Administration of galacto-oligosaccharide prebiotics in the Flinders Sensitive Line animal model of depression

INTRODUCTION: Major depressive disorder is the leading source of disability globally and current pharmacological treatments are less than adequate. Animal models such as the Flinders Sensitive Line (FSL) rats are used to mimic aspects of the phenotype in the human disorder and to characterise candidate antidepressant agents. Communication between the gut microbiome and the brain may play an important role in psychiatric disorders such as depression. Interventions targeting the gut microbiota may serve as potential treatments for depression, and this drives increasing research into the effect of probiotics and prebiotics in neuropsychiatric disorders. Prebiotics, galacto-oligosaccharides and fructooligosaccharides that stimulate the activity of gut bacteria have been reported to have a positive impact, reducing anxiety and depressive-like phenotypes and stress-related physiology in mice and rats, as well as in humans. Bimuno, the commercially available beta-galacto-oligosaccharide, has been shown to increase gut microbiota diversity. AIM: Here, we aim to investigate the effect of Bimuno on rat anxiety-like and depressive-like behaviour and gut microbiota composition in the FSL model, a genetic model of depression, in comparison to their control, the Flinders Resistant Line (FRL) rats. METHODS: Sixty-four male rats aged 5–7 weeks, 32 FSL and 32 FRL rats, will be randomised to receive Bimuno or control (4 g/kg) daily for 4 weeks. Animals will be tested by an experimenter unaware of group allocation on the forced swim test to assessed depressive-like behaviour, the elevated plus maze to assess anxiety-like behaviour and the open field test to assess locomotion. Animals will be weighed and food and water intake, per kilogram of bodyweight, will be recorded. Faeces will be collected from each animal prior to the start of the experiment and on the final day to assess the bacterial diversity and relative abundance of bacterial genera in the gut. All outcomes and statistical analysis will be carried out blinded to group allocation, group assignments will be revealed after raw data have been uploaded to Open Science Framework. Two-way analysis of variance will be carried out to investigate the effect of treatment (control or prebiotic) and strain (FSL or FRL) on depressive-like and anxiety-like behaviours

Using median survival in meta-analysis of experimental time-to-event data

Abstract Background Time-to-event data is frequently reported in both clinical and preclinical research spheres. Systematic review and meta-analysis is a tool that can help to identify pitfalls in preclinical research conduct and reporting that can help to improve translational efficacy. However, pooling of studies using hazard ratios (HRs) is cumbersome especially in preclinical meta-analyses including large numbers of small studies. Median survival is a much simpler metric although because of some limitations, which may not apply to preclinical data, it is generally not used in survival meta-analysis. We aimed to appraise its performance when compared with hazard ratio-based meta-analysis when pooling large numbers of small, imprecise studies. Methods We simulated a survival dataset with features representative of a typical preclinical survival meta-analysis, including with influence of a treatment and a number of covariates. We calculated individual patient data-based hazard ratios and median survival ratios (MSRs), comparing the summary statistics directly and their performance at random-effects meta-analysis. Finally, we compared their sensitivity to detect associations between treatment and influential covariates at meta-regression. Results There was an imperfect correlation between MSR and HR, although the opposing direction of treatment effects between summary statistics appeared not to be a major issue. Precision was more conservative for HR than MSR, meaning that estimates of heterogeneity were lower. There was a slight sensitivity advantage for MSR at meta-analysis and meta-regression, although power was low in all circumstances. Conclusions We believe we have validated MSR as a summary statistic for use in a meta-analysis of small, imprecise experimental survival studies—helping to increase confidence and efficiency in future reviews in this area. While assessment of study precision and therefore weighting is less reliable, MSR appears to perform favourably during meta-analysis. Sensitivity of meta-regression was low for this set of parameters, so pooling of treatments to increase sample size may be required to ensure confidence in preclinical survival meta-regressions

Marine-derived n-3 fatty acids therapy for stroke

We thank the Cochrane Stroke Group, and in particular Hazel Fraser (Managing Editor) and Joshua Cheyne (Trials Search Coordinator and Information Specialist), for their support in the development of this protocol. CG Alvarez Campano is funded by the Mexican Council for Science and Technology (CONACyT) and the Institute of Innovation and Technology Transfer (I²T²) (grant number 457349).Peer reviewedPublisher PD

Effects of heat stress and dehydration on cognitive function in elite female field hockey players

