4-Octyl itaconate inhibits inflammation via the NLRP3 pathway in neuromyelitis optica spectrum disorders.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) are rare inflammatory astrocytic diseases of the central nervous system (CNS). The roles of immune response gene-1 (IRG1) and the IRG1-itaconic acid-NLRP3 inflammatory pathway in the pathogenesis of NMOSD and the effects of 4-octyl itaconate (4-OI) on the NLRP3 inflammatory pathway in NMOSD are unclear. This study aimed to determine the role of IRG1 and the activation status of the NLRP3 inflammatory pathway in acute-onset NMOSD and to investigate the inhibitory effects of 4-OI on NLRP3 inflammasome activation via the IRG1-itaconic acid-NLRP3 pathway in monocytes and macrophages by using in vitro models. METHODS: Peripheral blood mononuclear cells (PBMCs) and serum were collected from patients with acute NMOSDs and healthy controls (HC), followed by monocyte typing and detection of the expression of NLRP3-related inflammatory factors. Subsequently, the effects of 4-OI on the IRG1-itaconic acid-NLRP3 pathway were investigated in peripheral monocytes from patients with NMOSD and in macrophages induced by human myeloid leukemia mononuclear cells (THP-1 cells) via in vitro experiments. RESULTS: Patients with acute NMOSD exhibited upregulated IRG1 expression. In particular, the upregulation of the expression of the NLRP3 inflammasome and proinflammatory factors was notable in monocytes in acute NMOSD patients. 4-OI inhibited the activation of the IRG1-itaconic acid-NLRP3 inflammatory pathway in the PBMCs of patients with NMOSD. INTERPRETATION: 4-OI could effectively inhibit NLRP3 signaling, leading to the inhibition of proinflammatory cytokine production in patients with NMOSD-derived PBMCs and in a human macrophage model. Thus, 4-OI and itaconate could have important therapeutic value for the treatment of NMOSD in the future.

Bibliometric and visualization analysis of risk management in the doctor-patient relationship: A systematic quantitative literature review.

OBJECTIVES: This paper analyzed the research on risk management in the doctor-patient relationship (DPR) based on a systematic quantitative literature review approach using bibliometric software. It aims to uncover potential information about current research and predict future research hotspots and trends. METHODS: We conducted a comprehensive search for relevant publications in the Scopus database and the Web of Science Core Collection database from January 1, 2000 to December 31, 2023. We analyzed the data using CiteSpace 6.2.R2 and VOSviewer 1.6.19 software to examine the annual number of publications, countries/regions, journals, citations, authors, and keywords in the field. RESULTS: A total of 553 articles and reviews that met the criteria were included in this study. There is an overall upward trend in the number of publications issued; in terms of countries/regions, the United States and the United Kingdom are the largest contributors; Patient Education and Counseling is the most productive journal (17); Physician communication and patient adherence to treatment: a meta-analysis is the most cited article (1637); the field has not yet to form a stable and obvious core team; the analysis of high-frequency keywords revealed four main research directions: the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the causes of DPR risks, coping strategies, measurement tools, and research related to people prone to doctor-patient risk characteristics; the keyword burst analysis revealed several shifts in the research hotspots for risk management in the DPR, suggesting that chronic disease management, is a future research direction for the continued development of risk management in the DPR. CONCLUSIONS: The visualization analysis of risk management literature in the DPR using CiteSpace and VOSviewer software provides insights into the current research status and highlights future research directions.

Risk management and empirical study of the doctor-patient relationship: based on 1790 litigation cases of medical damage liability disputes in China.

