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Animal advocacy is a complex phenomenon. As a social movement encompassing diverse moral stances and lifestyle choices, veganism and vegetarianism (veg*) are at its core, and animal testing raises as a notably contentious issue within its members. This paper addresses this critical topic. Employing data from an international quantitative survey conducted between June and July 2021, our research explores how ethical vegans and vegetarians responded during the COVID-19 crisis. By comparing the experiences and choices between the two groups, we aimed to understand the variances in attitudes and behaviors in the face of an ethical dilemma, highlighting the interplay between personal beliefs and social pressures in times of a health crisis. Our findings reveal stark contrasts in how vegans and vegetarians navigated the pandemic; vegans displayed less conformity yet experienced a significant compromise of their ethical values, particularly in their overwhelming acceptance of vaccination. This study enhances the field of veg* research and social movement studies by exploring how a social crisis shapes members' behaviors and perspectives. Our findings also contribute to a better understanding of the challenges and prejudices that a minority group such as vegans may face and how they cope with the pressure to go against the mainstream at a time when society is polarized by a single discourse that goes against their moral values. [ABSTRACT FROM AUTHOR]

Neuronal optogenetics is a technique to control the activity of neurons with light. This is achieved by artificial expression of light-sensitive ion channels in the target cells. By optogenetic methods, cells that are naturally light-insensitive can be made photosensitive and addressable by illumination and precisely controllable in time and space. So far, optogenetics has primarily been a basic research tool to better understand the brain. However, initial studies are already investigating the possibility of using optogenetics in humans for future therapeutic approaches for neuronal based diseases such as Parkinson's disease, epilepsy, or to promote stroke recovery. In addition, optogenetic methods have already been successfully applied to a human in an experimental setting. Neuronal optogenetics also raises ethical and legal issues, e.g., in relation to, animal experiments, and its application in humans. Additional ethical and legal questions may arise when optogenetic methods are investigated on cerebral organoids. Thus, for the successful translation of optogenetics from basic research to medical practice, the ethical and legal questions of this technology must also be answered, because open ethical and legal questions can hamper the translation. The paper provides an overview of the ethical and legal issues raised by neuronal optogenetics. In addition, considering the technical prerequisites for translation, the paper shows consistent approaches to address these open questions. The paper also aims to support the interdisciplinary dialogue between scientists and physicians on the one hand, and ethicists and lawyers on the other, to enable an interdisciplinary coordinated realization of neuronal optogenetics. [ABSTRACT FROM AUTHOR]

Advanced general visual object tracking models have been drastically developed with the access of large annotated datasets and progressive network architectures. However, a general tracker always suffers domain shift when directly adopting to specific testing scenarios. In this paper, we dedicate to addressing the animal tracking problem by proposing a spatio-temporal inference module and a coarse-to-fine tracking strategy. In terms of tracking animals, non-rigid deformation is a typical challenge. Therefore, we particularly design a novel transformer-based inference structure where the changing animal state is transmitted across continuous frames. By explicitly transmitting the appearance variations, this spatio-temporal module enables adaptive target learning, boosting the animal tracking performance compared to the fixed template matching approaches. Besides, considering the altered contours of animals in different frames, we propose to perform coarse-to-fine tracking to obtain a fine-grained animal bounding box with a dedicated distribution-aware regression module. The coarse tracking phase focuses on distinguishing the target against potential distractors in the background. While the fine-grained tracking phase aims at accurately regressing the final animal bounding box. To facilitate animal tracking evaluation, we captured and annotated 145 video sequences with 20 categories from the zoo, forming a new test set for animal tracking, coined ZOO145. We also collected a dataset, AnimalSOT, with 162 video sequences from existing tracking test benchmarks. The experimental performance on animal tracking datasets, MoCA, ZOO145, and AnimalSOT, demonstrate the merit of the proposed approach against advanced general tracking approaches, providing a baseline for future animal tracking studies. [ABSTRACT FROM AUTHOR]

Air pollution caused by SARS-CoV-2 and other viruses in human settlements will have a great impact on human health, but also a great risk of transmission. The transmission power of the virus can be represented by quanta number in the Wells-Riley model. In order to solve the problem of different dynamic transmission scenarios, only a single influencing factor is considered when predicting the infection rate, which leads to large differences in quanta calculated in the same space. In this paper, an analog model is established to define the indoor air cleaning index RL and the space ratio parameter. Based on infection data analysis and rule summary in animal experiments, factors affecting quanta in interpersonal communication were explored. Finally, by analogy, the factors affecting person-to-person transmission mainly include viral load of infected person, distance between individuals, etc., the more severe the symptoms, the closer the number of days of illness to the peak, and the closer the distance to the quanta. In summary, there are many factors that affect the infection rate of susceptible people in the human settlement environment. This study provides reference indicators for environmental governance under the COVID-19 epidemic, provides reference opinions for healthy interpersonal communication and human behavior, and provides some reference for accurately judging the trend of epidemic spread and responding to the epidemic. [ABSTRACT FROM AUTHOR]

Spleen tissue segmentation is an essential process for analyzing various immunological diseases as observed in the cryo-imaging data. Because manual labeling of the spleen tissue by human experts is not efficient, an automatic segmentation algorithm is needed. In this study, we developed a novel algorithm for automatically segmenting spleen substructures including white pulp and red pulp for the first time. The algorithm is designed for datasets created by a cryo-imaging system. This unique technology can effectively enable cellular tracking anywhere in the whole mouse with single-cell sensitivity. The proposed algorithm consists of four components: initial spleen mask creation, feature extraction, Supervised Patch-based Fuzzy c-Mean (spFCM) classification, and post-processing. The algorithm accurately and efficiently labeled spleen tissues in all experiment settings. The algorithm also improved the spleen segmentation throughput by 90 folds as compared to the manual segmentation. Moreover, we show that our novel spFCM algorithm outperformed traditional fast-learning classifiers as well as the U-Net deep-learning model in many aspects. Two major contributions of this paper are (1) an explainable algorithm for segmenting spleen tissues in cryo-images for the first time and (2) an spFCM algorithm as a new classifier. We also discussed that our work can be beneficial to researchers who work not only in the fields of graft-versus-host disease (GVHD) mouse models, but also in that of other immunological disease models where spleen analysis is essential. Future work building upon our research may lay the foundations for biomedical studies that utilize cryo-imaging technology. [ABSTRACT FROM AUTHOR]

Animals are protected under national animal welfare legislation, against intentional acts of cruelty and a failure to act, resulting in neglect and causing an animal to suffer. The Royal Society for the Prevention of Cruelty to Animals (RSPCA) bears the responsibility of investigating and prosecuting the majority of animal welfare offences in England and Wales. In recent years, how they operate has been criticised, and it has been debated whether they should be able to bring private prosecutions, and what their role should actually be. This criticism calls for a change in the way in which the RSPCA approach cases of animal welfare, to strengthen their continuing role in ensuring positive animal welfare is achieved and, where not, prosecuted. This paper outlines the need for a new approach and how it can be managed. Honess and Wolfensohn (Altern Lab Anim 38:205, 2010) have developed an Extended Welfare Assessment Grid (EWAG), a visualisation mapping tool of welfare impact, which has been useful for assessing the welfare of animals used in laboratories. This tool has proven so useful, veterinarians are now using it in veterinary hospitals to help assess whether an animal is likely to further deteriorate, due to disease and illness, and to show any short-term welfare impact on the animal (Williams in UFAW conference, Newcastle upon Tyne, 2018). This paper will explore the potential for the EWAG to be adapted to assess the welfare of animals when owners are not meeting the welfare needs of their companion animals. RSPCA can use it to support their assessments of the current welfare of an animal under a person's ownership and whether the animal's welfare will deteriorate should they remain under that ownership. The EWAG will be a useful tool for those working in animal welfare, such as the RSPCA, to help organisations to intervene earlier, work in partnership with an owner, and support their claims of a risk to animal welfare. [ABSTRACT FROM AUTHOR]

