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A transition from nonhuman animal models to engineered microphysiological systems (MPS), such as organoids and organ-on-a-chip technologies, would signal a paradigm shift in biomedical research. Despite MPS' potential to more accurately model human physiology, reduce high failure rates of drugs in clinical trials, and limit unnecessary animal use, widespread adoption is hampered by public opinion and lack of scalability, standardization, and current regulatory uptake. This article suggests how 5 key concepts (awareness, access, education, application, and rewards) could help address these barriers. These concepts are part of a framework that underscores a need to integrate MPS into mainstream biomedical research and to better promote ethical responsibility for the means of biomedical innovation.

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Although urine bladder transplantation is currently being conducted, the procedure is an incompletely resolved problem in clinical transplantology. A small number of en bloc bladder and kidney transplants from pediatric donors to adult recipients in humans have been reported. A small number of bladder transplants with and without combinations with kidneys have also been performed in experiments on different animal models. Here, we aimed to highlight the experiences of various scientists in bladder transplantation in humans and animals. We also presented our small experience in conducting transplant of 1 kidney, ureters, and a segment of the bladder in an experiment on pigs in 2023 (5 cases), which is a promising direction for further successful development of this technology in humans. In 2024, we plan to conduct another 10 transplants of a single block ofthe kidney and bladderin pigs, results of which will be published after the completion of the experimental work.

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Microtus genus is the herbivorous animal with multiple stomachs, and some of them possess a mating system similar to human and thereby has been expected as a model animal for the large herbivory and human mating system model, respectively. Thus, it is significant to maintain Microtus as an animal genetic resource. We have studied the establishment of assisted reproductive technologies in Alexandromys. montebelli (formerly as Microtus motebelli: A. motebelli), and here, we investigated the effects of hypotaurine treatment to frozen-thawed (FT) spermatozoa and modified timing of nonsurgical artificial insemination (AI) on the number of offspring. As the results, regardless of without or with hypotaurine treatment, when the timing of nonsurgical AI was made closer to the estimated ovulation time (at 7-9 h post coitus), the total number of offspring derived from FT spermatozoa (27 and 28 pups, respectively) increased compared with AI at 4-6 h (five and six pups, respectively) and was equivalent to those of fresh spermatozoa (43 pups) or natural mating (33 pups). These results will lead to further dissemination of nonsurgical AI and could support the "3R principle," which is the standard philosophy of animal experiment because the procedure declines the stress and the recipient can be used repeatedly.

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The aim of the present study was to evaluate the photothermal effects of a subdermal high-power diode laser at a wavelength (λ) of 1470 nm in the skin of rats. Twenty male Wistar rats were used, divided into 2 groups: placebo laser (PL) and active laser (AL). A high-power diode laser equipment was applied to 5 subdermal vectors on the animal's back region. The results demonstrated that active laser animals showed a better arrangement of collagen fiber bands, an increase in the thickness of the dermis and the number of vessels. Furthermore, animals treated with active laser showed an increased immunoexpression of TGF-ß and VEGF compared to the placebo. The present work demonstrated that the subdermal high-power diode laser increases the vascularization and the expression of factors that enhance skin regeneration and may be promising resource in the esthetic and dermatology clinical treatment of skin rejuvenation.

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Research directly on human embryos has gone through cycles of interest and neglect. The recent revitalization, including the making of 'human developmental biology', depended on fresh supplies of material and demand for medically relevant work. Human studies relied on mice but rejected simple extrapolation from this model mammal. Now, it is time to take stock while scanning the horizon for further change. Will research on human development be facilitated or frustrated? Will comparative approaches bring a greater variety of animal models into the picture? Will human stem-cell-based embryo models secure ever larger roles as exemplars of vertebrate development?