BACKGROUND: Compensation for medical damage liability disputes (CMDLD) seriously hinders the healthy development of hospitals and undermines the harmony of the doctor-patient relationships (DPR). Risk management in the DPR has become an urgent issue of the day. The study aims to provide a comprehensive description of CMDLD in China and explore its influencing factors, and make corresponding recommendations for the management of risks in the DPR. METHODS: This study extracted data from the China Judgment Online - the official judicial search website with the most comprehensive coverage. Statistical analysis of 1,790 litigation cases of medical damage liability disputes (COMDLD) available from 2015 to 2021. RESULTS: COMDLD generally tended to increase with the year and was unevenly distributed by regions; the compensation rate was 52.46%, the median compensation was 134,900 yuan and the maximum was 2,234,666 yuan; the results of the single factor analysis showed that there were statistically significant differences between the compensation for different years, regions, treatment attributes, and trial procedures (P < 0.05); the correlation analysis showed that types of hospitals were significantly negatively associated with regions (R=-0.082, P < 0.05); trial procedures were significantly negatively correlated with years (R=-0.484, P < 0.001); compensat- ion was significantly positively correlated with years, regions, and treatment attributes (R = 0.098-0.294, P < 0.001) and negatively correlated with trial procedures (R=-0.090, P < 0.01); regression analysis showed that years, treatment attributes, and regions were the main factors affecting the CMDLD (P < 0.05). CONCLUSIONS: Years, regions, treatment attributes, and trial procedures affect the outcome of CMDLD. This paper further puts forward relevant suggestions and countermeasures for the governance of doctor-patient risks based on the empirical results. Including rational allocation of medical resources to narrow the differences between regions; promoting the expansion and sinking of high-quality resources to improve the level of medical services in hospitals at all levels; and developing a third-party negotiation mechanism for medical disputes to reduce the cost of medical litigation.

Projections of functional dependence among the late middle-aged and older population from 2018-2048 in China: a dynamic microsimulation.

BACKGROUND: The population of China is aging rapidly. However, the long-term trajectories of functionally dependent late middle-aged and older Chinese people are currently absent. The present study aimed to estimate the population size and proportion of late middle-aged and older adults with difficulties and dependence on activities of daily living (ADL) and instrumental activities of daily living (IADL) in China from 2018 to 2048. METHODS: We constructed a dynamic microsimulation model to project the population size and proportions of late middle-aged and older Chinese people who have difficulty and dependence in ADL and IADL from 2018-2048. The model was populated with a representative sample of the target population and allowed individual-level interaction between risk factors, diseases, and health outcomes. Analyses by socioeconomic subgroups were also conducted. RESULTS: Almost 25% and 38% of late middle-aged and older people in China will become ADL- and IADL-dependent by 2048, respectively. Also, 17% of the target population will be severely ADL-disabled by 2048. The inequity in functional status across subgroups by sex, educational level, and urban/rural residency will become substantial. CONCLUSIONS: The numbers and percentages of China's functionally difficult and dependent late middle-aged and older population will increase by magnitudes as of the mid-21st century, the pressure of which is compounded by its disproportionate distribution across subgroups. To alleviate the overwhelming challenge, efforts to improve the functional status of the underserved subpopulation should also be iterated.

Rare homozygous disease-associated sequence variants in children with spinal muscular atrophy: a phenotypic description and review of the literature.

5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene. Most of the remaining 4-5 % are compound heterozygous for deletion and a disease-associated sequence variant in the non-deleted allele. Individuals with SMA due to bi-allelic SMN1 sequence variants have rarely been reported. Data regarding their clinical phenotype, disease progression, outcome and treatment response are sparse. This study describes six individuals from three families, all with homozygous sequence variants in SMN1, and four of whom received treatment with disease-modifying therapies. We also describe the challenges faced during the diagnostic process and intrafamilial phenotypic variability observed between siblings.

Mechanism study of aging oil demulsification and dehydration under ultrasonic irradiation.

With the tertiary oil recovery in the oilfield, the content of aging oil emulsion with high water content and complex components has become more prevalent, so it is crucial for aging oil to break the emulsification. In this paper, the experimental laws of water content are explored under the conditions of different transducer input powers through the ultrasonic reforming of aging oil, and the microscopic topography, particle size, components, etc. of oil samples before and after the irradiation of ultrasound are characterized through the microscopic analysis, particle size analysis and component analysis and other ways. The results show that the oil samples achieve the effect of demulsification and dehydration in the presence of ultrasonic cavitation effect, with a maximum dehydration rate of 98.24 %, and that the dehydration rate follows an "M-type" trend with the increase of power. The results of microscopic and particle size analyses demonstrate that ultrasonic irradiation destabilizes the oil-water interfacial membrane, and causes droplets of different sizes to collide, agglomerate, and settle. It was also observed that the droplets of the emulsion system are more evenly distributed and the intervals are increased. Furthermore, we hypothesize that ultrasound may be less irreversible in demulsification and dehydration of aging oil.

Structural characteristics and paste properties of wheat starch in natural fermentation during traditional Chinese Mianpi processing.