Regulatory ethical frameworks governing animal experimentation are a hallmark of modern biology. While most countries have ethical standards regarding the use of animals for scientific purposes, experiments involving insects are not included in these standards. With studies in recent years suggesting that insects may possess faculties akin to emotive states, there is growing discussion surrounding the ethical implications of scientific experimentation involving insects. This paper explores some of the current evidence for the ability of insects to experience emotive states and highlights how current formal animal experimentation ethics frameworks are unnecessary for governing the use of insects for scientific purposes. At its conclusion, this paper discusses ways in which scientists can, and should, uniformly maximise the welfare of insects used in their experiments in a way that is of benefit to their science as well as to the dignity and welfare of their study organisms. [ABSTRACT FROM AUTHOR]

This article, titled "Ethical Responsibilities of the Authors," discusses the international standards for including an ethical responsibilities section in research papers. The section should include acknowledgements of financial and organizational support, mention of research grants and their recipients, and expressions of gratitude to individuals or organizations that provided assistance. It should also state that research procedures were in accordance with international ethical standards, including compliance with regulations for experiments on animals or tests on humans. Additionally, authors should disclose any potential conflicts of interest. [Extracted from the article]

Noise as an environmental stressor becomes of increasing importance in our industrialized world, and especially traffic noise from the environment represents a potential novel neurodegenerative risk factor, as well as for hearing loss. A significant number of studies have been suggested that the overproduction of reactive oxygen species (ROS) has a complex role in stimulation of pathologic events. Experimental studies upon molecular pathways of traffic noise exposure proposed that it increased the level of stress hormones and mediated the inflammatory and oxidative stress (OS) pathways resulting in endothelial and neuronal dysfunction. Studies have shown that neurons are especially sensitive to OS due to high polyunsaturated fatty acids content in membranes, high oxygen uptake, and weak antioxidant defense. However, OS induces the necrotic and apoptotic cell deaths in the cochlea. Chronic noise is one of the many overall reasons of obtained sensorineural hearing loss which destroys cognitive functions in human and animals, as well as suppresses neurogenesis in the hippocampus. Nevertheless, behavioral disorders caused by noise are mainly accompanied with oxidative stress, but the clear molecular mechanism of neurodegeneration due to disruption of the pro- and antioxidant systems is still not fully understood. This paper aims to highlight the down-stream pathophysiology of noise-induced mental disorders, including hearing loss, annoyance, anxiety, depression, memory loss, and Alzheimer's disease, describing the underlying mechanisms of induction of inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Research papers involving animal studies often display poor reporting standards, leading to lower study reproducibility. We aim to determine the difference in reporting animal studies regarding abdominal wall hernia repair with mesh placement, before and after the publication of ARRIVE-2010 (Animal Research: Reporting of In Vivo Experiments) guidelines. Furthermore, we aim to present the most up-to-date reporting quality using the updated ARRIVE-2020 as criteria. Methods: All animal studies concerning hernia repair with meshes were systematically searched. Articles published in the 5 years leading up to the ARRIVE-2010 (pre-ARRIVE) and articles within the last 5 years until the updated ARRIVE 2.0 (post-ARRIVE) were compared for overall species and specific species separately. Articles published last year were evaluated for presenting fully reported (sub)items. Results: The number of fully reported (sub)items per article was on average significantly higher for pre-ARRIVE than post-ARRIVE for overall species (mean (SD) = 14.0 (2.8) vs. 12.6 (2.5), P < 0.001). The same applies to rabbit (mean (SD) = 14.8 (2.6) vs. 12.6 (2.6), P = 0.001) and pig studies (mean (SD) = 14.5 (2.7) vs. 11.6 (2.6), P = 0.004), with no significance in rat studies (mean (SD) = 13.6 (2.9) vs. 12.9 (2.3), P = 0.076). Significance was found in several (sub)items between pre-ARRIVE and post-ARRIVE (n = 7, 3, 8, and 3 for overall species, rat, rabbit, and pig studies, respectively). Conclusion: General reporting quality of animal experiments has been improved markedly by ARRIVE guidelines. However, more improvements are required considering the arrival of ARRIVE 2.0 guidelines. [ABSTRACT FROM AUTHOR]

Purpose: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data.This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound (fup\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$f_{up}$$\end{document}), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a “bottom-up” PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform’s accuracy.Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy.The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development.Methods: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data.This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound (fup\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$f_{up}$$\end{document}), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a “bottom-up” PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform’s accuracy.Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy.The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development.Results: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data.This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound (fup\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$f_{up}$$\end{document}), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a “bottom-up” PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform’s accuracy.Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy.The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development.Conclusion: Recently, there has been rapid development in model-informed drug development, which has the potential to reduce animal experiments and accelerate drug discovery. Physiologically based pharmacokinetic (PBPK) and machine learning (ML) models are commonly used in early drug discovery to predict drug properties. However, basic PBPK models require a large number of molecule-specific inputs from in vitro experiments, which hinders the efficiency and accuracy of these models. To address this issue, this paper introduces a new computational platform that combines ML and PBPK models. The platform predicts molecule PK profiles with high accuracy and without the need for experimental data.This study developed a whole-body PBPK model and ML models of plasma protein fraction unbound (fup\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$f_{up}$$\end{document}), Caco-2 cell permeability, and total plasma clearance to predict the PK of small molecules after intravenous administration. Pharmacokinetic profiles were simulated using a “bottom-up” PBPK modeling approach with ML inputs. Additionally, 40 compounds were used to evaluate the platform’s accuracy.Results showed that the ML-PBPK model predicted the area under the concentration-time curve (AUC) with 65.0%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy within a 2-fold range, which was higher than using in vitro inputs with 47.5%\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$\%$$\end{document} accuracy.The ML-PBPK model platform provides high accuracy in prediction and reduces the number of experiments and time required compared to traditional PBPK approaches. The platform successfully predicts human PK parameters without in vitro and in vivo experiments and can potentially guide early drug discovery and development. [ABSTRACT FROM AUTHOR]

Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of SDSCs are a hot topic. In this paper, we explore the link between the transcriptional regulator yes-associated protein (YAP) and the fate of porcine SDSCs (pSDSCs). We found that lysophosphatidylcholine (LPC) activates YAP, promotes pSDSCs pluripotency, and counteracts transdifferentiation of pSDSCs into porcine primordial germ cell-like cells (pPGCLCs). YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Oct4 and Sox2. The overexpression of YAP prevented the differentiation of pSDSCs, and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP, the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939, an inhibitor of the Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Taken together, our results suggested that YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs. [ABSTRACT FROM AUTHOR]

In this article, we move from sensory physiology to psychology and consider the proverbially lazy drone. I will describe how some simple experiments permitted us to understand why males in the Indian paper wasp Ropalidia marginata do no work in the colony even during the time they live in it. Taking the behaviour of feeding larvae as an example of work, we show that male wasps normally do not feed larvae, not because they are incapable of doing so, but because they do not have access to enough food and also because female wasps are so much better at this job. As a confirmation of this conclusion, we could cure the males of their laziness, i.e., get them to feed the larvae by providing them with excess food and leaving them in the presence of hungry larvae, without the presence of females. [ABSTRACT FROM AUTHOR]

