Experimental Model Research Articles

A Review of Cartilage Defect Treatments Using Chitosan Hydrogels in Experimental Animal Models.

Chitosan (CS) is a polycationic polysaccharide comprising glucosamine and N-acetylglucosamine and constitutes a potential material for use in cartilage tissue engineering. Moreover, CS hydrogels are able to promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediator production by chondrocytes. Although all the positive outcomes, no review has analyzed the effects of CS hydrogels on cartilage repair in animal models. This study aimed to review the literature to examine the effects of CS hydrogels on cartilage repair in experimental animal models. The search was done by the descriptors of the Medical Subject Headings (MeSH) defined below: "Chitosan," "hydrogel," "cartilage repair," and "in vivo." A total of 420 articles were retrieved from the databases Pubmed, Scopus, Embase, Lilacs, and Web of Science. After the eligibility analyses, this review reported 9 different papers from the beginning of 2002 through the middle of 2022. It was found that cartilage repair was improved with the treatment of CS hydrogel, especially the one enriched with cells. In addition, CS hydrogel produced an upregulation of genes and proteins that act in the cartilage repair process, improving the biomechanical properties of gait. In conclusion, CS hydrogels were able to stimulate tissue ingrowth and accelerate the process of cartilage repair in animal studies.

The cerebral and cardiac effects of Norepinephrine in an experimental cardiac arrest model

IntroductionEpinephrine has been the main drug recommended for decades during cardiopulmonary resuscitation (CPR). But epinephrine’s ß-adrenergic effects might increase myocardial oxygen consumption and may cause arrythmias after ROSC. Norepinephrine has a weaker ß-adrenergic effect and could be useful during CPR. Studies on norepinephrine’s effect on hemodynamic parameters and cerebral perfusion are scarce. This study aimed to assess norepinephrine's hemodynamic impact in an experimental model of cardiac arrest. MethodsAfter an initial dose study to determine the optimal dose, we conducted a prospective randomized study with 19 pigs. After 3 minutes of untreated ventricular fibrillation, animals received boluses of 0.5 mg Epinephrine (EPI) or 1 mg Norepinephrine (NE) every 5 minutes during CPR. Coronary perfusion pressure (CPP), carotid blood flow (CBF) and cerebral perfusion pressure (CePP) were evaluated. ResultsAt baseline, hemodynamic parameters did not differ between the two groups. During CPR, CPP and CBF were similar: 17.3 (12.8; 31.8) in the EPI group vs 16.0 (11.1; 37.7) in the NE group, p = 0.9 and 28.4 (22.0; 54.8) vs 30.8 (12.2; 56.3) respectively, p = 0.9. CePP was not significantly lower during resuscitation in the NE group compared to the EPI group: 12.2 (−8.2; 42.2) vs 7.8 (−2.0; 32.0) p = 0.4. Survival rate was low with only one animal in the EPI group and 2 in the NE group. ConclusionCerebral perfusion pressure, coronary perfusion pressure and carotid blood flow during CPR did not significantly differ between the norepinephrine group and the epinephrine group. Further investigations should evaluate different options such as a continuous NE infusion.

Arterial Blood Flow and Effects on Limb Tissue Perfusion During Endoshunting of the Common Iliac Artery in an Experimental Porcine Model

Arterial Blood Flow and Effects on Limb Tissue Perfusion During Endoshunting of the Common Iliac Artery in an Experimental Porcine Model

Automated feature selection using improved migrating birds optimization for enhanced medical diagnosis

The feature selection task is a crucial phase in data analysis, aiming to identify a minimized set of relevant features for the target class, thereby eliminating irrelevant and redundant attributes used for model training. While population-based feature selection approaches offer prominent solutions for classification performance, their computational time can be prohibitive. To mitigate delays and optimize resource utilization, this study adopts machine learning operations (MLOps). MLOps involves the seamless transition of experimental Machine Learning models into production, serving them to end users and automating the feature selection phase. This paper introduces a novel feature selection method based on improved migrating bird optimization and its automated variant integrated into MLOps. Experiments conducted on six medical datasets validate the effectiveness of our proposed feature selection method in improving the outcomes of medical diagnosis systems. The results showcase satisfactory performance in terms of classification compared to concurrent feature selection algorithms.

