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As the integration of mechanical engineering and deep learning fields becomes increasingly intertwined, the application of experimental thermal error modeling in intelligent manufacturing has gained significant importance. In this paper, the issue of spindle thermal error is treated as a multivariate time series problem due to the thermal transfer characteristics. This study aims to address the challenge of modeling intermittent multivariate time series spindle thermal errors under a wide range of environmental temperatures and various operational scenarios. To tackle this challenge, a substantial volume of experimental data, capable of effectively reflecting the patterns of spindle thermal error variations, was collected through experiments conducted at multiple speeds and under various operational scenarios. Subsequently, the acquired thermal error data underwent intermittent multivariate time series transformation (IMTS) to suit the serialized deep learning model. The study introduces the Crossformer model into the field of thermal error modeling for the first time, which is a variant of the Transformer model. The Crossformer model exhibits remarkable adaptability to temporal aspects while effectively maintaining its focus on data features. Ultimately, this study resulted in the development of the IMTS-CrossformerR experimental thermal error model. Throughout the research, a comprehensive examination of various models was undertaken, including two traditional Transformer models and other thermal error deep learning and machine learning models. The results indicate that the proposed model outperforms its counterparts across multiple model metrics and predictive capabilities. Particularly noteworthy is its substantial improvement in the range (± 5) ratio of residual fluctuations reaching 95.7%, a key engineering metric. [ABSTRACT FROM AUTHOR]

Over the last four decades, the Fontan operation has been the treatment of choice for children born with complex congenital heart diseases and a single-ventricle physiology. However, therapeutic options remain limited and despite ongoing improvements in initial surgical repair, patients still experience a multiplicity of cardiovascular complications. The causes for cardiovascular failure are multifactorial and include systemic ventricular dysfunction, pulmonary vascular resistance, atrioventricular valve regurgitation, arrhythmia, development of collaterals, protein-losing enteropathy, hepatic dysfunction, and plastic bronchitis, among others. The mechanisms leading to these late complications remain to be fully elucidated. Experimental animal models have been developed as preclinical steps that enable a better understanding of the underlying pathophysiology. They furthermore play a key role in the evaluation of the efficacy and safety of new medical devices prior to their use in human clinical studies. However, these experimental models have several limitations. In this review, we aim to provide an overview of the evolution and progress of the various types of experimental animal models used in the Fontan procedure published to date in the literature. A special focus is placed on experimental studies performed on animal models of the Fontan procedure with or without mechanical circulatory support as well as a description of their impact in the evolution of the Fontan design. We also highlight the contribution of animal models to our understanding of the pathophysiology and assess forthcoming developments that may improve the contribution of animal models for the testing of new therapeutic solutions. [ABSTRACT FROM AUTHOR]

In experimental medicine, a wide variety of sensory measurements are used. One of these is real-time precision pressure measurement. For comparative studies of the complex pathophysiology and surgical management of abdominal compartment syndrome, a multichannel pressure measurement system is essential. An important aspect is that this multichannel pressure measurement system should be able to monitor the pressure conditions in different tissue layers, and compartments, under different settings. We created a 12-channel positive–negative sensor system for simultaneous detection of pressure conditions in the abdominal cavity, the intestines, and the circulatory system. The same pressure sensor was used with different measurement ranges. In this paper, we describe the device and major experiences, advantages, and disadvantages. The sensory systems are capable of real-time, variable frequency sampling and data collection. It is also important to note that the pressure measurement system should be able to measure pressure with high sensitivity, independently of the filling medium (gas, liquid). The multichannel pressure measurement system we developed was well suited for abdominal compartment syndrome experiments and provided data for optimizing the method of negative pressure wound management. The system is also suitable for direct blood pressure measurement, making it appropriate for use in additional experimental surgical models. [ABSTRACT FROM AUTHOR]

Arteriovenous malformations (AVMs) are vascular anomalies characterized by abnormal shunting between arteries and veins. The progression of the AVMs and their hemodynamic and rheological relations are poorly studied, and there is a lack of a feasible experimental model. To establish a model that cause only minimal micro-rheological alterations, compared to other AV models. Sixteen female Sprague Dawley rats were randomly divided into control and AVM groups. End-to-end anastomoses were created between the saphenous veins and arteries to mimic AVM nidus. Hematological and hemorheological parameters were analyzed before surgery and on the 1st, 3rd, 5th, 7th, 9th, and 12th postoperative weeks. Compared to sham-operated Control group the AVM group did not show important alterations in hematological parameters nor in erythrocyte aggregation and deformability. However, slightly increased aggregation and moderately decreased deformability values were found, without significant differences. The changes normalized by the 12th postoperative week. The presented rat model of a small-caliber AVM created on saphenous vessels does not cause significant micro-rheological changes. The alterations found were most likely related to the acute phase reactions and not to the presence of a small-caliber shunt. The model seems to be suitable for further studies of AVM progression. [ABSTRACT FROM AUTHOR]

Sepsis is a major health problem that causes millions of deaths worldwide every year. Due to the complexity of its pathophysiology, there is no clear treatment method for it. Existing treatments impose an additional financial burden on the health systems of countries every year. Clinical and preclinical studies are continuously being conducted in order to prevent the development of sepsis, treat patients with sepsis, reduce mortality, and solve the socioeconomic problems that arise from it. However, it is not possible to directly test every study and potential new treatment in humans. Preclinical studies enable an understanding of pathophysiological events and the development of targeted therapies. For this purpose, many experimental sepsis models have been and continue to be applied. The extent to which these models can reflect the human sepsis condition is an important issue that needs to be emphasized. Each method has different strengths and weaknesses. Researchers should choose the most appropriate experimental model according to the characteristics of the experiments they plan and, if possible, conduct their studies on different models. [ABSTRACT FROM AUTHOR]

Introduction: Anastomotic leaks (ALs) are serious postoperative complications. Current experimental studies designed to investigate leaks are based on acute intraoperative dehiscence of the anastomosis. Clinically, however, AL usually happens later in the postoperative course. Presented here is a clinically relevant colonic AL model in swine. Methods: Seventeen Yorkshire pigs were divided into 2 groups: the control group (n = 6) and the experimental group (n = 11). An enterotomy was performed on the descending colon and an end-to-end handsewn anastomosis was created in the groups. The proximal and distal ends of the suture were exteriorized and tied to a plastic tube. Subsequently, the suture was cut and pulled to induce breakdown of the anastomosis in the experimental group 3–4 h postoperatively. Study endpoints included behavioral changes, clinical assessment, laboratory indicators, and macroscopic indicators of leakage. Results: Leaks were successfully created in 8/11 of the experimental group animals and confirmed through exploratory relaparotomy. Seven of the experimental pigs showed complete anastomotic breakdown and one showed partial rupture. Fecal peritonitis and enteric spillage were observed macroscopically within the abdomen of the experimental pigs, confirming the presence of a leak. The remaining (3/11) experimental pigs did not experience those findings due to either a tamponade/containment by the abdominal wall or surrounding organs. Statistical significance (p < 0.05) was achieved between the experimental and control cohorts for laboratory and clinical indicators including fever, leukocytosis, and decreased blood potassium. Conclusion: This animal model generated postoperative induced leak in approximately three-quarters (8/11) of experimental pigs, allowing control over the time of leak onset to simulate clinical settings. [ABSTRACT FROM AUTHOR]