The drug development process involves a variety of drug activity evaluations, which can determine drug efficacy, strictly analyze the biological indicators after the drug action, and use these indicators as the preclinical drug evaluation criteria. At present, most of the screening of preclinical anticancer drugs mainly relies on traditional 2D cell culture. However, this traditional technology cannot simulate the tumor microenvironment in vivo, let alone reflect the characteristics of solid tumors in vivo, and has a relatively poor ability to predict drug activity. 3D cell culture is a technology between 2D cell culture and animal experiments, which can better reflect the biological state in vivo and reduce the consumption of animal experiments. 3D cell culture can link the individual study of cells with the study of the whole organism, reproduce in vitro the biological phenotype of cells in vivo more greatly, and thus predict the activity and resistance of anti-tumor drugs more accurately. In this paper, the common techniques of 3D cell culture are discussed, with emphasis on its main advantages and application in the evaluation of anti-tumor resistance, which can provide strategies for the screening of anti-tumor drugs. [ABSTRACT FROM AUTHOR]

Committees established for the ethical review of research involving animals have become a widespread legal standard around the world. Despite many differences in their composition, powers, and institutional settings, they share many common problems related to the well-established standards of procedural justice in administrative practice. The paper adapts the general theory of procedural justice to the specific context of ethical review committees. From this perspective, the main concerns over the procedural aspects of the ethical evaluation of research projects are identified and examined. They include in particular the standards of the committees' composition, impartiality, fair hearing, appeal, transparency, and benevolence. Their proper reflection in the regulatory regimes of animal ethics committees is necessary to secure the standards of fairness of the ethical review itself. This, in turn, is a condition of the moral and social legitimacy of all administrative and quasi-administrative procedures, including the committees' operations (irrespective of whether they are legally entrusted with the task of authorizing or only evaluating research projects). [ABSTRACT FROM AUTHOR]

A focal point in the safety evaluation of cosmetic ingredients includes oral repeated dose toxicity testing, which is intended to address the most complex human endpoints. Seven years after the full implementation of the animal testing ban for cosmetic ingredients in the EU, there are still no alternative methods available capable of fully replacing oral repeated dose toxicity testing. Until this issue is resolved, the development of new cosmetic ingredients remains seriously hampered. The present paper describes a thorough screening of the oral repeated dose toxicity data included in safety evaluation reports of cosmetic ingredients addressed in the Annexes of the Cosmetics Regulation (EC) No 1223/2009, issued by the Scientific Committee on Consumer Safety between 2009 and 2019. The liver and the haematological system were identified as the potentially most frequently affected organs upon oral administration of cosmetic ingredients to animals. Evaluation of altered biochemical, morphological, and histopathological parameters related to hepatotoxicity indicated that the most recurrent events are liver weight changes, elevated liver enzymes, and alterations in serum cholesterol and bilirubin levels. Combined listing of affected parameters associated with steatosis and cholestasis indicated the possible occurrence of cholestasis, provoked by a limited number of cosmetic ingredients. The most frequently affected parameters related to the haematological system were indicative of anaemia. An in-depth analysis allowed characterisation of both regenerative and non-regenerative anaemia, pointing to direct and indirect haematotoxicity, respectively. The results presented in this study call for prioritisation of research targeted towards the development of new approach methodologies fit for animal-free repeated dose toxicity evaluation of cosmetic ingredients. [ABSTRACT FROM AUTHOR]

Objectives: This study was to evaluate the diagnostic value of liver extracellular volume (LECV) for the staging of liver fibrosis in a cynomolgus monkey model of nonalcoholic steatohepatitis (NASH).Methods: Forty-eight cynomolgus monkeys were enrolled in this prospective study. There are 17 healthy monkeys and 31 monkeys with NASH. Ten of these monkeys were used for repeatability assessment. The remaining 38 monkeys were used to compare LECV with other indicators including pathology fibrosis score, native T1, and serum chemical indexes by Spearman, Pearson correlation test, and ROC curves. The inter-reader variability was assessed by interclass correlation. The repeatability measurement of LECV was analyzed using Bland-Altman plots and the coefficient of variation. Partial correlation analysis was performed to assess the effects of fat content and inflammation scores on the correlation between LECV/T1 and liver fibrosis score.Results: This study demonstrated a good intra-reader agreement (intraclass correlation = 0.79) of LECV in all monkeys and an excellent repeatability in 10 monkeys (coefficient of variation = 2.01%). The LECV has a strong correlation with the fibrosis score (r = 0.949; p < 0.0001), low-density lipoprotein (r = 0.72; p < 0.0001), and cholesterol (r = 0.70; p < 0.0001). LECV showed high diagnostic efficacy in the diagnosis of liver fibrosis (area under the curve of ROC, 0.945~1; p < 0.001).Conclusions: LECV may serve as a noninvasive valuable biomarker for the quantification and differentiating of the non-severe liver fibrosis (stage ≤ F3). However, circulating serum markers low-density lipoprotein and cholesterol (CHO) may not serve for this purpose.Key Points: • This paper demonstrated the excellent repeatability (intraclass correlation coefficient = 0.79) of LECV in monkey animal model. • LECV-MRI has a strong correlation with histopathological fibrosis score stage (r = 0.949; p < 0.0001) and shows high diagnostic efficacy in the staging of non-severe liver fibrosis (the area under ROC curve ≥ 0.945). • The new fibrosis score maps appeared to provide a better imaging tool for the spatial assessment of liver fibrosis. It may eventually facilitate the diagnosis of liver fibrosis distribution. [ABSTRACT FROM AUTHOR]

Introduction: Apple vinegar (AV) has been proclaimed to have different health benefits, such as a weight loss, the ability to lower blood glucose levels, and reducing the risk of heart diseases. Studies on animals have demonstrated effects of AV consumption, deepening our knowledge of the beneficial effects and side effects. Aim: The aims of this study were to evaluate the evidence of the effect of AV on metabolic parameters and body weight in humans, furthermore, to evaluate the safety and side effects of ingesting AV, and additionally to evaluate the evidence of the effect of AV on metabolic parameters, safety, and side effects of AV from studies performed on animals (mammals). Methods: A systematic literature search was performed. The databases PubMed (MEDLINE), PsycInfo (Ebsco), CINAHL (Ebsco), and Embase (Ovid) were searched for relevant articles. Primary outcomes were glycated hemoglobin, postprandial glucose, and synonyms for blood glucose. Secondary outcomes were waist circumference, visceral fat, high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol. Studies performed on humans and animals were included. The included studies performed on humans were quality assessed for risk of bias using a version of the Cochrane Collaboration's tool. Results: A total of 487 papers were identified in the literature search. Of these, 13 studies performed on humans and 12 studies performed on animals were included. There may be beneficial health effects from the consumption of AV. The risk of side effects when ingested in recommended quantities and in recommended ways seems inconsiderable. Conclusion: Due to inadequate research of high quality, the evidence for the health effects of AV is insufficient. Therefore, more large-scale, long-term clinical studies with a low risk of bias are needed before definitive conclusions can be made. [ABSTRACT FROM AUTHOR]

