Steven R. Talbot

Steven R. Talbot
Hannover Medical School | MHH · Laboratory Animal Science

Dr. rer. nat.

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81
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423
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Publications

Publications (81)
Article
In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct animal experiments in multiple research facilities, and assessed whether 20% body-weight reduction is a valid humane en...
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Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research. We here systematically evaluated other measures as surrogates for a more reliabl...
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Hematopoietic stem cell gene therapy is emerging as a promising therapeutic strategy for many diseases of the blood and immune system. However, several patients that underwent gene therapy in different trials developed hematological malignancies caused by insertional mutagenesis. Preclinical assessment of vector safety remains challenging as there...
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Despite its long establishment and applicability in mice pain detection, the Mouse Grimace Scale still seems to be underused in acute pain detection during chronic experiments. However, broadening its applicability can identify possible refinement approaches such as cumulative severity and habituation to painful stimuli. Therefore, this study focus...
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Hemochromatosis is one of the most common inherited metabolic diseases among white populations and predominantly originates from a homozygous C282Y mutation in the HFE gene. The G > A transition at position c.845 of the gene causes misfolding of the HFE protein, ultimately resulting in its absence at the cell membrane. Consequently, the lack of int...
Article
Current liver‐directed gene therapies quest for adeno‐associated virus (AAV) vectors with improved efficacy. On this background, capsid engineering is explored. Whereas shuffled‐capsid library screenings have resulted in potent liver‐targeting variants with one first vector in human clinical trials, modifying natural serotypes by peptide insertion...
Preprint
The assessment of animals’ health and nutritional status using a Body Condition Score (BCS) has become a common and reliable tool in lab-animal science. It enables a simple, semi-objective, and non-invasive assessment (palpation of osteal prominences and subcutaneous fat tissue) in routine examination of an animal. In mammals, the BCS classificatio...
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The use of animals in neurosciences is pivotal to gaining insights into complex functions and dysfunctions of behavior. For example, various forms of physical and/or psychological stress are inherent to various animal models for psychiatric disorders, e.g., depression. Regarding animal welfare, it would be mandatory to use models that inflict the l...
Article
BACKGROUND AND AIMS Acute kidney injury (AKI) is a common complication in allogeneic stem cell transplantation (SCT). Although short-lived, i.e. < 90 days, in the majority of patients renal injury can persist for more than 3 months fulfilling the criteria of chronic kidney disease (CKD). So far, only a few publications have shown robust data based...
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Epilepsy is the most common chronic neurological disease in humans and dogs. Epilepsy is thought to be caused by an imbalance of excitatory and inhibitory neurotransmission. Intact neurotransmitters are transported from the central nervous system to the periphery, from where they are subsequently excreted through the urine. In human medicine, non-i...
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With an incidence of ~50%, the absence or reduced protein level of p53 is much more common than TP53 mutations in acute myeloid leukemia (AML). AML with FLT3-ITD (internal tandem duplication) mutations has an unfavorable prognosis and is highly associated with wt-p53 dysfunction. While TP53 mutation in the presence of FLT3-ITD does not induce AML i...
Article
In mice, burrowing is considered a species-typical parameter for assessing well-being, while this is less clear in rats. This exploratory study evaluated burrowing behaviour in three rat strains during training and in the direct postoperative phase after complex intracranial surgery in different neuroscience rat models established at Hannover Medic...
Article
Introduction: Chronic epilepsy models require neurosurgical procedures including depth electrode implants. The intrahippocampal kainate model is a frequently used chronic paradigm, which is based on chemoconvulsant administration and status epilepticus induction during the surgical procedure. This experimental approach raises the question to what...
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Although therapeutic options are gradually improving, the overall prognosis for patients with hepatocellular carcinoma (HCC) is still poor. Gene therapy-based strategies are developed to complement the therapeutic armamentarium, both in early and late-stage disease. For efficient delivery of transgenes with antitumor activity, vectors demonstrating...
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Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancre...
Preprint
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Despite its long establishment and its applicability in pain detection in mice, the Mouse Grimace Scale still seems to be underused in terms of acute pain detection during chronic experiments. However, a broadening of its applicability can identify possible refinement approaches such as cumulative severity and habituation to painful stimuli. Theref...
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Pancreatitis is known to be painful in humans and companion animals. However, the extent of pain in experimental mouse models of acute pancreatitis is unknown. Consequently, the severity classification of acute pancreatitis in mice is controversially discussed and standardized pain management is missing. In this study, we investigated acute Cerulei...
Preprint
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Background: Severe progression of coronavirus disease 2019 (COVID‑19) causes respiratory failure and critical illness. Recently, these pathologies have been associated with necroptosis, a receptor‑interacting serine/threonine‑protein kinase 3 (RIPK3) dependent regulated form of inflammatory cell death. Investigations of indicator necroptosis protei...
