Animal Research Research Articles

Experimental animal research on the subchronic toxicity of “Dứa Tre Lão Nhà Quê” extract

“Dứa tre Lão nhà quê” extract (DTLNQ extract) was intended to treat several diseases such as dyslipidemia and venous insufficiency. To provide information on the its safety, this study evaluated the subchronic toxicity of DTLNQ extract. Wistar rats were divided into three groups and were given orally for 12 weeks: group 1 distilled water; group 2 and group 3: DTLNQ extract at 0.6g and 1.8g/kg b.w./day, respectively. General conditions and body weight change, hematological and biochemical parameters, and hepatic and renal histological examinations were evaluated in treated rats compared with the control group and baseline. The results showed that DTLNQ extract did not cause significant changes in general conditions, body weight gain, hematological parameters, biochemical parameters of hepatic and renal function tests and the histological examination of the liver and kidneys. Though the values of AST and ALT increased after 12 weeks of administration compared with the control group and baseline, they were within the normal limits or slightly greater than the upper limit of normal in rats.

Role of Orai1 and Ca2+-stimulated adenylyl cyclase 8 in the adverse cardiac remodeling after myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Agencia Estatal de Investigación. Background It is well established that abnormalities in the regulation of the intracellular concentration of Ca2+ ([Ca2+]i) occurs in diseased heart such as under acute myocardial infarction (AMI). Recent studies have demonstrated that proteins related to the Store Operated Calcium Entry (SOCE), such as Orai1/2/3 and TRPC channels, play a role in the adverse cardiac remodelling. Previously, we demonstrated that the expression of Orai1 increased in heart subjected to ischemia and reperfusion (I/R) syndrome. However, the signalling pathway implicated in Orai1 regulation has not been addressed. Objective The aim of this study was to examine the molecular mechanism and signalling pathways involved in the of Orai1 upregulation after I/R in cardiomyocytes. Materials and Methods The experiments were performed in adult (ARVM) and neonatal rat ventricular cardiomyocytes (NRVM), in a rat model of myocardial I/R and in ventricular biopsies of patients with ischemic heart failure. Ca2+ studies were realized using microfluorimetric technique in FURA-2AM loaded cardiomyocytes. Immunofluorescence was used to investigate CREB activation using a specific phospho-CREB antibody and Orai1 and AC8 protein expression were analysed by Western Blot. This study was performed in accordance with the recommendations of the Royal Decree 53/2013 in agreement to the Directive 2010/63/EU of the European Parliament and approved by the local Ethics Committee on human Research and the Animal Research Committee. Results We found that under I/R diastolic level of [Ca2+]i was significantly increased in cardiac myocytes isolated from I/R hearts, which was inhibited by SOCE blockers. Moreover, we found that Orai1 and Ca2+-sensitive adenylyl cyclase 8 (AC8) are overexpressed in the heart isolated from I/R rat model, as compared to sham. Similarly, we found significant increase in the expression of Orai1 and AC8 in ventricle biopsies of post-infarction patients with HF. We also observed that I/R stimulated cAMP production, involving Orai1 and AC8 activation in rats, indicating that Ca2+ entry through Orai1 stimulated AC8. Moreover, I/R phosphorylated cAMP response element-binding protein (CREB) through PKA activation, but not via EPAC2 or ERK1/2. Interestingly, we found that CREB facilitated I/R-induced Orai1 upregulation and related exacerbated SOCE by its activation of Orai1 promoter under I/R. Finally, the intramyocardial administration of AAV9 holding AC8 shRNA decreased the expression of AC8, Orai1 and CREB, which restored diastolic [Ca2+]i. Conclusions Our results show that the activation of Orai1/AC8/CREB axis plays a key role in the I/R-induced Orai1 upregulation, which participated in diastolic [Ca2+]i mishandling related to the adverse cardiac remodelling.