To date, there is no compilation of evidence-based information associating photobiomodulation effect and salivary glands. This systematic review aims to assess photobiomodulation effect of low intensity laser on salivary glands in the presence of systemic diseases. MEDLINE databases were searched in duplicate through December 2018. In vivo studies and clinical trials were included if photobiomodulation was performed in salivary glands of animal (rat or mice) or human in the presence of systemic disease. The methodological quality was assessed in duplicate using the modified Newcastle-Ottawa scale (NOS). Search strategy identified 483 potentially eligible articles, and 449 were included. The Boolean search naturally leads to a high amount of works the majority of which were excluded because the analysis of the title and abstract demonstrated it was not focusing on PBM. Only 34 studies were selected for the full-text analysis, of which 5 were excluded due to non-use of photobiomodulation, 4 due to lack of control group, 2 because they were studies of cell cultures and 1 because they did not have the total of animals used. Thus, 21 papers were included for the critical evaluation of the impact of photobiomodulation on the major salivary glands; the studies used rats (n = 10) and humans (n = 11). Although studies reported an increase in the salivary rate, decrease in pain, and increase in quality of life after the PBM, the lack of standards for the application of light and reporting of the parameters, make it hard to reproduce the results. This topic is still in need for further research. [ABSTRACT FROM AUTHOR]

Background: Pedicle screw and rod instrumentation based on titanium can produce satisfying strength and stiffness for spinal fusion. However, excessive stiffness produced by titanium rods may cause stress shielding. Thus, polyetheretherketone (PEEK) rods with a low modulus of elasticity were introduced as substitutes for titanium rods. The purpose of this paper is to compare the effectiveness of PEEK rods versus titanium alloy rods in anterior spinal fusion with a new sheep model.Methods: Sheep models of anterior-posterior cervical fusion were innovatively adopted in our study. Twenty-four sheep were randomly divided into a control group and a treatment group that received anterior-posterior cervical fixation with titanium rods or PEEK rods, respectively. Then, surgical segments were harvested and assessed by X-ray, micro-CT and histological examination to evaluate the efficiency of bone fusion.Results: No complications related to fixation were found during the research process. The results of the X-ray showed a stronger spinal fusion in the PEEK rod groups than in the titanium rod group at 12 weeks postoperatively, and both groups underwent bone fusion at 24 weeks postoperatively. The results of micro-CT showed that fixation with PEEK rods achieved better bone ingrowth at an early postoperative stage (12 weeks) compared to fixation with titanium rods (bone volume fraction (BVF): 20.26 ± 4.36% vs 14.48 ± 3.49%, p < 0.05). The same trend was detected in the histological analysis, where the mineralized bone fraction in the experiment group (21.01 ± 3.48%) was significantly higher than that in the control group (16.73 ± 2.95%). In addition, better osseointegration was found in the experiment group at the early postoperative stage at 12 weeks (bone apposition (BA): 16.22 ± 3.24% vs 11.67 ± 3.63%, p < 0.05). However, there were no significant differences at 24 weeks postoperatively.Conclusion: PEEK rods can be used safely in a sheep model of anterior-posterior cervical fixation. Compared to traditional titanium rods, earlier and more evident bone fusion was found in the PEEK rods group. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

The human gut microbiome partakes in a bidirectional communication pathway with the central nervous system (CNS), named the microbiota-gut-brain axis. The microbiota-gut-brain axis is believed to modulate various central processes through the vagus nerve as well as production of microbial metabolites and immune mediators which trigger changes in neurotransmission, neuroinflammation, and behavior. Little is understood about the utilization of microbiome manipulation to treat disease. Though studies exploring the role of the microbiome in various disease processes have shown promise, mechanisms remain unclear and evidence-based treatments for most illnesses have not yet been developed. The animal studies reviewed here offer an excellent array of basic science research that continues to clarify mechanisms by which the microbiome may affect mental health. More evidence is needed, particularly as it relates to translating this work to human subjects. The studies presented in this paper largely demonstrate encouraging results in the treatment of depression. Limitations include small sample sizes and heterogeneous methodology. The exact mechanism by which the gut microbiota causes or alters neuropsychiatric disease states is not fully understood. In this review, we focus on recent studies investigating the relationship between gut microbiome dysbiosis and the pathogenesis of depression. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. [ABSTRACT FROM AUTHOR]

The paper examines the effects of the antimicrobial agent triclosan on the functioning of the liver mitochondria of marsh frog (Pelophylax ridibundus (Pallas, 1771)). It was established that triclosan inhibits DNP-stimulated respiration of mitochondria and decreases respiratory control ratio. In addition, triclosan causes the collapse of the mitochondrial membrane potential on both types of substrates. Such an action of triclosan can be mediated by both a protonophore effect and suppression of the activity of complex II and combined activity of complexes II + III (and, to a lesser degree, the combined activity of complexes I + III) of the mitochondrial respiratory chain. It is shown that high concentrations of triclosan enhance the production of hydrogen peroxide during the oxidation of substrates of the complex I by mitochondria, and decrease it in the case of succinate oxidation. It is found that triclosan is able to induce nonspecific permeability of the liver mitochondria of these amphibians, as well as the plasma membrane of erythrocytes. The possible mechanisms of triclosan effect on marsh frog liver mitochondria and red blood cells are discussed. [ABSTRACT FROM AUTHOR]

Continuing to explore the intriguing world of the Indian paper wasp Ropalidia marginata for one last time, here we will focus on the function of fighting behaviour in two additional contexts (i) the hyper-aggression of the potential queen during queen succession and (ii) during encounters with non-nestmate wasps. We will see again that the function of fighting is different in different contexts. We have already seen two different functions of fighting in two different contexts—to decide who will be the queen and who will be the worker in the context of founding new nests, and to regulate foraging in mature colonies by conveying colony hunger levels to foragers. Here we will see that the function of the potential queen's hyper-aggression is to boost her own ovarian development and the function of aggression towards non-nestmates is to keep them away, and if necessary, to kill! As before, our primary focus will be on how to design simple experiments that will help answer a direct question, while minimising the need for expensive equipment or other facilities. [ABSTRACT FROM AUTHOR]

At the request of French Regulatory Authorities, a new formulation of Levothyrox® was licensed in France in 2017, with the objective of avoiding the stability deficiencies of an existing licensed formulation. Before launching the new formulation, an average bioequivalence (ABE) trial was conducted, having enrolled 204 subjects and selected for interpretation a narrow a priori bioequivalence range of 0.90-1.11. Bioequivalence was concluded. In a previous publication, we questioned the ability of an ABE trial to guarantee the switchability within patients of the new and old levothyroxine formulations. It was suggested that the two formulations should be compared using the conceptual framework of individual bioequivalence. The present paper is a response to those claiming that, despite the fact that ABE analysis does not formally address the switchability of the two formulations, future patients will nevertheless be fully protected. The basis for this claim is that the ABE study was established in a large trial and analyzed using a stringent a priori acceptance interval of equivalence. These claims are questionable, because the use of a very large number of subjects nullifies the implicit precautionary intention of the European guideline when, for a Narrow Therapeutic Index drug, it recommends shortening the a priori acceptance interval from 0.80-1.25 to 0.90-1.11. [ABSTRACT FROM AUTHOR]

