Macroscopic Index Research Articles

Refined evaluation methods for preventive maintenance of project-level asphalt pavement based on confusion-regression model

Accurate evaluation of the performance of airport pavement can help managers make scientific and systematic preventive maintenance (PM) decisions, ensuring pavement safety and extending service life. To this end, firstly, this paper sorted out the pavement performance evaluation index system, based on which a multi-dimensional evaluation system for PM was proposed, including control indexes, macroscopic indexes, and microscopic indexes. Then, the pavement decay model based on the pavement condition index (PCI) was developed, and the regression model between PCI and International roughness index (IRI) and friction coefficient (μ) was established. Finally, by converting the PM decisions for project-level pavement into a binary classification problem in machine learning, the optimal maintenance thresholds and intervals for PM of each index were determined using receiver operating characteristic (ROC) curve and Kolmogorov-Smirnov (K-S) curve. The optimal threshold represents the threshold when the index can separate the binary classification problem (PM decisions) with maximum probability. Based on confusion-regression model, the pavement performance can be evaluated more comprehensively, and the timing of PM can be accurately determined. The model helps airport managers develop accurate PM plans to address future maintenance needs.

Gastroprotective effect of the flavonoid fustin isolated from Cotinus coggygria heartwood in a rat model of indomethacin-induced gastric ulceration

Abstract Gastric ulcer is a common health issue. Cotinus coggygria heartwood extracts rich in the flavonoids fustin and sulfuretin have shown protective effects in a rat model of indomethacin-induced gastric ulceration. Fustin itself has been protective in a rat model of ethanol-induced gastric ulcer. In the present study we aimed to reveal the effect of the flavonoid fustin isolated from Cotinus coggygria heartwood in a rat model of indomethacin-induced gastric ulceration. Fustin was isolated from Cotinus coggygria heartwood and purified. The experiment was performed on 30 male Wistar rats allocated to three groups – Control, Indo and F10. F10 group was pretreated with fustin (10 mg/kg b.w. for 7 days). Rats were sacrificed and macroscopic, histopathological and immunohistochemical investigations of the stomachs were performed. Indomethacin caused severe mucosal damage, proven by the macroscopic, microscopic and immunohistochemical gastric mucosa investigation. Fustin pretreatment slightly reduced the macroscopic indices for gastric damage (ulcer number, area, score and index), and significantly alleviated the severity of the microscopic indices (mucosal erosions, necrosis, hemorrhages and inflammation). In fustin-pretreated rats, the expression of NF-κB was reduced in comparison with indomethacin-treated animals. In conclusion, fustin exerted a gastroprotective action in an indomethacin-induced gastric ulceration model, probably due to its anti-inflammatory activity.

The Modification Mechanism, Evaluation Method, and Construction Technology of Direct-to-Plant SBS Modifiers in Asphalt Mixture: A Review

To further promote the development of research on direct-to-plant SBS-modified asphalt, this article analyzes the development of direct-to-plant SBS modifiers. Starting from the material composition and mechanism of action, common direct-to-plant SBS modifiers were analyzed and classified into four categories based on their mechanism of action, including the instant dissolution principle, intramolecular lubrication principle, non-granulation principle, and vulcanization principle. From the evaluation of the modification effect, the method of studying the performance of direct-to-plant SBS-modified asphalt is summarized, including fluorescence microscopy, AFM technology, and molecular dynamics simulation technology. From the perspective of practical application, the construction process of direct-to-plant SBS-modified asphalt was discussed, including the design stage, raw material preparation stage, mix design stage, and on-site construction stage. The results show that common direct-to-plant SBS modifiers are primarily SBS with a small particle size (less than 200 mesh) or specific model, supplemented by additives (EVA, naphthenic oil, sulfur, petroleum resin, etc.), which improve melting efficiency and lubricity or make it undergo vulcanization reaction, change the proportion of asphalt components, and improve stability. In the evaluation of the modification effect of direct-to-plant SBS-modified asphalt, the disparity of the direct-to-plant SBS modifier is determined by observing the particle residue after dry mixing. Macroscopic indexes of modified asphalt and modified asphalt mixture are used to determine the cross-linking effect of direct-to-plant SBS modifier and asphalt, and the modification mechanism and modification effect of wet SBS modifier are evaluated at the microscopic level. The development of direct-to-plant SBS-modified asphalt should combine the characteristics of direct-to-plant SBS modifiers and the attributes of field application, targeted research, and the development of high-performance direct-to-plant SBS modifiers and complete production technologies applicable to different regions, strengthen the improvement of modification effect evaluation, and form a complete theoretical system.

