Measuring endogenous corticosterone in laboratory mice - a mapping review, meta-analysis, and open source database

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., enzyme immunoassay or radioimmunoassay). Here, the authors present a mapping review and a searchable database, giving a complete overview of all studies mea­suring endogenous corticosterone in mice up to February 2018. For each study, information was recorded regarding mouse strain and sex; corticosterone sample matrix and quantification technique; and whether the study covered the research theme animal welfare, neuroscience, stress, inflammation, or pain (the themes of specific interest in our con­sortium). Using all database entries for the year 2012, an exploratory meta-regression was performed to determine the effect of predictors on basal corticosterone concentrations. Seventy-five studies were included using the predictors sex, time-since-lights-on, sample matrix, quantification technique, age of the mice, and type of control. Sex, time-since-lights-on, and type of control significantly affected basal corticosterone concentrations. The resulting database can be used, inter alia, for preventing unnecessary duplication of experiments, identifying knowledge gaps, and standardizing or heterogenizing methodologies. These results will help plan more efficient and valid experiments in the future and can answer new questions in silico using meta-analyses

A systematic mapping review of the evolution of the rat Forced Swim Test: Protocols and outcome parameters

As depression is projected to become the leading mental disease burden globally by 2030, understanding the underlying pathology, as well as screening potential anti-depressants with a higher efficacy, faster onset of action, and/or fewer side-effects is essential. A commonly used test for screening novel antidepressants and studying depression-linked aspects in rodents is the Porsolt Forced Swim Test. The present systematic mappping review gives a comprehensive overview of the evolution and of the most prevalently used set-ups of this test in rats, including the choice of animals (strain, sex, and age), technical aspects of protocol and environment, as well as reported outcome measures. Additionally, we provide an accessible list of all existing publications, to support informed decision-making for procedural and technical aspects of the test, to thereby enhance reproducibility and comparability. This should further contribute to reducing the number of unnecessarily replicated experiments, and consequently, reduce the number of animals used in future

Measuring Endogenous Corticosterone in Laboratory Mice - a Mapping Review, Meta-Analysis, and Open Source Database

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., enzyme immunoassay or radioimmunoassay). Here, the authors present a mapping review and a searchable database, giving a complete overview of all studies measuring endogenous corticosterone in mice up to February 2018. For each study, information was recorded regarding mouse strain and sex; corticosterone sample matrix and quantification technique; and whether the study covered the research theme animal welfare, neuroscience, stress, inflammation, or pain (the themes of specific interest in our consortium). Using all database entries for the year 2012, an exploratory meta-regression was performed to determine the effect of predictors on basal corticosterone concentrations. Seventy-five studies were included using the predictors sex, time-since-lights-on, sample matrix, quantification technique, age of the mice, and type of control. Sex, time-since-lights-on, and type of control significantly affected basal corticosterone concentrations. The resulting database can be used, inter alia, for preventing unnecessary duplication of experiments, identifying knowledge gaps, and standardizing or heterogenizing methodologies. These results will help plan more efficient and valid experiments in the future and can answer new questions in silico using meta-analyses

Altered emotional experiences attributed to antipsychotic medications - A potential link with estimated dopamine D-2 receptor occupancy

Altered emotional experiences in response to antipsychotics may increase the burden of disease in patients with schizophrenia. In a large cross-sectional study, patients with schizophrenia completed the Subjects Reaction to Antipsychotics questionnaire (SRA) to assess whether they attributed altered emotional experiences (flattened affect or depressive symptoms) to their antipsychotics. Association with antipsychotic D-2 receptor affinity and occupancy was examined using logistic regression. We compared antipsychotic-attributed emotional experiences between patients using antipsychotic monotherapy and combination therapy. Of the 1298 included patients, 23% attributed flattened affect to their anti psychotics and 16% attributed depressive symptoms to their antipsychotics, based on the SRA. No differences were observed between antipsychotics in patients on monotherapy. We discuss that within these patients' relatively low dose range, altered emotional experiences did not appear to relate to the level of D-2 receptor affinity of antipsychotic monotherapy. Patients using antipsychotic combination therapy (22%) were more likely to attribute depressive symptoms to their antipsychotics than patients using antipsychotic monotherapy (OR [95%CI]=1.443 [1.033-2.015]); possibly due to higher D-2 receptor occupancies as estimated by dose equivalents. (C) 2016 Published by Elsevier Ireland Ltd

