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Physiology is a scientific discipline of how people's and animals' bodies function that requires traditionally suitable experimental models that often rely on animals. However, at the end of the 50th of the last century, researchers themselves addressed concerns about the use of animals for biomedical science and physiology in particular. At that time, the so-called 3R strategy was implicated where the three "R" stand for replacement, reduction, and refinement. When addressing these concerns, researchers nevertheless realized that a critical dispute about experimental models in the light of the 3R initiative may require further attention to other points such as robustness, registration, reporting, reproducibility, and rigor of the work. The question that has to be addressed now is first whether the use of animals in physiology changed in the post-3R period, whether it led to a replacement, reduction, or refinement of animal handling, and most importantly, how this affected the scientific progress in (patho)physiology. In order to address open questions concerning the relationship between the use of animals and physiological research, complete volumes of the Pflügers Archiv – European Journal of Physiology were analyzed every 10 years starting in 1950 and ending in 2020 and compared to volumes of the Journal of Physiology. It analyzed how scientists organize their projects published in the journal and what kind of models they used. The results show that physiological science has dramatically changed in the last 70 years. Replacement, reduction, and refinement were achieved to a certain level. However, during the last years, no further achievement could be seen. It seems that a certain level of animal testing is required for biomedical science and physiology in particular. Physiological studies in the present time are dominated by investigation of the physiological function of small rodents mainly mice and rats with only a few exceptions. The analysis also shows that in the future, researchers must have a critical look at further requirements of their research such as data robustness, improvement of reproducibility of data, and generation of rigor data as a prerequisite to improve our physiological view on life. [ABSTRACT FROM AUTHOR]

Introduction Despite the significant need for mechanical ventilation in- and out-of-hospital, mechanical ventilators remain inaccessible in many instances because of cost or size constraints. Mechanical ventilation is especially critical in trauma scenarios, but the impractical size and weight of standard mechanical ventilators restrict first responders from carrying them in medical aid bags, leading to reliance on imprecise manual bag-mask ventilation. This is particularly important in combat-related injury, where airway compromise and respiratory failure are leading causes of preventable death, but medics are left without necessary mechanical ventilation. To address the serious gaps in mechanical ventilation accessibility, we are developing an Autonomous, Modular, and Portable Ventilation platform (AMP-Vent) suitable for austere environments, prolonged critical care, surgical applications, mass casualty incidents, and stockpiling. The core system is remarkably compact, weighing <2.3 kg, and can fit inside a shoebox (23.4 cm × 17.8 cm × 10.7 cm). Notably, this device is 65% lighter than standard transport ventilators and astoundingly 96% lighter than typical intensive care unit ventilators. Beyond its exceptional portability, AMP-Vent can be manufactured at less than one-tenth the cost of conventional ventilators. Despite its reduced size and cost, the system's functionality is uncompromised. The core system is equipped with closed-loop sensors and advanced modes of ventilation (pressure-control, volume-control, and synchronized intermittent mandatory ventilation), enabling quality care in a portable form factor. The current prototype has undergone preliminary preclinical testing and optimization through trials using a breathing simulator (ASL 5000) and in a large animal model (swine). This report aims to introduce a novel ventilation system and substantiate its promising performance through evidence gathered from preclinical studies. Materials and Methods Lung simulator testing was performed using the ASL 5000, in accordance with table 201.105 "pressure-control inflation-type testing" from ISO 80601-2-12:2020. Following simulations, AMP-Vent was tested in healthy 10-kg female domestic piglets. The Children's Hospital of Philadelphia Institutional Animal Care and Use Committee approved all animal procedures. Swine received 4-min blocks of alternating ventilation, where AMP-Vent and a conventional anesthesia ventilator (GE AISYS CS2) were used to titrate to varied end-tidal carbon dioxide (EtCO2) goals with the initial ventilator switching for each ascending target (35, 40, 45, 50, 55 mmHg). Results During ASL 5000 simulations, AMP-Vent exhibited consistent performance under varied conditions, maintaining a coefficient of variation of 2% or less within each test. In a large animal study, AMP-Vent maintained EtCO2 and SpO2 targets with comparable performance to a conventional anesthesia ventilator (GE AISYS CS2). Furthermore, the comparison of minute ventilation (V e) distributions between the conventional anesthesia ventilator and AMP-Vent at several EtCO2 goals (35, 40, 45, 50, and 55 mmHg) revealed no statistically significant differences (p  = 0.46 using the Kruskal–Wallis rank sum test). Conclusions Preclinical results from this study highlight AMP-Vent's core functionality and consistent performance across varied scenarios. AMP-Vent sets a benchmark for portability with its remarkably compact design, positioning it to revolutionize trauma care in previously inaccessible medical scenarios. [ABSTRACT FROM AUTHOR]