Alternanthera brasiliana (L.) Kuntze decreases pain and inflammation in acute colitis model without hepatotoxicity

Objectives: To investigate antinociceptive and anti-inflammatory activities of the keto-alcoholic extract of A. brasiliana leaves in a mice model of acute colitis. Methods: The experiments were performed in Swiss mice; the keto-alcoholic extract of A. brasiliana leaves was prepared and flavonoids were quantified. The antinociceptive/analgesic activity was evaluated by the writhing test. The keto-alcoholic extract of A. brasiliana, saline and Dipyrone monohydrate were tested. Acute colitis was induced by 7.5% (v/v) acetic acid intrarectally and the animals were treated, by gavage, with keto-alcoholic extract of A. brasiliana, saline and Mesalazine. After euthanasia, intestinal segments of the mice were analyzed by macroscopic index and quantification of colonic edema. The mechanical hyperalgesia test was performed after induction of acute colitis with acetic acid and treatment of the mice using the electronic Von Frey test. Hepatotoxicity of the keto-alcoholic extract of A. brasiliana was tested by plasma dosage of the aspartate transaminase (AST) and alanine transaminase (ALT) enzymes. Data were analyzed by ANOVA followed by Tukey post-test considering P < 0.05 as significant. Results: In vivo results indicate that mice treated with the keto-alcoholic extract of A. brasiliana leaves at 100 and 300 mg/kg (0.872 and 2.616 mg total flavonoids/kg) showed a significant decrease in the number of writhing compared to the negative control. Between the two concentrations that were shown to be effective, no significant difference was observed. The Von Frey test points that mice treated with A. brasiliana extract at 30 (0.2616 mg of total flavonoids/kg), 100 and 300 mg/kg showed greater hyperalgesia. Regarding colitis, the mice treated with keto-alcoholic extract of A. brasiliana leaves at 10, 30, 100 and 300 mg/kg showed no lesions or lower-grade lesions when compared to the untreated group. In the quantification of edema no significant difference was observed among any experimental group. Plasma AST and ALT values were within normal reference values indicating no liver damage by the extract. Conclusion: The keto-alcoholic extract of A. brasiliana shows antinociceptive/analgesic and anti-inflammatory activity in an acute colitis model in mice without causing hepatotoxicity in the mice.

Lafoensia pacari alleviates intestinal damage by modulating cyclooxygenase-2: In silico and in vivo evaluation in a colitis model.