A study on metrological cross-validation of hydrogen refueling stations using a hybrid metrology evaluation system

Hydrogen refueling stations play a pivotal role in advancing hydrogen fuel cell vehicles. Ensuring the accuracy and reliability of these stations is crucial for their safe and efficient operation. This study proposes a hybrid metrology evaluation system for the comprehensive cross-validation of hydrogen refueling stations. The system combines experimental measurements with computational models to thoroughly assess the stations' performance.The main objectives of this study are to evaluate the precision, accuracy, and reliability of hydrogen refueling stations and to identify potential uncertainties or sources of error in measurements. Six refueling experiments were conducted, varying the refueling pressure from 476bar to 735bar and the refueling rate from 0.601486kg/min to 0.702694kg/min. The maximum refueling capacity was determined to be approximately 6.3kg, based on the specifications of the NEXO vehicle.Throughout the experiments, data on critical parameters such as pressure, weight, and flow rate were collected. These data were meticulously analyzed and compared with expected values derived from computational models. The results convincingly demonstrate that the hybrid metrology evaluation system offers a robust and precise evaluation of hydrogen refueling stations. The system adeptly identifies discrepancies between experimental measurements and computational models, facilitating the correction of potential measurement errors.This study contributes significantly to the enhancement of metrological cross-validation techniques for hydrogen refueling stations, ensuring their precision and dependability. The study findings can inform the development of standardized metrological protocols and guidelines for the certification and calibration of hydrogen refueling stations. By establishing accurate and dependable metrological validation methods, the adoption of hydrogen fuel cell vehicles can be expedited, promoting a sustainable and environmentally friendly transportation system.

Ambient intelligent framework for modelling critical medical events based on context awareness

With the rapid pace of communication technology, the modern communication system still encounters challenges in meeting the dynamic requirements of users. Facilitating emergency services for patients without a caretaker side by is quite challenging. This work contributes a solution towards state-of-the-art research problems by introducing a novel architecture using collaboration, coordination and user activity detection using contextual information. A prototype is built and experiment is carried out to emphasize the importance of real-time activity-based context awareness in ambient intelligence (AmI) applications. The primary contributions of this work are introduction of novel architecture and usage of both static and dynamic activity-based contextual parameters. The secondary contribution of this model is to integrate ambient intelligence with context awareness to offer higher accuracy in determining the critical condition of a patient. Initially, analytical models are built using the context-based attributes that consider both clinical and non-clinical entities based on the minimal and essential vital information of patient. This paper further discusses the experimental model, which is highly cost-efficient both from an operational and usage viewpoint. Different assessment environments have been used for assessing the performance of the model.

Evaluation of anti- inflammatory and analgesic activity of Bhasmas in experimental animal models

Acute toxicity studies of both the bhasmas showed no mortality at 2000 mg/kg.The Scanning electron microscopy of both Tamra and Lauha bhasma indicated the nanomaterial characteristics which justifies claim of Ayurvedic bhasmas as ancient nanomaterials. Tamra and Lauha bhasma were found to be effective as anti-inflammatory agent in acute models of inflammation. It inhibits all phases of inflammation induced by carrageenan. Tamra and Lauha bhasma were found to be effective as anti-inflammatory agent in chronic model of inflammation. It significantly inhibits wet as well as dry weight of cotton pellet granuloma at highest doses only. Analgesic activity of both Tamra and Lauha bhasma in hot plate and tail immersion models were found to be significant at 120-240 mins. Analgesic activity of both Tamra and Lauha bhasma in acetic acid models were found to be non-significant in nature, while found to be significant at late phase in formalin induced model. Tamra and Lauha bhasma also were found to have significant anti-arthritic activity in animal study.The whole pharmacological investigations were indicated that activity was only significant at therapeutic and more than therapeutic dose but nonsignificant at dose lower than therapeutic doses. The obtained results indicates the anti-inflammatory and analgesic potential of both these bhasmas probably by inhibiting inflammatory mediators.