Introduction Non-compressible torso hemorrhagic (NCTH) shock is the leading cause of potentially survivable trauma on the battlefield. New hypotensive drug therapies are urgently required to resuscitate and protect the heart and brain following NCTH. Our aim was to examine the strengths and limitations of permissive hypotension and discuss the development of small-volume adenosine, lidocaine, and Mg2+ (ALM) fluid resuscitation in rats and pigs. Materials and Methods For review of permissive hypotension, a literature search was performed from inception up to November 2023 using PubMed, Cochrane, and Embase databases, with inclusion of animal studies, clinical trials and reviews with military and clinical relevance. For the preclinical study, adult female pigs underwent laparoscopic liver resection. After 30 minutes of bleeding, animals were resuscitated with 4 mL/kg 3% NaCl ± ALM bolus followed 60 minutes later with 4 h 3 mL/kg/h 0.9% NaCl ± ALM drip (n  = 10 per group), then blood transfusion. Mean arterial pressure (MAP) and cardiac output (CO) were continuously measured via a left ventricular pressure catheter and pulmonary artery catheter, respectively. Systemic vascular resistance (SVR) was calculated using the formula: 80 × (MAP − CVP)/CI. Oxygen delivery was calculated as the product of CO and arterial oxygen content. Results Targeting a MAP of ∼50 mmHg can be harmful or beneficial, depending on how CO and SVR are regulated. A theoretical example shows that for the same MAP of 50 mmHg, a higher CO and lower SVR can lead to a nearly 2-fold increase in O2 supply. We further show that in animal models of NCTH, 3% NaCl ALM bolus and 0.9% NaCl ALM drip induce a hypotensive, high flow, vasodilatory state with maintained tissue O2 supply and neuroprotection. ALM therapy increases survival by resuscitating the heart, reducing internal bleeding by correcting coagulopathy, and decreasing secondary injury. Conclusions In rat and pig models of NCTH, small-volume ALM therapy resuscitates at hypotensive pressures by increasing CO and reducing SVR. This strategy is associated with heart and brain protection and maintained tissue O2 delivery. Translational studies are required to determine reproducibility and optimal component dosing. ALM therapy may find wide utility in prehospital and far-forward military environments. [ABSTRACT FROM AUTHOR]

Introduction: There have been relatively few attempts to quantitatively assess if, and in which areas, the use of non-animal methods (NAMs) is increasing in biomedical research and importantly, how this compares to the use of live animals. Methods: We conducted a bibliometric analysis of the relative publication of papers reporting the use of NAMs-only compared to those reporting the use of animals, even if they also reported the use of NAMs, over the period 2003 to 2022 across seven research areas (breast cancer, lung disease, blood cancer, heart disease, neurodegenerative diseases, diabetes and toxicology) and five regions (USA, China, France, Germany, United Kingdom). Results: We found that the relative number of publications of research using NAMs-only has been higher than animal-based research for the last 20 years for all research areas and is growing. Research areas differed in their relative publication of NAMs-only based work, with breast cancer and lung disease having consistently the highest ratio of NAMs-only to animal-based publications and heart disease, diabetes and toxicology showing the greatest change over the time period. A key period of change was 2016--18. By 2022 the UK had the highest NAMs-only to animal-based research ratio than any other country for five of the seven research areas and China the lowest for six, accounting for publication rate. Tissue and in silico-based methods were the most common of all NAMs-only publications; lab-on-a-chip and stem cell models are increasing in their use but at much lower levels and rate of increase. Conclusion: We found that proportionately the reliance on animals in these research areas is decreasing, which will be encouraging to those that support the replacement of animal experiments. [ABSTRACT FROM AUTHOR]

Fiddler crabs have been used as model organisms in many laboratory and field studies. In their natural environment, social interaction with other fiddler crabs (conspecific or heterospecific) is recurrent, but manipulative studies involving these crabs as models are often performed with isolated individuals. The isolation of an animal can interfere in the behaviors recorded as response variables. Thus, the aim of this study was to evaluate whether the presence of other individuals affects the performance of behaviors of fiddler crabs Leptuca uruguayensis. We tested two hypotheses in the field: (1) the visual stimulus of the crab assemblage affects the activity of male fiddler crabs; and (2) the presence of other conspecific affects the activity of male fiddler crabs depending on the sexes of the individuals present. We found the activities of L. uruguayensis males mediated by social interactions does not depend exclusively on visual stimuli. Physical interaction with other conspecifics of both sexes enables the perception of stimuli which can influence the waving behavior of L. uruguayensis males. We suggest that behavioral studies with this model should consider the presence of other individuals. Understanding the behavioral complexity of a model organism contributes to more robust experiments with greater control of interfering variables. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Raw materials of biological origin can contaminate medicines with depressor substances, such as histamine, acetylcholine, bradykinin, serotonin, and prostaglandins. In the Russian Federation, tests for the content of these impurities are conducted in anaesthetised healthy cats in accordance with the General Chapter Test for depressor substances of the State Pharmacopoeia of the Russian Federation. The global trend towards ending animal testing and the search for ways to eliminate animal tests for depressor substances motivate researchers to study international approaches to the determination of histamine-like substances.AIM. This study aimed to analyse Russian and international approaches to the control of biologicals for depressor substances and to consider the applicability of alternative instrument-based physicochemical methods for the determination of histamine-like impurities, with a view to reducing animal testing.DISCUSSION. The rationale for reducing the use of animals as test systems is set forth in Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. In 2023, the European Pharmacopoeia Commission initiated the removal of in vivo tests for histamine-like substances from the European Pharmacopoeia. However, China and India use animal testing as the basic method for assessing the safety of medicines. In the Russian Federation, the control of depressor substances is regulated under General Chapter 1.2.4.0008.18 of the State Pharmacopoeia of the Russian Federation. Since the publication of General Chapter 42-0063-07 Test for histamine in edition XII in 2007, the State Pharmacopoeia of the Russian Federation has included a compendial text providing for a reduction in the number of cats used for testing. At present, Russian scientists are searching for targeted physicochemical and immunochemical methods for the determination of depressor substances. It has been demonstrated that a reasonable approach is to assess the need for testing a particular medicinal product in animals on a case-by-case basis. This approach will help minimise the number of in vivo tests and maintain an adequate quality of medicines at the same time.CONCLUSIONS. Despite the global trend towards ending animal testing, it is still necessary and required to control medicines for the content of depressor substances. Nevertheless, there is no global consensus on the need to use animals for this purpose. The absence of a separate general chapter/monograph, or references to it, will not change the fact that histamine-like substances are controlled worldwide. The decision to exclude in vivo methods from the European Pharmacopoeia necessitates the search for alternative test methods and the implementation of additional manufacturing controls to minimise the contamination risk for finished medicinal products. Studies have shown that high-performance liquid chromatography can determine the content of histamine in a limited amount of a medicinal product.

