assisting the tutor during the arterial anastomosis. Results The three-step and the live rats groups evidenced similar scores in term of acquired basic skill levels. Conclusions The three-step model allows to progressively gain skills on microsurgical techniques and to perform a good vascular anastomosis without the need of further steps on rats. The availability of both endovascular prosthesis and human placenta makes this training model definitely accessible from a practical and logistical point of view.

A non-living, effective model for microvascular training.

PURPOSE: To introduce a nonliving microvascular training model based on vessels diameter and feasibility. METHODS: We dissected ten oxen tongues, and divided the pedicles into three-thirds: proximal, middle and distal. We measured the external vessels diameter in all regions. We performed a descriptive statistical analysis. Three students (two beginner level and one intermediate level) performed this training. We evaluated the confidence, according Likert scale. RESULTS: We dissected all oxen tongues, each tongue showed two parallel pedicles. Each pedicle was located at 1.5 - 2.0 cm from the midline. Proximal median artery and vein diameter were 3.9 ± 0.7, and 5.04 ± 1.44mm, respectively. In the middle third, the mean artery diameter was 3.3 ± 0.4mm, and the vein diameter was 3.5 ± 0.9mm. The distal third showed a mean artery diameter of 2.0 ± 0.42mm, and a vein diameter of 2.4 ± 0.82mm. The students performed ten anastomoses. This study showed a higher confidence level (CL) (p=0.03) than the pre training CL assessment. CONCLUSION: This study suggested a feasible non-animal model for microsurgical training process for beginners and intermediate trainees.

Brazilian attitudes towards the use of animals in research / Atitudes de brasileiros no uso de animais em pesquisa

Little research has examined the views of Latin Americans on the use of animals in research. This study examined the degree to which Brazilians support the use of animals in research and the reasons they put forth to explain their position. Participants were randomly assigned to research scenarios describing the use of animals for biomedical or environmental benefits, and varying in the number of pigs required. Each scenario began by proposing the use of conventional pigs and then advanced to the development and use of genetically modified animals (GMA). A total of 151 quantitative and 307 qualitative answers were analysed. Scenario and number of animals had little effect on support, but opposition increased from 25% to 58% when pigs were used to develop a GM strain for the environmental scenario. Support to use of animals was often conditional upon adequate protection of the animals' welfare. Participants were less willing to support research on environmental scenario when this involved the creation of GMA, in part because they feared the risk associated with this technology.(AU)

Há poucos estudos sobre a opinião de latino-americanos quanto ao uso de animais em pesquisa. Este estudo avaliou o grau de apoio e as motivações de brasileiros em relação a essa questão. Os participantes foram aleatoriamente apresentados a dois cenários, um biomédico e outro ambiental, variando também o número de animais usados. Cada cenário se iniciava com o uso de suínos convencionais e prosseguia com o desenvolvimento e uso de animais geneticamente modificados. Foram analisadas 151 respostas quantitativas e 307 qualitativas. O cenário e o número de animais tiveram pouco efeito no apoio ao uso dos animais, no entanto, a oposição aumentou de 25% para 58% quando o uso de suínos geneticamente modificados foram apresentados no cenário ambiental. O apoio ao uso de animais em pesquisa estava frequentemente condicionado ao grau de bem-estar animal, e o apoio à pesquisa diminuiu com o uso de animais geneticamente modificados, em parte, devido aos riscos associados a essa tecnologia.(AU)

Evolución de aspectos bioéticos de la experimentación en animales: el origen del concepto "cruelty free" / Evolution of bioethical aspects of experimentation in animals: the origin of the concept "cruelty free"

Existe una preocupación creciente por los aspectos éticos involucrados en el uso de animales en los distintos aspectos de la vida cotidiana. Si bien gran parte del desarrollo científico actual se ha logrado gracias a la experimentación en animales, es una de las áreas más cuestionadas, ya que generalmente implica algún grado de sufrimiento y, en ocasiones, se busca validar productos prescindibles a través de modelos experimentales poco refinados. Los aspectos bioéticos involucrados en el uso de animales en investigación han evolucionado a través de la historia. Dada la necesidad de modelos científicos de alto estándar y la visión social crítica sobre el uso de animales de experimentación, durante el siglo XX aparecen las primeras legislaciones regulatorias. Actualmente, el uso de animales en la experimentación conlleva no solo una responsabilidad legal, sino también la obligación ética de asegurar su bienestar y minimizar los efectos adversos de las intervenciones, lo que es beneficioso tanto para el animal como para el resultado experimental. La industria cosmética es uno de los mercados donde la experimentación animal continúa siendo utilizada, amparada en la legislación de algunos países. Sin embargo, se han generado nuevas restricciones internacionales al uso de sujetos de prueba, respondiendo a la tendencia creciente en el uso de productos "libres de crueldad".

There is an increasing concern for the ethical aspects involved in the use of animals in different aspects of daily life. Although much of the current scientific development has been achieved through animal experimentation, it is one of the most questioned areas, since it generally implies some degree of suffering and, on occasions, it is sought to validate dispensable products through experimental models that are imperfect. The bioethical considerations associated with the use of research animals have evolved throughout history. Given the need for high standard scientific models and the critical social vision on the use of experimental animals, the first regulatory legislations appear during the 20th century. However, the use of animals in experimentation entails not only a legal responsibility but also the ethical obligation to ensure their welfare and minimize the adverse effects of interventions, which is beneficial both for the animal and for the experimental result. The cosmetic industry is one of the markets where animal experimentation continues to be used, protected under the legislation of some countries. However, new international restrictions have been generated on the use of test subjects, responding to the expanding trend in the use of "cruelty-free" products.