82Rb-PET is feasible in rodent AMI model after positron range correction

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Prof. Andreas Kjær Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark Background Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, necessitating innovative approaches for accurate diagnosis and treatment. Positron emission tomography (PET) using 82-Rubidium (82Rb) is well-established as non-invasive myocardial perfusion imaging (MPI). However, the long position range of 82Rb disables MPI and analysis of MI through 82Rb-scans in rats. Exact assessment of myocardial infarction (MI) in small animal models is important for translational research. Purpose To investigates if positron range correction (PRC) of 82Rb PET can improve the quantification of infarct size in a rat model of MI. Method 10 Sprague-Dawley rats were included. 8 rats with MI established through coronary artery ligation and 2 rats with sham operations, where the rats underwent the same open chest procedure as the MI-rats except for the ligation of the coronary artery. Rats were PET scanned with ~ 60 MBq 82Rb PET one week after MI induction/sham operation (acute scan) in a preclinical PET/CT scanner. At 30-days following MI induction/sham operation the rats were re-scanned with 82Rb PET and 18 flu-deoxy-glucose (18F-FDG) to assess final infarct size. 82Rb PET data were reconstructed both with and without positron range correction. All acquisitions were gated by pulse and respiratory frequency. The image analysis of the static reconstructions was conducted using Corridor4DM version 2023. Infarct size was quantified by summed rest score (SRS). Due to n=10 Spearman’s rank correlation was used. Results Acute 82Rb SRS without PRC showed no correlation to the SRS of 18F-FDG follow-up PET (r=0,015 and p=0,67). Nor was there a correlation between the acute 82Rb with PRC and 18F-FDG-scans (r=0,067, p= 0,85). (Figure1) However, the follow up scan at 30 days post MI induction showed a significant correlation between infarct size of 82Rb with PRC and infarct size of the 18F-FDG scans (r=0,71 and p=0,02). No such correlation was found 82Rb results without PRC and the 18F-FDG results (r=0,51 and p=0,13) (Figure2). The 82Rb PRC scans revealed a significant correlation with 18F-FDG scans, indicating improved alignment between the two in assessing infarct size. This contrasted with the original 82Rb-images. Conclusion In this study we show the possibility of utilizing 82Rb-PET as a cardiac perfusion radioisotope in small animal research by applying positron range correction. 82Rb-PET with positron range correction provides a useful tool to delineate perfusion defects more accurately in a rodent MI-model and shows significant correlation to 18F-FDG results. Further research is warranted to validate the translational potential of these findings.Figure 1Figure 2

How to optimize communication about animal and animal-free research methods.

There is a long-standing debate about experimental non-human animals and animal-free methods in scientific research. Among the various stakeholders involved in the debate are the scientists. During media broadcasts we, animal researchers and animal-free methods researchers, were positioned as 'opponents'. In this essay we describe our initial rational thoughts and emotions after these events, and how we came together to explore our common ground on animal(-free) experimentation. Realizing that all models have advantages and limitations, our common ground lies in the principles of good scientific research and responsible experimentation. Our communication emanating from the broadcasts has been instrumental in improving communication on animal(-free) experimentation issues by teaming up. We strongly believe that this is essential for making well-informed decisions for the methods we are using now and will be using in the future.

Consumer behavioral factors of the new EU regulatory framework for the feeding of insect-derived products

PurposeTo analyze the intention to consume insect derivatives after the 2023 regulatory changes in Europe that allow their commercialization for human consumption. It is necessary to know if society is willing to consume these new foods taking into consideration their ecological value, animal empathy, social stigma and neophobia. Design and methodologyThe research was carried out by means of a survey of 1,278 consumers in Spain. The analysis of the results obtained was carried out through a mixed PLS-SEM and fs/QCA methodology. FindingsEcological value and social stigma are the most significant variables in terms of the intention to consume insect derivatives by humans. In contrast, empathy for animals does not influence this behavior, suggesting changes from parallels shown in animal research. Practical and social implicationsThe findings of this study are significant as they provide valuable information on how ecological value and social stigma are key to the intention to consume insect derivatives, while animal empathy is a construct that does not exert an influence. These results are relevant for society, as the consumption of insect derivatives is becoming an increasingly popular alternative in terms of sustainability and food security in compliance with the goals of the 2030 Agenda. In addition, this study contributes to filling a gap in the scientific literature on edible insect derivatives in the context of their recent commercialization and the variables that influence or not their acceptance. Value and originalityThis paper provides useful information after the regulation of January 3, 2023 which proceeds to the amendment of the Implementing Regulation (EU) 2017/2470 on the consumption of insect derivatives, so it can be a tool that helps to raise business strategies. The results obtained are original, being a new growing field, and relevant, due to the importance that this new form of food is sustainably acquiring worldwide.