OBJECTIVES Our objective was to explore the safety and efficacy of a graphene oxide-loaded rapamycin-coated self-expandable metallic airway stent (GO@RAPA-SEMS) in a rabbit model. METHODS The dip coating method was used to develop a GO@RAPA-SEMS and a poly(lactic-co-glycolic)-acid loaded rapamycin-coated self-expandable metallic airway stent (PLGA@RAPA-SEMS). The surface structure was evaluated using a scanning electronic microscope. The in vitro drug-release profiles of the 2 stents were explored and compared. In the animal study, a total of 45 rabbits were randomly divided into 3 groups and underwent 3 kinds of stent placements. Computed tomography was performed to evaluate the degree of stenosis at 1, 2 and 3 months after the stent operation. Five rabbits in each group were sacrificed after the computed tomography scan. The stented trachea and blood were collected for further pathological analysis and laboratory testing. RESULTS The in vitro drug-release study revealed that GO@RAPA-SEMS exhibited a sudden release on the first day and maintained a certain release rate on the 14th day. The PLGA@RAPA-SEMS exhibited a longer sustained release time. All 45 rabbits underwent successful stent placement. Pathological results indicated that the granulation tissue thickness in the GO@RAPA-SEMS group was less than that in the PLGA@RAPA-SEMS group. The TUNEL and hypoxia-inducible factor-1α staining results support the fact that the granulation inhibition effect in the GO@RAPA-SEMS group was greater than that in the PLGA@RAPA-SEMS group. CONCLUSIONS GO@RAPA-SEMS effectively inhibited stent-related granulation tissue hyperplasia. [ABSTRACT FROM AUTHOR]

A new accessory was developed to allow implantation of left ventricular assist devices (LVADs) without requiring an anastomosis to the ascending aorta. The accessory combines the LVAD inflow and outflow into a dual-lumen device. Initial prototypes encountered reduced pump performance in vitro, but a second-generation prototype successfully addressed this issue. This feasibility study aimed to demonstrate the anatomic fit, safe implantation, and hemodynamic effectiveness of the LVAD with the accessory. The accessory was implanted in ten female pigs (104 ± 13 kg). Following sternotomy and apical coring under cardiopulmonary bypass, a balloon catheter was retrogradely inserted and exteriorized through the coring site, where it was inflated within the distal third of the outflow graft. It was utilized to pull the accessory's outflow across the aortic valve. After LVAD attachment, the catheter was removed. Echocardiography revealed no relevant valve regurgitation post-implantation. During ramp testing, pump flow increased from 3.7 ± 1.2 to 5.4 ± 1.2 L/min. Necropsy confirmed correct accessory placement in nine animals. No valve lesions or device thrombosis were observed. The accessory enabled LVAD implantation without compromising pump performance. Future work includes design refinements for implantation without cardiopulmonary bypass and long-term testing in a chronic heart failure model. [ABSTRACT FROM AUTHOR]

IntroductionHemorrhage remains the leading cause of preventable death on the battlefield. The most effective means to increase survivability is early hemorrhage control and fluid resuscitation. Unfortunately, fluid resuscitation requires constant adjustments to ensure casualty is properly managed, which is often not feasible in the pre-hospital setting. In this study, we showed how an adaptive closed-loop controller for hemorrhage resuscitation can be used to automate hemodynamic management using a swine hemorrhagic shock injury model.MethodsThe adaptive resuscitation controller (ARC) was previously developed to track pressure–volume responsiveness in real time and adjust its infusion rate to reach the target mean arterial pressure (MAP). Swine while maintained under a surgical plane of anesthesia and analgesia underwent a splenectomy, followed by two hemorrhage and resuscitation events. For the first resuscitation event, hemorrhage was induced to reduce the MAP to 35 mmHg until arterial lactate reached 4 mmol/L. The ARC system then infused whole blood (WB) to reach the target MAP and maintained the subject using crystalloids for 120 min. For the second resuscitation event, the subjects were hemorrhaged again but resuscitated using only crystalloid infusion to reach the target MAP and 120-min maintenance.ResultsThe ARC was effective at WB resuscitation, reaching the target MAP in 2.0 ± 1.0 min. The median performance error was 1.1% ± 4.6%, and target overshoot was 14.4% ± 7.0% of the target MAP. The ARC maintained all animals throughout the 120 min maintenance period. For the second crystalloid-based resuscitation, ARC required a longer time to reach the target MAP, at an average rise time of 4.3 ± 4.0 min. However, target overshoot was reduced to 8.4% ± 7.3% of the target MAP. Much higher flow rates were required to maintain the target MAP during the second resuscitation event than during the first resuscitation event.DiscussionThe ARC was able to rapidly reach and maintain the target MAP effectively. However, this sometimes required large volumes of fluid as the ARC’s only goal was to reach the target MAP. Further clinical insight is needed regarding the preferred aggression level to achieve the target MAP. In conclusion, the ARC was successful in its programmed objective of reaching and maintaining the target MAP for extended periods of time in vivo, a critical next step toward improving hemorrhage treatment in the pre-hospital environment.

This study focuses on storytelling in activist public relations. Stories emerge as an important "activist public relations" tool in non-governmental organizations' social change and awareness-raising efforts. The research aims to investigate both short and long-term effects of storytelling on emotions, awareness levels, and behavioral changes across different age groups. To illustrate the use of storytelling in activist public relations within the cosmetics industry, the researchers selected the short film "Save Ralph," produced by Humane Society International in 2021. The short film tells in an emotional tone, from the mouth of a rabbit, what happened to him during cosmetic experiments. The research, employing a qualitative research design, comprises three stages. Firstly, a survey was conducted among 30 women from various age groups to gather insights into their definitions of cosmetic products, usage frequency, and factors influencing their preferences. In the second stage, participants were shown the selected short film, followed by in-depth interviews. Lastly, follow-up interviews were conducted with the same group of women three months later. The findings revealed that storytelling had the most significant impact on emotions, awareness levels, and behavioral changes among women aged 18-23. This underscores the effectiveness of storytelling as a strategy for driving social change and raising awareness within activist public relations initiatives.