Read-across is one of the most frequently used alternative tools for hazard assessment, in particular for complex endpoints such as repeated dose or developmental and reproductive toxicity. Read-across extrapolates the outcome of a specific toxicological in vivo endpoint from tested (source) compounds to "similar" (target) compound(s). If appropriately applied, a read-across approach can be used instead of de novo animal testing. The read-across approach starts with structural/physicochemical similarity between target and source compounds, assuming that similar structural characteristics lead to similar human hazards. In addition, similarity also has to be shown for the toxicokinetic and toxicodynamic properties of the grouped compounds. To date, many read-across cases fail to demonstrate toxicokinetic and toxicodynamic similarities. New concepts, in vitro and in silico tools are needed to better characterise these properties, collectively called new approach methodologies (NAMs). This white paper outlines a general read-across assessment concept using NAMs to support hazard characterization of the grouped compounds by generating data on their dynamic and kinetic properties. Based on the overarching read-across hypothesis, the read-across workflow suggests targeted or untargeted NAM testing also outlining how mechanistic knowledge such as adverse outcome pathways (AOPs) can be utilized. Toxicokinetic models (biokinetic and PBPK), enriched by in vitro parameters such as plasma protein binding and hepatocellular clearance, are proposed to show (dis)similarity of target and source compound toxicokinetics. Furthermore, in vitro to in vivo extrapolation is proposed to predict a human equivalent dose, as potential point of departure for risk assessment. Finally, the generated NAM data are anchored to the existing in vivo data of source compounds to predict the hazard of the target compound in a qualitative and/or quantitative manner. To build this EU-ToxRisk read-across concept, case studies have been conducted and discussed with the regulatory community. These case studies are briefly outlined. [ABSTRACT FROM AUTHOR]

Continuing to explore the intriguing world of the Indian paper wasp Ropalidia marginata, here we will focus on their fighting behaviour. When wasps fight, there is, as expected, a winner and a loser. The winner is said to have shown dominance behaviour, and the loser is said to have shown subordinate behaviour. What is the function of such dominance-subordinate behaviour? We saw in the 7th article in this series [1] that in the context of founding new nests, wasps fight to decide who would be the queen and who would be the worker. We then saw in the 8th article in this series [2] that when wasps have to decide who would be their next queen in a mature colony, they do not decide by fighting, although they fight for other reasons. We will see in this article that workers continue to show dominance-subordinate behaviour in mature colonies. What is the function of this aggression displayed by the workers? In this article, I will describe two simple experiments that help us answer this question, and show that the function of wasp aggression can be quite different in different contexts. [ABSTRACT FROM AUTHOR]

Human germline gene editing is often debated in hypothetical terms: if it were safe and efficient, on what further conditions would it then be ethically acceptable? This paper takes another course. The key question is: how can scientists reduce uncertainty about safety and efficiency to a level that may justify initiation of first-time clinical trials? The only way to proceed is by well-designed preclinical studies. However, what kinds of investigation should preclinical studies include and what specific conditions should they satisfy in order to be considered well-designed? It is argued that multispecies and multigenerational animal studies are needed as well as human embryo editing without implantation. In order to be possible to translate to first-time clinical trials, animal studies need to satisfy strict conditions of validity. Moreover, embryo studies intended for translation to first-time clinical trials need to correspond to the animal studies in experimental design (with exception of implantation). Only in this way can uncertainty about risk for harm (safety) and prospect of benefit (efficiency) in first-time clinical trials be reduced to a modest level. If uncertainty is not reduced to such a level, first-time clinical trials in germline gene editing should not be initiated. [ABSTRACT FROM AUTHOR]

Continuing to explore the fascinating world of the Indian paper wasp Ropalidia marginata, in this article, we will ask how wasps choose their queens in another context. In the previous article in this series, we saw how a simple experiment revealed that wasps fight, i.e., indulge in dominance-subordinate interactions, and the winner becomes the queen and the loser becomes the worker. This was in the context of new nest foundation. But context matters. When the same wasps once again have to decide who will be their next queen if the first one dies or is experimentally removed, the same rules do not hold. The wasps in a mature colony continue to show dominance-subordinate interactions and can even be arranged in a dominance hierarchy, but the dominance ranks of the wasps do not predict who their next queen will be. How they choose their next queen in this context continues to be an enduring mystery. In this article, I will describe four simple experiments that have helped us come close to nailing the culprit, although I must confess that we have not yet found the smoking gun—the chase is on, and we are hot on the trail—please join in! [ABSTRACT FROM AUTHOR]

There are various methods and algorithms to detect the optic discs in retinal images. In recent years, much attention has been given to the utilization of the intelligent algorithms. In this paper, we present a new automated method of optic disc detection in human retinal images using the firefly algorithm. The firefly intelligent algorithm is an emerging intelligent algorithm that was inspired by the social behavior of fireflies. The population in this algorithm includes the fireflies, each of which has a specific rate of lighting or fitness. In this method, the insects are compared two by two, and the less attractive insects can be observed to move toward the more attractive insects. Finally, one of the insects is selected as the most attractive, and this insect presents the optimum response to the problem in question. Here, we used the light intensity of the pixels of the retinal image pixels instead of firefly lightings. The movement of these insects due to local fluctuations produces different light intensity values in the images. Because the optic disc is the brightest area in the retinal images, all of the insects move toward brightest area and thus specify the location of the optic disc in the image. The results of implementation show that proposed algorithm could acquire an accuracy rate of 100 % in DRIVE dataset, 95 % in STARE dataset, and 94.38 % in DiaRetDB1 dataset. The results of implementation reveal high capability and accuracy of proposed algorithm in the detection of the optic disc from retinal images. Also, recorded required time for the detection of the optic disc in these images is 2.13 s for DRIVE dataset, 2.81 s for STARE dataset, and 3.52 s for DiaRetDB1 dataset accordingly. These time values are average value. [ABSTRACT FROM AUTHOR]

Previous studies showed that all the vascular parameters from both the morphological and topological parameters were affected with the altering of imaging resolutions. However, neither the sensitivity analysis of the vascular parameters at multiple resolutions nor the distinguishability estimation of vascular parameters from different data groups has been discussed. In this paper, we proposed a quantitative analysis method of vascular parameters for vascular networks of multi-resolution, by analyzing the sensitivity of vascular parameters at multiple resolutions and estimating the distinguishability of vascular parameters from different data groups. Combining the sensitivity and distinguishability, we designed a hybrid formulation to estimate the integrated performance of vascular parameters in a multi-resolution framework. Among the vascular parameters, degree of anisotropy and junction degree were two insensitive parameters that were nearly irrelevant with resolution degradation; vascular area, connectivity density, vascular length, vascular junction and segment number were five parameters that could better distinguish the vascular networks from different groups and abide by the ground truth. Vascular area, connectivity density, vascular length and segment number not only were insensitive to multi-resolution but could also better distinguish vascular networks from different groups, which provided guidance for the quantification of the vascular networks in multi-resolution frameworks. [ABSTRACT FROM AUTHOR]