Validation of a White Light and Fluorescence Augmented Panoramic Endoscopic Imaging System on a Bimodal Bladder Wall Experimental Model

Background: Fluorescence visualization of pathologies, primarily neoplasms in human internal cavities, is one of the most popular forms of diagnostics during endoscopic examination in medical practice. Currently, visualization can be performed in the augmented reality mode, which allows to observe areas of increased fluorescence directly on top of a usual color image. Another no less informative form of endoscopic visualization in the future can be mapping (creating a mosaic) of the acquired image sequence into a single map covering the area under study. The originality of the present contribution lies in the development of a new 3D bimodal experimental bladder model and its validation as an appropriate phantom for testing the combination of bimodal cystoscopy and image mosaicking. Methods: An original 3D real bladder-based phantom (physical model) including cancer-like fluorescent foci was developed and used to validate the combination of (i) a simultaneous white light and fluorescence cystoscopy imager with augmented reality mode and (ii) an image mosaicking algorithm superimposing both information. Results: Simultaneous registration and real-time visualization of a color image as a reference and a black-and-white fluorescence image with an overlay of the two images was made possible. The panoramic image build allowed to precisely visualize the relative location of the five fluorescent foci along the trajectory of the endoscope tip. Conclusions: The method has broad prospects and opportunities for further developments in bimodal endoscopy instrumentation and automatic image mosaicking.

Analysis of Out-of-Plane Displacements of a Light Steel Keel Fireproof Exterior Wall and Its Connection with the Steel Frame

Light steel keel fireproof exterior walls are one of the new composite walls that have been widely used in recent years. This paper analyzes the factors affecting the displacements of the connectors and wall panels and modifies the corresponding displacement model. ABAQUS was used to establish the simulation analysis of the L-shaped and special-shaped steel angle component, and the results were compared with the experimental model to verify the rationality. The effect of vertical keel spacing and layout, the number of special-shaped steel angles, the L-shaped steel angle thickness, and the number of self-tapping screws for L-shaped steel angles to steel beams were explored based on the validated finite element model. The calculation model was modified based on the results of the simulation. The results showed that the simulation results fit well with the experimental results, which verified the reliability of the finite element model. The number of connectors and the number of self-tapping screws are the main factors affecting the special-shaped and L-shaped steel angle components, respectively. By modifying the rotation constraint factor of the L-shaped steel angle and adding a discount factor for the wall panel, the accuracy of the associated displacement calculation model could be improved.

Applications of 3D organoids in toxicological studies: a comprehensive analysis based on bibliometrics and advances in toxicological mechanisms.

A mechanism exploration is an important part of toxicological studies. However, traditional cell and animal models can no longer meet the current needs for in-depth studies of toxicological mechanisms. The three-dimensional (3D) organoid derived from human embryonic stem cells (hESC) or induced pluripotent stem cells (hiPSC) is an ideal experimental model for the study of toxicological effects and mechanisms, which further recapitulates the human tissue microenvironment and provides a reliable method for studying complex cell-cell interactions. This article provides a comprehensive overview of the state of the 3D organoid technology in toxicological studies, including a bibliometric analysis of the existing literature and an exploration of the latest advances in toxicological mechanisms. The use of 3D organoids in toxicology research is growing rapidly, with applications in disease modeling, organ-on-chips, and drug toxicity screening being emphasized, but academic communications among countries/regions, institutions, and research scholars need to be further strengthened. Attempts to study the toxicological mechanisms of exogenous chemicals such as heavy metals, nanoparticles, drugs and organic pollutants are also increasing. It can be expected that 3D organoids can be better applied to the safety evaluation of exogenous chemicals by establishing a standardized methodology.