Society's compassion towards nonhuman animals used in experimentation has grown exponentially. This paper adopts critical discourse analysis to examine how the animal experimentation industry negotiates this societal moral response. To this end, the discourse of the largest animal experimentation interest group in Spain has been studied. Our findings show that the industry, as represented by this interest group, does not negotiate compassion with authenticity but rather creates an illusion of it through opportunistic lexical choices and suppressions, including contradictions and incongruities. We conclude by defining such a discourse as illusory authenticity, a discourse with which the industry conveniently frames itself as altruistic and concerned about animal suffering while at the same time discouraging the public's cultivation of compassion towards nonhuman animal suffering. This is done by means of perpetuating a logic that frames nonhuman animals as inferior beings whose existence is at the service of humanity. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Selcuk University Social Sciences Institute / Selçuk Üniversitesi Sosyal Bilimler Enstitüsü Dergisi is the property of Journal of Selcuk University Social Sciences Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IntroductionThere have been relatively few attempts to quantitatively assess if, and in which areas, the use of non-animal methods (NAMs) is increasing in biomedical research and importantly, how this compares to the use of live animals.MethodsWe conducted a bibliometric analysis of the relative publication of papers reporting the use of NAMs-only compared to those reporting the use of animals, even if they also reported the use of NAMs, over the period 2003 to 2022 across seven research areas (breast cancer, lung disease, blood cancer, heart disease, neurodegenerative diseases, diabetes and toxicology) and five regions (USA, China, France, Germany, United Kingdom).ResultsWe found that the relative number of publications of research using NAMs-only has been higher than animal-based research for the last 20 years for all research areas and is growing. Research areas differed in their relative publication of NAMs-only based work, with breast cancer and lung disease having consistently the highest ratio of NAMs-only to animal-based publications and heart disease, diabetes and toxicology showing the greatest change over the time period. A key period of change was 2016–18. By 2022 the UK had the highest NAMs-only to animal-based research ratio than any other country for five of the seven research areas and China the lowest for six, accounting for publication rate. Tissue and in silico-based methods were the most common of all NAMs-only publications; lab-on-a-chip and stem cell models are increasing in their use but at much lower levels and rate of increase.ConclusionWe found that proportionately the reliance on animals in these research areas is decreasing, which will be encouraging to those that support the replacement of animal experiments.

Animal testing is required in drug development research and is crucial for assessing the efficacy and safety of medications before they are commercialized. However, the newly furnished Food and Drug Administration Modernization Act 2.0 has given new insight into drug development. It opens a new door by offering an alternative testing method for developing a new drug without using animals. This newly proposed system may potentially significantly impact nondeveloped countries worldwide. In this study, we explore the alternative testing options such as in silico modeling, human tissue‐on‐chip engineering, animal‐free recombinant antibodies, tissue engineering, and artificial intelligence presented by this act and discuss its implications for nondeveloped countries. [ABSTRACT FROM AUTHOR]

There is a large gender gap in support for animal experimentation, with men endorsing this practice more than women. However, little is known about the psychological factors associated with these differences. Drawing on a large and gender-balanced sample (nwomen = 551, nmen = 454), we conducted a cross-sectional survey to examine whether gender differences in empathy, social dominance orientation (SDO), and speciesism mediate gender differences in attitudes toward animal experimentation. Our results indicate that gender differences in empathy and speciesism mediate the link between gender and support for animal experimentation, but SDO does not. An integrative model also confirmed the role of gender differences in dispositional empathy related directly to speciesist attitudes, which as a result were related to attitudes toward animal testing. This research brings new insights into gender differences in the acceptance of animal experimentation and may explain why women are more likely than men to be opposed to this practice. [ABSTRACT FROM AUTHOR]

Abstract Background Anatomic anomalies in the ascending aorta may impair the implantation and testing of cardiovascular devices in humans and animal models. Case presentation We present the rare case of an intra-aortic band in a German Landrace pig. During terminal animal testing, the band hindered the implantation of a left ventricular assist device (LVAD) with transventricular outflow graft across the aortic valve. After lower partial sternotomy, epicardial echocardiography displayed an intraluminal echogenic structure at the sinotubular junction causing unspecific flow turbulences. Under cardiopulmonary bypass, coring of the left ventricular apex was performed. Due to strong resistance in the proximal aorta, accurate positioning of the transventricular LVAD outflow graft was impossible. After euthanasia, necropsy revealed a fibrous band located at the sinotubular junction, dividing the lumen of the ascending aorta. Conclusions The occurrence of an intra-aortic band represents an extremely rare case of a most likely congenital anomaly. Awareness of such anomalies is important for planning and performing animal testing. Perioperative echocardiography may help to either remove such anomalies or allow discontinuing the procedure prior to device implantation.

A new accessory was developed to allow implantation of left ventricular assist devices (LVADs) without requiring an anastomosis to the ascending aorta. The accessory combines the LVAD inflow and outflow into a dual-lumen device. Initial prototypes encountered reduced pump performance in vitro, but a second-generation prototype successfully addressed this issue. This feasibility study aimed to demonstrate the anatomic fit, safe implantation, and hemodynamic effectiveness of the LVAD with the accessory. The accessory was implanted in ten female pigs (104 ± 13 kg). Following sternotomy and apical coring under cardiopulmonary bypass, a balloon catheter was retrogradely inserted and exteriorized through the coring site, where it was inflated within the distal third of the outflow graft. It was utilized to pull the accessory’s outflow across the aortic valve. After LVAD attachment, the catheter was removed. Echocardiography revealed no relevant valve regurgitation post-implantation. During ramp testing, pump flow increased from 3.7 ± 1.2 to 5.4 ± 1.2 L/min. Necropsy confirmed correct accessory placement in nine animals. No valve lesions or device thrombosis were observed. The accessory enabled LVAD implantation without compromising pump performance. Future work includes design refinements for implantation without cardiopulmonary bypass and long-term testing in a chronic heart failure model.