Artificial Intelligence and Machine Learning in Hepatocellular Carcinoma Screening, Diagnosis and Treatment - A Comprehensive Systematic Review

Background: Medical image analysis plays a crucial role in the screening, monitoring, diagnosis, and prognosis of diseases. Hepatocellular Carcinoma (HCC) often remain asymptomatic in their early stages. Timely identification and intervention are crucial to prevent the progression to decompensated liver diseases and advanced-stage HCC, minimizing morbidity and mortality. Methodology: This study examined twenty relevant research articles that met the inclusion criteria. Utilizing the PRISMA criteria, a systematic search was conducted on PubMed/MEDLINE and Google Scholar for studies on HCC screening employing Artificial Intelligence (AI) and Machine Learning (ML). The search focused on the keywords "artificial intelligence" and "hepatocellular carcinoma," with inclusion criteria specifying studies in the English language published in and after 2020. Exclusions were made for histology, animal research, and investigations conducted before 2020. Titles and abstracts were thoroughly reviewed, and any discrepancies were discussed. Results: The comprehensive review reveals the transformative impact of AI and ML on HCC screening, diagnosis, and therapy. ML models demonstrated effectiveness in early HCC diagnosis, distinguishing hepatic lesions, predicting treatment responses, and assessing recurrence risks across various techniques. Integration of mass spectrometry-based technologies, advanced imaging, and real-world data significantly improved diagnostic accuracy and clinical decision support. AI models exhibited diagnostic expertise with potential applications in therapy suggestions, personalized surveillance, and prognostic evaluations. However, further validation and seamless integration into clinical practice are essential for realizing their full potential. Conclusion: This systematic study underscores the progress made in the application of AI and ML in HCC screening, diagnosis, and treatment. Numerous studies highlight the capability of AI and ML systems to enhance hepatocellular carcinoma diagnosis, predict outcomes, and optimize therapy. The enduring and versatile nature of these technologies points towards a revolutionary future in personalized and efficient HCC management.

Utilizing marine algal metabolites to fight neurodegenerative diseases

Marine algae are thought to be a source of various metabolites that have a wide range of positive effects on human health. The pharmacological properties of algal metabolites, including their antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance, and anti-amyloidergic effects, lend credence to their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis, all of which are involved in the pathophysiology of neurodegenerative disorders. There are currently no clinical trials on the effects of marine algae on neuroinflammation; however, considering the significant biological activities that have been established by in vitro and animal research, we expect that there will be clinical trials on this topic in the not-too-distant future. The most recent and important findings on the potentially neuroprotective effects of the anti-inflammatory properties of marine algae were chosen for this study. Next, we conducted a literature review on the neuroprotective potential of algal compounds, along with the underlying pharmacological mechanism, and finally, we evaluated recent advances in therapeutics.

Investigation of reno-protective efficacy of thymoquinone in a unilateral hydronephrosis model

ABSTRACT We aimed to evaluate the effects of the antioxidant thymoquinone on treated and untreated kidneys on histological and oxidative parameters as well as Kidney Injury Molecule (KIM-1) levels in an experimental unilateral ureteropelvic junction obstruction (UPJO) with resultant hydronephrosis (HN) model. In adherence to the Animal research: reporting of in vivo exepriments guidelines, 34 male Wistar rats were randomly divided into four groups which were named accordingly: “CO” (corn oil), “TQ” (thymoquinone and corn oil), “HNCO” (UPJO-HN and corn oil), “HNTQ” (UPJO-HN, thymoquinone and corn oil). Histologically, pelvic epithelial damage, glomerular shrinkage and sclerosis, tubular damage, interstitial edema-inflammation-fibrosis (IEIF), and vascular congestion were assessed. Biochemically, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GR) and KIM-1 levels were assessed. Macroscopic HN developed in all obstructed kidneys. Ipsilateral obstructed kidneys deteriorated in all histological parameters. Thymoquinone attenuated glomerular shrinkage and sclerosis alterations but increased vascular congestion. Contralateral non-obstructed kidneys also showed histological deterioration. Thymoquinone had beneficial effects in terms of IEIF presence in contralateral kidneys but it increased vascular congestion. MDA and SOD results were inconclusive. UPJO caused decreased GR levels in the ipsilateral kidneys but not in the contralateral ones. This effect was not ameliorated by thymoquinone treatment. KIM-1 levels were increased in ipsilateral obstructed kidneys with a lower level in HNTQ group than in HNCO. KIM-1 level of the ipsilateral HNTQ group was higher than in both non-obstructed ipsilateral kidney groups. The effect of thymoquinone in ameliorating bilaterally observed histological alterations was limited and controversial. Oxidative damage detected by GR measurements was not prevented by thymoquinone. Thymoquinone partially decreased the damage as evidenced by reduced KIM-1 levels in thymoquinone-treated obstructed kidneys.