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I outline the perspective that searching the contents of memory is a form of mental time travel (MTT) in non-humans that is relatively tractable because it focuses on the contents of memory. I propose that an animal model of MTT requires three elements: (i) the animal remembers multiple events using episodic memory, (ii) the order of events in time is included in the representation, and (iii) the sequence of events can be searched to find a target that occurred at a particular time. I review experiments suggesting that rats represent multiple items in episodic memory (element 1) in order of occurrence (element 2) and engage in memory replay to search representations in episodic memory in sequential order to find information at particular points in the sequence (element 3). The cognitive building blocks needed for MTT may be quite old in the evolutionary timescale.This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

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PURPOSE: To compare the endothelial coverage of different stents in porcine carotid arteries. Research problem: How effective are polyurethane stents (PU) and PU + rapamycin (PU + RAPA) compared to bare-metal stents on endothelial coverage by neointima in pigs after 28 days? METHODS: The methodology had two phases for an interventional, experimental, prospective study, with three Moura pigs, 12 weeks old and weighing between 19 and 22.5 kg. In phase I, eight stents were implanted in carotid arteries; three stents coated with PU, three coated with PU + RAPA, and two without coating. After 28 days, phase II was carried out, consisting of euthanasia, removal of the stents, to evaluate the exposed area of the stent struts, and the percentage of endothelialization through optical microscopy and scanning electron microscopy. RESULTS: The eight stents implanted with ultrasound sizing and post-dilation with a larger diameter balloon were analyzed by Doppler ultrasound, intravascular ultrasound, and angiography after 28 days. CONCLUSIONS: This study showed complete endothelial coverage by the endoluminal neointima of the stent struts, good integration and coverage with the arterial wall, with no exposed struts showing the presence of intimal hyperplasia (whitish tissue).

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Evaluating sharp force trauma (SFT) injuries to bone inflicted by a larger class of chopping/hacking tools (i.e., swords, axes, hatchets, machetes, and cleavers) is a growing area within the field of forensics. Previous studies have demonstrated promise regarding tool differentiation through the utilization of microscopic cut mark characteristics. However, this is an area that warrants additional investigation as there has yet to be a comprehensive study that incorporates the majority of these microscopic chopping/hacking cut mark characteristics into one analysis. The purpose of the current research was to analyze a large sample of microscopic cut mark characteristics derived from the current chopping/hacking literature to determine if differentiation of tool type could be made based on the microscopic cut mark characteristics. An additional goal of the current research is to develop standardization guidelines for the assessment of cut marks, focusing on a comprehensive suite of microscopic cut mark characteristics commonly observed in the existing literature. The skeletal sample for the current research was derived from a previous macroscopic cut mark characteristic experiment where trauma was inflicted to 20 partially fleshed domestic pig (Sus scrofa domesticus) limbs utilizing four chopping/hacking tools (i.e., axe, hatchet, machete, and cleaver) as well as a large carving knife for comparison. Cut marks were evaluated for 15 microscopic cut mark characteristics to assess statistical significance. Utilizing a chi-square analysis, nine of the 15 microscopic cut mark characteristics demonstrated statistically significant differences in relation to the tool utilized, indicating moderate to relatively strong effect sizes. For example, it should be possible to use a combination of microscopic cut mark characteristics to potentially indicate which chopping/hacking tool inflicted trauma when analyzing bones. In particular, examining the characteristics such as regularity of the cut mark edges along with the occurrence of uprising, fossae/depressions, and microscopic fractures can suggest or exclude tool class within forensic contexts.

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Glial cells modulate brain development, function, and health across all bilaterian animals, and studies in the past two decades have made rapid strides to uncover the underlying molecular mechanisms of glial functions. The nervous system of the invertebrate genetic model Caenorhabditis elegans (C. elegans) has small cell numbers with invariant lineages, mapped connectome, easy genetic manipulation, and a short lifespan, and the animal is also optically transparent. These characteristics are revealing C. elegans to be a powerful experimental platform for studying glial biology. This chapter discusses studies in C. elegans that add to our understanding of how glia modulate adult neural functions, and thereby animal behaviors, as well as emerging evidence of their roles as autonomous sensory cells. The rapid molecular and cellular advancements in understanding C. elegans glia in recent years underscore the utility of this model in studies of glial biology. We conclude with a perspective on future research avenues for C. elegans glia that may readily contribute molecular mechanistic insights into glial functions in the nervous system.