Fermentation plays a crucial role in traditional Chinese mianpi processing, where short-term natural fermentation (within 24 h) is considered advantageous for mianpi production. However, the influence of short-term natural fermentation on the properties of wheat starch is not explored yet. Hence, structural characteristics and paste properties of wheat starch during natural fermentation were investigated in this study. The findings revealed that fermenting for 24 h had a slight effect on the morphology of wheat starch but significantly decreased the particle size of starch. Compared to native wheat starch, the enzyme activity produced during fermentation may destroy the integrity of starch granules, resulting in a lower molecular weight but higher relative crystallinity and orderliness of starch. After 24 h of natural fermentation, higher solubility and swelling power were obtained compared to non-fermentation. Regarding paste properties, fermented starches exhibited higher peak viscosity and breakdown, along with lower final viscosity, tough viscosity, and setback. Furthermore, the hardness, gel strength, G', and G" decreased after fermentation. Clarifying changes in starch during the short-term natural fermentation process could provide theoretical guidance for improving the quality and production of short-term naturally fermented foods such as mianpi, as discussed in this study.

Emerging trends and patterns in healthcare-seeking behavior: A systematic review.

OBJECTIVES: The study of healthcare-seeking behavior is essential for optimizing resource allocation and improving healthcare services. Its complexity and diversity have made it a prominent research area. Understanding factors influencing healthcare-seeking decisions allows targeted interventions and policy development to address barriers and ensure equitable access to quality healthcare for diverse populations. Such research plays a vital role in enhancing healthcare outcomes and overall population health. METHODS: The study utilized a systematic quantitative literature review approach, employing the Web of Science (WOS) Core Collection and PubMed databases as data sources. Additionally, bibliometric tools such as CiteSpace and VOSviewer were employed for analysis and visualization of the literature. RESULTS: A comprehensive statistical analysis and visualization were performed on the annual publication volume, publication countries, journals, keywords, and keyword co-occurrence patterns up until 2023. Through this analysis, a framework was established, identifying the determinants and fundamental elements of healthcare-seeking behavior. These findings contribute to the advancement of research in this field and inform future studies and interventions aimed at improving healthcare-seeking behavior. CONCLUSIONS: Based on the aforementioned literature review and framework, several conclusions were drawn. The determinants that facilitate healthcare-seeking behavior include improving health education awareness, enhancing healthcare resources, reducing costs, and ensuring system soundness. Additionally, providing social environment support was found to be crucial. Furthermore, the fundamental elements of healthcare-seeking behavior were identified as healthcare demand, healthcare choices, and the process of diagnosis and treatment. These findings provide valuable insights for developing interventions and policies to promote optimal healthcare-seeking behavior.

Blockade of pan-viral propagation by inhibition of host cell PNPT1.

For successful viral propagation within infected cells, the virus needs to overcome the cellular integrated stress response (ISR), triggered during viral infection, which, in turn, inhibits general protein translation. This paper reports a tactic employed by viruses to suppress the ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus and hepatovirus within their respective host cells induces PNPT1 expression. Notably, when PNPT1 is knocked down, the propagation of all three viruses is prevented. Mechanistically, the inhibition of PNPT1 facilitates the relocation of mitochondrial double-stranded RNAs (mt-dsRNAs) to the cytoplasm, where they activate RNA-activated protein kinase (PKR). This activation leads to eukaryotic initiation factor 2α (eIF2α) phosphorylation, resulting in the suppression of translation. Furthermore, by scrutinizing the PNPT1 recognition element and screening 17,728 drugs and bioactive compounds approved by the US Food and Drug Administration, lanatoside C was identified as a potent PNPT1 inhibitor. This compound impedes the propagation of adenovirus, murine cytomegalovirus and hepatovirus, and suppresses production of the severe acute respiratory syndrome coronavirus-2 spike protein. These discoveries shed light on a novel strategy to impede pan-viral propagation by activating the host cell mt-dsRNA-PKR-eIF2α signalling axis.

Elevated levels of ß2-microglobulin in cerebrospinal fluid in adult patients with viral encephalitis/meningitis.