Circadian rhythms are driven by an internal molecular clock which controls physiological and behavioral processes. Disruptions in these rhythms have been associated with health issues. Therefore, studying circadian rhythms is crucial for understanding physiology, behavior, and pathophysiology. However, it is challenging to study circadian rhythms over gene expression data, due to a scarcity of time labels. In this paper, we propose a novel approach to predict the phases of un-timed samples based on a deep neural network (DNN) architecture. This approach addresses two challenges: (1) prediction of sample phases and reliable identification of cyclic genes from high-dimensional expression data without relying on conserved circadian genes and (2) handling small sample-sized datasets. Our algorithm begins with initial gene screening to select candidate cyclic genes using a Minimum Distortion Embedding framework. This stage is then followed by greedy layer-wise pre-training of our DNN. Pre-training accomplishes two critical objectives: First, it initializes the hidden layers of our DNN model, enabling them to effectively capture features from the gene profiles with limited samples. Second, it provides suitable initial values for essential aspects of gene periodic oscillations. Subsequently, we fine-tune the pre-trained network to achieve precise sample phase predictions. Extensive experiments on both animal and human datasets show accurate and robust prediction of both sample phases and cyclic genes. Moreover, based on an Alzheimer’s disease (AD) dataset, we identify a set of hub genes that show significant oscillations in cognitively normal subjects but had disruptions in AD, as well as their potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is technically challenging and requires a high level of skill. However, there is no effective method of exposing the submucosal plane during dissection. In this study, the efficacy of robot arm-assisted tissue traction for gastric ESD was evaluated using an in vivo porcine model. The stomach of each pig was divided into eight locations. In the conventional ESD (C-ESD) group, one ESD was performed at each location (N = 8). In the robot arm-assisted ESD (R-ESD) group, two ESDs were performed at each location (N = 16). The primary endpoint was the submucosal dissection speed (mm2/s). The robot arm could apply tissue traction in the desired direction and successfully expose the submucosal plane during submucosal dissection in all lesion locations. The submucosal dissection speed was significantly faster in the R-ESD group than in the C-ESD group (p = 0.005). The blind dissection rate was significantly lower in the R-ESD group (P = 0.000). The robotic arm-assisted traction in ESD enabled a significant improvement in submucosal dissection speed, blind dissection rate which suggests the potential for making ESD easier and enhancing procedural efficiency and safety. [ABSTRACT FROM AUTHOR]

Background: Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges. Methods: A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR. Results: Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression. Conclusion: A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack. [ABSTRACT FROM AUTHOR]

The biomedical research community addresses reproducibility challenges in animal studies through standardized nomenclature, improved experimental design, transparent reporting, data sharing, and centralized repositories. The ARRIVE guidelines outline documentation standards for laboratory animals in experiments, but genetic information is often incomplete. To remedy this, we propose the Laboratory Animal Genetic Reporting (LAG-R) framework. LAG-R aims to document animals' genetic makeup in scientific publications, providing essential details for replication and appropriate model use. While verifying complete genetic compositions may be impractical, better reporting and validation efforts enhance reliability of research. LAG-R standardization will bolster reproducibility, peer review, and overall scientific rigor. Reproducibility is key to all fields of research, and in the case of animal research, this can be hampered by inconsistent reporting of animal genetics. Here the authors propose a reporting framework and guidelines designed to discuss the validation and standardise the reporting of genetic backgrounds and genetic alterations in animal models. [ABSTRACT FROM AUTHOR]

Coriandrum sativum L. (coriander), which is an annual herb of the Apiaceae family, has been traditionally used as a remedy. Here we tested whether heated extract of coriander leaf protects nigral dopaminergic neurodegeneration after exposure to 6-hydroxydopamine (6-OHDA). After injection of 6-OHDA into the rat substantia nigra pars compacta (SNpc), dopaminergic degeneration, which was determined by tyrosine hydroxylase immunostaining, was rescued by co-injection of CaEDTA, an extracellular Zn2+ chelator, suggesting that extracellular Zn2+ influx is involved in neurodegeneration. Both intracellular Zn2+ dysregulation determined by ZnAF-2 fluorescence and dopaminergic degeneration in the SNpc induced by 6-OHDA were rescued by co-injection of 0.25% coriander extract, which also reduced reactive oxygen species (ROS) production in the SNpc determined by aminophenyl fluorescein fluorescence. The present study suggests that coriander leaf extract protects nigral dopaminergic neurodegeneration induced by intracellular Zn2+ dysregulation. It is likely that the nutraceutical property of coriander leaf extract contributes to the protection via reducing ROS production. [ABSTRACT FROM AUTHOR]

Corrole is a kind of new and promising photosensitizer (PS) in cancer photodynamic therapy (PDT). However, the protein molecular mechanism of PDT activity for corrole under light irradiation is still not clear. In this paper, water-soluble cationic sulfonated corrole (1) and its metal complexes (1-Fe, 1-Mn, and 1-Cu) were prepared, and the photodynamic anti-cancer activity against various tumor cells was investigated by MTT assay. The potential molecular mechanism of PDT activity was elucidated by fluorescence microscope, flow cytometry, molecular docking, and western blotting analysis. Besides, the potential PDT anti-tumor effect of 1 in vivo was assessed in human tumor xenografts in mice. Quantitative analysis revealed that 1's phototoxicity triggered a significant generation of reactive oxygen species, causing disruption of mitochondrial membrane potential. The results of western blotting (WB) assay shown in 1's phototoxicity could induce cell apoptosis via ROS-mediated mitochondrial caspase apoptosis pathway, in which SIRT1 protein degradation played a key role. PTD activity in vivo shown in 1 could significantly reduce the growth of A549 xenografted tumor, without obvious loss of mice body weight. We clearly found that cationic sulfonated corrole is a potential candidate of PS in vitro and in vivo. The phototoxicity of 1 could induce A549 cell apoptosis by inducing ROS production increase, further to activate the mitochondrial apoptosis pathway. We concluded that SIRT1 protein is a more appropriate target in this progress. [ABSTRACT FROM AUTHOR]

A growing trend within feminist animal studies is to eschew the abolitionism/welfarism binary in favor of attending carefully to the politics of existing interspecies relationships in context. This literature maintains that domestication produces special interspecies relationships which generate ongoing responsibilities for human companions and communities. With the goal of clarifying how tending to these ongoing responsibilities to domesticated animals can qualify as enduring forms of interspecies justice, this paper unpacks the politics of these special relationships and obligations in context, specifically, that of fancy rat breeders' attempts to eliminate aganglionic megacolon. Contrasting fanciers' efforts with those of laboratory breeders and researchers, I argue that what sets the fancy apart is its shared code of ethics and the loving, principled form of life from which it emerges. Furthermore, the knowledge that rats are worth loving not only enables fanciers to attend to the injustice of megacolon but facilitates transformative justice for domestic rats more broadly. [ABSTRACT FROM AUTHOR]

The benefit of small animal imaging is directly linked to the validity and reliability of the collected data. If the data (regardless of the modality used) are not reproducible and/or reliable, then the outcome of the data is rather questionable. Therefore, standardization of the use of small animal imaging equipment, as well as of animal handling in general, is of paramount importance. In a recent paper, guidance for efficient small animal imaging quality control was offered and discussed, among others, the use of phantoms in setting up a quality control program (Osborne et al. 2016). The same phantoms can be used to standardize image quality parameters for multi-center studies or multi-scanners within center studies. In animal experiments, the additional complexity due to animal handling needs to be addressed to ensure standardized imaging procedures. In this review, we will address the current status of standardization in preclinical imaging, as well as potential benefits from increased levels of standardization. [ABSTRACT FROM AUTHOR]