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BACKGROUND: Cryoablation is less invasive for certain selected and inoperable pulmonary lesions, which can be treated via percutaneous or transbronchial approaches. OBJECTIVE: To examine the effect of percutaneous cryoablation using an porcine lung parenchyma model. MATERIALS AND METHODS: Nitrogen-cooled cryoprobe was inserted into the posterior lobe of the peripheral lung parenchyma of six healthy female pigs percutaneously under CT guidance. Double and triple freeze-thaw cycles were performed on the left lung and the right lung, respectively. CT images were obtained before, during and after cryoablation. Blood samples were collected at various time points for testing. Tissue samples from the ablation zone were obtained after cryoablation for histopathological analysis. Data from the percutaneous study were compared with previously published transbronchial cryoablation data. RESULTS: The cryoablation outcomes and inflammatory responses observed in the percutaneous group were largely consistent as compared to those previously published in the transbronchial groups. Similar trends in the histopathological transition from the center to the periphery of the ablation zone and tissue repair process was exhibited between two groups within 4 weeks. Two cases of pneumothorax occurred in the percutaneous group. CONCLUSION: Cryoablation of the peripheral lung parenchyma by both percutaneous and transbronchial methods is safe and effective. Transbronchial approach demonstrates a lower complication rate than the percutaneous method. Two approaches complement one another for minimally invasive treatment of lung cancers. Doi.org/10.54680/fr24510110312.

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In recent years, targeted genome editing has emerged as an indispensable tool for creating animal models, facilitating a comprehensive exploration of the molecular mechanisms governing a myriad of biological processes. Within this scientific landscape, the investigation of meiosis in mice has attracted considerable attention across numerous research laboratories. The precision and versatility of the CRISPR/Cas9 genome editing system have revolutionized our ability to generate mice with tailored genetic alterations, including point mutations and null mutations. These genetic modifications have provided invaluable insights into the intricate functionality of various meiotic genes and their associated variants. In this context, we present a detailed state of the art protocol for the creation of novel mouse models, each bearing specific genetic modifications within key meiotic genes, through the application of CRISPR/Cas9 technology. Furthermore, we showcase two distinct genetic modifications, accomplished within our laboratory, that can serve as valuable reference points for researchers seeking to elucidate the molecular intricacies of meiosis in mammals.

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BACKGROUND: Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period. METHODS: Eight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14-28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms (PP30), positive 30 ms (P30) and negative 50 ms (N50) components of the flash visual evoked potentials (fVEPs) and their interhemispheric latency (IL) were recorded in the frontal, central and occipital areas during ten 60-second stimulations for each eye. The dMRI imaging protocol consisted of fifteen b-shells (b = 0-3500 s/mm2) with 32 directions/shell, providing measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axonal water fraction (AWF), and the permeability-diffusivity index (PDI). RESULTS: Significant reductions (p < 0.05) in the latency and IL of fVEP measurements paralleled significant rises in FA, KA, AWF and PDI over the same period. The longitudinal latency changes in fVEPs were primarily associated with whole-brain changes in diffusion parameters, while fVEP IL changes were related to maturation of the corpus callosum. CONCLUSIONS: Good agreement between reduction in the latency of fVEPs and maturation of cerebral WM was interpreted as evidence for ongoing myelination and confirmation of the minipig as a viable research platform. Adolescent development in minipigs can be studied using human neuroimaging and neurophysiological protocols and followed up with more invasive assays to investigate key neurodevelopmental hypotheses in psychiatry.

