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The purpose of this paper was to study in vitro atomization properties of the self-developed sodium sivelestat for inhalation, evaluate the feasibility of this preparation as an aerosol inhalation, and provide the guidance for the following animal administration experiment. Firstly, in order to ensure accurate, uniform and stable doses of the self-developed product after administration, its atomization performance was analyzed through the testing of fine particle mass and the total emitted dose, and the results of its atomization parameters meet the requirement of inhalation. Next, Atomization characteristics of two commonly used nebulizers, air compressed nebulizer and mesh nebulizer, were studied and compared. The results showed that mesh atomizers have a smaller and more uniform particle size distribution. And then, the experiment of acute lung injury induced by aerosol inhalation of lipopolysaccharide in mice was used to test the therapeutic effect of our self-developed formulation, and compared with the positive control (sodium sivelestat for injection). The results showed that inhalation had a lower concentration and was equally effective than injection of sodium sivelestat. All the results support that the self-developed sodium sivelestat can be used as an aerosol inhaled drug. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell (hiPSC)-derived brain spheroids can recapitulate the complex cytoarchitecture of the brain, as well as the genetic/epigenetic footprint of human brain development. However, hiPSC-derived 3D models such as spheroid and organoids does not have a perfusable microvascular network, which plays a vital role in maintaining homeostasis in vivo. With the critical balance of positive and negative angiogenic modulators, 3D microvascular network can be achieved by angiogenesis. This paper reports on a microfluidic-based three-dimensional, cortical spheroid grafted on the vascular-network. Vascular network was formed by inducing angiogenic sprouting using concentration gradient-driven angiogenic factors in the microfluidic device. We investigate critical factors for angiogenic vascular network formation with spheroid placement, including 1) a PKCα activator, phorbol-12-myristate-13-acetate (PMA); 2) orientation of endothelial cells under perfusion and permeability of vascular network; 3) effect of extracellular matrix (ECM) types and their densities on angiogenesis; and 4) integration with cortical spheroid on vascular network. This paper demonstrates proof of concept for the potential utility of a membrane-free in vitro cortical spheroid tissue construct with perfusable microvascular network that can be scaled up to a high throughput platform. It can provide a cost-effective alternative platform to animal testing by modeling brain diseases and disorders, and screening drugs. [ABSTRACT FROM AUTHOR]