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For ethical and legal reasons it is necessary to assess the severity of procedures in animal experimentation. To estimate the degree of pain, suffering, distress or lasting harm, objective methods that provide gradebale parameters need to be tested and validated for various models. In this context, automated home-cage monitoring becomes more import...
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Humanized mouse models generated with human hematopoietic stem cells (HSCs) and reconstituting the human immune system (HIS-mice) are invigorating preclinical testing of vaccines and immunotherapies. We have recently shown that human engineered dendritic cells boosted bonafide human T and B cell maturation and antigen-specific responses in HIS-mice...
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This study assessed the postoperative severity after three different visceral surgical interventions in rats by using objective parameters pertaining to various disciplines. The objective was to evaluate whether the degree of severity increases with the invasiveness of the intervention and whether this is in accordance with the EU Directive 2010/63...
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While the use of local anesthesia as part of multimodal pain management is common practice in human and veterinarian surgery, these drugs are not applied routinely in rodent surgery. Several recommendations on the use of local anesthesia exist, but systematic studies on their efficacy and side effects are lacking. In the present study, male and fem...
Article
Background: In colorectal surgery, postoperative Anastomotic Leak (AL) is a serious complication. Besides the surgeon`s experience, bowel preparation may have an impact on AL, but the published data are still inconclusive. The purpose of this retrospective single center study was to investigate the role of preoperative Mechanical Bowel Preparation...
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Acute myeloid leukemia (AML) patients with minimal residual disease and receiving allogeneic hematopoietic stem cell transplantation (HCT) have poor survival. Adoptive administration of dendritic cells (DCs) presenting the WT1 leukemia-associated antigen can potentially stimulate de novo T and B cell development to harness the Graft-versus-Leukemia...
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Systematic reviews with meta‐analyses are powerful tools that can answer research questions based on data from published studies. Ideally, all relevant data is directly available in the text or tables, but often it is only presented in graphs. In those cases, the data can be extracted from graphs, but this potentially introduces errors. Here, we in...
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Objective Ethical decisions about an allowance for animal experiments need to be based on scientifically sound information about the burden and distress associated with the experimental procedure and models. Thereby, species differences need to be considered for recommendations regarding evidence-based severity assessment and refinement measures....
Article
Adult patients with relapsed B- cell precursor acute lymphoblastic leukemia (BCP-ALL) have a dismal prognosis. To improve pharmacotherapy we analyzed apoptosis induction by venetoclax and inotuzumab-ozogamicin in terms of cytotoxicity and mode of action. Flow cytometry-based analyses of mitochondrial outer membrane permeabilization (MOMP) and Ataxi...
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In animal experimentation, welfare and severity assessments of all procedures applied to animals are necessary to meet legal and ethical requirements, as well as public interests. So far, the methods suggested for this purpose are time consuming and personnel intensive. Also, evidence-based biostatistical methods for this purpose are still rare. We...
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In order to foster animal welfare as well as high quality of research, many countries regulate by law that the severity of animal experiments must be evaluated and considered when performing biomedical research. It is well accepted that multiple parameters rather than a single readout parameter should be applied to describe animal distress or suffe...
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Background: Constipation and intestinal obstructive episodes are major health problems in cystic fibrosis patients. Aim: Three FDA-approved drugs against constipation-prone irritable bowel syndrome were tested for their ability to increase luminal fluidity and alkalinity in CFTR null (cftr-/- ) and F508del mutant (F508delmut/mut ) murine intesti...
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Early life stress compromises brain development and can contribute to the development of mental illnesses. A common animal model used to study different facets of psychiatric disorders is social isolation from early life on. In rats, this isolation can induce long-lasting alterations in molecular expression and in behavior. Since social isolation m...
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Evaluating stress in laboratory animals is a key principle in animal welfare. Measuring corticosterone is a common method to assess stress in laboratory mice. There are, however, numerous methods to measure glucocorticoids with differences in sample matrix (e.g. plasma, urine) and quantification techniques (e.g. EIA, RIA). Here, the authors present...
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The Directive 2010/63 EU requires classifying burden and severity in all procedures using laboratory animals. This study evaluated the severity of liver fibrosis induction by intraperitoneal carbon tetrachloride (ccl 4) injections in mice. 29 male C57BL/6N mice were treated three times per week for 4 weeks with an intraperitoneal injection (50 µl)...
Preprint
Animal welfare and the refinement of experimental procedures are fundamental aspects of biomedical research. They provide the basis for robust experimental designs and reproducibility of results. In many countries, the determination of welfare is a mandatory legal requirement and implies the assessment of the degree of the severity that an animal e...
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Comparative severity assessment of animal models and experimental interventions is of utmost relevance for harm-benefit analysis during ethical evaluation, an animal welfare-based model prioritization as well as the validation of refinement measures. Unfortunately, there is a lack of evidence-based approaches to grade an animal’s burden in a sensit...