The influence of water on rock deformation and failure behavior is a critical variable to consider when developing unconventional shale reservoirs. To better understand this effect, we conducted a series of triaxial compression tests on four mudstone lithofacies, namely siliceous calcareous mudstones, siliceous mudstones, calcareous mudstones, and carbonate-rich mudstones from the Naparima Hill Formation, under water-saturated conditions at confining pressures up to 130 MPa. Our results showed that the mudstones displayed brittle, brittle–ductile transition, and ductile failure behaviors as the confining pressure increased. Mudstones with low strength, high porosity, and high silica and clay contents exhibited a strong water-weakening effect, leading to a significant reduction in failure strength. Conversely, high strength, low porosity, and carbonate-rich mudstones showed minor water-weakening effects. We also developed a failure behavior model to predict the brittle, brittle–ductile transition, and ductile zones in the mudstones. The model showed that the transition from brittle to ductile behavior occurs over a wide range of confining pressures, and it occurs at a lower pressure threshold in saturated compared to dry conditions. Additionally, the model suggests that the presence of water results in a wider transition zone between brittle and ductile behavior, as well as a larger ductile zone. Overall, our findings suggest that the water-weakening effect can significantly decrease the depth at which the brittle–ductile transition occurs in mudstones, emphasizing the importance of considering water as a critical variable in rock deformation and failure behavior. Highlights: Triaxial compression test was conducted on mudstone specimens to investigate the impact of water content on failure behavior. An experimental model that predicts the brittle, brittle–ductile transition, and ductile failure behavior is developed for water-saturated mudstones. Low-strength, high-porosity mudstones with high levels of silica and clay are significantly weakened in the presence of water. Brittle–ductile transition behavior is influenced by the strength, porosity, and mineralogy of the mudstones. Brittle–ductile transition occurred over a wide range of confining pressures, with a lower threshold in saturated than dry conditions. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment–insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-β was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain. [ABSTRACT FROM AUTHOR]

Background/Aim: Surfactant is a surface-active substance that, in addition to its detergent effect, also has effects that reduce inflammation and fibrosis. Because of these effects, it was aimed herein to investigate the effect of intraperitoneal surfactant application on preventing postoperative peritoneal adhesion formation in a uterine horn adhesion model. Materials and methods: Twenty-one Wistar albino rats were randomly divided into 3 groups (G1-G3), as follows: G1 (n = 7): control group. The abdomen was opened and then closed; G2 (n = 7): adhesion group. The abdomen was opened. Then, a 2-cm linear incision was made over the right uterine horn, 2 mL of isotonic saline was administered intraperitoneally, and the abdomen was closed; and G3 (n = 7): treatment group. The abdomen was opened, a 2-cm linear incision was made over the right uterine horn, 2 mL (70 mg/kg) of surfactant was administered intraperitoneally, and the abdomen was closed. After 15 days, the rats were euthanized, the abdomens were reopened, and adhesion scoring was performed. After the right uterine horns were removed and fixed with 10% formalin, appropriate sections were taken from the traumatized tissue, stained with Masson's trichrome, and fibrosis and inflammation scoring were performed. Results: The adhesion area and intensity were significantly higher in G2 than in G1 and G3 (p = 0.001) and were similar in G1 and G3 (p = 0.165). While fibrosis and inflammation were significantly higher in G2 than in G1 and G3 (p = 0.001), there was no difference between G1 and G3 (p = 0.5). Conclusion: Intraperitoneal surfactant administration at a dose of 70 mg/kg was found to be effective in preventing intraabdominal adhesion formation in a rat uterine horn model. [ABSTRACT FROM AUTHOR]

This work defined the development of a model for thin-film drying of tomatoes using an indirect solar dryer. Drying experiments were carried out and the drying model was approximated by a simplified model determined by the measurements collected during the experiments, in particular, the measurement of the relative humidity of the tomato during two days of drying coupled with the thermal behaviour of the drying device in free convection. The results show that with good measurements, it is possible to approximate the drying characteristic curve by a linear model with very high statistical performance indicators. The experiments also show that depending on the drying process adopted, the water behaviour of the tomato can change. In addition, the thin-film drying model adopted made it possible to assess the solar drying kinetics of the tomato variety studied. The results obtained finally show that the dryness of the tomato is reached after about 14 hours of drying. The drying temperature reaches an average of 80°C, and the final product water content after the optimal drying time is about 0.40 kg.water/kg.ms on a dry basis. At the end of this study, we concluded that the drying air temperature represents the most important parameter affecting the drying kinetics. The very good agreement between the experimental and numerical results obtained shows that the theoretical model and assumptions used are acceptable, and that our calculation model is reliable. [ABSTRACT FROM AUTHOR]

Background: Vonoprazan is a new potassium-competitive acid blocker (P-CAB) that was recently approved by the FDA. It is associated with a fast onset of action and a longer acid inhibition time. Vonoprazan-containing therapy for helicobacter pylori eradication is highly effective and several studies have demonstrated that a vonoprazan-antibiotic regimen affects gut microbiota. However, the impact of vonoprazan alone on gut microbiota is still unclear.Please check and confirm the authors (Maria Cristina Riascos, Hala Al Asadi) given name and family name are correct. Also, kindly confirm the details in the metadata are correct.Yes they are correct. Methods: We conducted a prospective randomized 12-week experimental trial with 18 Wistar rats. Rats were randomly assigned to one of 3 groups: (1) drinking water as negative control group, (2) oral vonoprazan (4 mg/kg) for 12 weeks, and (3) oral vonoprazan (4 mg/kg) for 4 weeks, followed by 8 weeks off vonoprazan. To investigate gut microbiota, we carried out a metagenomic shotgun sequencing of fecal samples at week 0 and week 12.Please confirm the inserted city and country name is correct for affiliation 2.Yes it's correct. Results: For alpha diversity metrics at week 12, both long and short vonoprazan groups had lower Pielou's evenness index than the control group (p = 0.019); however, observed operational taxonomic units (p = 0.332) and Shannon's diversity index (p = 0.070) were not statistically different between groups. Beta diversity was significantly different in the three groups, using Bray–Curtis (p = 0.003) and Jaccard distances (p = 0.002). At week 12, differences in relative abundance were observed at all levels. At phylum level, short vonoprazan group had less of Actinobacteria (log fold change = − 1.88, adjusted p-value = 0.048) and Verrucomicrobia (lfc = − 1.76, p = 0.009).Please check and confirm that the author (Ileana Miranda) and their respective affiliation 3 details have been correctly identified and amend if necessary.Yes it's correct. At the genus level, long vonoprazan group had more Bacteroidales (lfc = 5.01, p = 0.021) and Prevotella (lfc = 7.79, p = 0.001). At family level, long vonoprazan group had more Lactobacillaceae (lfc = 0.97, p = 0.001), Prevotellaceae (lfc = 8.01, p < 0.001), and less Erysipelotrichaceae (lfc = − 2.9, p = 0.029). Conclusion: This study provides evidence that vonoprazan impacts the gut microbiota and permits a precise delineation of the composition and relative abundance of the bacteria at all different taxonomic levels. [ABSTRACT FROM AUTHOR]

Context: The present experimental models of cystic diseases are not adequate and require further investigation. Aim: In this study, a new way of producing a tissue-mimicking model of cysts and cystic neoplasms was evaluated. Settings and Design: To simulate cysts and cystic neoplasms, ex vivo rabbit normal bladders and VX2-implanted tumor bladders were produced, fixed, and embedded in agarose gel. Methods and Materials: The samples were classified into four groups based on tumor features and the maximal transverse diameter of the rabbit bladder, which were assessed using computer tomography (CT) imaging and statistically analyzed. Statistical Analysis Used: Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software. The t-test was used for analyzing enumeration data. Results: Twenty-one rabbit bladders (21/24) were successfully removed and prepped for this experiment, comprising eleven normal bladders (11/24) and ten implanted with VX2 tumors (10/24). The gelling ingredient used to form the visualization and fixation matrix was agarose at a concentration of 4 g/200 mL. The temperature of the agarose solution was kept constant at 40-45°C, which is the optimal temperature range for ex vivo normal bladder and implanted VX2 tumor bladder insertion. The average time required to embed and fix the bladders in agarose gel was 45.0 ± 5.2 minutes per instance. The gel-fixing matrix's strength and light transmittance were enough for building the models. Conclusion: We created an experimental tissue-mimicking model of cysts and cystic neoplasms with stable physicochemical features, a safe manufacturing method, and high repeatability. These models may be used to assist with cystic lesion diagnosis and treatment techniques. [ABSTRACT FROM AUTHOR]