Social Jet-Lag in Tertiary Students Following a Modern Curriculum with Few Time-Tabled Contact Hours: A Pilot Study

Social jet-lag (SJL) impairs academic performance, specifically for late chronotypes faced with early start times. Most modern tertiary educational systems have fewer time-tabled contact hours and consequently fewer early starts, which may limit SJL. We performed a pilot study of SJL in a convenience sample of students from Maastricht University, where problem-based learning (PBL) is implemented throughout the curricula. PBL is a modern curriculum, with only few contact hours and student-driven learning, comprising substantial amounts of self-study. Fifty-two students kept a detailed sleep diary for one week, and completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Participants were divided into early and late sleepers based on a ranking of their reported sleeping times, combined with a single question on their self-reported chronotype. Late sleepers (for brevity: “Owls”; n = 22) had later midpoint-sleep (5:14 ± 0:11 on weekdays; 5:50 ± 0:07 on weekend days) than early sleepers (for brevity: “Larks”; n = 11, 3:21 ± 0:05 on weekdays; 3:41 ± 0:06 on weekend days, F = 10.8, p = 0.003). The difference between the midpoint of sleep on weekdays and weekend days was comparable for Larks and Owls (F = 1.5; p = 0.22). SJL (0:53 ± 0:06, T = 1.4; p = 0.16), total sleep duration (7:58 ± 0:08; p = 0.07), and PSQI score (4.7 ± 0.3, U = 137; p = 0.56) were comparable for Larks and Owls. Average ESS score was higher in Larks (10.7 ± 0.96) than in Owls (7.0 ± 0.72; U = 52; p = 0.007). Within this pilot study of students engaged in a problem-based learning curriculum, Owls have no selective disadvantage compared to Larks concerning sleep

Joining forces : the need to combine science and ethics to address problems of validity and translation in neuropsychiatry research using animal models

BACKGROUND: Current policies regulating the use of animals for scientific purposes are based on balancing between potential gain of knowledge and suffering of animals used in experimentation. The balancing process is complicated, on the one hand by plurality of views on our duties towards animals, and on the other hand by more recent discussions on uncertainty in the probability of reaching the final aim of the research and problems of translational failure. METHODS: The study combines ethical analysis based on a literature review with neuropsychiatry-related preclinical research as a case study. RESULTS: Based on the analysis and the case study we show that neuropsychiatry-related preclinical research is an especially interesting case from an ethical perspective. The 3R principles (Replacement, Reduction and Refinement) are used to minimize the negative consequences for the animals used in research. However, neuropsychiatric research is characterized by specific challenges in assessing the probability of success of reaching the final aim, due to our limited mechanistic knowledge of human neuropsychiatric illness. Consequently, the translational value of the currently used animal models may be difficult to prove, which undermines the validity of these models and complicated the ethical assessment. CONCLUSIONS: We conclude that a combined approach that deals with both science and the ethical dimensions is necessary to address the problems of validity and translation in neuropsychiatry-related preclinical research. We suggest this approach to comprise first, improved experimental methods, e.g. by using systematic reviews, second, a more patients-based approach that leads to models that reflect interindividual variation better, and third, more interdisciplinary cooperation

Software tools for literature screening in systematic reviews in biomedical research

Systematic Reviews (SRs) hold promise for implementing the 3Rs in animal sciences: they can retrieve available alternative models, help refining experiments, and identify insufficiencies, or an excess of, scientific knowledge on a particular topic. Unfortunately, SRs can be labour- and time-intensive, especially the reference screening and data extraction phases. Fortunately, there are several software tools available that help make screening faster and easier. However, it is not always clear which features the tools offer. Therefore, a feature analysis was performed to compare different reference screening tools as objectively as possible. This analysis enables researchers to select the most appropriate tool for their needs. Fifteen different tools were compared: CADIMA, Covidence, DistillerSR, Endnote, Endnote using Bramer's method, EROS, HAWC, Microsoft Excel, Excel using VonVille's method, Microsoft Word, Rayyan, RevMan, SyRF, SysRev.com, and SWIFT Active Screener. Their support of 21 features was tested. Features were categorised as mandatory, desirable, and optional. DistillerSR, Covidence, and SWIFT Active Screener are the tools that support all mandatory features. These tools are preferred for screening references, but none of them are free. The best scoring free tool is Rayyan, which lacks one mandatory function: distinct title/abstract and full-text phases. The lowest scoring tools are those not specifically designed for SRs, like Microsoft Word and Endnote. Their use can only be advised for small and simple SRs. A well-informed selection of SR screening tools will benefit review quality and speed, which can contribute to the advancement of the 3Rs in animal studies