Background: Anatomic anomalies in the ascending aorta may impair the implantation and testing of cardiovascular devices in humans and animal models. Case presentation: We present the rare case of an intra-aortic band in a German Landrace pig. During terminal animal testing, the band hindered the implantation of a left ventricular assist device (LVAD) with transventricular outflow graft across the aortic valve. After lower partial sternotomy, epicardial echocardiography displayed an intraluminal echogenic structure at the sinotubular junction causing unspecific flow turbulences. Under cardiopulmonary bypass, coring of the left ventricular apex was performed. Due to strong resistance in the proximal aorta, accurate positioning of the transventricular LVAD outflow graft was impossible. After euthanasia, necropsy revealed a fibrous band located at the sinotubular junction, dividing the lumen of the ascending aorta. Conclusions: The occurrence of an intra-aortic band represents an extremely rare case of a most likely congenital anomaly. Awareness of such anomalies is important for planning and performing animal testing. Perioperative echocardiography may help to either remove such anomalies or allow discontinuing the procedure prior to device implantation. [ABSTRACT FROM AUTHOR]

Many of the major diseases of our time, such as stroke, heart disease, cancer, and Alzheimer's, remain poorly understood and lack adequate treatments. A novel drug can take 10 to 15 years and about 2 billion euros to develop, and failure rates occur in about 95 percent of human studies. This failure has been at least largely attributed to the inadequacy of current preclinical models. Much of biomedical and toxicological research has been conventionally based on the use of simplistic in vitro systems or animal models which do not adequately mimic complex human physio-pathological conditions. Animal research also poses important ethical concerns. During the last decade, extraordinary advancement in tissue engineering, stem cell culturing, nucleotide sequencing technologies, and computer science has occurred, which has originated an array of innovative human-based and more physiologically-relevant tools. These tools, also known as "new approach methodologies" (NAMs), which comprise patient-derived organoids, organs-on-chip, along with computational analysis and models, have already proved to be more efficient than traditional methods, representing novel and exciting tools to forward biomedical research from a human-biology-focused perspective. After a brief introduction on the limits of traditional methods, here I describe some examples of the main novel available and emerging NAMs. The aim is to encourage discussion on the opportunity to explore innovative paths in biomedical research and to promote a paradigm-shift towards a more human biology-focused approach to better understand human physiopathology and to develop more effective targeted preventive or therapeutic strategies, while replacing animals employed for biomedical research. [ABSTRACT FROM AUTHOR]

The use of animal models to learn about human physiology or toxicology or to study drugs and therapies for use on humans dates back a long time, but it developed mainly in the nineteenth century. Since then, the research have changed and the limits of the animal model for obtaining data that can be extrapolated to humans have become increasingly evident. Today it is necessary to change the paradigm and use truly scientific human based research methods. [ABSTRACT FROM AUTHOR]

Copyright of Biologie Aujourd'hui is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Biologie Aujourd'hui is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Testing-culling is a very effective measure for the prevention and control of animal diseases. In this paper, based on sheep brucellosis control policies and animal testing characteristics and considering the limitation of culling resources, a dynamic model is established to study the impact of testing-culling measure. Theoretical analysis reveals that the model may have one or three positive equilibria. The equilibrium in the middle is always unstable, and the model shows saddle-node bifurcation, generalized Hopf bifurcation and Bogdanov-Takens bifurcation. Moreover, the theoretical results are verified via numerical analysis. These results reveal that testing and culling strategies can induce complex transmission dynamics that can help us develop appropriate prevention and control measures for animal brucellosis.

When registering a new pesticide, 90-day oral toxicity studies performed with both rodent and non-rodent species, typically rats and dogs, are part of a standard battery of animal tests required in most countries for human health risk assessment (RA). This analysis set out to determine the need for the 90-day dog study in RA by reviewing data from 195 pesticides evaluated by the US Environmental Protection Agency (USEPA) from 1998 through 2021. The dog study was used in RA for only 42 pesticides, mostly to set the point of departure (POD) for shorter-term non-dietary pesticide exposures. Dog no-observed-adverse-effect-levels (NOAELs) were lower than rat NOAELs in 90-day studies for 36 of the above 42 pesticides, suggesting that the dog was the more sensitive species. However, lower NOAELs may not necessarily correspond to greater sensitivity as factors such as dose spacing and/or allometric scaling need to be considered. Normalizing doses between rats and dogs explained the lower NOAELs in 22/36 pesticides, indicating that in those cases the dog was not more sensitive, and the comparable rat study could have been used instead for RA. For five of the remaining pesticides, other studies of appropriate duration besides the 90-day rat study were available that would have offered a similar level of protection if used to set PODs. In only nine cases could no alternative be found in the pesticide's database to use in place of the 90-day dog study for setting safe exposure levels or to identify unique hazards. The present analysis demonstrates that for most pesticide risk determinations the 90-day dog study provided no benefit beyond the rat or other available data. [ABSTRACT FROM AUTHOR]

In this study, an overview of the regulations in force in some extra-EU states belonging to different geoeconomic areas is provided, starting from the current EU legislation on cosmetic products. We focused on their legislative frameworks and the location of the relevant regulatory documentation. Furthermore, for each state considered, our analysis examined the notification/authorization processes, approaches to animal testing, and allowed/prohibited ingredient lists, as these aspects are considered to be among the primary restrictions hindering the cosmetic market. It can be observed that many states are working towards standardising their regulations to promote greater international trade. However, it is essential to recognize that different countries belonging to distinct geoeconomic areas may have unique requirements, and harmonization may not necessarily be the best solution. It is crucial to consider different needs and preferences when approaching the global regulation of the cosmetic industry. [ABSTRACT FROM AUTHOR]