Investigating the Potential Therapeutic Mechanisms of Puerarin in Neurological Diseases.

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, β-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more.

Characterization of Humanized Mouse Model of Organophosphate Poisoning and Detection of Countermeasures via MALDI-MSI.

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals' resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood-brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.

Big data and its impact on the 3Rs: a home cage monitoring oriented review.

Undisturbed home cage recording of mouse activity and behavior has received increasing attention in recent years. In parallel, several technologies have been developed in a bid to automate data collection and interpretation. Thanks to these expanding technologies, massive datasets can be recorded and saved in the long term, providing a wealth of information concerning animal wellbeing, clinical status, baseline activity, and subsequent deviations in case of experimental interventions. Such large datasets can also serve as a long-term reservoir of scientific data that can be reanalyzed and repurposed upon need. In this review, we present how the impact of Big Data deriving from home cage monitoring (HCM) data acquisition, particularly through Digital Ventilated Cages (DVCs), can support the application of the 3Rs by enhancing Refinement, Reduction, and even Replacement of research in animals.

Animal models for partial heart transplantation.

Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression. Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non-human primates. This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon. Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non-human primate partial heart xenotransplantation. Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open-heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open-heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation. Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants.

The Applications of Nanopore Sequencing Technology in Animal and Human Virus Research

In recent years, an increasing number of viruses have triggered outbreaks that pose a severe threat to both human and animal life, as well as caused substantial economic losses. It is crucial to understand the genomic structure and epidemiology of these viruses to guide effective clinical prevention and treatment strategies. Nanopore sequencing, a third-generation sequencing technology, has been widely used in genomic research since 2014. This technology offers several advantages over traditional methods and next-generation sequencing (NGS), such as the ability to generate ultra-long reads, high efficiency, real-time monitoring and analysis, portability, and the ability to directly sequence RNA or DNA molecules. As a result, it exhibits excellent applicability and flexibility in virus research, including viral detection and surveillance, genome assembly, the discovery of new variants and novel viruses, and the identification of chemical modifications. In this paper, we provide a comprehensive review of the development, principles, advantages, and applications of nanopore sequencing technology in animal and human virus research, aiming to offer fresh perspectives for future studies in this field.

Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism.

Glioblastoma is the most aggressive brain tumor with poor prognosis. Although Resveratrol (Rsv) is known to have therapeutic effects on glioma, the effects of gold-conjugated resveratrol nanoparticles (Rsv-AuNPs) on glioma cells are rarely reported. We aimed to investigate the effects of Rsv-AuNPs on glioma cells and its underlying mechanism. Human glioma cell line U87 was treated with different concentrations of Rsv-AuNPs. CCK-8, transwell, and wound healing assay were performed to measure the effects of Rsv-AuNPs on cell proliferation, invasion, and migration ability, respectively. Flow cytometry assay was used to detect the effects of Rsv-AuNPs on apoptosis. Changes of protein expressions related to proliferation, invasion, migration, and apoptosis were measured by Western blot assay. In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002. Rsv-AuNPs treatment significantly suppressed proliferation, migration, and invasion of U87 cells (allP <0.05) and increased the apoptosis rate (P <0.05). The changes of proteins related to proliferation, migration, invasion and apoptosis were consistent (allP <0.05). Moreover, Rsv-AuNPs treatment significantly inhibited the phosphorylation of PI3K, AKT and mTOR proteins in U87 cells (P <0.05). The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.

Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review.

Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.

Perceptions of Animal Welfare on Livestock: Evidence from College Agronomy Students in Costa Rica.

Ethical considerations regarding our treatment of animals have gained strength, leading to legislation and a societal focus across various disciplines. This is a subject of study within curricula related to agri-food sciences. The aim was to determine the perceptions of agronomy university students concerning animal welfare in livestock production systems. A survey was conducted to encompass various aspects, from participants' sociodemographic attributes to their attitudes and behaviors regarding animal welfare and the consumption of animal products. Statistical analysis, performed using R software, delved into the associations between participants' characteristics and their perspectives on the ethical, bioethical, and legal dimensions of animal welfare. Associations between demographic factors and ethical viewpoints among students were identified. Gender differences emerged in animal treatment perceptions, while rural and urban environments impacted perspectives on various animals. Bioethical considerations revealed distinctive disparities based on gender and education in concerns regarding animal welfare, value perceptions, evaluations of animal behaviors, and opinions on animal research. It is crucial to distinguish between animal welfare and the ethical considerations arising from coexisting with sentient beings capable of experiencing suffering. Ethical theories provide a lens through which we perceive our obligations toward animals. The responsibility to ensure animal welfare is firmly rooted in recognizing that animals, like humans, experience pain and physical suffering. Consequently, actions causing unjustified suffering or mistreatment, particularly for entertainment purposes, are considered morally unacceptable.

Perceptions on the Ethical and Legal Principles that Influence Global Brain Data Governance

Advances in neuroscience and other disciplines are producing large-scale brain data consisting of datasets from multiple organisms, disciplines, and jurisdictions in different formats. However, due to the lack of an international data governance framework brain data is currently being produced under various contextual ethical and legal principles which may influence key stakeholders involved in the generation, collection, processing and sharing of brain data thereby raising ethical and legal challenges. In addition, despite the demand for a brain data governance framework that accounts for culture, there is a gap in empirical research and actions to understand how key stakeholders around the world view these issues using neuroscientists who are affected by these ethical and legal principles. Therefore, using the research question how do ethical and legal principles influence data governance in neuroscience? we attempt to understand the perceptions of key actors on the principles, issues and concerns that can arise from brain data research. We carried out interviews with 21 leading international neuroscientists. The analytical insights revealed key ethical and legal principles, areas of convergence, visibility, and the contextual issues and concerns that arise in brain data research around these principles. These issues and concerns circulate around intimately connected areas which include ethics, human rights, regulations, policies and guidelines, and participatory governance. Also, key contextual insights around animal research and ethics were identified. The research identifies key principles, issues, and concerns that need to be addressed in advancing the development of a framework for global brain data governance. By presenting contextual insights from neuroscientists across regions, the study contributes to informing discussions and shaping policies aimed at promoting responsible and ethical practices in brain data research. The research answers the call for a cross cultural study of global brain data governance and the results of the study will assist in understanding the issues and concerns that arise in brain data governance.

Development of a protocol for using geo-trackers to identify zoonotic enteric pathogen transmission pathways in a pilot study in Kenya