Background: It has previously been suggested that heat exposure and hypohydration have negative effects on cognitive performance, which may impact upon sporting performance. The aim of the present study was to examine the independent effects of heat stress and hypohydration on cognitive performance in elite female field hockey players. Methods: Eight unacclimatised elite field hockey players (age: 22 ± 3 y; height: 1.68 ± 0.05 m; body mass: 63.1 ± 6.0 kg) completed a cognitive test battery before and after 50 min of field hockey specific exercise on a treadmill in four experimental trials; two in hot conditions (33.3 ± 0.1 °C), and two in moderate (16.0 ± 3.0 °C), both with and without ad libitum water intake. Results: On the visual search test, participants were faster overall in the heat (1941 vs. 2104 ms, p = 0.001). Response times were quicker in the heat on the Sternberg paradigm (463 vs. 473 ms, p = 0.024) and accuracy was improved (by 1.9%, p = 0.004). There was no effect of hydration status on any of the markers of cognitive function. Conclusions: Overall, the findings suggest that in elite field hockey players exposure to heat enhances response times and/or accuracy on a battery of cognitive function tests. However, hypohydration does not appear to affect cognitive performance in elite field hockey players

The reproducibility debate is an opportunity, not a crisis

There are many factors that contribute to the reproducibility and replicability of scientific research. There is a need to understand the research ecosystem, and improvements will require combined efforts across all parts of this ecosystem. National structures can play an important role in coordinating these efforts, working collaboratively with researchers, institutions, funders, publishers, learned societies and other sectoral organisations, and providing a monitoring and reporting function. Whilst many new ways of working and emerging innovations hold a great deal of promise, it will be important to invest in meta-research activity to ensure that these approaches are evidence based, work as intended, and do not have unintended consequences. Addressing reproducibility will require working collaboratively across the research ecosystem to share best practice and to make the most effective use of resources. The UK Reproducibility Network (UKRN) brings together Local Networks of researchers, Institutions, and External Stakeholders (funders, publishers, learned societies and other sectoral organisations), to coordinate action on reproducibility and work to ensure the UK retains its place as a centre for world-leading research. This activity is coordinated by the UKRN Steering Group. We consider this structure as valuable, bringing together a range of voices at a range of levels to support the combined efforts required to enact change

A Systematic Online Living Evidence Summary of experimental Alzheimer's disease research

BACKGROUND: Despite extensive investment, the development of effective treatments for Alzheimer's disease (AD) has been largely unsuccessful. To improve translation, it is crucial to ensure the quality and reproducibility of foundational evidence generated from laboratory models. Systematic reviews play a key role in providing an unbiased overview of the evidence, assessing rigour and reporting, and identifying factors that influence reproducibility. However, the sheer pace of evidence generation is prohibitive to evidence synthesis and assessment.NEW METHOD: To address these challenges, we have developed AD-SOLES, an integrated workflow of automated tools that collect, curate, and visualise the totality of evidence from in vivo experiments.RESULTS: AD-SOLES is a publicly accessible interactive dashboard aiming to surface and expose data from in vivo experiments. It summarises the latest evidence, tracks reporting quality and transparency, and allows research users to easily locate evidence relevant to their specific research question.COMPARISON WITH EXISTING METHODS: Using automated screening methodologies within AD-SOLES, systematic reviews can begin at an accelerated starting point compared to traditional approaches. Furthermore, through text-mining approaches within the full-text of publications, users can identify research of interest using specific models, outcomes, or interventions without relying on details in the title and/or abstract.CONCLUSIONS: By automating the collection, curation, and visualisation of evidence from in vivo experiments, AD-SOLES addresses the challenges posed by the rapid pace of evidence generation. AD-SOLES aims to offer guidance for research improvement, reduce research waste, highlight knowledge gaps, and support informed decision making for researchers, funders, patients, and the public.</p

Effect size and statistical power in the rodent fear conditioning literature - A systematic review

<div><p>Proposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of experiments. However, it is unclear to what extent these two concepts are indeed taken into account in basic biomedical science. To study this in a real-case scenario, we performed a systematic review of effect sizes and statistical power in studies on learning of rodent fear conditioning, a widely used behavioral task to evaluate memory. Our search criteria yielded 410 experiments comparing control and treated groups in 122 articles. Interventions had a mean effect size of 29.5%, and amnesia caused by memory-impairing interventions was nearly always partial. Mean statistical power to detect the average effect size observed in well-powered experiments with significant differences (37.2%) was 65%, and was lower among studies with non-significant results. Only one article reported a sample size calculation, and our estimated sample size to achieve 80% power considering typical effect sizes and variances (15 animals per group) was reached in only 12.2% of experiments. Actual effect sizes correlated with effect size inferences made by readers on the basis of textual descriptions of results only when findings were non-significant, and neither effect size nor power correlated with study quality indicators, number of citations or impact factor of the publishing journal. In summary, effect sizes and statistical power have a wide distribution in the rodent fear conditioning literature, but do not seem to have a large influence on how results are described or cited. Failure to take these concepts into consideration might limit attempts to improve reproducibility in this field of science.</p></div