The goaf formed by coal seam mining would dramatically reduce the strength and stiffness of the ground in and around the goaf, which is not conducive to tunnel excavation near the mined-out area. By establishing the Finite differential method and Discrete element method coupling numerical analysis method and conducting similar model test, the influence of dip angle, thickness and distance of coal seam goaf on the stability of unsupported tunnel excavation is studied. The results show that when the tunnel under the goaf is excavated, the circumferential stress increment increases first and then decreases along the radial direction of the tunnel, the radial stress increment gradually decreases to zero along the radial direction of the tunnel, the displacement is approximately distributed in a trough shape, and the maximum displacement is at the top of the tunnel. The area of the stress loosening zone (SLZ) is negatively correlated with the dip angle and the distance of the goaf, and positively correlated with the thickness. The SLZ near the goaf is larger, and the peak value of the asymmetry is about 1.35. When the thickness of the mined-out area is 1.8-2.1 m, the SLZ and displacement around the tunnel increase sharply and then become stable. When the dip angle of the mined-out area is greater than 30° or the distance exceeds 1.3 times tunnel diameter (D), the asymmetry converges. The research results of this paper are of great importance to the design and construction of tunnel support and the formulation of excavation schemes. [ABSTRACT FROM AUTHOR]

Background: Allergen‐specific immunotherapy (AIT) is the only disease‐modifying treatment approach to change disease‐causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. Methods: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. Results: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL‐10 and IFN‐γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis‐challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. Conclusions: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre‐clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis‐induced allergy. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. Methods: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. Results: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. Conclusions: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Johne's disease is a global economic burden. The disease contributes to reduced milk yield, reduced fertility, higher rates of susceptibility to other diseases and eventual death. Unhealthy animals are less efficient, producing higher kg of greenhouse gases per kg of output (milk and meat). Therefore, prognosis and diagnosis are important in terms of animal welfare and future climate change policies by reducing the impact of livestock on climate change. In the past decade, our knowledge around the microbiome in health and disease has increased. Next generation sequencing technologies have provided a new understanding of the interactions between the host microbiome and pathogens. The microbiome is a target for treatment, prevention of disease and a source of novel biomarkers of disease risk. The potential to improve animal health is highly dependent on our ever growing knowledge of the gut microbiome and their interactions with the host. With the aim to gain knowledge in the early months of exposure to MAP in calves, we investigated the dynamics of the gut microbiome (using faecal sample) of calves 3, 6 and 9 months post inoculation with MAP relative to unexposed controls. Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne's disease in ruminants, a chronic enteritis which results in emaciation and eventual loss of the animal. Recent advances in metagenomics have allowed a more in-depth study of complex microbiomes, including that of gastrointestinal tracts, and have the potential to provide insights into consequences of the exposure of an animal to MAP or other pathogens. This study aimed to investigate taxonomic diversity and compositional changes of the faecal microbiome of cattle experimentally challenged with MAP compared to an unexposed control group. Faecal swab samples were collected from a total of 55 animals [exposed group (n = 35) and a control group (n = 20)], across three time points (months 3, 6 and 9 post-inoculation). The composition and functional potential of the faecal microbiota differed across time and between the groups (p < 0.05), with the primary differences, from both a taxonomic and functional perspective, occurring at 3 months post inoculation. These included significant differences in the relative abundance of the genera Methanobrevibacter and Bifidobacterium and also of 11 other species (4 at a higher relative abundance in the exposed group and 7 at a higher relative abundance in the control group). Correlations were made between microbiome data and immunopathology measurements and it was noted that changes in the microbial composition correlated with miRNA-155, miR-146b and IFN-ɣ. In summary, this study illustrates the impact of exposure to MAP on the ruminant faecal microbiome with a number of species that may have relevance in veterinary medicine for tracking exposure to MAP. [ABSTRACT FROM AUTHOR]

Background and Aim: Infectious bovine keratoconjunctivitis is the most crucial ophthalmic disease among ruminants worldwide. Moraxella is the bacteria generally associated with this disease and leads to keratitis, conjunctivitis, corneal ulcers, or blindness. Platelet-rich plasma (PRP) effects in corneal ulcers and different ocular superficial diseases in animals and humans are beneficial and enhance rapid healing and improvement, but the effects in infectious keratoconjunctivitis in ruminants are uncertain. This study aimed to examine the effect of PRP on re-epithelization, corneal tissue, clinical signs, and matrix metalloproteinase (MMP) expression in sheep with infectious keratoconjunctivitis. Materials and Methods: Eighteen sheep were divided into three groups and subjected to a disease-induction experiment. Group 1 (G1) was administered 1.0 mL PRP subconjunctivally, Group 2 (G2) was administered 1.0 mL PRP subconjunctivally and 50 µL gentamicin drops, and the control group (CG) was administered 50 µL saline solution topically every 12 h. Clinical ophthalmologic examination, fluorescein staining, and photography were carried out. Ulcerated areas were measured employing J-Image software. Five and eleven days following the procedure, half of the animals from each group were euthanized, and their corneas were evaluated by histopathology and zymography. Results: Control Group and G2 epithelialized more rapidly. The CG exhibited fewer clinical signs of ocular disease. In histopathological analysis, in G2, alterations were observed only in the epithelium. The CG and G1 exhibited alterations in the epithelium, stroma, and Descemet's membrane. In zymography, a decline in MMP-2 expression in the animals treated with PRP was detected. Matrix metalloproteinase-9 was significantly expressed in the animals treated with PRP monotherapy, whereas PRP + gentamicin and CG caused a decrease. Conclusion: Platelet-rich plasma alone did not demonstrate any beneficial effect on re-epithelialization, a decline in clinical signs, tissue alterations, and expression of metalloproteinases. Platelet-rich plasma combined with gentamicin was capable of suppressing MMPs, primarily MMP-9, but do not display positive effects in re-epithelization, reduction of clinical signs, or tissue effects. These outcomes are similar to those discovered in untreated animals, so the use of PRP in patients with infectious keratoconjunctivitis does not offer greater benefits in sheep. Additional research is required to validate the results of PRP use in natural disease presentation. [ABSTRACT FROM AUTHOR]

Purposes: A preventive strategy against lung ischemia reperfusion injury (LIRI) is pretreatment with certain drugs to make them more resistant to LIRI. The aim of this study was to investigate the preventive effects of everolimus (RAD001) on LIRI in a rat-ventilated ischemia-reperfusion model. Methods:Rats were divided into 8 groups;1 control(I), 6 LIRI (IIa,b,c;IIIa,b,c) and 1 everolimus(IV). LIRI groups underwent 90 min of ischemia and 30 min (IIa-IIIa), 120 min (IIb-IIIb) and 240min (IIc-IIIc) of reperfusion, respectively, and were randomized into two, one without (II) and one with everolimus (III) pretreatment. Groups III received 1mg/kg/day everolimus via oral gavage for 1 week before IR. After reperfusion, bronchoalveolar lavage and lung tissue samples were collected. The mRNA expressions of the samples’ proinflammatory genes were determined via qPCR. TNF-α and macrophage inflammatory protein 2 (MIP2) concentrations and caspase-3 activity were measured using ELISA kits. Also, myeloperoxidase (MPO) activity was measured spectrophotometrically. Results:Everolimus significantly decreased the expression of all study mRNA proinflammatory genes for groups IIIb and IIIc(p<0.05). It also decreased MIP2 protein levels in groups IIIb and IIIc, whereas TNF-α protein levels decreased only in group IIIc’s lung tissue samples(p<0.05). A significant downregulation of caspase-3 enzyme activity was detected only in group IIIa(p<0.05). Conclusion:This study shows that everolimus pretreatment, effectively prevents LIRI by decreasing pro-inflammatory genes’ mRNA expressions, the protein expressions of TNF-α and MIP2, and the activity of caspase 3 and myeloperoxidase. [ABSTRACT FROM AUTHOR]