There is an ongoing debate about the value of animal experiments to inform medical practice, yet there are limited data on how well therapies developed in animal studies translate to humans. We aimed to assess 2 measures of translation across various biomedical fields: (1) The proportion of therapies which transition from animal studies to human application, including involved timeframes; and (2) the consistency between animal and human study results. Thus, we conducted an umbrella review, including English systematic reviews that evaluated the translation of therapies from animals to humans. Medline, Embase, and Web of Science Core Collection were searched from inception until August 1, 2023. We assessed the proportion of therapeutic interventions advancing to any human study, a randomized controlled trial (RCT), and regulatory approval. We meta-analyzed the concordance between animal and human studies. The risk of bias was probed using a 10-item checklist for systematic reviews. We included 122 articles, describing 54 distinct human diseases and 367 therapeutic interventions. Neurological diseases were the focus of 32% of reviews. The overall proportion of therapies progressing from animal studies was 50% to human studies, 40% to RCTs, and 5% to regulatory approval. Notably, our meta-analysis showed an 86% concordance between positive results in animal and clinical studies. The median transition times from animal studies were 5, 7, and 10 years to reach any human study, an RCT, and regulatory approval, respectively. We conclude that, contrary to widespread assertions, the rate of successful animal-to-human translation may be higher than previously reported. Nonetheless, the low rate of final approval indicates potential deficiencies in the design of both animal studies and early clinical trials. To ameliorate the efficacy of translating therapies from bench to bedside, we advocate for enhanced study design robustness and the reinforcement of generalizability. Based on the analysis of 376 therapies in 54 human diseases, this study shows that, contrary to widespread assertions, the proportion of successful animal-to-human translation may be higher than anticipated; however, the low rate of final regulatory approval indicates potential design flaws of both animal studies and early clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Arthritis has been postulated as a prevalent potential risk factor for the emergence of dementia and cognitive impairment. This conjecture prompted an examination of the correlation between arthritis and cognitive impairment using the National Health and Nutrition Examination Survey (NHANES) repository. The analysis was meticulously adjusted for potential confounders such as age and assorted systemic comorbidities, to ensure robustness in the results obtained. Methods: Among 2,398 adults aged 60 years and above, logistic regression and cubic spline models were employed to elucidate the relationship between arthritis and cognitive performance. This was assessed utilizing tests such as Immediate Recall test (IRT), Delayed Recall test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Results: In our investigation, a total of 19931 individuals were analyzed, among which 2,398 patients (12.03%) were identified with arthritis. Subjects with arthritis inflammation had lower DSST and AFT scores compared to the healthy group, indicating cognitive decline. After adjusting for all covariates, arthritis was significantly associated with higher DSST and AFT scores by logistic regression modeling (OR: 0.796, 95% CI: 0.649–0.975; OR: 0.769, 95% CI: 0.611–0.968). Conclusion: Our analysis underscores the potential linkage between arthritis prevalence and cognitive impairment within a nationally representative of US older adults. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications. Author summary: Severe fever with thrombocytopenia syndrome virus (SFTSV) infection has emerged as a global public health issue, and its incidence is increasing annually. Neutralizing antibodies offer rapid and efficient therapeutic potential against viral infections. In this report, we elucidated the crystal structure of a highly effective and broad-spectrum murine neutralizing antibody, mAb 40C10, in complex with the SFTSV glycoprotein N (Gn) head domain. Through structural and sequence analyses, we revealed the molecular mechanism underlying the neutralization activity of mAb 40C10 and unveiled a new, potent, and broad-spectrum neutralizing epitope. Notably, this epitope is conserved across different genotypes of SFTSV and SFTSV-related viruses. The newly identified epitope provides valuable insights for reverse vaccine or drug design. Furthermore, we humanized mAb 40C10 and demonstrated the sustained efficacy of the humanized antibody in animal experiments, potentially advancing the development of clinical antibody therapeutics targeting SFTSV. [ABSTRACT FROM AUTHOR]

Objective: There is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity. Method: This study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3. Results: A meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20–1.38, p<0.01). Conclusion: The results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy. [ABSTRACT FROM AUTHOR]

Antigen-presenting cells (APCs) play a crucial role in the immune system by breaking down antigens into peptide fragments that subsequently bind to major histocompatibility complex (MHC) molecules. Previous studies indicate that stable proteins can impede CD4+ T cell stimulation by hindering antigen processing and presentation. Conversely, certain proteins require stabilization in order to activate the immune response. Several factors, including the characteristics of the protein and the utilization of different adjuvants in animal experiments, may contribute to this disparity. In this study, we investigated the impact of adjuvants on antigen administration in mice, specifically focusing on the stability of the CH2 domain. Consequently, the CH2 domain induced a stronger IgG response in comparison to the stabilized one when using Alum and PBS (without adjuvant). On the other hand, animal experiment using Freund's adjuvant showed the opposite results. These findings indicate the significance of considering the intrinsic conformational stability of a protein when eliciting its immunogenicity, particularly within the context of vaccine development. [ABSTRACT FROM AUTHOR]

Background and aim: Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. Methods: We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32–34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. Results: Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. Conclusion: Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function. [ABSTRACT FROM AUTHOR]

This study addressed enamel demineralization, a common complication in fixed orthodontic treatment, by evaluating a novel orthodontic adhesive with DMAHDM-PCL composite fibers. These fibers, produced through electrospinning, were incorporated into orthodontic adhesive to create experimental formulations at different concentrations and a control group. The study assessed antimicrobial properties, biosafety, and mechanical characteristics. New orthodontic adhesive exhibited significant bacteriostatic effects, reducing bacterial biofilm activity and concentrations. Incorporating 1% and 3% DMAHDM-PCL did not affect cytocompatibility. Animal tests confirmed no inflammatory irritation. Shear bond strength and adhesive residual index results indicated that antimicrobial fibers didn't impact bonding ability. In conclusion, orthodontic adhesives with 3% DMAHDM-PCL fibers are potential antimicrobial bonding materials, offering a comprehensive solution to enamel demineralization in orthodontic patients. [ABSTRACT FROM AUTHOR]