Inflammatory bowel diseases (IBD) are a worldwide health problem and mainly affect young people, consequently affecting the workforce. Available treatments are often associated with side effects, and new therapeutic options are needed. For centuries, plants have represented important substrates in the field of drug development. Lafoensia pacari (L. pacari) is a plant whose pharmaceutical potential has been described, and may have biological activity relevant to the treatment of IBD symptoms. To investigate the activity of keto-alcoholic extracts of L. pacari with respect to ameliorating the inflammatory and nociceptive symptoms of acute experimental colitis in mice. Keto-alcoholic extracts of L. pacari leaves and bark were administered to male and female Swiss mice weighing 25 g to 30 g (n = 8 male mice and n = 8 female mice). The effect of these extracts was observed in an acetic acid-induced acute experimental model of colitis with regard to antinociception/analgesia and inflammatory tissue damage. Recorded macroscopic indices included the Wallace score and the colon weight obtained using a precision scale. Mechanical hyperalgesia was determined using an electronic analgesimeter. Behavior related to overt pain was determined by quantifying the number of writhing instances within 20 min of administration of acetic acid. Molecular docking was performed using human and murine cyclooxygenase-2 (COX-2) with 3 flavonoids (ellagic acid, kaempferol, and quercetin) on the AutoDock Vina software. Analysis of variance followed by Tukey's posttest was used with P < 0.05 indicating significance. In this murine model of colitis, administration of extracts from L. pacari ameliorated acetic acid-induced writhing and colitis-associated inflammatory pain. These improvements may be attributable to the reduction in edema, inflammation (e.g., ulcers, hyperemia, and bowel wall damage), and the intensity of abdominal hyperalgesia. The keto-alcoholic extracts of L. pacari leaves and bark administered at a dose of either 100 mg/kg or 300 mg/kg significantly reduced the number of writhing events when compared to the negative control (P < 0.05). Additionally, extracts of L. pacari bark also performed better than Dipyrone. Leaf extracts administered at 10 mg/kg, 30 mg/kg, and 100 mg/kg and bark extracts administered at 30 mg/kg significantly reduced or prevented the development of edema in the colon of treated mice, while mesalazine did not. Moreover, using molecular docking, we observed that the flavonoids present in L. pacari extracts bind to COX-2, an event not unique to ellagic acid. The results of this study demonstrate a potential novel application of L. pacari extracts for the reduction of inflammation and promotion of antinociception/analgesia as demonstrated by our findings in a murine model of colitis. These findings were also corroborated by in silico analyses, and suggest that L. pacari extracts may be a promising therapeutic agent in the treatment of IBD.

Interrelationships among Adjustable Design Parameters and Rate Performance of Porous Electrodes in Lithium‐Ion Batteries

A combination of experiments and physics-based modeling is used to highlight the complex interaction among the adjustable design parameters of porous electrodes in determining the capacity and rate performance of lithium-ion batteries (LIBs). A series of 52 LiMn2O4 electrodes are prepared with loading and porosity in the range of 10 to 30 mg cm−2 and 0.2 to 0.5, respectively, and cycled at different C-rates in front of Li. A detailed polarization analysis of the 96 discharge profiles points to the absence of any ubiquitous sharp and universal correlation between the lumped macroscopic indexes such as the electrode thickness and the battery performance. The results call for a careful attention to the nonlinear response of the LIBs to the design variations and the significance of big data analysis to reveal the peculiar interrelationships between the battery performance and the detailed features of the electrodes such as the configuration and spatial distribution of the (in)active particles.

Quantitative anatomy or macroscopic parameters of compression wood of Picea abies (L.) H. Karst.? Defining the optimal parameters for dendrogeomorphic purposes

Summary The quantification of the intensities of tree growth responses to the impact of geomorphic processes is a modern research trend in dendrogeomorphology. It enables a more sensitive assessment of the activity of the studied geomorphic process compared to the traditional use of growth disturbances. The advanced definitions of individual intensity classes of growth disturbances are based exclusively on macroscopic observations. This study evaluates the possibility of anatomical quantification of compression wood (CW) intensity in the case of common spruce (Picea abies (L.) Karst.) and compares it with subjective macroscopic evidence of CW with respect to stem tilting intensity. In total, 25 disturbed (tilted) individuals of P. abies occupying a landslide active during July 1997 were sampled, and 21 of them were analysed. The intensity of external disturbance (stem tilting) was compared against the macroscopic (intensity and duration) and microscopic (quantitative change of the tracheid lumen area and the cell wall proportion) parameters of compression wood suitable for practical application in common dendrogeomorphic analysis. Generally, the macroscopic indices of CW were strongly correlated with stem tilting. The intensity of the anatomical growth response was stronger in the earlywood zone than in the latewood zone. Nevertheless, their dependence on stem tilting was not detected. Results suggest that CW classification based on the quantification of anatomical changes is not possible for dendrogeomorphic purposes. Nevertheless, based on the obtained results, the present study suggests preferring the most intensively tilted trees during future dendrogeomorphic research to obtain the most intensive macroscopic and subjective observable anatomical evidence for studying compression wood.