BACKGROUND: Increased cerebrospinal fluid (CSF) ß2-microglobulin (ß2-MG) values are attributed to immune activation, lymphoid cell turnover and release of tissue destruction in the central nervous system (CNS). We investigated plasma and CSF ß2-MG levels in adult patients with viral encephalitis/meningitis and their correlations with clinical parameters. METHOD: CSF samples from 26 patients with viral encephalitis/meningitis were collected. Moreover, 24 CSF samples from patients with non-inflammatory neurological disorders (NIND) as controls were collected. Plasma samples from 22 enrolled patients and 20 healthy individuals were collected. The ß2-MG levels were measured by immunoturbidimetry on an automatic biochemical analyzer. Clinical data were extracted from an electronic patient documentation system. RESULT: CSF levels of ß2-MG, adenosine deaminase (ADA), white blood cell (WBC), lactate dehydrogenase (LDH), protein and lactate were significantly increased in patients with viral encephalitis/meningitis respectively (p < 0.001, p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.013). In contrast, no statistically significant difference was found in plasma levels of ß2-MG. Furthermore, CSF levels of ß2-MG were weakly correlated with WBC (r = 0.426, p = 0.030), lymphocyte percentage (r = 0.599, p = 0.018), ADA (r = 0.545, p = 0.004) and LDH (r = 0.414, p = 0.036), but not with lactate (r = 0.381, p = 0.055), protein (r = 0.179, p = 0.381) and plasma levels of ß2-MG (r = -0.156, p = 0.537) in viral encephalitis/meningitis patients. CONCLUSION: CSF ß2-MG may be a potential inflammatory marker for viral encephalitis/meningitis in adult patients diagnosed with viral encephalitis/meningitis.

Research on the risk governance of fraudulent reimbursement of patient consultation fees.

Background: The fundamental medical insurance fund, often referred to as the public's "life-saving fund," plays a crucial role in both individual well-being and the pursuit of social justice. Medicare fraudulent claims reduce "life-saving money" to "Tang's monk meat", undermining social justice and affecting social stability. Methods: We utilized crawler technology to gather textual data from 215 cases involving fraudulent health insurance claims. Simultaneously, statistical data spanning 2018 to 2021 was collected from the official websites of the China Medical Insurance Bureau and Anhui Medical Insurance Bureau. The collected data underwent comprehensive analysis through Excel, SPSS 26.0 and R4.2.1. Differential Auto-Regressive Moving Average Model (ARIMA (p, d, q)) was used to fit the fund safety forecast model, and test the predictive validity of the forecast model on the fund security data from July 2021 to October 2023 (the fund security data of Anhui Province from September 2021 to October 2023). Results: The outcomes revealed that fraudulent claims by health insurance stakeholders adversely impact the equity of health insurance funds. Furthermore, the risk management practices of Medicare fund administrators influence the publication of fraudulent claims cases. Notably, differences among Medicare stakeholders were observed in the prevalence of fraudulent claims. Additionally, effective governance of fraudulent claims risks was found to have a positive impact on the overall health of healthcare funds. Moreover, the predictive validity of the forecast model on the national and Anhui province's fund security data was 92.86% and 100% respectively. Conclusion: We propose four recommendations for the governance of health insurance fraudulent claims risk behaviors. These recommendations include strategies such as "combatting health insurance fraudulent claims to preserve the fairness of health insurance funds", "introducing initiatives for fraud risk governance and strengthening awareness of the rule of law", "focusing on designated medical institutions and establishing a robust long-term regulatory system", and "adapting to contemporary needs while maintaining a focus on long-term regulation".

Spin-state Conversion by Asymmetrical Orbital Hybridization in Ni-doped Co3 O4 to Boost Singlet Oxygen Generation for Microbial Disinfection.

Singlet oxygen (1 O2 ) plays a significant role in environmental and biomedical disinfection fields. Electrocatalytic processes hold great potential for 1 O2 generation, but remain challenging. Herein, a facile Ni doping converted spin-state transition approach is reported for boosting 1 O2 production. Magnetic analysis and theoretical calculations reveal that Ni occupied at the octahedral site of Co3 O4 can effectively induce a low-to-high spin-state transition. The high-spin Ni-Co3 O4 generate appropriate binding strength and enhance electron transfer between the Co centers with oxygen intermediates, thereby improving the catalytic activity of Ni-Co3 O4 for effective generating 1 O2 . In neutral conditions, 1×106  CFU mL-1 Gram-negative ESBL-producing Escherichia coli (E. coli) could be inactivated by Ni-Co3 O4 system within 5 min. Further antibacterial mechanisms indicate that 1 O2 can lead to cell membrane damage and DNA degradation so as to irreversible cell death. Additionally, the developed Ni-Co3 O4 system can effectively inactivate bacteria from wastewater and bioaerosols. This work provides an effective strategy for designing high-spin electrocatalysis to boost 1 O2 generation for disinfection process.

Single substrate-functionalized molybdenum oxide nanozyme for specific colorimetric monitoring of xanthine oxidase activity.