Software tools for literature screening in systematic reviews in biomedical research

Systematic Reviews (SRs) hold promise for implementing the 3Rs in animal sciences: they can retrieve available alternative models, help refining experiments, and identify insufficiencies, or an excess of, scientific knowledge on a particular topic. Unfortunately, SRs can be labour- and time-intensive, especially the reference screening and data extraction phases. Fortunately, there are several software tools available that help make screening faster and easier. However, it is not always clear which features the tools offer. Therefore, a feature analysis was performed to compare different reference screening tools as objectively as possible. This analysis enables researchers to select the most appropriate tool for their needs. Fifteen different tools were compared: CADIMA, Covidence, DistillerSR, Endnote, Endnote using Bramer's method, EROS, HAWC, Microsoft Excel, Excel using VonVille's method, Microsoft Word, Rayyan, RevMan, SyRF, SysRev.com, and SWIFT Active Screener. Their support of 21 features was tested. Features were categorised as mandatory, desirable, and optional. DistillerSR, Covidence, and SWIFT Active Screener are the tools that support all mandatory features. These tools are preferred for screening references, but none of them are free. The best scoring free tool is Rayyan, which lacks one mandatory function: distinct title/abstract and full-text phases. The lowest scoring tools are those not specifically designed for SRs, like Microsoft Word and Endnote. Their use can only be advised for small and simple SRs. A well-informed selection of SR screening tools will benefit review quality and speed, which can contribute to the advancement of the 3Rs in animal studies

Addressing the challenges of reconstructing systematic reviews datasets: a case study and a noisy label filter procedure

Abstract Systematic reviews and meta-analyses typically require significant time and effort. Machine learning models have the potential to enhance screening efficiency in these processes. To effectively evaluate such models, fully labeled datasets—detailing all records screened by humans and their labeling decisions—are imperative. This paper presents the creation of a comprehensive dataset for a systematic review of treatments for Borderline Personality Disorder, as reported by Oud et al. (2018) for running a simulation study. The authors adhered to the PRISMA guidelines and published both the search query and the list of included records, but the complete dataset with all labels was not disclosed. We replicated their search and, facing the absence of initial screening data, introduced a Noisy Label Filter (NLF) procedure using active learning to validate noisy labels. Following the NLF application, no further relevant records were found. A simulation study employing the reconstructed dataset demonstrated that active learning could reduce screening time by 82.30% compared to random reading. The paper discusses potential causes for discrepancies, provides recommendations, and introduces a decision tree to assist in reconstructing datasets for the purpose of running simulation studies

The Leeds food preference questionnaire after mild sleep restriction - A small feasibility study

Besides the increased sedentary lifestyle and increased caloric intake, changes in dietary composition may play an important role in the increased prevalence of obesity. Because inadequate sleep could be a risk factor in the aetiology of obesity, reliable methods for assessing food intake and food choice after sleep restriction are needed. We translated the Leeds food preference questionnaire (LFPQ), addressing preferences for sweet/savoury tastes and low-fat/high-fat foods, into Dutch, and tested it in 15 mildly sleep-restricted psychology students. The participants completed the LFPQ in our laboratory on two separate occasions, with approximately one week in between. Sleep on the preceding night was not controlled, but mild sleep-restriction was confirmed by a short sleep latency test (sSLT) or a short maintenance of wakefulness test (sMWT). Each participant completed the sSLT and sMWT once, just before the LFPQ, in a cross-over design randomised for the first test. Differences were present in preferences for food items from different categories (sweet/savoury and low-fat/high-fat; p <0.001). The choice frequencies for various food categories were comparable on both occasions (p=0.27). The choice frequencies for individual items were also comparable on both occasions (p=0.27). The LFPQ is easily implemented under mild sleep-restricted conditions, and translation is straightforward. Future studies using the LFPQ after sleep restriction could elucidate if restricting sleep or longer periods affects food choice, which could underlie increases in obesity ris