The EU's decision to ban animal testing for toxicity testing, has positively influenced the pace of developing New Approach Methodologies (NAMs). This development also supports replacing animal methods in other forms of risk assessment (RA), such as for oral-toxicity testing. This study aims to identify the hurdles and opportunities for validation and implementation of NAMs in the current EU's chemical RA. Through conducting semi-structured interviews with 14 stakeholders, experiences and perspectives about the validation and implementation of NAMs in RA for orally ingested chemicals were analyzed. Stakeholders considered the use of NAMs for RA processes both a cultural and generational issue. Both were perceived as hurdles for reaching the next generation RA approach. The differing views on NAMs originated from experience and stakeholder positions, but communication and collaboration on developing future RA approaches could support overcoming this skepticism. Irrespectively of their background, all interviewees were generally optimistic that NAMs will support the development of more accurate and sustainable RA. This research highlights the need for the EU to adjust legislation and guidance documents to shift in testing requirements from the traditional overexposure approach to more predictive, mechanistic testing in RA, which will take time. This study, however, shows that—when all stakeholders engage in communication and confidence building—NAMs can already play an important role in reducing and refining animal testing. [ABSTRACT FROM AUTHOR]

Simple Summary: In February 2022, the university course Replacing Animal Testing (RAT) Challenge was organized for the first time by an alliance of Dutch universities with the aim of engaging future generations in finding solutions to replace the use of animals in testing. Educating the next generations of researchers and professionals is an important step in the transition to promote animal-free science, to which the Dutch government is committed. Students are key stakeholders in the transition to animal-free innovations but their perspective still remains underrepresented. Therefore, our study aimed to explore their viewpoints focusing on their beliefs, values, and the motivations of students to join the course. We conclude that students share the ethical and scientific values that inspire the transition, and that their reflections on the socio-political landscape provide valuable insights on current and future challenges to the acceptance of animal-free innovations. In 2016, the Dutch government declared its commitment to phasing out animal experiments by 2025. Although a high number of animal experiments are still performed and the 2025 target will not be met, the commitment remains. Efforts are being made to identify levers that might foster the transition to animal-free science. Education has been found to play a key role in the future of animal-free science and young generations are increasingly seen as key stakeholders. However, their attitudes toward the transition to animal-free innovations have not been investigated. The present article focuses on the values and beliefs held by students, who in 2022, participated in the course 'Replacing Animal Testing' (RAT) Challenge, organized by a consortium of Dutch universities. Contextually, students' motivations to follow the course were investigated. The research was based on a qualitative study, including semi-structured interviews and a literature review. Our analysis of the findings revealed that students feel aligned with the social, ethical, and scientific reasons that support the transition to animal-free innovations. Moreover, the participants identified a series of regulatory, educational, cultural, and political obstacles to the transition that align with those identified in recent literature. From the discussion of these findings, we extrapolated six fundamental challenges that need to be addressed to foster the transition to animal-free science in an acceptable and responsible way. [ABSTRACT FROM AUTHOR]

Pooled testing can enhance the efficiency of diagnosing individuals with diseases of low prevalence. Often, pooling is implemented using standard groupings (2, 5, 10, etc.). On the other hand, optimization theory can provide specific guidelines in finding the ideal pool size and pooling strategy. This article focuses on optimizing the precision of disease prevalence estimators calculated from multiplex pooled testing data. In the context of a surveillance application of animal diseases, we study the estimation efficiency (i.e., precision) and cost efficiency of the estimators with adjustments for the number of expended tests. This enables us to determine the pooling strategies that offer the highest benefits when jointly estimating the prevalence of multiple diseases, such as theileriosis and anaplasmosis. The outcomes of our work can be used in designing pooled testing protocols, not only in simple pooling scenarios but also in more complex scenarios where individual retesting is performed in order to identify positive cases. A software application using the shiny package in R is provided with this article to facilitate implementation of our methods. Supplementary materials accompanying this paper appear online. [ABSTRACT FROM AUTHOR]

Animal (in vivo) potency tests have been utilized for over a century in support of vaccine development and for quality testing. This is a legacy of the best science at the time of their introduction. Advances in knowledge and technology, however, have provided opportunities to utilize more sensitive assays during development and replace legacy animal tests with in vitro alternatives. This coupled with initiatives such as replacement, reduction, and refinement (the 3-R's) and quality by design (QbD) have brought industry and regulators together in the introduction of advanced vaccine control strategies. This article examines historical and current uses of animals in vaccines technical development and control, and their replacement with in vitro alternatives from a risk point of view. An overarching risk is that a vaccine tested with an alternative potency assay fails to protect its target recipient. This can be addressed from the perspective of the assay's association with the vaccine mechanism of action, and the rules used to introduce the vaccine into the patient population (e.g., specifications). Commonly understood concepts such as analytical precision play a role in risk evaluation based on its impact on the sensitivity of a test to detect meaningful product changes caused by variations in manufacture or over a vaccine's shelf life. This should be considered when evaluating solutions such as the reduction of multi-concentration (or dilution) in vivo assays to a single concentration test. While the use of animals in vaccine development will not go away all together, the paradigm must shift from in vivo tests to in vivo models. To help ensure success, principles and practices related to introduction of in vitro alternatives require global collaboration among industry, regulators, pharmacopeias, and supporting organizations. [ABSTRACT FROM AUTHOR]