Sleep is essential for health: Adequate sleep is essential for healthy development and sleep deprivation results in several consequences. Indeed, sleep deprivation early in life is associated with poor behaviour and cognition, as well as impaired mental and physical health. Preclinical studies have shown that sleep deprivation alters several physiological functions later in life such as the cardiovascular, immune and endocrine systems, resulting in altered oxidative states. Most of the preclinical literature is focused on adult animals, and little is known about oxidative alterations during development, especially in the context of sleep deprivation. Hence, we adapted a classic and well‐documented model of sleep deprivation, paradoxical sleep deprivation using multiple platforms, for juvenile rats and explored central and peripheral oxidative parameters, as well as the behavioural consequences of sleep deprivation post‐weaning. We showed that 96 h of paradoxical sleep deprivation induced a significant reduction in body weight, decreased sucrose preference—a behaviour suggestive of anhedonia—and increased glucose and decreased cholesterol in the plasma. In the brain, we observed a decrease in reduced glutathione levels in the medial prefrontal cortex and an increase in thiobarbituric acid reactive substance levels in the hypothalamus, indicating oxidative damage in these regions. Taken together, our findings suggest that paradoxical sleep deprivation during development induces anhedonic behaviour and promotes central and peripheral alterations in oxidative parameters. [ABSTRACT FROM AUTHOR]

Objectives: Crush syndrome (CS) is characterized by a systemic manifestation of traumatic rhabdomyolysis, leading to multiple organ dysfunction and death. Ischemia-reperfusion (IR) injury is commonly responsible for systemic response. Extending studies have shown that hydrogen gas treatment ameliorated IR injury in numerous experimental models; however, its effect on CS has not been well examined. This study aimed to investigate the effects of hydrogen gas inhalation following crush injury in an experimental model of CS. Methods: Male Sprague-Dawley rats were subjected to experimental CS by applying a total of 3.0 kg weight to both hindlimb under general anesthesia for 6 h. Immediately after decompression, the animals were randomly placed in a gas chamber filled with either air or 1.3% hydrogen gas. Animals were sacrificed 18 h or 24 h following gas exposure for non-survival studies or for survival study, respectively. Results: The rats with hydrogen treatment (n = 6) had a higher 24-h survival than the rats with air treatment (n = 9) (100% vs. 44%, p = 0.035). Lactate concentrations (2.9 ± 0.2 vs. 2.2 ± 0.2 mmol/L, p = 0.040) and creatine kinase (34,178 ± 13,580 vs. 5005 ± 842 IU/L, p = 0.016) were lower in the hydrogen group compared with the air group 18 h after decompression (n = 4 in the air group, and n = 5 in the H2 group). Histological analysis revealed that the damage to the rectus femoris muscle and kidney appeared to be ameliorated by hydrogen treatment. Conclusion: Hydrogen gas inhalation may be a promising therapeutic approach in the treatment of CS. [ABSTRACT FROM AUTHOR]

Introduction: Surgical replacement of dysfunctional cardiac muscle with regenerative tissue is an important option to combat heart failure. But, current available myocardial prostheses like a Dacron or a pericardium patch neither have a regenerative capacity nor do they actively contribute to the heart's pump function. This study aimed to show the feasibility of utilizing a vascularized stomach patch for transmural left ventricular wall reconstruction. Methods: A left ventricular transmural myocardial defect was reconstructed by performing transdiaphragmatic autologous transplantation of a vascularized stomach segment in six Lewe minipigs. Three further animals received a conventional Dacron patch as a control treatment. The first 3 animals were followed up for 3 months until planned euthanasia, whereas the observation period for the remaining 3 animals was scheduled 6 months following surgery. Functional assessment of the grafts was carried out via cardiac magnetic resonance tomography and angiography. Physiological remodeling was evaluated histologically and immunohistochemically after heart explantation. Results: Five out of six test animals and all control animals survived the complex surgery and completed the follow-up without clinical complications. One animal died intraoperatively due to excessive bleeding. No animal experienced rupture of the stomach graft. Functional integration of the heterotopically transplanted stomach into the surrounding myocardium was observed. Angiography showed development of connections between the gastric graft vasculature and the coronary system of the host cardiac tissue. Conclusions: The clinical results and the observed physiological integration of gastric grafts into the cardiac structure demonstrate the feasibility of vascularized stomach tissue as myocardial prosthesis. The physiological remodeling indicates a regenerative potential of the graft. Above all, the connection of the gastric vessels with the coronary system constitutes a rationale for the use of vascularized and, therefore, viable stomach tissue for versatile tissue engineering applications. [ABSTRACT FROM AUTHOR]

In view of global environmental deterioration and climate change, researchers from multiple fields of the behavioral sciences examine the determinants of pro-environmental behavior. Research on pro-environmental behavior is dominated by the use of self-report measures, which relates to critical validity problems. Some of these problems can be addressed by studying consequential behavior in behavioral paradigms (i.e., systematically arranged situations of actual environmental relevance). However, pro-environmental behavior paradigms have been scattered across disciplines, and many researchers may not be aware of the wealth of available paradigms. The present review aims to acquaint researchers across disciplinary borders with the behavioral paradigms developed to study pro-environmental behavior in different domains. A systematic literature search revealed 99 ad hoc paradigms and five validated paradigms of pro-environmental behavior. I review how different authors have succeeded in implementing the consequences of pro-environmental behavior in standardized field, laboratory, or online situations, point to caveats in the use of behavioral paradigms, and illustrate how researchers can select a paradigm for their own research. [ABSTRACT FROM AUTHOR]

Background: Migraine is considered a multifactorial genetic disorder. Different platforms and methods are used to unravel the genetic basis of migraine. Initially, linkage analysis in multigenerational families followed by Sanger sequencing of protein-coding parts (exons) of genes in the genomic region shared by affected family members identified high-effect risk DNA mutations for rare Mendelian forms of migraine, foremost hemiplegic migraine. More recently, genome-wide association studies testing millions of DNA variants in large groups of patients and controls have proven successful in identifying many dozens of low-effect risk DNA variants for the more common forms of migraine with the number of associated DNA variants increasing steadily with larger sample sizes. Currently, next-generation sequencing, utilising whole exome and whole genome sequence data, and other omics data are being used to facilitate their functional interpretation and the discovery of additional risk factors. Various methods and analysis tools, such as genetic correlation and causality analysis, are used to further characterise genetic risk factors. Findings: We describe recent findings in genome-wide association studies and next-generation sequencing analysis in migraine. We show that the combined results of the two most recent and most powerful migraine genome-wide association studies have identified a total of 178 LD-independent (r 2 < 0.1) genome-wide significant single nucleotide polymorphisms (SNPs), of which 99 were unique to Hautakangas et al., 11 were unique to Choquet et al., and 68 were identified by both studies. When considering that Choquet et al. also identified three SNPs in a female-specific genome-wide association studies then these two recent studies identified 181 independent SNPs robustly associated with migraine. Cross-trait and causal analyses are beginning to identify and characterise specific biological factors that contribute to migraine risk and its comorbid conditions. Conclusion: This review provides a timely update and overview of recent genetic findings in migraine. [ABSTRACT FROM AUTHOR]

In this study, total antioxidant and radical scavenging capacity wound healing and anti-analgesic effects of creams prepared from Nigella sativa EOs, hydrosol, and seed oil were determined in the experimental rat model. For this purpose, the volatile components of N. sativa EOs and hydrosol were characterized using GC-FID and GC-MS and the total antioxidant capacity of creams was determined by CUPRAC and DPPH assays. The analgesic effect of the creams was determined by the formalin test, while the wound-healing effects of creams were evaluated in vivo by experimentally creating skin wounds in rats. The main components in the group of monoterpene hydrocarbons, accounting for 52.61% of the total composition of N. sativa EOs, were as follows: p-cymene (28.76%), α-thujene (12.88%), trans-verbenol (5.99%), β-pinene (3.71%), α-pinene (3.69%), sabinene (1.7%), and limonene (1.69%). The group of oxygenated monoterpenes of N. sativa EOs was dominated by 2-isopropyl-5-methyl-1,4-benzoquinone (35.7%), known as thymoquinone (TQ). On the other hand, the analyses of GC-FID and GC-MS revealed that N. sativa hydrosol contains five components. These ingredients were as follows: 1,8-cineole (0.4%), linalool (0.5%), trans-verbenol (2.83%), terpinen-4-ol (7.21%), and TQ (89.05%). Research findings revealed the strong antioxidant effect and radical scavenging ability of the prepared creams. It was found that the cream, especially enriched with N. sativa hydrosol, had a better antioxidant effect and wound healing potential. [ABSTRACT FROM AUTHOR]