Dioscin promotes autophagy by regulating the AMPK-mTOR pathway in ulcerative colitis

Background Dioscin is reported to alleviate the dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice. Autophagy plays an anti-inflammatory role in UC. We herein aimed to explore the biological functions of dioscin in autophagy in UC. Methods To explore the effects of dioscin on UC progression, a DSS-induced mouse model of UC was established. Body weight, disease activity index and macroscopic damage index scores were recorded for seven days. Hematoxylin & Eosin (HE) staining was used to stain colon sections and an BX53 microscope was prepared to observe pathological changes. The activities of glutathione, superoxidative dismutase, and malondialdehyde were determined by commercially available kits. Western blotting was performed to measure the protein levels of p-AMPK/AMPK, p-mTOR/mTOR and autophagy-related genes. Results The DSS-induced colitis and oxidative stress in mice were ameliorated after dioscin treatment. Dioscin promoted the phosphorylation of AMPK to inhibit mTOR activation and facilitated autophagy in DSS-induced mice model of UC. Conclusion Dioscin promotes autophagy by promoting the phosphorylation of AMPK to inhibit mTOR activation in ulcerative colitis.

Prediction and Optimization of the Cost of Energy Resources in Greek Public Hospitals

The continuous operation and the specialized conditions needed for safely delivering healthcare services make hospitals among the most expensive buildings. Several studies in different countries have investigated the potential role and contribution of macroscopic indices of hospitals in total energy requirements. In this work, we tried to investigate the energy requirements of Greek hospitals in terms of cost. We collected data from all public hospitals in Greece over a 2 year period (2018–2019) and evaluated the contribution of various factors in the total energy cost. The data revealed large variability by region and by hospital, even regarding structures of the same category and size. The analysis also showed that structural and operational data of each hospital differently influence the hospitals’ energy requirements. Using regression methods, we developed two models for calculating annual energy costs. One only contains hospital structural data (number of beds, type of hospital, number of employees, and the non/use of alternative energy sources such as natural gas), and it reached an R² of 0.84. The second model contains not only structural but also operational data from each hospital (number of the internal patients, number of surgeries and number of medical imaging tests), and it reached an R² of 0.87. The former model is easier to compute since it only relies on data that can be easily gathered, but the latter has slightly better performance. These tools can help the Ministry of Health and hospitals’ management to identify the factors that contribute to the energy cost in order to plan targeted interventions, be well-prepared regarding budgeting, and be able to progressively measure, monitor, and improve the environmental footprint of hospitals by investing in renewable energy resources.

Comparative analysis of thermal aging behavior and comprehensive performance of high viscosity asphalt (HVA) from cohesion, adhesion and rheology perspectives