The IQ Consortium's DruSafe Leadership Group previously reported results of a nonclinical to clinical translational database for First-In-Human (FIH)-enabling animal toxicology studies. We have completed an additional translational database populated with longer duration (>1 month) animal toxicology studies and longer duration (Phase 2 and beyond) clinical trials. The blinded database was composed of 127 molecules. Animal and clinical data were categorized by organ system and animal model (e.g. rodent, dog). The 2 × 2 contingency table (true positive, false positive, true negative, false negative) was used for statistical analysis and both the positive predictive value (PPV) and negative predictive value (NPV) were determined. As also reported in the FIH database, the NPV was the strongest predictive performance measure at 96 %. The PPV was lower than the FIH database with the rodent at 29 %, dog at 21 % and NHP at 20 %. No new additional target organs were observed in 62 % of the entries. A new target organ was identified in 38 % of the entries, with the majority in a rodent (26 %) and fewer in the dog (8 %) or NHP (12 %). However, new target organ data resulted in only a PPV of 13 %, suggesting that current ICH requirements for longer duration animal general toxicology studies should be re-evaluated and better aligned with the 3Rs. A newer paradigm could include an appropriately justified single animal model for longer duration studies, in addition to utilizing New Approach Methods (NAMs) that would provide translational safety data, but additional research is needed. • Longer duration nonclinical to clinical translational database created. • 127 molecules with animal and clinical data; concordance parameters determined. • Negative predictive value was the strongest performance indicator. • New identified target organs had a very low positive predictive value. • A newer nonclinical testing paradigm should be considered to support registration. [ABSTRACT FROM AUTHOR]

IntroductionThe study aim was to test the safety and efficacy of a pad with optic fibers developed for monitoring newborn respiratory rate (RR) and heart rate (HR).MethodsThirty New Zealand White rabbits were included, divided by weight into three groups. RR and HR were measured using two methods for each rabbit: ECG electrodes as the reference method and a newly developed pad with an experimental fiber optic system (EFOS) as the experimental method.ResultsAnalysis was performed on data for 29 rabbits (10 female, 34%; 19 male, 66%). EFOS performed better at measuring RR compared with HR. RR values did not differ significantly between the methods for the whole group (p = 0.151) or within each sex (female: p > 0.999; male: p = 0.075). Values for HR, however, did differ between methods for the whole group of animals (p

Background: Congenital tracheomalacia is a pathology with no consensus of medical or surgical approach. The permanent nature and the major complications associated with metallic stents have limited their use over the years. The purpose of this study was to evaluate the feasibility of a helical stent design removal. Methods: Ten dogs diagnosed with tracheal collapse and treated with the helical stent were involved in the study. Animals were classified into three groups depending on stent indwelling time. Prior to the removal, endoscopic evaluation was performed to assess endothelization grade, mucous accumulation, and the presence of stenosis. During the removal, bleeding, fracture, or impossibility of removal were noted. After the removal, all macroscopic mucosal changes were recorded. Results: Technical success was 100%, without any complications. Complete epithelization of the stent was visualized in 7/10 animals. The removal procedure duration ranged from 2–12 min. At post-removal endoscopy, bleeding or epithelial damage, was visualized in any case. Stent fracture during removal occurred in one animal. Conclusions: The removal of a metallic stent with spiral geometry is feasible, simple, and without complications, regardless of the degree of neo-epithelialization. [ABSTRACT FROM AUTHOR]

This study demonstrates the effectiveness of biologics made from Bacillus, as research proves that these bacteria are food safe if they enter organisms(humans, animals) because they have no negative effects on biological systems. Bacillus Subtilis. Based on animal testing, it is considered food safe. No changes in normal parameters were observed when examining tissue sections compared to control treatments. In addition, no clinical symptoms were observed when examining the natural indicators of experimental animals during administration. They are in normal condition. This proves that their use in biological control is harmless. [ABSTRACT FROM AUTHOR]

Scientific, technical, and bioinformatics advances have made it possible to establish analytics-based molecular biosimilarity for the approval of biosimilars. If the molecular structure is identical and other product- and process-related attributes are comparable within the testing limits, then a biosimilar candidate will have the same safety and efficacy as its reference product. Classical testing in animals and patients is much less sensitive in terms of identifying clinically meaningful differences, as is reported in the literature. The recent artificial intelligence (AI)-based protein structure prediction model, AlphaFold-2, has confirmed that the primary structure of proteins always determines their 3D structure; thus, we can deduce that a biosimilar with an identical primary structure will have the same efficacy and safety. Further confirmation of the thesis has been established using technologies that are now much more sensitive. For example, mass spectrometry (MS) is thousands of times more sensitive and accurate when compared to any form of biological testing. While regulatory agencies have begun waiving animal testing and, in some cases, clinical efficacy testing, the removal of clinical pharmacology profiling brings with it a dramatic paradigm shift, reducing development costs without compromising safety or efficacy. A list of 160+ products that are ready to enter as biosimilars has been shared. Major actions from regulatory agencies and developers are required to facilitate this paradigm shift. [ABSTRACT FROM AUTHOR]

Biosimilar approval guidelines need rationalization and harmonization to remove the inconsistencies and misconceptions to enable faster, safer, and more cost-effective biosimilars. This paper proposes a platform for a model guideline based on the scientific evaluation of the regulatory filings of the 130+ products approved in the US, UK, and EU and hundreds more in the WHO member countries. Extensive literature survey of clinical data published and reported, including Clinicaltrials.gov, a review of all current guidelines in the US, UK and EU, and WHO, and detailed discussions with the FDA have confirmed that removing the animal and clinical efficacy testing and fixing other minor approaches will enable the creation of a harmonized guideline that will best suit an ICH designation. [ABSTRACT FROM AUTHOR]

