Innovative analysis of diazepam, zolpidem and their main metabolites in human urine by micelle-to-solvent stacking in capillary electrophoresis.

Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations.

Online Parameter Estimation for Student Evaluation of Teaching.

Student evaluation of teaching (SET) assesses students' experiences in a class to evaluate teachers' performance in class. SET essentially comprises three facets: teaching proficiency, student rating harshness, and item properties. The computerized adaptive testing form of SET with an established item pool has been used in educational environments. However, conventional scoring methods ignore the harshness of students toward teachers and, therefore, are unable to provide a valid assessment. In addition, simultaneously estimating teachers' teaching proficiency and students' harshness remains an unaddressed issue in the context of online SET. In the current study, we develop and compare three novel methods-marginal, iterative once, and hybrid approaches-to improve the precision of parameter estimations. A simulation study is conducted to demonstrate that the hybrid method is a promising technique that can substantially outperform traditional methods.

Relationship between Aspartame-Induced Cerebral Cortex Injury and Oxidative Stress, Inflammation, Mitochondrial Dysfunction, and Apoptosis in Sprague Dawley Rats.

There are emerging concerns about the potential cerebral cortex injury from aspartame due to the accumulation of the various neurotoxic metabolic components in the central nervous system after long-term dietary exposure. The aim of this study was to evaluate the effect of oral aspartame consumption on cerebral cortex injury in the rat brain, and further evaluate the various underlying molecular mechanisms, with a special focus on oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis pathways. Sprague Dawley rats (nineteen, female) were randomly sub-divided into three groups: (i) normal diet with vehicle: control group (five rats), (ii) low dose of aspartame group (LA): seven rats received 30 mg/kg body weight (bw) daily doses of aspartame, (iii) high dose of aspartame group (HA): seven rats received 60 mg/kg bw daily doses of aspartame. After 8 weeks, the LA and HA groups showed lower expression levels of brain-derived neurotrophic factor (BDNF), antioxidant enzyme activity (SOD2, CAT), antioxidant marker (Nrf2), inflammatory response (IκB), mitochondrial biogenesis (Sirt1, PGC1α, Nrf1, TFAM), mitochondrial DNA (mtDNA) copy number, and apoptosis-related proteins (Bax, Caspase-3) expressions. Aspartame administration also elevated oxidative stress levels (Malondialdehyde, MDA), 8-hydroxy-2-deoxy guanosine (8-OHdG), PGE2 and COX-2 expressions, pro-inflammatory cytokines (TNFα, IL6, IL1ß), antioxidant marker expression (Keap1), inflammatory responses (iNOS, NFκB), and glial fibrillary acidic protein (GFAP) levels in the cerebral cortex of the rats, thereby contributing to the reduced survival of pyramidal cells and astrocyte glial cells of the cerebral cortex. Therefore, these findings imply that aspartame-induced neurotoxicity in rats' cerebral cortex could be regulated through four mechanisms: inflammation, enhanced oxidant stress, decreased mitochondrial biogenesis, and apoptosis pathways.

Mangosteen Pericarp Extract Supplementation Boosts Antioxidant Status via Rebuilding Gut Microbiota to Attenuate Motor Deficit in 6-OHDA-Induced Parkinson's Disease.

Oxidative stress and gut dysbiosis have been known to precede Parkinson's disease (PD). An antioxidant-rich product, mangosteen pericarp (MP), has the ability to counterbalance excessive free radicals and the imbalanced gut microbiota composition, suggesting the MP's capacity to delay PD progression. In this study, we explored the effects of two doses of MP extract in a unilateral 6-hydroxydopamine (6-OHDA)-induced PD rat model. We revealed that the 8-week supplementation of a low dose (LMP) and a high dose of the MP extract (HMP) improved motor function, as observed in decreased contralateral rotation, improved time spent on rod, and higher dopamine binding transporter (DAT) in the substantia nigra pars compacta (SNc). The MP extract, especially the HMP, also increased antioxidant-related gene expressions, restored muscle mitochondrial function, and remodeled fecal microbiota composition, which were followed by reduced reactive oxygen species levels in brain and inflammation in plasma. Importantly, bacterial genera Sutterella, Rothia, and Aggregatibacter, which were negatively correlated with antioxidant gene expressions, decreased in the HMP group. It is imperative to note that in addition to directly acting as an antioxidant to reduce excessive free radicals, MP extract might also increase antioxidant state by rebuilding gut microbiota, thereby enhanced anti-inflammatory capacity and restored mitochondrial function to attenuate motor deficit in 6-OHDA-induced PD-like condition. All in all, MP extract is a potential candidate for auxiliary therapy for PD.