High viscosity asphalt (HVA) has been widely utilized in the paving of large-void asphalt pavement, and it will be affected by thermal aging and exhibit different pavement performance. In this study, through a series of macroscopic and microscopic experiments, the change behaviors of cohesion, adhesion, high- and low-temperature rheological properties, microscopic phase structure and functional groups of HVA under different thermal aging conditions were first analyzed—in comparison with the three asphalts viz. styrene-butadienestyrene (SBS) modified asphalt (SBSMA), crumb rubber modified asphalt (CRMA) and neat asphalt (NA). Further, the relationship between macro-micro properties of asphalt binders was investigated by grey correlation theory, and the comprehensive performance of HVA at different aging stages and its aging resistance were contrastively evaluated via using radar chart analysis method. Results showed that aging degraded the cohesion and adhesion of asphalt binders as well as the water stability of asphalt-aggregate systems, and weakened the low-temperature property of asphalt binders—compared to the unaged sample, the short- and long-term aging reduced the cohesion work of HVA by 1.10% and 3.41%, respectively, and decreased the water stability index of HVA-limestone system by 0.54% and 1.86%, respectively. However, the variations of viscoelastic properties, temperature sensitivity, creep recovery ability and rutting resistance of HVA under aging were inconsistent with those of SBSMA, CRMA and NA. Aging decreased the microscopic surface roughness Ra of HVA and altered the intensity of functional groups at different wavenumbers, and the short- and long-term aging diminished its Ra by 21.26% and 37.85% compared to the unaged sample, respectively. Grey correlation analysis showed that the microscopic surface roughness Ra and the functional group indexes at different wavenumbers correlated well with several macroscopic indexes, which successfully explicated the variations of macroscopic properties of HVA from the micro perspective. Radar chart analysis displayed that the comprehensive performance of HVA in the original and short-term aging stages was second only to CRMA, but its comprehensive performance after long-term aging was only superior to NA; overall, HVA exhibited the most favorable anti-aging performance.

Nonlinear Simulation and Vulnerability Analysis of Masonry Structures Impacted by Flash Floods

The vulnerability of buildings impacted by flash floods is often assessed by empirical approaches. However, the damage-developing mechanisms of buildings remain unclear. This study presented a nonlinear numerical analysis for the interaction between flash floods and masonry structures. A new Structured ALE (S-ALE) solver in an explicit finite element platform LS-DYNA was applied. Thirty different scenarios, including two different FE models, three different water depths, and five different flow velocities, were studied. Nonlinear structural responses and failure mechanisms of masonry structures were analyzed and compared. Results showed that due to the consideration of wall damage, the time evolution of the impact force on the entire building was distributed in a multipeak pattern. Under the impact of flash floods, the building was in a complex bending-shear state, and the overturning moment was the principal reason for the building damage. The critical role played by the structural measure was reaffirmed. Moreover, the physical vulnerability was quantified through a macroscopic damage index, the lateral drift ratio of the ground floor. It can be concluded that the physical vulnerability depends on both the local structural strength (local view) and the structural resistance hierarchies (global view).

Relation Between Adhesion Properties and Microscopic Characterization of Polyphosphoric Acid Composite SBS Modified Asphalt Binder

The purpose of this study was to investigate the adhesive properties of polyphosphoric acid compounded SBS (PPA/SBS) modified asphalt. Three base asphalt binders, one SBS, one dibutyl phthalate (DBP), one furfural extraction oil, and two polyphosphoric acids (PPA), were used to produce the modified binders. The adhesive properties tested in this study included contact angle, cohesive work, adhesive work, and peak area ratio. Cohesive work and adhesive work indicators were calculated from the contact angle, the contact angle between PPA/SBS modified asphalt and three liquids (distilled water, glycerin, formamide) were tested by the contact angle tester, and the peak area ratio of the microscopic adhesion performance index by AFM. The relation between the microscopic adhesion performance characterization method (peak area ratio) and the macroscopic adhesion performance index (cohesive work, adhesion work) was established. The test results indicated that the PPA/SBS modified asphalt had the highest cohesive work and adhesion work under the conditions of 0.5% PPA, 1% DBP, 1.5% extracted oil, and 3.5% SBS, which was clearly greater than the original SBS modified asphalt, while the peak area ratio was consistent with the cohesive work and adhesive work, in which the correlation coefficient between the peak area ratio and cohesive work was 0.77788, and that between the peak area ratio and adhesion work was 0.87203. We recommend adopting the peak area ratio to characterize PPA/SBS modified asphalt’s microscopic adhesion properties.