Xanthine-functionalized molybdenum oxide nanodots (X-MoO3-x NDs) with peroxidase (POD)-like activity were developed for selective, sensitive, and facile colorimetric quantification of xanthine oxidase (XO). Xanthine functionalization can not only be favorable for the successful nanozyme preparation, but also for the specific recognition of XO as well as the simultaneous generation of hydrogen peroxide, which was subsequently transformed into hydroxyl radical to oxidize the chromogenic reagent based on the POD-like catalysis. Under the optimized conditions, the colorimetric biosensing platform was established for XO assay without addition of further substrates, showing good linearity relationship between absorbance difference (ΔA) and XO concentrations in the range 0.05-0.5 U/mL (R2 = 0.998) with a limit of detection (LOD) of 0.019 U/mL. The quantification of XO occurs in 25 min, which is superior to the previously reported and commercial XO assays. The proposed method has been successfully used in the assay of human serum samples, showing its high potential in the field of clinical monitoring.

MoOxNWs with mechanical damage - oriented synergistic photothermal / photodynamic therapy for highly effective treating wound infections.

Reactive oxygen species (ROS)-based therapy has emerged as a promising antibacterial strategy. However, it faces the limitations of uncontrollable space-time release and excessive lipid peroxidation, which may lead to a series of metabolic disorders and decreased immune function. In this study, mechanical damage by molybdenum oxide nanowires (MoOxNWs) is introduced as a synergistic factor to enhance the photothermal and photodynamic effects for controllable and efficient antibacterial therapy. Through their sharp ends, the nanowires can effectively pierce and damage the bacterial cells, thus facilitating the entry of externally generated ROS into the cells. The ROS are generated via photodynamic effect of the nanowires under a mere 5 min of near-infrared light irradiation. This approach enhances the photothermal (by 27.3 %) and photodynamic properties of ROS generation. MoOxNWs (100 µg·mL-1) achieve sterilisation rates of 97.67 % for extended-spectrum ß-lactamase-producing E. coli and 96.34 % for methicillin-resistant Staphylococcus aureus, which are comparable or even exceeding the efficacy of most MoOx-based antibacterial agents. Moreover, they exhibit good biocompatibility and low in vivo toxicity.

The novel HLA-B*54:01:12 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*54:01:12 differs from HLA-B*54:01:01:01 by one nucleotide in exon 2.

Comparative study on nutritional and technological properties of two varieties of black wheat flour and their noodle-making potential.

Comparative studies were conducted on physicochemical and technological properties of two black wheat (BW) varieties (cultivated in Shanxi Agricultural University) and their noodle-making potential. Whole-grain BW noodles showed acceptable cooking loss (≤10%) and strong antioxidant capacity. However, their textural quality remains to be enhanced. Regarding refined flour (RF) of the two BW varieties, Yunhei 14207 showed more anthocyanins, brighter color, and greater thermal stability (as reflected by the higher pasting temperature). 16W16 resulted in greater gluten content and better gluten quality of flour and higher dough stability, which contributed to the lower cooking loss and stronger tensile property of noodles. RF noodles of Yunhei 14207 displayed brighter appearance, although they had weaker tensile property. The stronger gluten network in noodles of 16W16 protected phenolics from release and degradation during drying, cooking, and steaming. Despite phenolics loss, RF noodles of Yunhei 14207 showed antioxidant capacity up to 14.97 mg TE/100 g. This research would promote understanding of characteristics of BW varieties. Considering the stronger gluten network of 16W16, its fortification in common wheat noodles at high proportion (>50%) may be promising to develop antioxidant noodles with further improved sensory quality.

Analysis of Chromatin Accessibility Changes Induced by BMMC Recognition of Foot-and-Mouth Disease Virus-like Particles through ATAC-seq.

Mast cells can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) via mannose receptors (MRs) to produce differentially expressed cytokines. The regulatory role of chromatin accessibility in this process is unclear. Bone marrow-derived mast cells (BMMCs) were cultured, and an assay of transposase-accessible chromatin sequencing (ATAC-seq) was applied to demonstrate the regulation of chromatin accessibility in response to the BMMCs' recognition of FMDV-VLPs. A pathway enrichment analysis showed that peaks associated with the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), and other signaling pathways, especially the NF-κB pathway, were involved in the BMMCs' recognition of VLPs. Moreover, transcription factors including SP1, NRF1, AP1, GATA3, microphthalmia-associated transcription factor (MITF), and NF-κB-p65 may bind to the motifs with altered chromatin accessibility to regulate gene transcription. Furthermore, the expression of NF-κB, interleukin (IL)-9, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the BMMCs of the VLP group increased compared with that of the BMMCs in the control group, whereas the expression of IL-10 did not differ significantly between groups. After inhibiting the MRs, the expression of NF-κB, IL-9, TNF-α, and IFN-γ decreased significantly, whereas the expression of IL-10 increased. The expression of MAPK and IL-6 showed no significant change after MR inhibition. This study demonstrated that MRs expressed on BMMCs can affect the NF-κB pathway by changing chromatin accessibility to regulate the transcription of specific cytokines, ultimately leading to the differential expression of cytokines. These data provide a theoretical basis and new ideas for the development of a novel vaccine for FMD.