Animal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target word's presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals' ability to generalize across pitch, we manipulated the fundamental frequency (F0) of the speech stimuli across trials, and to assess the contribution of pitch to streaming, we roved the F0 from word token-to-token. We then implemented gradient-boosted regression and decision trees on the trial outcome and reaction time data to understand the behavioral factors behind the ferrets' decision-making. We visualized model contributions by implementing SHAPs feature importance and partial dependency plots. While ferrets could accurately perform the task across all pitch-shifted conditions, our models reveal subtle effects of shifting F0 on performance, with within-trial pitch shifting elevating false alarms and extending reaction times. Our models identified a subset of non-target words that animals commonly false alarmed to. Follow-up analysis demonstrated that the spectrotemporal similarity of target and non-target words rather than similarity in duration or amplitude waveform was the strongest predictor of the likelihood of false alarming. Finally, we compared the results with those obtained with traditional mixed effects models, revealing equivalent or better performance for the gradient-boosted models over these approaches. Author summary: The sorts of listening challenges faced by real-world listeners are rarely captured by most laboratory-based auditory paradigms, particularly those testing animal models. However, many labs are attempting to utilize more realistic experiments, and more complicated behavioral paradigms require more sophisticated approaches to analyzing the resulting data. Here, we used a new behavioral paradigm to test the ability of ferret listeners to identify target speech sounds and assess their ability to generalize across changes in pitch. To make sense of the resulting dataset, we used machine learning to understand how trained ferrets perform this task. Gradient-boosted regression and decision trees are well-established machine learning methods that do not require users to predetermine interaction effects and are accompanied by visualization tools that allow insights into how multiple factors ultimately shape behavior. We compare the use of gradient-boosted models to more standard regression approaches and that this machine learning approach is ideal for analyzing behavioral data in animal models. [ABSTRACT FROM AUTHOR]

Subclinical infection of laboratory animals with one or more of several pathogens affects the results of experiments on animals. Monitoring the health of laboratory animals encompasses routine surveillance for pathogens, including several viruses. This study aimed to explore the development of an alternative assay to the existing ones for detecting infection of mice and rats with the parvoviruses minute virus of mice (MVM) and Kilham rat virus (KRV), respectively. Full-length VP2 and NS1 proteins of these parvoviruses, besides fragments containing multiple predicted epitopes stitched together, were studied for serological detection. The optimal dilution of full-length proteins and antigenic regions containing predicted epitopes for coating, test sera, and conjugate was determined using a checkerboard titration at each step. The assays were evaluated vis-à-vis commercially available ELISA kits. The results showed that an engineered fusion of fragments containing multiple predicted MVM VP2 and NS1 epitopes was better than either of the full-length proteins for detecting antibodies in 90% of the tested sera samples. For KRV ELISA, full-length VP2 was better compared to other individual recombinant protein fragments or combinations thereof for the detection of antibodies in sera. This report is the first description of an ELISA for KRV and an improved assay for MVM. Importantly, our assays could be exploited with small volumes of sera. The results also demonstrate the utility of immunoinformatics-driven polypeptide engineering in the development of diagnostic assays and the potential to develop better tests for monitoring the health status of laboratory animals. [ABSTRACT FROM AUTHOR]

Objectives: Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA. Methods: A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis. Results: A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], P<0.00001). Moreover, it elicited a positive modulatory impact on the expression profiles of several inflammatory cytokines in the decidual tissue of URSA murine models, inclusive of IL4 (SMD 1.63, 95% CI [0.39, 2.86], P = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], P< 0.0001). Subgroup analyses underscored that the administration mode of intraperitoneal and uterine horn injections, and sources of bone MSCs and adipose-derived MSCs contributed positively to the expression of IL4, IL10, and decreased the expression of IFN-γ in decidual tissue of URSA (P<0.05). Conversely, the tail vein injections subgroup was observed with no statistical significance (P>0.05). Conclusions: The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation. [ABSTRACT FROM AUTHOR]