Objectives: Crush syndrome (CS) is characterized by a systemic manifestation of traumatic rhabdomyolysis, leading to multiple organ dysfunction and death. Ischemia-reperfusion (IR) injury is commonly responsible for systemic response. Extending studies have shown that hydrogen gas treatment ameliorated IR injury in numerous experimental models; however, its effect on CS has not been well examined. This study aimed to investigate the effects of hydrogen gas inhalation following crush injury in an experimental model of CS. Methods: Male Sprague-Dawley rats were subjected to experimental CS by applying a total of 3.0 kg weight to both hindlimb under general anesthesia for 6 h. Immediately after decompression, the animals were randomly placed in a gas chamber filled with either air or 1.3% hydrogen gas. Animals were sacrificed 18 h or 24 h following gas exposure for non-survival studies or for survival study, respectively. Results: The rats with hydrogen treatment (n = 6) had a higher 24-h survival than the rats with air treatment (n = 9) (100% vs. 44%, p = 0.035). Lactate concentrations (2.9 ± 0.2 vs. 2.2 ± 0.2 mmol/L, p = 0.040) and creatine kinase (34,178 ± 13,580 vs. 5005 ± 842 IU/L, p = 0.016) were lower in the hydrogen group compared with the air group 18 h after decompression (n = 4 in the air group, and n = 5 in the H2 group). Histological analysis revealed that the damage to the rectus femoris muscle and kidney appeared to be ameliorated by hydrogen treatment. Conclusion: Hydrogen gas inhalation may be a promising therapeutic approach in the treatment of CS. [ABSTRACT FROM AUTHOR]

Little is known about alternative treatment options for rhinosinusitis (RS). We aimed to evaluate the efficacy of low-level laser therapy (LLLT) for RS in experimentally induced rabbit models of RS. A total of 18 rabbits were divided into four groups: a negative control group (n = 3), an RS group without treatment (n = 5, positive control group), an RS group with natural recovery (n = 5, natural recovery group), and an RS group with laser irradiation (n = 5, laser-treated group). Computed tomography and histopathological staining were performed for each group. mRNA and protein expression levels of local cytokines (IFN-γ, IL-17, and IL-5) were also measured. Tissue inflammation revealed a significant improvement in the laser-treated group compared with the RS and natural recovery groups (p < 0.01). In addition, sinus opacification in the CT scans and cytokine expression was reduced in the laser-treated group, though without statistical significance. LLLT could be an effective option for the management of RS concerning radiological, histological, and molecular parameters. [ABSTRACT FROM AUTHOR]

There are substantial differences in autonomic nervous system activation among heart (cardiac) failure (CF) patients. The effect of acute CF on autonomic function has not been well explored. The aim of our study was to assess the effect of experimental acute CF on heart rate variability (HRV). Twenty-four female pigs with a mean body weight of 45 kg were used. Acute severe CF was induced by global myocardial hypoxia. In each subject, two 5-min electrocardiogram segments were analyzed and compared: before the induction of myocardial hypoxia and >60 min after the development of severe CF. HRV was assessed by time-domain, frequency-domain and nonlinear analytic methods. The induction of acute CF led to a significant decrease in cardiac output, left ventricular ejection fraction and an increase in heart rate. The development of acute CF was associated with a significant reduction in the standard deviation of intervals between normal beats (50.8 [20.5–88.1] ms versus 5.9 [2.4–11.7] ms, p < 0.001). Uniform HRV reduction was also observed in other time-domain and major nonlinear analytic methods. Similarly, frequency-domain HRV parameters were significantly changed. Acute severe CF induced by global myocardial hypoxia is associated with a significant reduction in HRV. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to establish a novel and reversible experimental ocular hypertension primate model by blocking Schlemm's canal. Methods: A model was induced in adult cynomolgus monkeys (n = 4) by blocking Schlemm's canal with an inserted microcatheter (200 μm diameter); it was removed 6 weeks later from one monkey to reverse the elevated intraocular hypertension. All animals were monitored for 11 months; weekly measurements of intraocular pressure and biweekly examinations with spectral domain optical coherence tomography and disc photography were performed. Histopathology of the eye and retinal ganglion cell counts were completed at the end of the study. Results: The intraocular pressure of the blocked eyes was significantly higher than that of the contralateral eyes at 1 month after the blockage (p < 0.001); the mean intraocular pressure was similar to the contralateral eye from 1 week to 11 months after the microcatheter was removed in monkey A (p = 0.170). The mean intraocular pressure of the blocked eyes of the remaining monkeys was significantly higher than that of the contralateral eyes throughout the follow-up period (p < 0.001). The fundus imaging showed decreases in the retinal nerve fibre layer thickness, and localized defects were observed in two blocked eyes. A histological examination demonstrated that the number of retinal ganglion cells in the blocked eyes of monkeys A, B, and C was significantly decreased compared with the control. Conclusion: Schlemm's canal blockage alone in the monkey model produces sustained elevation of intraocular pressure, which presents a novel animal model for studying the pathogenesis of glaucoma. [ABSTRACT FROM AUTHOR]

Objectives This study aims to develop valid experimental models for depression through chronic reserpine exposure to zebrafish (Danio rerio). Methods The effect of chronic reserpine on zebrafish behavior in the novel tank was examined. Changes of gene expression on telencephalon were also investigated. Results Chronic reserpine (40 mg/L, 7 days) induced overt behavioral effects, but markedly reduced activity, resembling motor retardation in depression. In telencephalon of zebrafish, gene expression associated with monoamine oxidase and norepinephrine transporter was decreased. Expression of serotonin transporter gene was increased. Conclusions Our results show that the pharmacological model of depression in zebrafish can induce not only behavioral changes, but also monoamine changes in the homology of human mood regulation centers. [ABSTRACT FROM AUTHOR]

Introduction: High‐power short‐duration (HPSD) has been proposed to shorten procedure times while maintaining efficacy and safety. We evaluated the differences in size and geometry between radiofrequency lesions obtained with this method and conventional ones. Methods and Results: Twenty‐eight sets of 10 perpendicular radiofrequency applications were performed with two commercially available catheters: a temperature‐controlled HPSD catheter (QDot‐Micro) and a conventional power‐controlled catheter (Thermocool SmartTouch) on porcine left ventricle. Different power settings (35, 40, 50, and 90 W), contact force (CF; 10 and 20 g), ablation index (AI; 400 and 550), and application times were combined to create conventional (35–40 W), HPSD (50 W) and very‐high‐power short‐duration (VHPSD; 90 W) lesions, that were cross‐sectioned and measured. About 4‐s VHPSD lesions were smaller, shallower, and thinner than HPSD performed with the QDot‐Micro catheter in any scenario of CF or AI (61 ± 7.8 mm3, 6.1 ± 0.3 mm wide, and 2.9 ± 0.1 mm deep with 10 g; 72.2 ± 0.5 mm3, 6.8 ± 0.3 mm wide, and 2.9 ± 0.2 mm deep with 20 g). Conventional and HPSD lesions performed with the temperature‐controlled catheter were generally bigger, deeper, and wider than the ones obtained with the power‐controlled catheter, as well as more consistent in size. This was especially true with the lower CF and AI scenario, while differences were less notable with other setting combinations. Conclusion: VHPSD lesions performed with QDot‐Micro catheter were smaller than any other lesions, which is especially attractive for posterior left atrial wall ablation. On the contrary, conventional‐powered and HPSD lesions performed with this catheter were equally sized (or even bigger with lower CF and AI objectives), as well as more consistent in size, which would guarantee transmurality in other locations. [ABSTRACT FROM AUTHOR]