Abstract Humans and animals can be exposed to fecally-transmitted pathogens in both private and public domain environments. Animals may also acquire pathogen infections from these two environments and transmit them to humans through different pathways. Evidence on how often and where interactions occur between the two environments could improve the effectiveness of public health programs for preventing zoonotic disease transmission and response to disease outbreaks. This study aimed to develop a protocol for using geo-trackers to measure the spatial-temporal movement and interaction between animals and children in households and public areas in low- and middle-income categories of urban neighbourhoods in Kenya. It also aimed to identify opportunities and challenges for the scale-up of these methods’ for surveillance of other zoonotic diseases of public health significance. One commercial geo-tracker device with the best technological performance and usability that met pre-defined criteria for the study context was identified. Community engagement meetings were then conducted to gather input on a proposed study protocol. Afterwards, infants and animals were geo-tracked in 10 households in urban informal settlements of Kibera and Jericho, Nairobi over two consecutive weeks with iterative improvements to protocols. The effectiveness of the geo-tracking exercise was evaluated through in-depth interviews with Community Health Volunteers (CHVs) and infant caregivers. Animal and infant behaviour and battery reliability of the geo-trackers were also monitored; and observed opportunities and challenges in implementing the protocol during the exercise were documented. Community members were receptive and accepted the use of geo-trackers on animals and children. In pilot testing, there was no change of behaviour from 10 infants tracked. Discomfort was observed for up to 30 min after the placement for some of the seven animals tracked, but the animals quickly adjusted. The battery for all geo-tracker devices lasted for the 24-h geo-tracking period. Some caregivers and CHVs were concerned whether the geo-trackers could record personal information. It was shown that geo-tracker devices can be successfully deployed to study animal-child interactions and movement in different categories of urban neighbourhoods. Recommendations have been made on the lessons learnt from the study to help scientists who would use geo-trackers for future community-based human and animal research. One Health impact statement Assessing human and animal risks of acquiring enteric infections from environmental contamination, or contributing to pathogen contamination of the environment requires understanding spatial-temporal patterns of human and animal movement between private households and the community. Movement of domestic animals is relevant for understanding household-community spatial patterns of pathogen transmission because animal ownership and contact with humans is common, and free-roaming animals carrying enteric pathogens can spread diverse faecal pathogens between environments. The community-based participatory research approach of this study evaluated implementation feasibility from the lens of technical usability and reliability of geo-tracking devices, as well as social acceptability and ethics related to using such devices for the community-based study of human and animal subjects in urban settings. Evidence and recommendations from this study will be useful to anyone interested in understanding human-animal-environment interactions and their contributions to infectious disease transmission.

118 Gene editing: A European perspective

Abstract Gene editing by CRISPR/Cas has revolutionized numerous facets of biotechnology within a remarkably short period of time. Its combined use with either somatic cell nuclear transfer or microinjection into fertilized oocytes is highly useful for mutating genes in a very precise and specific manner. This technology has profoundly transformed the world of animal research, particularly for biomedical and productive applications. Gene editing can now be applied to animal modeling and therapeutic research, bringing us closer to the possibility of using animals as organ donors for xenotransplantation. Furthermore, it has become an effective tool in animal production for purposes such as increasing disease tolerance or resistance and enhancing animal welfare. In this presentation, we will explore how this genome editing tool has influenced the research conducted in Europe, examining the current landscape and addressing the challenges, with a special focus on pigs. We will also discuss the regulation of gene-edited animals in the EU.

Pharmacokinetics and pharmacodynamics of standard nerve agent medical countermeasures in Göttingen Minipigs

Animal research continues to serve a critical role in the testing and development of medical countermeasures. The Göttingen minipig, developed for laboratory research, may provide many benefits for addressing research questions within chemical defense. Targeted development of the Göttingen minipig model could reduce reliance upon non-human primates, and improve study design, statistical power, and throughput to advance medical countermeasures for regulatory approval and fielding. In this vein, we completed foundational pharmacokinetics and physiological safety studies of intramuscularly administered atropine sulfate, pralidoxime chloride (2-PAM), and diazepam across a broad range of doses (1–6 autoinjector equivalent) using adult male Göttingen minipigs (n=11; n=4–8/study) surgically implanted with vascular access ports and telemetric devices to monitor cardiovascular, respiratory, arterial pressure, and temperature signals. Pharmacokinetic data were orderly and the concentration maximum mirrored available human data at comparably scaled doses clearly for atropine, moderately for 2-PAM, and poorly for diazepam. Time to peak concentration approximated 2, 7, and 20 min for atropine, 2-PAM, and diazepam, respectively, and the elimination half-life of these drugs approximated 2 hr (atropine), 3 hr (2-PAM), and 8 hr (diazepam). Atropine sulfate dose-dependently increased the magnitude and duration of tachycardia and decreased the PR and ST intervals (consistent with findings obtained from other species). Mild hypothermia was observed at the highest diazepam dose. Göttingen minipigs appear to provide a ready and appropriate large animal alternative to non-human primates, and further development and evaluation of novel nerve agent medical countermeasures and treatment strategies in this model are justified.