The vast amount of images generated by aerial imagery in the context of regular wildlife surveys nowadays require automatic processing tools. At the top of the mountain of different methods to automatically detect objects in images reigns deep learning's object detection. The recent focus given to this task has led to an influx of many different architectures of neural networks that are benchmarked against standard datasets like Microsoft's Common Objects in COntext (COCO). Performance on COCO, a large dataset of computer vision images, is given in terms of mean Average Precision (mAP). In this study, we use six pretrained networks to detect red deer from aerial images, three of which have never been used, to our knowledge, in a context of aerial wildlife surveys. We compare their performance along COCO's mAP and a common test metric in animal surveys, the F1-score. We also evaluate how dataset imbalance and background uniformity, two common difficulties in wildlife surveys, impact the performance of our models. Our results show that the mAP is not a reliable metric to select the best model to count animals in aerial images and that a counting-focused metric like the F1-score should be favored instead. Our best overall performance was achieved with Generalized Focal Loss (GFL). It scored the highest along both metrics, combining most accurate counting and localization (with average F1-score of 0.96 and 0.97 and average mAP scores of 0.77 and 0.89 on both datasets respectively) and is therefore very promising for future applications. While both imbalance and background uniformity improved the performance of our models, their combined effect had twice as much impact as the choice of architecture. This finding seems to confirm that the recent data-centric shift in the deep learning field could also lead to performance gains in wildlife surveys. [ABSTRACT FROM AUTHOR]

With the increasing incidence and mortality of chronic kidney disease (CKD), targeted therapies for CKD have been explored constantly. The important role of gut microbiota on CKD has been emphasized increasingly, it is necessary to analyze the metabolic mechanism of CKD patients from the perspective of gut microbiota. In this study, bioinformatics was used to analyze the changes of gut microbiota between CKD and healthy control (HC) groups using 315 samples from NCBI database. Diversity analysis showed significant changes in evenness compared to the HC group. PCoA analysis revealed significant differences between the two groups at phylum level. In addition, the F/B ratio was higher in CKD group than in HC group, suggesting the disorder of gut microbiota, imbalance of energy absorption and the occurrence of metabolic syndrome in CKD group. The study found that compared with HC group, the abundance of bacteria associated with impaired kidney was increased in CKD group, such as Ralstonia and Porphyromonas, which were negatively associated with eGFR. PICRUSt2 was used to predict related functions and found that different pathways between the two groups were mainly related to metabolism, involving the metabolism of exogenous and endogenous substances, as well as Glycerophospholipid metabolism, which provided evidence for exploring the relationship between gut microbiota and lipid metabolism. Therefore, in subsequent studies, special attention should be paid to these bacteria and metabolic pathway, and animal experiments and metabolomics studies should be conducted explore the association between bacterial community and CKD, as well as the therapeutic effects of these microbial populations on CKD. [ABSTRACT FROM AUTHOR]

Introduction: Ischemic stroke has high morbidity, disability and mortality rates. The effective treatments recommended by guideline have considerable limitations due to their strict range of adaptation and narrow time window. Acupuncture is an effective and safe treatment for ischemic stroke, and the mechanism may be related to autophagy. In this systematic review, we aim to summarize and evaluate the evidence of autophagy in acupuncture therapy for animal models of middle cerebral artery occlusion (MCAO). Methods: Publications will be retrieved from the MEDLINE, Embase, Cochrane Library, Web of Science, CNKI, CBM, CVIP and Wanfang databases. We will include animal experimental studies of acupuncture for MCAO, and the control group will receive placebo/sham acupuncture or no treatment after model establishment. Outcome measures must include autophagy and will include neurologic scores and/or infarct size. The Systematic Review Center for Laboratory animal Experimentation (SYRCLE) risk of bias tool will be used to assess the risk of bias. A meta-analysis will be performed if the included studies are sufficiently homogenous. Subgroup analyses will be conducted according to different intervention types and different types of outcomes. Sensitivity analyses will also performed to explore the heterogeneity and to assess the stability of the results. Publication bias will be assessed by funnel plots. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system will be applied to evaluate the quality of evidence in this systematic review. Discussion: The results of this study may help to explain autophagy in acupuncture therapy for ischemic stroke. The limitation of this review is that all included studies will be retrieved from Chinese or English medical databases due to language barriers. Registration: We registered in PROSPERO on May 31, 2022. (https://www.crd.york.ac.uk/PROSPERO/display%5frecord.php?RecordID=329917) (CRD42022329917). [ABSTRACT FROM AUTHOR]