The effect of low-level laser therapy (LLLT) on the healing of skin lesions has been evaluated in many studies; however, the molecular mechanisms involved in the biostimulatory effects resulting from this treatment need to be better understood. The paper aims to analyze the effects of LLLT (660 nm) at doses of 1 and 5 J/cm2 on cell viability and expression of vascular endothelial growth factor (VEGF) and interleukin (IL6) genes in L929 fibroblast cells. The dose-response curve was performed with the GaInAlAs (660 nm) laser-treated cells at energy rates of 1 and 5 J/cm2. Cell viability was quantified at 24, 48, and 72 h after irradiation and the effects of TLBP on the cytoskeleton and endoplasmic reticulum were evaluated by fluorescence microscopy and the RT-qPCR method was used for the analysis of gene expression. It was observed that the 72 h group had a statistically significant increase in cell viability compared to the 48 h group (p < 0.01) and when compared to the 72 h control (p = 0.03). In 72 h, a greater distribution of the cytoskeleton filaments and the more evident endoplasmatic reticulum was verified, indicating an increase in the protein synthesis when compared with the control group. In the expression of the VEGF gene, a significant increase of 1.98 times (p < 0.05) in the number of transcripts was observed; whereas for the IL6 gene, a decrease of the transcripts was 4.05 times (p < 0.05), both occurring within 72 h after irradiation at 5 J/cm2. The LLLT (660 nm) at the dose of 5 J/cm2 should modulate cellular viability, upregulated VEGF, and downregulated IL6 expression of messenger RNA in culture of L929 fibroblast cells. [ABSTRACT FROM AUTHOR]

This study aimed at assessing the feasibility of a discrete algebraic reconstruction technique (DART) to be used in in vivo small animal bone studies. The advantage of discrete tomography is the possibility to reduce the amount of X-ray projection images, which makes scans faster and implies also a significant reduction of radiation dose, without compromising the reconstruction results. Bone studies are ideal for being performed with discrete tomography, due to the relatively small number of attenuation coefficients contained in the image [namely three: background (air), soft tissue and bone]. In this paper, a validation is made by comparing trabecular bone morphometric parameters calculated from images obtained by using DART and the commonly used standard filtered back-projection (FBP). Female rats were divided into an ovariectomized (OVX) and a sham-operated group. In vivo micro-CT scanning of the tibia was done at baseline and at 2, 4, 8 and 12 weeks after surgery. The cross-section images were reconstructed using first the full set of projection images and afterwards reducing them in number to a quarter and one-sixth (248, 62, 42 projection images, respectively). For both reconstruction methods, similar changes in morphometric parameters were observed over time: bone loss for OVX and bone growth for sham-operated rats, although for DART the actual values were systematically higher (bone volume fraction) or lower (structure model index) compared to FBP, depending on the morphometric parameter. The DART algorithm was, however, more robust when using fewer projection images, where the standard FBP reconstruction was more prone to noise, showing a significantly bigger deviation from the morphometric parameters obtained using all projection images. This study supports the use of DART as a potential alternative method to FBP in X-ray micro-CT animal studies, in particular, when the number of projections has to be drastically minimized, which directly reduces scanning time and dose. [ABSTRACT FROM AUTHOR]

Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play an important role in cluster headache pathophysiology. More refined human studies are warranted with regard to assay validation and using larger sample sizes. The results from RCTs may reveal the therapeutic potential of CGRP monoclonal antibodies and antagonists for cluster headache treatment. [ABSTRACT FROM AUTHOR]

Purpose: The mechanisms of soft tissue injury by bullets are reviewed, in the belief that the current incidence of firearm injuries in many urban areas necessitates an understanding of wound ballistics on the part of trauma surgeons who may not be familiar with the wounding factors involved. Methods: Review of the literature, with technical information obtained from appropriate non-medical texts. Results: Despite numerous publications concerning the treatment of gunshot wounds, relatively few papers contain details on the mechanisms of ballistic trauma, with the main body of evidence derived from previous laboratory and animal studies which have only recently been systematically appraised. These studies have shown that in rifle injuries the main wound tract is surrounded by an area of damaged tissue as a result of the temporary cavitation induced once the bullet becomes destabilized or deformed. On the other hand, the more commonly encountered non-deforming handgun bullets cause damage limited to the bullet's path, mainly as a result of localized crush injury. Conclusions: The bullet's construction and ballistic behavior within tissue determine to what extent the previously overestimated velocity factor may influence wound severity. The damage produced from temporary cavitation depends on the tensile properties of the tissues involved, and in high-energy injuries may lead to progressive muscle tissue necrosis. Therefore, the term 'high-energy' should be reserved for those injuries with substantial tissue damage extending beyond the visible wound tract. [ABSTRACT FROM AUTHOR]

The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox. There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein. [ABSTRACT FROM AUTHOR]

Background: Pain, an evolutionarily conserved warning system, lets us recognize threats and motivates us to adapt to those threats. Headache pain from migraine affects approximately 15% of the global population. However, the identity of any putative threat that migraine or headache warns us to avoid is unknown because migraine pathogenesis is poorly understood. Here, we show that a stress-induced increase in pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), known as an initiator of allosteric load inducing unbalanced homeostasis, causes headache-like behaviour in male mice via mas-related G protein-coupled receptor B2 (MrgprB2) in mast cells. Methods: The repetitive stress model and dural injection of PACAP38 were performed to induce headache behaviours. We assessed headache behaviours using the facial von Frey test and the grimace scale in wild-type and MrgprB2-deficient mice. We further examined the activities of trigeminal ganglion neurons using in vivo Pirt-GCaMP Ca2+ imaging of intact trigeminal ganglion (TG). Results: Repetitive stress and dural injection of PACAP38 induced MrgprB2-dependent headache behaviours. Blood levels of PACAP38 were increased after repetitive stress. PACAP38/MrgprB2-induced mast cell degranulation sensitizes the trigeminovascular system in dura mater. Moreover, using in vivo intact TG Pirt-GCaMP Ca2+ imaging, we show that stress or/and elevation of PACAP38 sensitized the TG neurons via MrgprB2. MrgprB2-deficient mice showed no sensitization of TG neurons or mast cell activation. We found that repetitive stress and dural injection of PACAP38 induced headache behaviour through TNF-a and TRPV1 pathways. Conclusions: Our findings highlight the PACAP38-MrgprB2 pathway as a new target for the treatment of stress-related migraine headache. Furthermore, our results pertaining to stress interoception via the MrgprB2/PACAP38 axis suggests that migraine headache warns us of stress-induced homeostatic imbalance. [ABSTRACT FROM AUTHOR]

Objectives: The single-energy metal artifact reduction (SEMAR) algorithm effectively reduces metal artifacts in computed tomography (CT). The study aimed to evaluate the effect of the occlusal plane angle on metal artifacts caused by dental implants and zirconia upper structures, and the effectiveness of SEMAR for CT prognostic evaluation. Methods: Part of a bovine rib was used as the mandibular implant phantom. First, the phantom immersed in a water tank was scanned using CT to obtain the control image under certain conditions. Subsequently, three titanium implant bodies were implanted in a straight line into the phantom, and a zirconia superstructure was attached. CT scans were performed. The CT-reconstructed images were obtained with and without SEMAR processing. Twelve regions of interest (ROIs) were set at the same site on each sagittal image, and the CT values were measured at all the ROIs. The CT values of the ROIs in the control images and those of the ROIs with and without SEMAR were compared. Results: The variations in the occlusal plane angle during CT imaging negligibly affected the number of regions in which metal artifacts appeared. SEMAR improved the CT value of the trabecular bone, which was affected by metal artifacts. Conclusion: This study showed that the occlusal plane angle occasionally did not affect the area of metal artifacts caused by dental implants or zirconia upper structures. Other results indicate that SEMAR is effective for accurately evaluating the alveolar bone around the implant body by reducing metal artifacts. [ABSTRACT FROM AUTHOR]