Simple Summary: There are comparatively many studies that explore how adults judge animal experiments. But how do young people think about this topic? Our group interviews conducted with Austrian teenagers showed that the participants assessed animal tests more positively than we had expected. The teenagers evaluated animal experiments mainly based on the following criteria: the relevance of research, the extent of animal suffering, and the existence of alternatives. All groups found positive aspects for animal experiments and identified acceptable animal experiments among the examples discussed. Particularly with regard to the approval of animal experiments, a key consideration was the extent to which the research is relevant to humans. The present study focused on an in-depth analysis of adolescents' (aged 15–16) attitudes towards animal experimentation. Focus group interviews were conducted to gain a deeper understanding regarding the ethical considerations of this age group. The data were analyzed using a qualitative content analysis. All participants considered their own knowledge about the whole topic as low. Our results show that adolescents in the study had considerably more positive attitudes toward animal experimentation than the literature had suggested. All groups identified positive aspects of animal experimentation and accepted at least one scenario of animal experimentation. Most of the groups rated half of the examples presented as acceptable. The participants tended to make specific assessments in view of a concrete scenario and seemed to form their positions anew. In their discussion, students focused mainly on the following criteria: the relevance of research, the extent of animal suffering, and the existence of alternatives. Generally, we hypothesize that the focus group discussions took place largely within the framework of anthropocentric ethics. [ABSTRACT FROM AUTHOR]

Background: Often after large animal experiments in spinal research, the question arises-histology or biomechanics? While biomechanics are essential for informed decisions on the functionality of the therapy being studied, scientists often choose histological analysis alone. For biomechanical testing, for example, flexibility, specimens must be shipped to institutions with special testing equipment, as spine testers are complex and immobile. The specimens must usually be shipped frozen, and, thus, biological and histological investigations are not possible anymore. To allow both biomechanical and biological investigations with the same specimen and, thus, to reduce the number of required animals, the aim of the study was to develop a spine tester that can be shipped worldwide to test on-site., Methods: The "Spine Tester TO GO" was designed consisting of a frame with three motors that initiate pure moments and rotate the specimen in three motion planes. A load cell and an optical motion tracking system controlled the applied loads and measured range of motion (ROM) and neutral zone (NZ). As a proof of concept, the new machine was validated and compared under real experimental conditions with an existing testing machine already validated employing fresh bovine tail discs CY34 ( n  = 10)., Results: The new spine tester measured reasonable ROM and NZ from hysteresis curves, and the ROM of the two testing machines formed a high coefficient of determination R 2  = 0.986. However, higher ROM results of the new testing machine might be explained by the lower friction of the air bearings, which allowed more translational motion., Conclusions: The spine tester TO GO now opens up new opportunities for on-site flexibility tests and contributes hereby to the 3R principle by limiting the number of experimental animals needed to obtain full characterization of spine units at the macroscopic, biomechanical, biochemical, and histological level., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

The Virtual Human Platform for Safety Assessment (VHP4Safety) project aims to build a Virtual Human Platform (VHP) to protect human health and revolutionize the safety assessment of chemicals and pharmaceuticals by transitioning from animal-based to human-based approaches. The goal of this article is to introduce the project and its interdisciplinary approach to co-creation with multiple academic, regulatory, industrial and societal partners covering the entire safety assessment knowledge chain. Three research lines drive the project: 1) building the VHP; 2) feeding the VHP with human data; and 3) implementing the VHP. The project focusses on three case studies that incorporate human relevant scenarios not included in current animal-based safety assessment strategies. The VHP is built on tools and services, including pharmacokinetic and computational models, and integrates several data sources within each case study, including data on human physiology, epidemiology, toxicokinetic and -dynamic parameters, as well as data on chemical characteristics and exposures. In addition, the VHP integrates new data generated within the project using new approach methodologies representing key events within adverse outcome pathways. Implementation of the VHP is investigated using an innovation systems approach, engaging stakeholders and organizing training and education. Central to the VHP4Safety project is our co-creative approach, which facilitated by biannual designathons and hackathons that foster active involvement of all project participants from over 30 partner organizations. By integrating technological innovations with transparency and stakeholder collaboration, the VHP4Safety project will help shape the transition to the next generation safety assessment in which animal testing becomes redundant.

The European regulatory framework on chemicals is at a crossroads. There are calls for the framework to be more effective, by better protecting people and the environment. There is also room for it to be more efficient and cost-effective, by harmonising assessment practices across sectors and avoiding the need for unnecessary testing. At the same time, there is a political commitment to phase out animal testing in chemical safety assessments. In this commentary, we argue that these needs are not at odds with other. On the contrary, the roadmap to phase out animal testing could also be the transition pathway to a more efficient, effective and sustainable regulatory ecosystem. Central to our proposal is a framework based on biological reasoning in which biological questions can be answered by a choice of methods, with non-animal methods progressively becoming the only choice. Within this framework, a tiered approach to testing and assessment allows for greater efficiency and effectiveness, while also introducing considerations of proportionality and cost-effectiveness. Testing strategies, and their component methods, should be developed in tandem and judged in terms of their outcomes, the protection levels they inform, rather than their ability to predict the outputs of animal tests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology.)

Pen‐side testing of farm animals for infectious diseases is critical for preventing transmission in herds and providing timely intervention. However, most existing pathogen tests have to be conducted in centralized labs with sample‐to‐result times of 2–4 days. Herein we introduce a test that uses a dual‐electrode electrochemical chip (DEE‐Chip) and a barcode‐releasing electroactive aptamer for rapid on‐farm detection of porcine epidemic diarrhea viruses (PEDv). The sensor exploits inter‐electrode spacing reduction and active field mediated transport to accelerate barcode movement from electroactive aptamers to the detection electrode, thus expediting assay operation. The test yielded a clinically relevant limit‐of‐detection of 6 nM (0.37 μg mL−1) in saliva‐spiked PEDv samples. Clinical evaluation of this biosensor with 12 porcine saliva samples demonstrated a diagnostic sensitivity of 83 % and specificity of 100 % with a concordance value of 92 % at an analysis time of one hour. [ABSTRACT FROM AUTHOR]