Research on the performance changes of the binder of the wear layer of open-graded asphalt mixture under different aging methods

In order to study the effect of asphalt aging of open-graded friction course (OGFC) on the performance of high-viscosity styrene-butadiene-styrene(SBS) modified asphalt during the mixing of the asphalt mixtures and the whole life cycle, Thin Film Oven Test (TFOT), Rolling Thin Film Oven Test (RTFOT), and Pressurized Aging Vessel Accelerated Asphalt Aging Test (PAV) were used to conduct aging tests on the high-viscosity SBS modified asphalt. And then the aging of SBS modified asphalt is studied at two levels: microscopic and macroscopic. In the microscopic aspect, first use the fluorescence microscope technology to image the asphalt samples before and after aging. The above images were processed by MATLAB and Image-pro plus software, and the micro-structures of high viscosity SBS modified asphalt before and after aging were obtained. At the same time, use the DSR test to observe the changes in the rheological properties of the SBS modified asphalt before and after aging. On the macro level, the softening point, viscous toughness and pull strength are used to analyse the changes in the mechanical properties of the high-viscosity SBS modified asphalt before and after aging, and the aging conditions of the SBS modified asphalt under the micro and macro indexes are compared. The research shows that after short-term aging (simulation of asphalt aging during the mixing ), RTFOT and TFOT the loss ratio of SBS in modified asphalt are at 78.5% and 68.3%, respectively, the degradation of SBS in modified asphalt is serious, and the SBS modified asphalt aging conditions under the macro and micro indicators are consistent. After long-term aging (simulating the aging of the asphalt during the whole life cycle), the loss ratio of SBS in modified asphalt is 83.4% (RTFOT + PAV) and 84.6% (TFOT + PAV). However, the macroscopic index of SBS modified asphalt shows obvious differences. The aging degree of SBS modified asphalt using RTFOT + PAV aging method is significantly higher than that of TFOT + PAV aging method, indicating that the performance of SBS modified was affected at the degradation of SBS during long-term aging, it is also significantly affected by the aging of the basic asphalt itself. Therefore, when mixing OGFC asphalt mixtures, the mixing time should be strictly controlled, and the mixing time should not be extended. OGFC asphalt mixtures should be maintained properly in time to keep their excellent road performance.

Improvement of soft clay by vacuum preloading incorporated with electroosmosis using electric vertical drains

Vacuum preloading combined with electroosmosis (VE) has a good drainage effect, but electric vertical drains (EVDs) as the drainage plate and electrode will cause the offset of water flow near the anode. Therefore, there is an alternate time for the optimal use of the two methods. In this paper, some macroscopic indexes were monitored through laboratory tests to explore the optimal alternate time of the two methods in the drainage stage, and the microscopic characteristics of the soil after treatment were explored through scanning electron micrographs and X-ray diffractometer tests. The results indicated that the alternating time of vacuum preloading and an electroosmosis time of 100 min can obtain a better drainage effect in the early stage. The vacuum preloading time of the alternate forms should be prolonged to 550 min during the later stages. The electroosmosis duration should not be too long, which was limited to 100 min in all the electroosmosis stages.

Mechanisms of ivermectin-induced wound healing

BackgroundWounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques.ResultsNon-irritant dose of ivermectin cream (0.03–1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-β1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03–0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine.ConclusionIvermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation.

An Evaluation Method for the Skeleton Structure of Cement-Stabilized Crushed Rock Material Using X-Ray CT Images