Prevalence of nail biting and its chronological relationship with tics in child and adolescent outpatients with Tourette syndrome: a single-centre, retrospective observational study.

OBJECTIVE: To evaluate the prevalence of nail biting in child and adolescent outpatients at a single institution and the chronological relationship between nail biting and tics in patients with Tourette syndrome (TS) with or without attention-deficit hyperactivity disorder (ADHD). DESIGN: Retrospective observational study. SETTING: Teaching hospital in Taiwan. PARTICIPANTS: All participants were aged 4-18 years, including 535 patients with TS, 230 patients with provisional tic disorder and 1460 patients without neurological or psychiatric disorders (controls). OUTCOME MEASURES: Presence of nail biting, starting age for nail biting and starting age for motor and/or vocal tics. RESULTS: Nail biting was more commonly observed in patients with TS (56.6%) than in patients with provisional tic disorder (27.4%) or controls (15.0%), regardless of sex (all p<0.020). Nail biting was also more common in patients with TS with ADHD than in those without (75.0% vs 47.6%; p<0.001), but the starting age was significantly later in those with concomitant ADHD than without (5.3 vs 3.8 years; p<0.001). In patients with TS, the onset of nail biting occurred earlier than that of tics, regardless of ADHD status. CONCLUSION: Nail biting was more prevalent and occurred earlier than tics in patients with TS, regardless of ADHD status, in the study population.

Study of the operative conditions and the optimum amount of municipal incinerator bottom ash for the obtainment of ceramic floor tiles.

The idea of reusing municipal incinerator bottom ash (MIBA), the residue from incinerating municipal solid wastes, fits nicely in a circular economy scheme, which leads to an avoided impact of landfill disposal, and at the same time reduces the demand of natural resources. Past studies have attempted to add 20 to 60% MIBA for ceramic production, and resulted in some inspiring success. Focused on delivering quality interior and exterior floor tiles meeting industrial standards, this study investigated the operative conditions and the optimum amount of MIBA in the mix. In this study, only the kaolinite clay and MIBA were used. Before making specimens, raw materials of clay and MIBA underwent SEM, EDS, and TCLP tests to determine their chemical contents. Six sets of specimens with different replacement levels of MIBA (0%, 5%, 10%, 15%, 20%, and 30%) were then prepared. These specimens were fired at 1000°C, 1050°C,1100°C, and 1150°C and the products underwent a series of mechanical tests to verify their performance. NMR (nuclear magnetic resonance spectroscopy) were also used to determining the organic compound structure after each specimens' crystallization. Research results showed that proper mix of MIBA up to 20% could result in quality tiles complying with specifications for interior and exterior flooring applications at certain kiln temperatures, while the specimens with 30% MIBA failed to meet either bending strength or size shrinkage requirement at all four kiln temperatures, and could not deliver a satisfactory result.

A Lognormal Ipsative Model for Multidimensional Compositional Items.

Compositional items - a form of forced-choice items - require respondents to allocate a fixed total number of points to a set of statements. To describe the responses to these items, the Thurstonian item response theory (IRT) model was developed. Despite its prominence, the model requires that items composed of parts of statements result in a factor loading matrix with full rank. Without this requirement, the model cannot be identified, and the latent trait estimates would be seriously biased. Besides, the estimation of the Thurstonian IRT model often results in convergence problems. To address these issues, this study developed a new version of the Thurstonian IRT model for analyzing compositional items - the lognormal ipsative model (LIM) - that would be sufficient for tests using items with all statements positively phrased and with equal factor loadings. We developed an online value test following Schwartz's values theory using compositional items and collected response data from a sample size of N = 512 participants with ages from 13 to 51 years. The results showed that our LIM had an acceptable fit to the data, and that the reliabilities exceeded 0.85. A simulation study resulted in good parameter recovery, high convergence rate, and the sufficient precision of estimation in the various conditions of covariance matrices between traits, test lengths and sample sizes. Overall, our results indicate that the proposed model can overcome the problems of the Thurstonian IRT model when all statements are positively phrased and factor loadings are similar.