Introduction: Beta-aminopropionitrile (BAPN) administration is a chemically induced model for preclinical aortic pathologies research. Angiotensin II (AngII) has been widely used to promotes aortic dissections in mice. Here, we provide insight on a modified aortic dissection model in rats. The effect of smooth muscle cell (SMC) relaxation with vasodilators is studied in this model. Methods: Forty Sprague-Dawley rats were divided in 4 groups: control, isosorbide dinitrate (ISDN, 30 mg/kg/day) in the drinking water, BAPN (0.02%) in the food, BAPN + ISDN (same doses). Thoracic and abdominal aortic diameters were evaluated through transthoracic ultrasound echography. After 6 weeks, all rats were infused with AngII (1 mg/kg/day) subcutaneously. Survival and type of aortic events were numbered. Histological and histochemical analyses of aorta were performed. Results: Initial telesystolic ascending aorta diameters were equal in all groups and became significantly larger in the BAPN + ISDN group compared to the BAPN group (control: 3.37 ± 0.17 mm, ISDN: 3.49 ± 0.16 mm, BAPN: 3.53 ± 0.13 mm, BAPN + ISDN: 3.61 ± 0.16 mm, analysis of variance p < 0.0001). BAPN followed by AngII infusion showed a significant lower survival rate (p = 0.029) and produced a large panel of aortic events. Association of ISDN and BAPN significantly reduces survival (p = 0.001) and provides more aortic events compared to BAPN alone (p = 0.031). In both BAPN-treated groups, orcein staining revealed split and dissected elastic fibers in the media, alcian blue staining showed mucoid degeneration of the aortic wall, and Perls-diaminobenzidine staining revealed an accumulation of Fe2+. Conclusion: SMC relaxation with ISDN increases aortic dilatation, worsens aortic prognosis, and reproduces human histological findings in a low-dose BAPN/AngII-induced aortic dissection model in rats. [ABSTRACT FROM AUTHOR]

In this study, the SCVW (a novel type of Sharp-Crested V-notch weirs) is employed for more experimentally and theoretically investigations. The length of the hydraulic jump at downstream of the SCVW (LjSCVW) is measured via new supplementary experimental datasets via most popular vertex angles θ (128° and 60°). The experiments are conducted under aerated, steady, and free overflow conditions in an open channel for large physical models. To assess the variations of LjSCVW versus the θ, extensive laboratory work is performed at different discharges (Q), diverse triangular segments number (Nst) in the SCVW, and various tailgate angles (ɸ). Via dimensional analysis and pre-processing method, most effectual parameters on the LjSCVW were obtained as Fr1 (approaching Froude number), Re1 (incoming Reynolds number), and y 2 y 1 (relative sequent depths). Based on the experimental results, by increasing the values of Fr1 and Re1, the values of LjSCVW noticeably increased. Three types of data-driven models (DDMs), namely, support vector regression (SVR), gene expression programming (GEP), and a robust hybrid model entitled hybrid (SVR-ACO) are developed to estimate the LjSCVW. The suggested hybrid model is a coupled form of SVR with ant colony optimization (ACO) algorithm, which is used to enhance the estimation precision of the LjSCVW. According to the attained statistical indices (determination coefficient (R2) = 0.98, root mean square error (RMSE) = 0.191, and value of total grade (TG) = 19.78) and scatter plots, the hybrid SVR-ACO model was determined as the most superior method to estimate the LjSCVW with high accuracy. [ABSTRACT FROM AUTHOR]

It has previously been shown that current smoking is protective against endoscopic retrograde cholangiopancreatography (ERCP)-induced acute pancreatitis, but the mechanism of this effect was not identified. We tested the hypothesis that nicotine is the active factor in this protection in a mouse model of ERCP. Pretreatment with nicotine dose dependently inhibited acute pancreatitis caused by infusion of ERCP contrast solution into the main pancreatic duct in mice. 3-2,4-Dimethoxybenzylidene anabaseine (GTS-21), a specific partial agonist of the a7 nicotinic cholinergic receptor (a7nAChR), also protected the pancreas against ERCP-induced acute pancreatitis. The effects of GTS-21 were abolished by pretreatment with the nicotinic receptor antagonist mecamylamine. Surgical splenectomy performed 7 days before ERCP-induced pancreatitis blocked the protective effects of GTS- 21. Intravenous injection of a crude preparation of total splenocytes prepared from mice pretreated with GTS-21 inhibited ERCPinduced pancreatitis; splenocytes from mice treated with vehicle had no effect. When T cells were removed from the crude GTS- 21-treated splenocyte preparation by immunomagnetic separation, the remaining non-T-cell splenocytes did not protect against ERCP-induced acute pancreatitis. We conclude that nicotine protects against ERCP-induced acute pancreatitis and that splenic T cells are required for this effect. Stimulation of a7 nicotinic cholinergic receptors may protect against ERCP-induced acute pancreatitis and may also be a novel approach to therapeutic reversal of ongoing acute pancreatitis. [ABSTRACT FROM AUTHOR]

Introduction: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with sildenafil, zafirlukast, and pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral zafirlukast, sildenafil, or pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. Methods: Four groups, each of 10 male Wistar rats weighing 250–300 g, were used. A midline laparotomy was used to excise an area of 1.5 × 1.5 cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of zafirlukast (1.25 mg/kg, group B), sildenafil (15 mg/kg, group C), or pirfenidone (500 mg/kg, group D) were given every day for 8 days. The control group, A, received no treatment. At day 9, animals were reoperated. The implant was resected after ethically approved euthanasia, and specimens were fixed in 10% formaldehyde for histopathology. Results: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (p = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (p = 0.04). Adhesions in group C had less fibrovascular density (p = 0.03) with decreased serosal injuries (p = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (p < 0.01) and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than group B or C (p < 0.01). Conclusions: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral pirfenidone offered the best performance and could be recommended for human use. [ABSTRACT FROM AUTHOR]

Tissue-hardening effect and health-hazard issue of formaldehyde (FA) have long been a great disadvantage of this conventional fixative in anatomical research. We recently developed a FA-free embalming method for cadavers which utilizes N-vinyl-2-pyrrolidone (NVP) and enables assessment of motion kinetics by maintaining the softness of embalmed tissue. By assessing the feasibility of NVP-embalmed tissue to mimic vocalization, this study aimed to prove the potential of embalmed cadavers, which have previously been used only for the understanding of anatomical morphology, for the assessment of precise motion physiology in the human body. Ten cadavers embalmed in NVP (n = 6) and FA (n = 4) were incorporated in this study. Excised larynges underwent experimental phonation to mimic vocalization with fast and pliable vibration of vocal folds. High-speed digital imaging was utilized for the assessment of vocal fold vibration. Furthermore, acoustic analysis of the voiced sound, and reproducibility examination were also performed. Regular vocal fold vibrations successfully produced voiced sounds during experimental phonation using NVP-embalmed larynges. The vibratory frequency, vibration amplitude, and stretch rate of the vocal folds were comparable to those of living humans. Six months after the first experiment, the vocal parameters were reproduced, to suggest the long-term preservation potential of our NVP-embalming technique. On the other hand, neither voiced sound nor vocal fold vibration were observed in FA-embalmed larynges. This novel embalming technique could pioneer the next era to utilize embalmed cadavers for the examination of motion physiology in the human body. [ABSTRACT FROM AUTHOR]

Most urological cancers treated by chemo or hormonal therapies acquire treatment resistance. Elucidation of the mechanisms behind treatment resistance could potentially lead to the development of novel therapies. However, it is difficult to obtain clinical samples after treatment resistance has developed. We used patient-derived xenograft (PDX) models to examine the mechanisms behind treatment resistance for each urological cancer. PDX models are useful for not only evaluating treatment efficacy but also for examining molecular profiling. The results of basic research for urological cancer using PDX models are reviewed and the possibility of future application for precision medicine is described. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraperitoneal adhesions are bands of scar tissue that occur frequently after abdominal surgery. These scars bind the abdominal organs together, producing symptoms such as intestinal obstruction, infertility, chronic pain, and a greater risk of injury in subsequent surgery. Currently, the only treatment approach for this disease is a risky surgical intervention that may cause additional adhesions or other complications. In this article we propose the use of collagenase in the peritoneal cavity to facilitate adhesion disruption. Using a simple experimental rat model, we produced an array of adhesions resembling those presented in humans. We demonstrate that the application of collagenase at the concentration and time described is safe and facilitates the disruption of adhesions with no organ damage due to contact with collagenase. The further development of this therapy and application route, published for the first time in this article, may improve the quality of life of patients with this disease. (1) Background: Abdominal adhesions are a common disease appearing after any type of abdominal surgery and may prolong surgical time and cause intestinal obstruction, infertility, or chronic pain. We propose the use of intraperitoneal collagenase to perform chemical adhesiolysis based on the pathophysiology and histology of adhesions. (2) Methods: We generated an adhesion model with intraperitoneal polypropylene meshes. Four months later, we evaluated the efficacy of the treatment in blinded form, i.e., 0.05% collagenase vs. placebo at 37 °C for 20 min. Protocol 1: Ten rats with ten mesh fragments, in which an attempt was made to remove the maximum number of meshes in a 5-min period. Protocol 2: Six rats with four mesh fragments in the sides of the abdominal cavity in which adhesiolysis was performed using a device that measures burst pressure. (3) Results: Protocol 1: 42% efficacy in the collagenase group versus 8% in the control group (p < 0.013). Protocol 2: 188.25 mmHg (SD 69.65) in the collagenase group vs. 325.76 mmHg (SD 50.25) in the control group (p < 0.001). (4) Conclusions: Collagenase allows for the safe and effective chemical adhesiolysis in this experimental model of adhesions. [ABSTRACT FROM AUTHOR]