Expectations for the methodology and translation of animal research: a survey of the general public, medical students and animal researchers in North America.

To determine what are considered acceptable standards for animal research (AR) methodology and translation rate to humans, a validated survey was sent to: a) a sample of the general public, via Sampling Survey International (SSI; Canada), Amazon Mechanical Turk (AMT; USA), a Canadian city festival (CF) and a Canadian children's hospital (CH); b) a sample of medical students (two first-year classes); and c) a sample of scientists (corresponding authors and academic paediatricians). There were 1379 responses from the general public sample (SSI, n = 557; AMT, n = 590; CF, n = 195; CH, n = 102), 205/330 (62%) medical student responses, and 23/323 (7%, too few to report) scientist responses. Asked about methodological quality, most of the general public and medical student respondents expect that: AR is of high quality (e.g. anaesthesia and analgesia are monitored, even overnight, and 'humane' euthanasia, optimal statistical design, comprehensive literature review, randomisation and blinding, are performed), and costs and difficulty are not acceptable justifications for lower quality (e.g. costs of expert consultation, or more laboratory staff). Asked about their expectations of translation to humans (of toxicity, carcinogenicity, teratogenicity and treatment findings), most expect translation more than 60% of the time. If translation occurred less than 20% of the time, a minority disagreed that this would "significantly reduce your support for AR". Medical students were more supportive of AR, even if translation occurred less than 20% of the time. Expectations for AR are much higher than empirical data show to have been achieved.

Avaliação dos efeitos do subgalato de bismuto na proliferação de miofibroblastos / Assessment of the effects of bismuth subgallate on proliferation of myofibroblasts: an experimental study in rats

Resumo Contexto O subgalato de bismuto é um metal pesado e insolúvel, utilizado por suas propriedades adstringentes e hemostáticas. Objetivo Avaliar os efeitos do subgalato de bismuto na cicatrização mediante observação de miofibroblastos em pele de ratos. Métodos Foram utilizados 60 ratos da linhagem Wistar, que receberam uma ferida no dorso da pele. Os animais foram divididos em dois grupos: controle (aplicação diária de cloreto de sódio a 0,9%) e experimental (aplicação diária de 0,5 mg de subgalato de bismuto). Cada grupo foi subdividido em três subgrupos, que foram reoperados para retirada da ferida em 3, 7 e 14 dias. Foi realizada coloração de hematoxilina eosina, picrosirius e imuno-histoquímica para avaliar contagem de miofibroblastos, resposta inflamatória e síntese de colágeno. Resultados Não foi encontrada diferença entre os grupos controle e experimento com relação ao processo inflamatório – subgrupos 3 dias (p = 1), 7 dias (p = 0,474) e 14 dias (p = 303). A avaliação dos colágenos tipo I e III no grupo-controle não demonstrou benefícios de cicatrização – 3 dias (p = 0,436), 7 dias (p = 0,853) e 14 dias (p = 0,436); já no grupo experimental, houve aumento dos colágenos tipos I e III nos subgrupos 3 e 14 dias (p = 0,005). A imuno-histoquímica confirmou os resultados encontrados na coloração hematoxilina eosina, na qual a área de miofibroblastos entre os subgrupos, nos grupos experimental (p = 0,4) e controle (p = 0,336), foi indiferente. Conclusão A utilização do subgalato de bismuto em ferida de pele de ratos não evidenciou benefícios na cicatrização, ou seja, não houve diferença na fibroplasia quando comparados os grupos experimental e controle.

Abstract Background Bismuth subgallate is an insoluble heavy metal that is used for its astringent and hemostatic properties. Objective To evaluate the effects of bismuth subgallate on the healing process by observation of myofibroblasts in the skin of rats. Methods A sample of 60 Wistar rats was used. Each rat was subjected to a dorsal skin wound and allocated to one of two groups: a control group, in which 0.9% sodium chloride was administered daily, or an experimental group, in which 0.5 mg of bismuth subgallate was administered daily. Each of these groups was further subdivided into three subsets, which were reoperated after 3, 7 and 14 days respectively for excision and collection of the skin wound specimens. Samples were treated with hematoxylin eosin, picrosirius, and immunohistochemical staining to enable assessment of myofibroblast counts, inflammatory response phase, and collagen synthesis. Results No inflammatory process differences were detected between the control and experimental groups at 3 days (p = 1), 7 days (p = 0.474), or 14 days (p = 303). Evaluation of types I and III collagen in the control group did not demonstrate healing benefits at 3 days (p = 0.436), 7 days (p = 0.853), or 14 days (p = 0.436); whereas in the experimental group there were increases in types I and III collagen at 3 and 14 days (p = 0.005). Immunohistochemical analysis confirmed the results of hematoxylin eosin staining, since there were no differences between subsets in terms of area of myofibroblasts, in the experimental (p = 0.4) or the control (p = 0.336) groups. Conclusions Administration of bismuth subgallate to skin wounds in rats did not result in any evidence of benefits to healing, i.e., no difference in fibroplasia was detected when experimental and control groups were compared.