Abstract No appropriate or accurate skeleton evaluation indexes currently exist for cement-stabilized crushed rock materials (CCRMs). To establish new skeleton evaluation indexes for a CCRM, different skeleton tightness–influenced regions of coarse aggregates were defined and compared to accurately capture the degree of tightness of a skeleton based on computed tomography images. The skeleton denseness index (φ¯) and skeleton stability index (φ¯) were proposed. Moreover, φ¯ was used to evaluate a CCRM that was compacted using the vertical vibration compaction method (VVCM) with different gradations to verify its feasibility. The meso-skeleton and macroscopic indexes (maximum dry density and compressive strength) of a CCRM with different compaction methods and vibration times, along with a field CCRM, were measured and compared. The results show that a range with twice the equivalent radius is rational as the influenced region. The φ¯ of a CCRM compacted using VVCM decreases as the gradation becomes finer, revealing that φ¯ can capture a CCRM skeleton. A CCRM compacted using a quasistatic compaction method has smaller meso-skeleton and macroscopic indexes than a CCRM using VVCM or a field CCRM; all indexes of the CCRM applying VVCM increase as the vibration time increases, whereas the growth rate slows. The results of vibration compaction (90 s) for CCRM match the common outdoor compaction results when constructing semirigid bases (common gradation and cement dosage) in Guangdong Province, China. Moreover, a strong correlation exists between meso-skeleton evaluation indexes and the compressive strength for a 7-day period.

Protective Effect of Thalidomide on 2,4,6-Trinitrobenzenesulfonic Acid-Induced Experimental Colitis in Rats via the Inhibition of T Helper 17 Cells

Objective To observe the effects of thalidomide on 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced experimental colitis in rats and to explore the possible mechanism of thalidomide in the treatment of CD. Methods Forty SD rats were randomly assigned into a healthy control group and TNBS-induced colitis groups, including an untreated TNBS-induced colitis group, a low-dose thalidomide group, and a high-dose thalidomide group, with 10 rats in each. After 7 days, the disease activity index (DAI), colon macroscopic damage index (CMDI), and tissue damage index (TDI) were evaluated. The colonic protein and mRNA expression levels of interleukin-6 (IL-6), IL-17, IL-23, and retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt) were determined using immunohistochemistry, western blot, and qRT-PCR. Results Relative to the untreated TNBS-induced colitis group, the DAI, CMDI, and TDI were all reduced following the administration of thalidomide. Analytical testing (immunohistochemistry, western blot, and qRT-PCR) shows that IL-6, IL-17, IL-23, and RORγt protein and mRNA expression levels were significantly reduced by thalidomide (p < 0.05 for all) and that these levels were significantly lower in the high-dose thalidomide group than in the low-dose thalidomide group (p < 0.05 for all). Conclusions Thalidomide effectively alleviated the symptoms and intestinal inflammatory injury induced by TNBS in rats, the effect of which was dose-dependent. The underlying mechanism may be a reduction in the expression levels of IL-6, IL-17, IL-23, and RORγt in colonic tissue and then subsequent inhibition of the differentiation and function of Th17 cells, thus further alleviating the intestinal inflammatory response.

Methodology to Evaluate the Quality of Service of Traffic Flow on Intercity Expressway Sections by using Follower Percentage

This study estimated composite headway distributions consisting of follower and non-follower headway elements and used the follower percentage obtained as the estimated parameters of those distributions to evaluate the quality of service (QOS) of traffic flow on Japanese intercity expressways under uncongested conditions. Analysis of pulse data obtained by vehicle detectors at multiple points with differing geometric structures showed that follower percentage is influenced by lane traffic volume, vehicle pair, and lane operation. Use of follower percentage also enabled clear and quantitative comparison and evaluation of the QOS of traffic flow for different lane operation formats, which could not be adequately expressed by such conventional macroscopic indices as average speed and traffic density. This indicates that follower percentage is a suitable performance measure for evaluating the QOS of traffic flow.