Research on Alzheimer's Disease (AD) Involving the Use of In vivo and In vitro Models and Mechanisms.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the progressive formation of extracellular amyloid plaques, intracellular neurofibrillary tangles, inflammation, and impaired antioxidant systems. Early detection and intervention are vital for managing AD effectively. This review scrutinizes both in-vivo and in-vitro screening models employed in Alzheimer's disease research. In-vivo models, including transgenic mice expressing AD-related mutations, offer profound insights into disease progression and potential therapeutic targets. A thorough understanding of these models and mechanisms will facilitate the development of novel therapies and interventions for Alzheimer's disease. This review aims to provide an overview of the current experimental models in AD research, assess their strengths and weaknesses as model systems, and underscore the future prospects of experimental AD modeling. We conducted a systematic literature search across multiple databases, such as Pub- Med, Bentham Science, Elsevier, Springer Nature, Wiley, and Research Gate. The search strategy incorporated pertinent keywords related to Alzheimer's disease, in-vivo models, in-vitro models, and screening mechanisms. Inclusion criteria were established to identify studies focused on in-vivo and in-vitro screening models and their mechanisms in Alzheimer's disease research. Studies not meeting the predefined criteria were excluded from the review. A well-structured experimental animal model can yield significant insights into the neurobiology of AD, enhancing our comprehension of its pathogenesis and the potential for cutting-edge therapeutic strategies. Given the limited efficacy of current AD medications, there is a pressing need for the development of experimental models that can mimic the disease, particularly in pre-symptomatic stages, to investigate prevention and treatment approaches. To address this requirement, numerous experimental models replicating human AD pathology have been established, serving as invaluable tools for assessing potential treatments. In summary, this comprehensive review underscores the pivotal role of in-vivo and in-vitro screening models in advancing our understanding of Alzheimer's disease. These models offer invaluable insights into disease progression, pathological mechanisms, and potential therapeutic targets. By conducting a rigorous investigation and evaluation of these models and mechanisms, effective screening and treatment methods for Alzheimer's disease can be devised. The review also outlines future research directions and areas for enhancing AD screening models.

Unveiling the Influence of Copy Number Variations on Genetic Diversity and Adaptive Evolution in China’s Native Pig Breeds via Whole-Genome Resequencing

Copy number variations (CNVs) critically influence individual genetic diversity and phenotypic traits. In this study, we employed whole-genome resequencing technology to conduct an in-depth analysis of 50 pigs from five local swine populations [Rongchang pig (RC), Wuzhishan pig (WZS), Tibetan pig (T), Yorkshire (YL) and Landrace (LR)], aiming to assess their genetic potential and explore their prospects in the field of animal model applications. We identified a total of 96,466 CNVs, which were subsequently integrated into 7112 non-redundant CNVRs, encompassing 1.3% of the swine genome. Functional enrichment analysis of the genes within these CNVRs revealed significant associations with sensory perception, energy metabolism, and neural-related pathways. Further selective scan analyses of the local pig breeds RC, T, WZS, along with YL and LR, uncovered that for the RC variety, the genes PLA2G10 and ABCA8 were found to be closely related to fat metabolism and cardiovascular health. In the T breed, the genes NCF2 and CSGALNACT1 were associated with immune response and connective tissue characteristics. As for the WZS breed, the genes PLIN4 and CPB2 were primarily linked to fat storage and anti-inflammatory responses. In summary, this research underscores the pivotal role of CNVs in fostering the diversity and adaptive evolution of pig breeds while also offering valuable insights for further exploration of the advantageous genetic traits inherent to China’s local pig breeds. This facilitates the creation of experimental animal models tailored to the specific characteristics of these breeds, contributing to the advancement of livestock and biomedical research.