In animal experiments, blinding (also known as masking) is a methodological strategy to reduce the risk that scientists, animal care staff, or other staff involved in the research may consciously or subconsciously influence the outcome. Lack of masking has been shown to correlate with an overestimation of treatment efficacy and false positive findings. We conducted exploratory interviews across academic and a commercial setting to discuss the implementation of masking at four stages of the experiment: during allocation and intervention, during the conduct of the experiment, during the outcome assessment, and during the data analysis. The objective was to explore the awareness, engagement, perceptions, and the barriers to implementing masking in animal experiments. We conducted multiple interviews, to explore 30 different experiments, and found examples of excellent practice but also areas where masking was rarely implemented. Significant barriers arose from the operational and informatic systems implemented. These systems have prioritised the management of welfare without considering how to allow researchers to use masking in their experiments. For some experiments, there was a conflict between the management of welfare for an individual animal versus delivering a robust experiment where all animals are treated in the same manner. We identified other challenges related to the level of knowledge on the purpose of masking or the implementation and the work culture. The exploration of these issues provides insight into how we, as a community, can identify the most significant barriers in a given research environment. Here, we offer practical solutions to enable researchers to implement masking as standard. To move forward, we need both the individual scientists to embrace the use of masking and the facility managers and institutes to engage and provide a framework that supports the scientists. In animal experiments, masking (blinding) is a methodological strategy to reduce the risk that staff involved in the research may consciously or subconsciously influence the outcome. This qualitative review of in vivo experiments explores the implementation of blinding at allocation, intervention, conduct, outcome assessment and data analysis, identifying examples of good practice and providing insight into how to address the barriers. [ABSTRACT FROM AUTHOR]

Our understanding of the firing behaviour of motoneuron (MN) pools during human voluntary muscle contractions is currently limited to electrophysiological findings from animal experiments extrapolated to humans, mathematical models of MN pools not validated for human data, and experimental results obtained from decomposition of electromyographical (EMG) signals. These approaches are limited in accuracy or provide information on only small partitions of the MN population. Here, we propose a method based on the combination of high-density EMG (HDEMG) data and realistic modelling for predicting the behaviour of entire pools of motoneurons in humans. The method builds on a physiologically realistic model of a MN pool which predicts, from the experimental spike trains of a smaller number of individual MNs identified from decomposed HDEMG signals, the unknown recruitment and firing activity of the remaining unidentified MNs in the complete MN pool. The MN pool model is described as a cohort of single-compartment leaky fire-and-integrate (LIF) models of MNs scaled by a physiologically realistic distribution of MN electrophysiological properties and driven by a spinal synaptic input, both derived from decomposed HDEMG data. The MN spike trains and effective neural drive to muscle, predicted with this method, have been successfully validated experimentally. A representative application of the method in MN-driven neuromuscular modelling is also presented. The proposed approach provides a validated tool for neuroscientists, experimentalists, and modelers to infer the firing activity of MNs that cannot be observed experimentally, investigate the neuromechanics of human MN pools, support future experimental investigations, and advance neuromuscular modelling for investigating the neural strategies controlling human voluntary contractions. Author summary: Our experimental understanding of the firing behaviour of motoneuron (MN) pools during human voluntary muscle contractions is currently limited to the observation of small samples of active MNs obtained from EMG decomposition. EMG decomposition therefore provides an important but incomplete description of the role of individual MNs in the firing activity of the complete MN pool, which limits our understanding of the neural strategies of the whole MN pool and of how the firing activity of each MN contributes to the neural drive to muscle. Here, we combine decomposed high-density EMG (HDEMG) data and a physiologically realistic model of MN population to predict the unknown recruitment and firing activity of the remaining unidentified MNs in the complete MN pool. In brief, an experimental estimation of the synaptic current is input to a cohort of MN models, which are calibrated using the available decomposed HDEMG data, and predict the MN spike trains fired by the entire MN population. This novel approach is experimentally validated and applied to muscle force prediction from neuromuscular modelling. [ABSTRACT FROM AUTHOR]