P098 Receptor-interacting protein 1 kinase inhibition therapeutically ameliorates experimental T-cell-dependent colitis in mice

Abstract Background Inflammatory bowel disease (IBD) is a multifactorial disorder characterised by chronic and relapsing intestinal inflammation. Receptor-interacting protein 1 (RIP1) kinase activity is emerging as a driver of pro-inflammatory cytokine production and cell death and has been implicated in multiple inflammatory diseases including IBD. To this end, recent work has shown that RIP1 kinase inhibition reduces the spontaneous production of cytokines from human ulcerative colitis (UC) and Crohn’s disease explants. Methods The aim of this study was to investigate the anti-inflammatory effect of a highly selective inhibitor of RIP1 kinase activity (GSK547A) in the mouse T-cell transfer model of colitis; a model that shares many features with human IBD. All animal studies were ethically reviewed and carried out in accordance with Animals (Scientific Procedures) Act 1986 and the GSK Policy on the Care, Welfare and Treatment of Animals. Chronic colitis was achieved by transferring CD4+CD45RBhigh T cells into immunodeficient female SCID mice (6/8 weeks old). After confirming the development of pathology using endoscopy and MRI, animals were treated therapeutically with the RIP1 inhibitor GSK547A (50 mg/kg twice a day PO) or vehicle (0.5% hydroxypropyl methylcellulose in water). The severity of colitis was measured 5 weeks after cell transfer both macro- and microscopically. Mucosal damage by endoscopy was also assessed. RT-PCR and MSD analysis were performed to detect colon cytokine/chemokine and calprotectin levels. SAA in the plasma was measured using ELISA. Results We found that treatment with GSK547 significantly ameliorated experimental T-cell-dependent colitis in mice. GSK547A-treated mice displayed decreased weight loss, colon density (ratio weight/length), macroscopic disease activity index, colon thickness compared with vehicle-treated animals. Mucosal damage, assessed by endoscopy and histopathology, was also reduced following treatment with RIP1 kinase inhibitor. In addition, GSK547A reduced the expression of cytokines in the colon (TNF-α, IL-17A, INF-γ, IL-6 and MCP-1), both at a protein and RNA level. Relevant translational biomarkers such as SAA in plasma and RNA calprotectin in the colon were also decreased in the GSK547A treated group when compared with vehicle. Conclusion Our results suggest that RIP1K inhibition is a strong protective factor with anti-inflammatory potential in the progression of chronic colitis, when applied to the translationally relevant T-cell transfer model of colitis. These findings suggest the potential application in the management of inflammatory bowel disease and support the ongoing clinical program evaluating the effect of RIP1 kinase inhibition in UC patients.

Revisiting the value of polysomnographic data in insomnia: more than meets the eye

BackgroundPolysomnography (PSG) is not recommended as a diagnostic tool in insomnia. However, this consensual approach might be tempered in the light of two ongoing transformations in sleep research: big data and artificial intelligence (AI). MethodWe analyzed the PSG of 347 patients with chronic insomnia, including 59 with Sleep State Misperception (SSM) and 288 without (INS). 89 good sleepers (GS) were used as controls. PSGs were compared regarding: (1) macroscopic indexes derived from the hypnogram, (2) mesoscopic indexes extracted from the electroencephalographic (EEG) spectrum, (3) sleep microstructure (slow waves, spindles). We used supervised algorithms to differentiate patients from GS. ResultsMacroscopic features illustrate the insomnia conundrum, with SSM patients displaying similar sleep metrics as GS, whereas INS patients show a deteriorated sleep. However, both SSM and INS patients showed marked differences in EEG spectral components (meso) compared to GS, with reduced power in the delta band and increased power in the theta/alpha, sigma and beta bands. INS and SSM patients showed decreased spectral slope in NREM. INS and SSM patients also differed from GS in sleep microstructure with fewer and slower slow waves and more and faster sleep spindles. Importantly, SSM and INS patients were almost indistinguishable at the meso and micro levels. Accordingly, unsupervised classifiers can reliably categorize insomnia patients and GS (Cohen's κ = 0.87) but fail to tease apart SSM and INS patients when restricting classifiers to micro and meso features (κ=0.004). ConclusionAI analyses of PSG recordings can help moving insomnia diagnosis beyond subjective complaints and shed light on the physiological substrate of insomnia.