Article
The aim of this pilot study was to evaluate whether behavioral or locomotor tests (Open Field (OF), rotarod (RR), and CatWalk (CW)) can help assess the severity of laparotomy in rats. The new EU Directive (2010/63/EU) mandates severity assessment in experiments involving animals. However, validated and objective methods are needed to relate trial-s...
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In order to combine high-quality research with minimal harm to animals, a prospective severity assessment for animal experiments is legally required in many countries. In addition, an assessment of the evidence-based severity level might allow realistic harm-benefit analysis and the appraisal of refinement methods. However, only a few examples desc...
Article
Animal models in psychiatric research are indispensable for insights into mechanisms of behaviour and mental disorders. Distress is an important aetiological factor in psychiatric diseases, especially depression, and is often used to mimic the human condition. Modern bioethics requires balancing scientific progress with animal welfare concerns. The...
Article
Reduction of animal suffering during in vivo experiments is usually ensured by continuously monitoring the health status using a score sheet and by applying humane endpoints. However, most studies do not evaluate the plausibility of score sheets and do not attempt to reduce the suffering of animals by determining earlier and therefore more humane e...
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Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We ha...
Article
Evidence-based severity assessment in laboratory animals is, apart from the ethical responsibility, imperative to generate reproducible, standardized and valid data. However, the path towards a valid study design determining the degree of pain, distress and suffering experienced by the animal is lined with pitfalls and obstacles as we will elucidat...
Article
Evidence-based severity assessment is essential as a basis for ethical evaluation in animal experimentation to ensure animal welfare, legal compliance and scientific quality. To fulfil these tasks scientists, animal care and veterinary personnel need assessment tools that provide species-relevant measurements of the animals' physical and affective...
Article
The Mouse Grimace Scale (MGS) is an established method for estimating pain in mice during animal studies. Recently, an improved and standardized MGS set-up and an algorithm for automated and blinded output of images for MGS evaluation were introduced. The present study evaluated the application of this standardized set-up and the robustness of the...
Article
Severity assessment for experiments conducted with laboratory animals is still based mainly on subjective evaluations; evidence-based methods are scarce. Objective measures, amongst which determination of the concentrations of stress hormones, can be used to aid severity assessment. Short-term increases in glucocorticoid concentrations generally re...
Article
The Mouse Grimace Scale (MGS) has been widely used for the noninvasive examination of distress/pain in mice. The aim of this study was to further improve its performance to generate repeatable, faster, blinded and reliable results for developing automated and standardized pictures for MGS scoring and simultaneous evaluation of up to four animals. V...
Chapter
Since 2010 it became a good tradition that colleagues from different research areas publish articles about their unsolved scientific problems, on-going work or research results in a joint book with the title “Autonomous Systems”. Those systems exist in several areas of science, describing self-contained and self-controlled groups of possibly intera...
Article
Severity assessment in animal models is a data-driven process. We therefore present a use case for building a repository for interlaboratory collaboration with the potential of uploading specific content, making group announcements and internal prepublication discussions. We clearly show that it is possible to offer such a structure with minimal ef...
Article
Hygienic monitoring of laboratory rodents has focused more and more on the analysis of environmental sample material by quantitative polymerase chain reaction (qPCR) assays. This approach requires profound knowledge of specific genetic sequences of the agents to be monitored and the assays need to be permanently adapted to take the latest research...
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Full-text available
The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly, the exact assessment of all signs of pain, suffering, and distress experienced by laboratory animals represents...
Data
Experimental set up. After a 2-week habituation to the animal room, animals were divided into treatment and control groups by applying a random selection procedure (drawing lots). A 2-week adaption phase to wheel running was chosen. (DOCX)
Data
Adaptation to the running wheel. (a) Monitoring of WR20 and (b) Vmax20 in B6 mice during the 14-day adaption phase (n = 52). ***P < 0.001 compared to d 1 of monitoring by Friedman test followed by Dunn’s multiple comparison test. The underlying numerical data are provided in S1 Data. B6, C57BL/6J; Vmax20, maximum velocity during 20 hours/day; WR20,...
Data
Assessment of running velocities (Vmax20). (a) Monitoring of Vmax20 in DSS-treated and control mice and (b) DSS-treated and control mice submitted to facial vein phlebotomy (for n values see S1 Table); colours indicate comparison between respective groups: medium grey between 0% and 1%, black between 0% and 1.5%, and light grey between 1% and 1.5%....
Data
Clinical scoring during colitis and restraint stress. (a) Clinical score determined in DSS-treated and control mice and (b) DSS-treated and control mice additionally submitted to facial vein phlebotomy (see S1 Table for groups and n values). (c) Clinical scoring in mice undergoing repeated restraint stress (n = 8). *P < 0.05, **P < 0.01, and ***P <...
Data
Scree plot analysis, Bayesian information criterion, and seeding permutation for clustering. (a) Determination of the cluster number by scree plot analysis. Within the scree plot method, three clusters were identified as the optimal size for k-means clustering (dashed line). (b) Utilization of the BIC to validate the number of clusters. All multiva...