Gastrointestinal mucositis is a complex inflammatory reaction of the mucous membranes, a side effect of both chemotherapy and radiotherapy. Currently, assessment scales are used to diagnose mucositis. However, a biomarker which would determine whether there is mucositis and thereby establish the severity objectively would be very useful. This will give the opportunity to evaluate studies, to determine risk factors and incidence, and it will make it possible to compare studies. Moreover, this biomarker might improve clinical management for patients. In this paper, we reviewed studies concerning potential biomarkers in blood samples and fecal samples, and potential tests in breath samples and urine samples. We include biomarkers and tests studied in animal models and/or in clinical trials, and discuss the validity, diagnostic accuracy, and applicability. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgery attracts more and more attention because of the advantages of minimal trauma, less bleeding and pain and low complication rate. However, minimally invasive surgery for beating hearts is still a challenge. Our goal is to develop a soft robot surgical system for single-port minimally invasive surgery on a beating heart.Materials and Methods: The soft robot described in this paper is inspired by the octopus arm. Although the octopus arm is soft and has more degrees of freedom (DOFs), it can be controlled flexibly. The soft robot is driven by cables that are embedded into the soft robot manipulator and can control the direction of the end and middle of the soft robot manipulator. The forward, backward and rotation movement of the soft robot is driven by a propulsion plant. The soft robot can move freely by properly controlling the cables and the propulsion plant. The soft surgical robot system can perform different thoracic operations by changing surgical instruments. To evaluate the flexibility, controllability and reachability of the designed soft robot surgical system, some testing experiments have been conducted in vivo on a swine.Results: Through the subxiphoid, the soft robot manipulator could enter into the thoracic cavity and pericardial cavity smoothly and perform some operations such as biopsy, ligation and ablation. The operations were performed successfully and did not cause any damage to the surrounding soft tissues. From the experiments, the flexibility, controllability and reachability of the soft robot surgical system have been verified. Also, it has been shown that this system can be used in the thoracic and pericardial cavity for different operations.Conclusions: Compared with other endoscopy robots, the soft robot surgical system is safer, has more DOFs and is more flexible for control. When performing operations in a beating heart, this system maybe more suitable than traditional endoscopy robots. [ABSTRACT FROM AUTHOR]

Purpose: X-ray micro-computed tomography (μCT) is a widely used imaging modality in preclinical research with applications in many areas including orthopedics, pulmonology, oncology, cardiology, and infectious disease. X-rays are a form of ionizing radiation and, therefore, can potentially induce damage and cause detrimental effects. Previous reviews have touched on these effects but have not comprehensively covered the possible implications on study results. Furthermore, interpreting data across these studies is difficult because there is no widely accepted dose characterization methodology for preclinical μCT. The purpose of this paper is to ensure in vivo μCT studies can be properly designed and the data can be appropriately interpreted.Procedures: Studies from the scientific literature that investigate the biological effects of radiation doses relevant to μCT were reviewed. The different dose measurement methodologies used in the peer-reviewed literature were also reviewed. The CT dose index 100 (CTDI100) was then measured on the Quantum GX μCT instrument. A low contrast phantom, a hydroxyapatite phantom, and a mouse were also imaged to provide examples of how the dose can affect image quality.Results: Data in the scientific literature indicate that scenarios exist where radiation doses used in μCT imaging are high enough to potentially bias experimental results. The significance of this effect may relate to the study outcome and tissue being imaged. CTDI100 is a reasonable metric to use for dose characterization in μCT. Dose rates in the Quantum GX vary based on the amount of material in the beam path and are a function of X-ray tube voltage. The CTDI100 in air for a Quantum GX can be as low as 5.1 mGy for a 50 kVp scan and 9.9 mGy for a 90 kVp scan. This dose is low enough to visualize bone both in a mouse image and in a hydroxyapatite phantom, but applications requiring higher resolution in a mouse or less noise in a low-contrast phantom benefit from longer scan times with increased dose.Conclusions: Dose management should be considered when designing μCT studies. Dose rates in the Quantum GX are compatible with longitudinal μCT imaging. [ABSTRACT FROM AUTHOR]

Descending neural pathways in the mammalian auditory system are known to modulate the function of the peripheral auditory system. These pathways include the medial olivocochlear (MOC) efferent innervation to outer hair cells (OHCs) and the acoustic reflex pathways mediating middle ear muscle (MEM) contractions. Based on measurements in humans (Marks and Siegel, companion paper), we applied a sensitive method to attempt to differentiate MEM and MOC reflexes using contralateral acoustic stimulation in mice under different levels of anesthesia. Separation of these effects is based on the knowledge that OHC-generated transient evoked otoacoustic emissions (TEOAE) are delayed relative to the stimulus, and that the MOC reflex affects the emission through its innervation of OHC. In contrast, the MEM-mediated changes in middle ear reflectance alter both the stimulus (with a short delay) and the emission. Using this approach, time averages to transient stimuli were evaluated to determine if thresholds for a contralateral effect on the delayed emission, indicating potential MOC activation, could be observed in the absence of a change in the stimulus pressure. This outcome was not observed in the majority of cases. There were also no statistically significant differences between MEM and putative MOC thresholds, and variability was high for both thresholds regardless of anesthesia level. Since the two reflex pathways could not be differentiated on the basis of activation thresholds, it was concluded that the MEM reflex dominates changes in TEOAEs induced by contralateral noise. This result complicates the identification of purely MOC-induced changes on OAEs in mice unless the MEM reflex is inactivated surgically or pharmacologically. [ABSTRACT FROM AUTHOR]

The use of eosin methylene blue according to Giemsa as photosensitizer is presented for the first time in this paper. The present study evaluated the potential application of chlorophyllin sodium copper salt (CuChlNa) and eosin methylene blue according to Giemsa (EMB) as antimicrobial photosensitizers (aPS) for photodynamic inactivation (PDI) of Staphylococcus aureus (gram-positive) and Escherichia coli (gram-negative) bacteria. The experiments were performed using S. aureus stain ATCC 25923 and E. coli ATCC 25922 in which five aPS concentrations (0.0, 1.0, 2.5, 5.0, 10.0, and 20.0 μM for S. aureus and 0.0, 5.0, 10.0, 20.0, 40.0, and 50.0 μM for E. coli) were prepared and added in 2 mL of a saline solution containing the bacterial inoculum. After aPS incubation, the samples were divided into two groups, one kept in the dark and another submitted to the illumination. Then, the bacterial inactivation was determined 18 h after the incubation at 37 °C by counting the colony-forming units (CFU). The results revealed that both EMB and CuChlNa can be used as aPS for the photoinactivation of S. aureus, while only EMB was able to photoinactivate E. coli. Nevertheless, a more complex experimental setup was needed for photoinactivation of E. coli. The data showed that EMB and CuChlNa presented similar photoinactivation effects on S. aureus, in which bacterial growth was completely inhibited at photosensitizer (PS) concentrations over 5 μM, when samples were previously incubated for 30 min and irradiated by a light dose of 30 J cm-2 as a result of an illumination of 1 h at 8.3 mW cm-2 by using a red light at 625 nm with a 1 cm beam diameter and output power of 6.5 mW. In the case of E. coli, bacterial growth was completely inhibited only when combining a PS incubation period of 120 min with concentrations over 20 μM. [ABSTRACT FROM AUTHOR]