Antidepressant Effect of Vincamine, Melatonin and their Combination in Experimental Rat Models of Depression

Background: Depression, a form of mood illness, is characterized by a lack of or diminished social life, melancholy, and symptoms linked to an uplifted or depressed mood. Vincamine and Melatonin combination may prove beneficial for treating depression because vincamine and melatonin have already been reported in the treatment of dementia. Dementia is a CNS disorder which is connected to the level of neurotransmitters at the synaptic cleft, which is similar to depression that is why it might be effective in the treatment of depression. Aim: The aim of this research is to conduct an experimental study on the antidepressant activity of Vincamine alone and along with Melatonin and comparison with standard antidepressant drugs. Method: In this study, all animals are trained for the experiment, and then animals are divided into groups according to the treatment protocol. Animals were placed for the rest for 1 week. Vincamine and melatonin were administered to the treated groups on days 8 and 21 for the behavioral analysis using different kinds of models like elevated plus maze, forced swim test, open field test and sucrose preference test. Animals were sacrificed at day 22 for the estimation of biochemical (SOD) and neurotransmitters (Serotonin, Norepinephrine and Dopamine). Results: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10 mg/kg), Melatonin (10 mg/kg), Vincamine + Melatonin (10 mg/kg + 10 mg/kg) and std (10 mg/kg) treatment showed significant result which are followed as for all groups (a) p < 0.0001 vs NC; (b) p < 0.0001 vs disease control; (c) p < 0.05 vs Std (10 mg/kg); (d) p < 0.001V vs M (10 mg/kg); (e) p < 0.0090 vs V+M (10 mg/kg+10 mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p < 0.0001) in the evaluation of the SOD antioxidant defence system. Also, it significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. result: After extensive investigation, it has been established that Vincamine, alone and in combination with Melatonin, is beneficial in treating depression. Positive results are obtained. The group treated with Vincamine taken per oral route ((10mg/kg), Melatonin (10mg/kg), Vincamine + Melatonin (10mg/kg + 10mg/kg) and std (10mg/kg) treatment showed significant result which are followed as for all groups (a) p < 0.0001 vs NC; (b) p < 0.0001 vs disease control; (c) p < 0.05 vs Std (10 mg/kg); (d) p < 0.001V vs M (10 mg/kg); (e) p < 0.0090 vs V+M (10mg/kg+10mg/kg). It was demonstrated by a number of behavioral (elevated plus maze, forced swim test, open field test, and sucrose preference test) and biochemical parameters (estimation of neurotransmitters such as serotonin, epinephrine, and dopamine). Vincamine alone and in combination with Melatonin demonstrated positive results (p<0.0001) in the evaluation of the SOD antioxidant defence system. Also, significantly attenuated the alteration in locomotor activity, oxidative stress and neurotransmitters in rat brain. Conclusion: It has been concluded that vincamine alone and along with melatonin is effective for the treatment of depression on the basis of behavioural and biochemical parameters. That’s why it might be useful for the future prospect.

Twinning–Detwinning-Dominated Cyclic Deformation Behavior of a High-Strength Mg-Al-Sn-Zn Alloy during Loading Reversals: Experiment and Modeling