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AIMS: Pulsed-field ablation (PFA) is a novel, myocardial-selective, non-thermal ablation modality used to target cardiac arrhythmias. Although prompt electrogram (EGM) signal disappearance is observed immediately after PFA application in the pulmonary veins, whether this finding results in adequate transmural lesions is unknown. The aim of this study is to check whether application repetition and catheter-tissue contact impact lesion formation during PFA. METHODS AND RESULTS: A circular loop PFA catheter was used to deliver repeated energy applications with various levels of contact force. A benchtop vegetal potato model and a beating heart ventricular myocardial model were utilized to evaluate the impact of application repetition, contact force, and catheter repositioning on contiguity and lesion depth. Lesion development occurred over 18 h in the vegetal model and over 6 h in the porcine model. Lesion formation was found to be dependent on application repetition and contact. In porcine ventricles, single and multiple stacked applications led to a lesion depth of 3.5 ± 0.7 and 4.4 ± 1.3 mm, respectively (P = 0.002). Furthermore, the greater the catheter-tissue contact, the more contiguous and deeper the lesions in the vegetal model (1.0 ± 0.9 mm with no contact vs. 5.4 ± 1.4 mm with 30 g of force; P = 0.0001). CONCLUSION: Pulsed-field ablation delivered via a circular catheter showed that both repetition and catheter contact led independently to deeper lesion formation. These findings indicate that endpoints for effective PFA are related more to PFA biophysics than to mere EGM attenuation.

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INTRODUCTION: Sufficient perfusion is essential for a safe intestinal anastomosis. Impaired microcirculation may lead to increased bacterial translocation and anastomosis insufficiency. Thus, it is important to estimate well the optimal distance of the anastomosis line from the last mesenterial vessel. However, it is still empiric. In this experiment the aim was to investigate the intestinal microcirculation at various distances from the anastomosis in a pig model. MATERIALS AND METHODS: On 8 anesthetized pigs paramedian laparotomy and end-to-end jejuno-jejunostomy were performed. Using Cytocam-IDF camera, microcirculatory recordings were taken before surgery at the planned suture line, and 1 to 3 mesenterial vessel mural trunk distance from it, and at the same sites 15 and 120 min after anastomosis completion. After the microcirculation monitoring, anastomosed and intact bowel segments were removed to test tensile strength. RESULTS: The proportion and the density of the perfused vessels decreased significantly after anastomosis completion. The perfusion rate increased gradually distal from the anastomosis, and after 120 min these values seemed to be normalized. Anastomosed bowels had significantly lower maximal tensile strength and higher slope of tensile strength curves than intact controls. CONCLUSION: Alterations in microcirculation and tensile strength were observed. After completing the anastomosis, the improvement in perfusion increased gradually away from the wound edge. The IDF device was useful to monitor intestinal microcirculation providing data to estimate better the optimal distance of the anastomosis from the last order mesenteric vessel.

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Previous studies have demonstrated the efficacy of betahistine mesylate in treating vertigo and angioneurotic headache, enhancing microcirculation, and facilitating histamine release. However, limited research has been conducted on the drug's potential in mitigating blue light-induced damage. Thus, this study utilized Drosophila as the model organism and employed the Siler model to investigate the impact of various concentrations of betahistine mesylate on the lifespan, under 3000 lx blue light irradiation. At the same time we measure food intake, spontaneous activity, and sleep duration of Drosophila. The findings of this study indicate that a high concentration of betahistine mesylate can decrease the initial mortality (b0) in male flies, mitigating the damage of blue light to Drosophila. Consequently, this delays the aging process in male Drosophila and extends their average lifespan. After betahistine mesylate ingestion, locomotor activity upon blue light exposure decreased significantly in male Drosophila. In conclusion, this study offers initial evidence supporting the investigation of the regulatory mechanisms of betahistine mesylate on lifespan and its potential anti-blue light effects.

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Current research using animal models to investigate retinal cell biology and model retinal degenerative diseases largely utilize small mammals that are nocturnal and lack the ability to restore lost vision. In contrast, the Mongolian gerbil (Meriones) is a diurnal rodent with good photopic vision, and the spiny mouse (Acomys) is a small desert-dwelling rodent with remarkable regenerative capabilities. The goal of this study was to identify antibodies that detect retinal cell classes in Meriones and Acomys, and to describe the retinal anatomy of these two species in comparison to outbred laboratory mice (Mus musculus). Immunohistochemistry was performed on retinal sections with antibodies for various retinal cell types. Sections were imaged by light, fluorescence, and confocal microscopy. Cell density, morphology, and placement were compared between species qualitatively and quantitatively. Our analyses revealed a classic assembly of retinal cells in Meriones and Acomys, with a few deviations compared to Mus. Meriones displayed the highest density of cones and Acomys the lowest. A higher density of bipolar cell bodies in the proximal portion of the inner nuclear layer was observed in both Acomys and Meriones compared to Mus, and both species exhibited an increase in amacrine cell density compared to Mus. Our results provide a foundation for future research into the visual system adaptations of these interesting species.