We developed a rat model of chronic osteomyelitis of the femur caused by Staphylococcus aureus. The clinical, histomorphological, and laboratory signs were compared in rats with osteomyelitis (infected) and control animals receiving saline. On day 21 after infection, clinical, histomorphological, and laboratory signs of chronic osteomyelitis were found in experimental rats. [ABSTRACT FROM AUTHOR]

This article describes in detail the essential stereotaxic neurosurgery to develop the electric experimental kindling model in mice. To date, available literature describing the methodology of the kindling model is very poor and usually neglects many relevant details about the neurosurgery, such as the manufacture of the electrodes, accurate stereotaxic coordinates of the amygdala nuclei, and the general surgery procedures (e.g., anesthesia, postsurgical recovery, fit survival of the animal's). The electric kindling model produces a progressive development of generalized tonic-clonic seizures, which can be assessed by electroencephalography and behavioral responses. The seizures displayed are produced by a repeated low-intensity electrical stimulation in specific regions of the brain that is achieved through the previous implantation of electrodes. In this study, the aim was to implant the electrodes in basolateral amygdaloid nucleus (BLA). In order to successfully establish the kindling experimental model, neurosurgery to place the electrodes is an essential step to develop the epileptogenic phenomenon. It crucial that the surgery is carried out with exceptional exactitude, because in that way the experimental model represents an accurate and valid tool to study and understand epilepsy and the results obtained can be used to develop further strategies in epilepsy clinical research. [ABSTRACT FROM AUTHOR]

Ocular ischemic syndrome (OIS) is one of the severe ocular disorders occurring from stenosis or occlusion of the carotid arteries. As the ophthalmic artery is derived from the branch of the carotid artery, stenosis or occlusion of the carotid arteries could induce chronic ocular hypoperfusion, finally leading to the development of OIS. To date, the pathophysiology of OIS is still not clearly unraveled. To better explore the pathophysiology of OIS, several experimental models have been developed in rats and mice. Surgical occlusion or stenosis of common carotid arteries or internal carotid arteries was conducted bilaterally or unilaterally for model development. In this regard, final ischemic outcomes in the eye varied depending on the surgical procedure, even though similar findings on ocular hypoperfusion could be observed. In the current review, we provide an overview of the pathophysiology of OIS from various experimental models, as well as several clinical cases. Moreover, we cover the status of current therapies for OIS along with promising preclinical treatments with recent advances. Our review will enable more comprehensive therapeutic approaches to prevent the development and/or progression of OIS. [ABSTRACT FROM AUTHOR]

Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future. [ABSTRACT FROM AUTHOR]

Coronavirus (SARS-CoV-2) enters the cell by binding to a transmembrane glycoprotein, angiotensin-converting enzyme-2 (ACE2), which is expressed on the surface of the bronchial and alveolar epithelium. In this regard, the aim of this study was to determine changes in the content and characteristics of tissue localization of ACE2 in the model of acute bronchopulmonary inflammation. The latter was modeled by endotracheal injection of a foreign body (Capron thread) and a solution of lipopolysaccharide (LPS; 50 μl at a dose of 12.5 mg/kg) against the background of systemic administration of LPS for two days before surgery (250 mg/kg). ACE2 localization and quantity were evaluated by immunohistochemical and western blot assays with the use of a specific monoclonal antibody. The experiment reproduced acute exudative-hemorrhagic bronchopneumonia with the development of diffuse progressive pulmonary fibrosis with lethality in 36% of animals. Acute exudative inflammation was accompanied by complete inhibition of ACE2 expression in bronchial epitheliocytes and its significant decrease in alveolocytes type II. With the development of the proliferative stage of bronchopneumonia, the level of ACE2 was restored, subsequently remaining without significant changes. The obtained experimental data suggest the existence of a relationship between the features of quantitative changes in the ACE2 level in the bronchopulmonary epithelium and the undulating course of the inflammatory process during SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective: Following bone trauma, several factors participate in making a balance between the activity of osteoblasts and osteoclasts. The receptor activator of nuclear factor kappa B ligand (RANKL), receptor activator of nuclear factor kappa B (RANK), and osteoprotegerin (OPG) molecules play critical roles in the healing process via regulation of osteoclasts function. Turmeric is suggested to have an anti-osteogenic potential; however, its effect on accelerating bone healing has not been adequately studied. Here, we used a rat model of femur fracture to explore the effect of treatment with turmeric extract on the bone repair and the expression of RANK, RANKL, and OPG molecules. Materials and Methods: Eight rats were subjected to surgery, randomly divided into two groups, and treated orally with turmeric (200 mg/kg), or olive oil. Four oil-treated rats without bone fracture were used as control group. After six weeks of treatment, the femurs of animals were examined for radiological, histological, and gene expression analysis. Results: X-ray radiography showed thicker callus and a more obscure fracture line in the turmeric group. Furthermore, higher osteoblast percentages but no osteoclasts were observed in turmeric-treated animals, representing better repair of bone in the fracture site. Also, real-time analyses showed that treatment with turmeric reduced RANK and RANKL expression (p<0.0001) and lowered RANKL/OPG ratio (p=0.01) in femoral bone tissue. Conclusion: Our findings indicated the turmeric ability to facilitate bone hemostasis and optimize the expression of key markers involved in the bone metabolism. [ABSTRACT FROM AUTHOR]

In this study, the hydraulic features of the SCVW (a novel type of sharp-crested V-notch weirs) were scrutinized in the popular vertex angles θ , i.e., 30°, 45°, 60°, 90°, 120°, 128°, and 150°, under aerated, steady and free overflow conditions in an open channel for large physical models. To assess the changes of the discharge coefficient of the SCVW (i.e., CdSCVW) versus weir height and θ , widespread laboratory works were performed by measuring the water head over the crest of the weir and the discharge. Special formulas for the CdSCVW in the θ=60° were checked, and an appropriate empirical equation was recommended. The calculated CdSCVW by the proposed equation was within 0%–10% of the measured values. Three types of nonparametric artificial intelligence (AI) methods, namely, support vector regression (SVR), gene expression programming (GEP), and a robust hybrid model entitled hybrid (SVR-ACO) were developed to estimate the CdSCVW. For the sake of modeling, 196 experimental datasets were applied in the mentioned methods to evaluate the CdSCVW by taking into consideration the dimensionless variables which impact the determining procedure of the CdSCVW. In this modeling, by varying the architecture and core factors of the aforementioned methods, several scenarios were defined. The generated mathematical equation of CdSCVW by the best scenario of the GEP was compared with the corresponding measured values in which the results were in 0%–10%. According to the attained statistical indices, scatter plots, and the values of the total grade (TG) technique, the hybrid SVR(RBF)-ACO model was determined as the superior and optimal method to estimate the CdSCVW with high performance and accuracy. [ABSTRACT FROM AUTHOR]