The deformation behavior of a high-strength Mg-Al-Sn-Zn alloy under loading reversals has been thoroughly examined through a combination of experimental measurements and crystal plasticity modeling. We focused on an age-treated alloy fortified by distributed Mg2Sn particles and Mg17Al12 precipitates, which underwent two distinct loading cycles: tension-compression-tension (TCT) and compression-tension-compression (CTC), aligned with the extrusion direction (ED). The initial and deformed microstructures of the alloy were analyzed using the electron backscattering diffraction (EBSD) technique. Notably, the alloy displays tensile and compressive yield strengths (YS) of 215 MPa and 160 MPa, respectively, with pronounced anelastic behavior observed during unloading and reverse loading phases. Utilizing the elasto-viscoplastic self-consistent model incorporating a twinning–detwinning scheme (EVPSC-TDT), the cyclic stress–strain responses and resultant textures of the alloy were accurately captured. The predicted alternation between various slip and twinning modes during plastic deformation was used to interpret the observed behaviors. It was found that prismatic <a> slip plays an important role during the plastic deformation of the studied alloy, and its relative activity in tensile loading processes accounts for up to ~66% and ~67% in the TCT and CTC cases, respectively. Moreover, it was discerned that detwinning and twinning behaviors are predominantly governed by stresses within the parent grain, and they can concurrently manifest during the reverse tensile loading phase in the TCT case. After cyclic deformation, the area fractions of residual twins were determined to be 7.51% and 0.93% in the TCT and CTC cases, respectively, which is a result of the varied twinning–detwinning behavior of the alloy in different loading paths.

The effects of doxapram and its potential interactions with K2P channels in experimental model preparations.

The channels commonly responsible for maintaining cell resting membrane potentials are referred to as K2P (two-P-domain K+ subunit) channels. These K+ ion channels generally remain open but can be modulated by their local environment. These channels are classified based on pharmacology, pH sensitivity, mechanical stretch, and ionic permeability. Little is known about the physiological nature of these K2P channels in invertebrates. Acidic conditions depolarize neurons and muscle fibers, which may be caused by K2P channels given that one subtype can be blocked by acidic conditions. Doxapram is used clinically as a respiratory aid known to block acid-sensitive K2P channels; thus, the effects of doxapram on the muscle fibers and synaptic transmission in larval Drosophila and crawfish were monitored. A dose-dependent response was observed via depolarization of the larval Drosophila muscle and an increase in evoked synaptic transmission, but doxapram blocked the production of action potentials in the crawfish motor neuron and had a minor effect on the resting membrane potential of the crawfish muscle. This indicates that the nerve and muscle tissues in larval Drosophila and crawfish likely express different K2P channel subtypes. Since these organisms serve as physiological models for neurobiology and physiology, it would be of interest to further investigate what types of K2P channel are expressed in these tissues. (212 words).

Chinese Bayberry Extract Regulates the Permeability of Blood-cerebrospinal Fluid Barrier and Ameliorates Experimental Colitis-Related Brain Comorbidities in Mice

Abstract Objectives The anxiety, depression symptoms, and cognitive decline related to inflammatory bowel disease (IBD) are recognized to have an impact on patients’ health. The blood-cerebrospinal fluid barrier (BCSFB) is important in somatic disease-related psychiatric and cognitive disorders, however, few treatments show efficacy. The objective of this research was to seek the protective effect of Chinese bayberry extract on inflammatory bowel disease-related brain comorbidities. Materials and Methods C57BL/6J mice were induced with dextran sulfate sodium (DSS) solution to establish the experimental model, followed by the administration of Chinese bayberry extract. Oxidative stress indexes, immunofluorescence of choroid plexus, and BCSFB permeability were further investigated. Results Chinese bayberry extract improved behavioral markers and reduced the level of oxidative stress in the brain. In addition, administration of the bayberry extract increased the tight junction proteins in the choroid plexus and a significant decrease in the permeability of the BCSFB. Conclusions Chinese bayberry extract has the potential therapeutic effect of relieving inflammatory bowel disease-related brain comorbidities. The underlying mechanism is associated with a decrease in oxidative stress in the brain and a decrease in the permeability of the BCSFB.