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INTRODUCTION: While the 44-mm clay penetration criterion was developed in the 1970s for soft body armor applications, and the researchers acknowledged the need to conduct additional tests, the same behind the armor blunt trauma displacement limit is used for both soft and hard body armor evaluations and design considerations. Because the human thoraco-abdominal contents are heterogeneous, have different skeletal coverage, and have different functional requirements, the same level of penetration limit does not imply the same level of protection. It is important to determine the regional responses of different thoraco-abdominal organs to better describe human tolerance and improve the current behind armor blunt trauma standard. The purpose of this study was to report on the methods, procedures, and data collected from swine. MATERIALS AND METHODS: Live swine tests were conducted after obtaining approvals from the local institution and the Army Care and Use Review Office of the U.S. Department of Defense. Trachea tubes and an intravenous line were introduced before administering anesthesia. Pressure transducers were inserted into the lungs and aorta. An indenter simulating the backface deformation profiles produced by body armor from military-relevant ballistics to human cadavers was used to deliver impact loading to the liver region. A triaxial accelerometer was included in the indenter design. The animals were monitored for 6 hours, necropsies were performed, and injuries were identified. Biomechanical data of the energy, velocity, deflection, viscous criterion, force, and impulse variables were obtained for each test. RESULTS: Peak accelerations, velocities, deflections, forces, impulse, and energies ranged from 897 to 5,808 g, 21 to 59 m/s, 1.96 to 8.87 cm, 2.3 to 13.1 kN, 1.1 to 7.1 Ns, and 58 to 387 J, respectively. The peak viscous criterion ranged from 0.8 to 5.8 m/s. All animals survived the 6-hour survival period. Three animals responded with liver lacerations while the remaining 4 did not have any injuries. CONCLUSION: The experimental design based on parallel tests with whole body human cadavers and cadaver swine was found to be successful in delivering controlled impacts to the liver region of live swine and reproducing liver injuries. Previously used biomechanical measures as potential candidates for injury criteria development were obtained. Using this proven model, tests with additional samples are needed to develop injury risk curves for liver impacts and obtain regional (liver) injury criteria.

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BACKGROUND: Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. METHODS: Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t -tests or Fisher's Exact tests. RESULTS: During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption ( P < 0.001), a higher arterial lactate level ( P = 0.001), and worse systolic ventricular function ( P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level ( P = 0.031). Adjusted cardiac troponin-I ( P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group ( P = 0.028). CONCLUSIONS: Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

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This paper proposes measurement and reduction of eye dose in real time for the physician and the assistant performing fluoroscopy guided arterial puncture. Eye dose rates were measured for 30 fluoroscopy-guided punctures of bilateral femoral arteries in pigs. Fifteen fluoroscopy-guided punctures were performed using real time radiation dosimeter without auditory and visual feedback and other fifteen punctures were done using real time radiation dosimeter with visual and auditory feedback worn on forehead by an interventional cardiologist having experience of more than 10 years. The mean radiation dose rate for eyes of physician during arterial puncturing with real time radiation dosimeter with auditory feedback was 0.07 mSv/h (n = 15) whereas it was 0.18 mSv/h (n = 15) without visual and auditory feedback. The percentage of reduction with the device was 61% for eyes. In case of assistant the reduction was 33% for eyes (n = 15). The real time visual and auditory feedback dosimeter has reduced the eye dose rate of the physician and assistant and also helped him staying away from the X-ray source. Real time radiation dosimeters can be an effective tool to measure and reduce the dose to the eyes. The radiation eye dose rate for physician and assistant was significantly reduced by using real time radiation dosimeter with visual and auditory feedback. The real time radiation dosimeter not only helps in measuring but also help in minimizing the radiation dose rate for the physician and assistant in real time.

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