As hydraulic control structures, side weirs are generally employed for irrigation, drainage, and many other water regulation purposes. Researchers have studied the use of labyrinth geometry to increase the length of side weir crests while maintaining the same channel opening length. The present work proposes a novel inclined-bed triangular side weir design and evaluates its discharge characteristics. A total of 159 experimental tests were performed using different geometric designs and hydraulic variables. The experimental data were analyzed, and results were evaluated to develop a nonlinear equation for the discharge coefficient of the introduced side weir. An error analysis for the equation showed fairly acceptable accuracy, with most results falling within ±7% of the measured values. Final results demonstrate a significant improvement in efficiency of up to 78% and 39% for the discharge coefficient of the proposed design compared with conventional rectangular side weirs and orthogonal-bed triangular side weirs, respectively. [ABSTRACT FROM AUTHOR]

Background: Peyronie's Disease (PD) is a connective tissue disorder that affects the tunica albuginea (TA) of the penis causing curvature and erectile dysfunction. The pathophysiology is not well understood and, for this reason, treatment options are limited. Objective: The aim of the present study is to analyze and compare whether single or multiple instillations of plasma in the TA of rats is capable of triggering macroscopic, histopathological, and molecular changes consistent with PD. Material/methods: Fifty male Wistar rats were divided into four groups: Group 1: a single instillation of plasma in the TA; Group 2: a single instillation of distilled water in the TA; Group 3: four instillations of plasma in the TA (1x per week); and Group 4: four instillations of distilled water in the TA (1× per week). Forty‐five days after the last instillation a manual inspection of the corpus cavernosum, a penile erection test and a penectomy were performed to obtain material for histopathological and molecular analysis. Results: It was observed that 31.25% of the rats that received repeated instillations of plasma presented penile curvature according to the erection test, while none of the rats from the control group or group with one instillation of plasma presented curvature. In the animals that received four instillations of plasma, the following differences were observed in relation to the control group: increase in fibrosis and the deposition of collagen I. The protein expression of heparanase (HPSE) and TGF‐β increased in the groups that received a single or four instillations of plasma, and the protein expression of heparanase‐2 (HPSE‐2), metalloproteinases (MMP‐2, MMP‐9) and metalloproteinase inhibitor (TIMP‐2) showed an increase in the group that received four instillations of plasma. There was a significant increase in the gene expression of HPSE, MMP‐9, and TGF‐β in the group that received four instillations of plasma. In the analysis of the glycosaminoglycans, an increase was observed in the secretion of galactosaminoglycans chondroitin sulfate and dermatan sulfate (CS/DS) in the group that received four instillations of plasma. Discussion: Previous studies have demonstrated increased protein expression. of HPSE, MMP‐9 and TGF‐β with instillation of blood in the TA; however, there was no increase in gene expression. In the present study, the increase in the expression of TGF‐β with plasma instillations, proved to be more reliable. The two models with plasma (one or four instillations) demonstrated significant histopathological and molecular changes when compared to the control group. However, only in the group with four plasma instillations there was a macroscopic change. The idea is that repeatedly extravasation of TGF‐β present in plasma of predisposed individuals acts as a trigger for the development and maintenance of changes in the extracellular matrix that perpetuate an anomalous inflammatory process present in PD. Conclusion: The present study shows that the repeated instillation of plasma is a low cost in vivo model for the study of PD. [ABSTRACT FROM AUTHOR]

Zebrafish have gained momentum as a leading experimental model in recent years. At present, the zebrafish vertebrate model is increasingly used due to its multifactorial similarities to humans that include genetic, organ, and cellular factors. With the emergence of novel research techniques that are very expensive, it is necessary to develop affordable and valid experimental models. This review aimed to highlight some of the most important similarities between zebrafish and humans by emphasizing the relevance of the first in simulating neurological disorders and craniofacial deformity. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to evaluate the effect of metformin as well as the possible role of Matrix metalloproteinase2 (MMP2) and oxidative stress parameters on the prostate cancer model. Materials and Methods: Male Copenhagen rats were divided into three groups. Control group, cancer group, cancer+metformin (CM) group. 2x104 Mat-LyLu cells were inoculated subcutaneously to generate prostate cancer. Metformin treatment was administered daily by gavage following inoculation of the Mat- Lylu cells. The experiment was terminated on the 14th day following MatLyLu cell injection. Serum glutathione (GSH), prostatespecific antigen (PSA), and malondialdehyde (MDA) levels were determined by employing the Enzyme-Linked ImmunoSorbent Assay (ELISA) method. In addition, the serum matrix metalloproteinase (MMP) 2 activities were determined via ELISA. Results: GSH was significantly increased in the CM group than in the cancer group. PSA, MDA and MMP2 were significantly lower in the CM group than in the cancer group. Oxidative stress parameters were significantly higher in the cancer group. Metformin reversed cancer’s effect in GSH, PSA, MDA, and MMP2 parameters. Conclusion: Prostate cancer model caused a detrimental effect on MMP and oxidative stress parameters, and metformin administration ameliorated the changes caused by cancer. Metformin showed its mechanism of action by inhibiting free radical products originating from prostate cancer and changing the antioxidant capacity. Metformin is a candidate to be a potential anticancer drug in the therapeutic cancer treatment process. [ABSTRACT FROM AUTHOR]

[Display omitted] • The effects of aging on the adrenal gland of Mongolian gerbil have been described. • Aging causes hypertrophy in the fasciculata and reticularis zones of the adrenal. • Aging causes an accumulation of lipofuscin granules in the adrenal cortex. • An experimental model for endocrinology studies has been described. The adrenal gland produces steroid hormones that act in the homeostasis of organisms. During aging, alterations in the hormonal balance affect the adrenal glands, but these have not yet been fully described due to the lack of adequate animal models. The adrenal gland of the Mongolian gerbil has a morphology similar to the primate's adrenal gland, which makes it a possible animal model for endocrine studies. Therefore, the current study aimed to study the morphophysiology of the adrenal gland under the effect of aging. For this purpose, males Meriones unguiculatus , aged three, six, nine, twelve, and fifteen months were used. Morphometric, immunohistochemical, and hormonal analyses were performed. It was observed that during aging the adrenal gland presents hypertrophy of the fasciculata and reticularis zones. Lipofuscin accumulation was observed during aging, in addition to changes in proliferation, cell death, and cell receptors. The analyses also showed that the gerbil presents steroidogenic enzymes and the production of steroid hormones, such as DHEA, like that found in humans. The data provide the first comprehensive assessment of the morphophysiology of the Mongolian gerbil adrenal cortex during aging, indicating that this species is a possible experimental model for studies of the adrenal gland and aging. [ABSTRACT FROM AUTHOR]

In this paper, the relationship between corrosion of prestressing steel strand and the corresponding induced cracking in concrete was investigated. Twelve prestressed concrete beams were cast in a precast/prestress concrete plant with various parameters including prestress level, concrete cover, strand diameter, and water-cement ratio. The beams were subjected to impressed current for different periods of time to accelerate corrosion of strands. Concrete cracks induced by corrosion of strands were monitored and recorded in terms of crack distribution and width. After obtaining the desired levels of corrosion, the beams were demolished to obtain the corroded strands and analyze their mass loss and pits. The corrosion pitting depth was studied against two stages of concrete cracking: initiation and propagation. The results showed that the effect of cover-diameter ratio on pitting depth is significant at concrete cracking initiation and marginal at propagation stage. The water-cement ratio had a significant effect on concrete cracking induced by strand corrosion at cracking initiation and propagation. The prestress of strand appeared to have a moderate influence on cracking of concrete, especially at initiation. An experimental model, including the significant influential parameters, that can be used to predict the corrosion pitting depth by observing and measuring the concrete crack width, was developed. Using this model, an empirical equation to estimate the residual cross-sectional area of corroded strands in prestressed concrete members was established. • The dominant corrosion of prestressing strands in concrete was the pitting corrosion. • Corrosion crack width can serve as an indicator of the strand corrosion damage. • Prestressing accelerates the initiation of corrosion concrete cracking and increases the propagation rate of cracking. • Proposed models were developed for predicting corrosion pitting depths at concrete cracking initiation and propagation. [ABSTRACT FROM AUTHOR]