Impact of wall thickness on tissue cooling effect of cryoballoon ablation: Investigation using an experimental heart model

Abstract Background Understanding of the tissue cooling properties of cryoballoon ablation during pulmonary vein isolation is lacking. Purpose To delineate the depth of the tissue cooling effect during cryoballoon freezing at the pulmonary venous ostium. Methods A left atrial-pulmonary vein model, produced by a 3-dimensional printer using CT data from a patient, was constructed so that porcine thigh muscles of various thicknesses could be fixed and thermocouples could be fixed at locations corresponding to the epicardial side of the pulmonary vein ostium. The model was placed in a 37-degree water bath with a pulmonary vein water flow at a rate that mimicked biological blood flow, and the cryoballoon was advanced into the left superior vein until the vein was completely occluded. Cryofreezing was performed 5 times each for a porcine thigh muscle of 2-, 4-, and 6-mm thickness, and epicardial tissue cooling was monitored as assessed by the mean temperature of 12 evenly distributed thermocouples covering the roof region of the left superior vein. Results Epicardial tissue cooling effects were more in the order of 2-mm, 4-mm, and 6-mm thickness (Figure) with a mean temperature of -41.4 ± 4.2 for 2 mm, -33.0 ± 4.0 for 4 mm, and 8.0 ± 8.7 °C for 6 mm at 180 sec (p for trend < 0.0001). In addition, tissue temperature drops were steeper in thin muscle (maximum temperature drop per 5 s: 5.2 ± 0.9, 3.9 ± 0.7, 1.3 ± 0.7 °C, p for trend < 0.0001). Conclusion The cooling effect is weaker in the deeper layers during cryobaloon freezing, and longer freezing duration would be recommended in case of thick myocardium.

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia

Abstract Introduction In the clinic, complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and state-of-the-art high density mapping during VT is complex, and often cannot be completed because of hemodynamic instability. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. Complementary imaging-based strategies including advanced analyses of scar tissue characteristics have been also proposed for procedure planning and identification of potential arrhythmogenic regions. However, the most recent expert consensus report on catheter ablation of ventricular arrhythmia highlights the lack of agreement on the preferable signal intensity (SI) cut-off values for assessment of tissue heterogeneity and scar areas on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images. The latter makes LGE-CMR imaging processing highly operator-dependent and potentially sensitive to selection bias. Purpose We aimed at developing and validating a systematic processing approach on LGE-CMR images to identify potential VT corridors that may include protected isthmuses associated with VT maintenance. Methods Translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicenter series of 33 patients with ischemic cardiomyopathy undergoing VT ablation. Three-dimensional CMR-LGE images were processed using systematic scanning of 15 signal intensity cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. Results In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically-defined isthmus sites (n=11 and n=19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically-guided ablation lesions at functionally relevant isthmus sites (Figure). However, in patients, decreasing from 15 to 7 the number of signal intensity cut-off ranges for systematic imaging processing significantly reduced the area of imaging-based potential VT corridors, without diminishing the capability to detect functionally relevant VT isthmus sites. Conclusions Systematic processing of 3D LGE-CMR images provides unbiased identification of imaging based potential VT corridors that contain functionally relevant protected isthmus sites.

Gastric emphysema and pneumatosis intestinalis in two common marmosets with duodenal dilation syndrome

BackgroundCommon marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood.Case presentationWe report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis.ConclusionsIn both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.

Safety evaluation of adenosine, lidocaine and magnesium (ALM) intranasal therapy toward human nasal epithelial cells in vitro.

Adenosine, lidocaine and Mg2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air-liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min. Safety was measured through viability, cytotoxicity, apoptosis, cellular and mitochondrial stress, and inflammatory mediator secretion assays. No differences were found in viability or cytotoxicity in cultures exposed to saline or ALM for up to 60 min, with no evidence of apoptosis after exposure to supratherapeutic ALM concentrations. Despite comparable inflammatory cytokine secretion profiles and mitochondrial activity, cellular stress responses were significantly lower in cultures exposed to ALM than saline. In summary, data show ALM therapy has neither adverse toxic nor inflammatory effects on human nasal epithelial cells, setting the stage for in vivo toxicity studies and possible clinical translation of intranasal ALM therapy for TBI treatment.