Background: Acute compartment syndrome (ACS) is a devastating complication which develops following a traumatic extremity injury that results in increased pressure within osteofascial compartments, thereby leading to ischemia, muscle and nerve necrosis, and creates a life-threatening condition if left untreated. Fasciotomy is the only available standard surgical intervention for ACS. Following fasciotomy the affected extremity is plagued by prolonged impairments in function. As such, an unmet clinical need exists for adjunct, non-surgical therapies which can facilitate accelerated functional recovery following ACS. Thus, the purpose of this systematic review was to examine the state of the literature for non-surgical interventions that aim to improve muscle contractile functional recovery of the affected limb following ACS. Methods: English language manuscripts which evaluated non-surgical interventions for ACS, namely those which evaluated the function of the affected extremity, were identified as per PRISMA protocols via searches within three databases from inception to February 2022. Qualitative narrative data synthesis was performed including: study characteristics, type of interventions, quality, and outcomes. Risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE) RoB tool and reported level of evidence for each article. Results: Upon review of all initially identified reports, 29 studies were found to be eligible and included. 23 distinct non-surgical interventions were found to facilitate improved muscle contractile function following ACS. Out of 29 studies, 15 studies which evaluated chemical and biological interventions, showed large effect sizes for muscle function improvement. Conclusions: This systematic review demonstrated that the majority of identified non-surgical interventions facilitated an improvement in muscle contractile function following pathological conditions of ACS. [ABSTRACT FROM AUTHOR]

Background: Existing evidence indicates that a significant amount of biomedical research involving animals remains unpublished. At the same time, we lack standards for measuring the extent of results reporting in animal research. Publication rates may vary significantly depending on the level of measurement such as an entire animal study, individual experiments within a study, or the number of animals used. Methods: Drawing on semi-structured interviews with 18 experts and qualitative content analysis, we investigated challenges and opportunities for the measurement of incomplete reporting of biomedical animal research with specific reference to the German situation. We further investigate causes of incomplete reporting. Results: The in-depth expert interviews revealed several reasons for why incomplete reporting in animal research is difficult to measure at all levels under the current circumstances. While precise quantification based on regulatory approval documentation is feasible at the level of entire studies, measuring incomplete reporting at the more individual experiment and animal levels presents formidable challenges. Expert-interviews further identified six drivers of incomplete reporting of results in animal research. Four of these are well documented in other fields of research: a lack of incentives to report non-positive results, pressures to 'deliver' positive results, perceptions that some data do not add value, and commercial pressures. The fifth driver, reputational concerns, appears to be far more salient in animal research than in human clinical trials. The final driver, socio-political pressures, may be unique to the field. Discussion: Stakeholders in animal research should collaborate to develop a clear conceptualisation of complete reporting in animal research, facilitate valid measurements of the phenomenon, and develop incentives and rewards to overcome the causes for incomplete reporting. [ABSTRACT FROM AUTHOR]

Background: In vivo and in vitro studies have shown that Se has an insulin-mimetic action associated with its antioxidant activity. Other studies, in turn, suggest that high Se doses and high selenoprotein expression interfere with insulin signaling. This study aims to evaluate the effects of Se supplementation on glycemic control markers in healthy rodents. Methods: The protocol was developed according to the Preferred Reporting Items for Systematic Review and Metaanalysis Protocol (PRISMA-P) and was published in the International Prospective Register of Systematic Reviews database (PROSPERO; CRD4202121201142019119181). Experimental, randomized, or non-randomized studies of healthy rodents models will be included. All forms of supplemented Se will be considered, including organic, inorganic, and synthetic compounds, selenium-enriched yeasts, zerovalent Se nanoparticles, and selenized polysaccharides. Fasting blood glucose will be considered the primary outcome. Homeostatic model assessment, plasma and erythrocyte Se concentration, GPX activity, SELENOP concentration, and other Se biomarkers will be considered secondary outcomes. EMBASE, Scopus, Pubmed/Medline, Web of Science, and CINAHL will be searched for articles published with no language restrictions. Two reviewers will independently conduct the search and selection of articles, data extraction, and quality analysis. The risk of bias and methodological quality analyses of the included studies will be performed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) and Collaborative Approach to Meta-Analysis and Review (CAMARADES) tools, respectively. The results will be presented as a narrative synthesis according to the Synthesis Without Meta-analysis (SWiM) Reporting Guideline. Meta-analyses will be conducted where appropriate using random-effects models. Discussion: The review may clarify the interaction between different forms of supplemented Se and glycemic control in rodents models. The results will provide evidence that will help select doses and forms of Se to administer in clinical trials while according to impact on the glycemic control while elucidating mechanisms of Se metabolism. [ABSTRACT FROM AUTHOR]