Structural and physicochemical characteristics of wheat starch as influenced by freeze-thawed cycles and antifreeze protein from Sabina chinensis (Linn.) Ant. cv. Kaizuca leaves.

The effects of freeze-thawed cycles (FTs) and a new antifreeze protein from Sabina chinensis (Linn.) Ant. cv. Kaizuca leaves (ScAFP) on the structure and physicochemical characteristics of wheat starch were studied. The mechanical breaking exerted by ice crystals on starch granules during FTs gradually deepened, sequentially squeezing the surface (2-6 FTs), amorphous region (8 FTs) and crystalline region (10 FTs) of starch granules. These changes led to reduced thermal stability, increased retrogradation tendency, and weakened gel network structure. The addition of ScAFP retarded the damage of ice crystals on starch granule structure and crystal structure during FTs, and significantly reduced the retrogradation tendency. Compared with native starch, the hardness of freeze-thawed starch without and with added ScAFP after 10 FTs decreased by 17.85% and 9.22%, respectively, indicating ScAFP improved the gel texture properties of freeze-thawed starch. This study provides new strategies for improving the quality of frozen starch-based foods.

A Design Method on Durable Asphalt Pavement of Flexible Base on Anti-Rutting Performance and Its Application.

To solve the durability of flexible base asphalt pavement, especially its anti-rutting problem, a design method on durable asphalt pavement of flexible base on anti-rutting performance was put forward in the paper, based on many experiments and calculations. Firstly, a method that asphalt could be selected according to penetration and the anti-rutting factor of its base asphalt was found, which solved the problem of the asphalt selection of the flexible base asphalt mixture design. Meanwhile, a method of skeleton-density structure gradation design was proposed based on the fractal void ratio of coarse aggregate, fractal volume of fine aggregate in coarse aggregate, penetration, fractal dimension of gradation particle size, and rutting tests, which effectively solved in advance the rutting and fatigue performance of flexible base asphalt mixtures. Then, on the basis of the fatigue damage, a calculation method of fatigue life was suggested, which solved the problem that the fatigue damage of asphalt mixtures rarely considered the combined effects of creep damage and fatigue damage. In addition, a calculation method of rutting was formulated based on vehicle dynamic load and ANSYS 16.0 software. Lastly, the feasibility of the design method on durable asphalt pavement of flexible base on anti-rutting performance was verified combining with the real engineering of a supporting project and several numerical calculations and tests.

The effectiveness of epilepsy educational intervention using computer game-based epilepsy educational program (Epigame) among Malaysian children with epilepsy: A prospective cohort study.

BACKGROUND: A computer game-based epilepsy educational programme (Epigame) can potentially improve the awareness, knowledge and attitude (AKA) and quality of life (QOL) of children with epilepsy (CWE). Our study among Malaysian CWE aimed to assess the: i) baseline level of epilepsy AKA and potential characteristics associated with poor levels of AKA, ii) effectiveness of Epigame in improving AKA and QOL of CWE. METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3. RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with < 2 antiseizure medication (OR 5.0, 95 % CI 1.34-18.98). The scores in the knowledge, attitude and total AKA score domains improved significantly after the introduction of Epigame at TP3. There were no significant improvements in the CHEQOL-25 scores over time except for the "Quest for Normality" subscale score (mean of score difference between TP1 and TP3 = 1.0, 95 % CI 0.19-1.81). CONCLUSION: Majority of Malaysian CWE had low levels of epilepsy AKA, particularly among parents with "negative to indifferent" for attitude domain, parents with "very poor to moderate" for total AKA domain and on polytherapy. Introduction of Epigame was effective in improving scores of the knowledge, attitude and total AKA domains, and the QOL "Quest for Normality" domain of the CHEQOL-25.