Applying Mixture of Municipal Incinerator Bottom Ash and Sewage Sludge Ash for Ceramic Tile Manufacturing.

Municipal incinerator bottom ash (MIBA) and sewage sludge ash (SSA) are secondary wastes produced from municipal incinerators. Landfills, disposal at sea, and agricultural use have been the major outlets for these secondary wastes. As global emphasis on sustainability arises, many have called for an increasing reuse of waste materials as valuable resources. In this study, MIBA and SSA were mixed with clay for ceramic tile manufacturing in this study. Raw materials firstly went through TCLP (Toxicity Characteristic Leaching Procedure) to ensure their feasibility for reuse. From scanning electron microscopy (SEM), clay's smooth surface was contrasted with the porous surface of MIBA and SSA, which led to a higher water requirement for the mixing. Specimens with five MIBA mix percentages of 0%, 5%, 10%, 15%, and 20% (wt) and three SSA mix percentages of 0%, 10%, and 20% (wt) were made to compare how the two waste materials affected the quality of the final product and to what extent. Shrinkage tests showed that MIBA and SSA contributed oppositely to tile shrinkage, as more MIBA reduced tile shrinkage, while more SSA encouraged tile shrinkage. However, as the kiln temperature reached 1150 °C, the SiO2-rich SSA adversely reduced the shrinkage due to the glass phase that formed to expand the tile instead. Both MIBA and SSA increased water tile absorption and reduced its bending strength and wear resistance. Increasing the kiln temperature could effectively improve the water absorption, bending strength, and wear resistance of high MIBA and SSA mixes, as SEM showed a more compact structure at higher temperatures. However, when the temperature reached 1100 °C, more pores appeared and seemingly exhausted the benefit brought by the higher temperature. Complex interactions between kiln temperature and MIBA/SSA mix percentage bring unpredictable performance of tile shrinkage, bending strength, and water absorption, which makes it very challenging to create a sample meeting all the specification requirements. We conclude that a mix with up to 20% of SSA and 5% of MIBA could result in quality tiles meeting the requirements for interior or exterior flooring applications when the kiln temperature is carefully controlled.

Biotin biosynthesis affected by the NADPH oxidase and lipid metabolism is required for growth, sporulation and infectivity in the citrus fungal pathogen Alternaria alternata.

The tangerine pathotype of Alternaria alternata affects many citrus cultivars, resulting in yield losses. The capability to produce the host-selective toxin and cell-wall-degrading enzymes and to mitigate toxic reactive oxygen species is crucial for A. alternata pathogenesis to citrus. Little is known about nutrient availability within citrus tissues to the fungal pathogen. In the present study, we assess the infectivity of a biotin deficiency mutant (ΔbioB) and a complementation strain (CP36) on citrus leaves to determine how biotin impacts A. alternata pathogenesis. Growth and sporulation of ΔbioB are highly dependent on biotin. ΔbioB retains its ability to acquire and transport biotin from the surrounding environment. Growth deficiency of ΔbioB can also be partially restored by the presence of oleic acid or Tween 20, suggesting the requirement of biotin in lipid metabolism. Experimental evidence indicates that de novo biotin biosynthesis is regulated by the NADPH oxidase, implicating in the production of H2O2, and is affected by the function of peroxisomes. Three genes involved in the biosynthesis of biotin are clustered and co-regulated by biotin indicating a transcriptional feedback loop activation. Infectivity assays using fungal mycelium reveal that ΔbioB cultured on medium without biotin fails to infect citrus leaves; co-inoculation with biotin fully restores infectivity. The CP36 strain re-expressing a functional copy of bioB displays wild-type growth, sporulation and virulence. Taken together, we conclude that the attainability or accessibility of biotin is extremely restricted in citrus cells. A. alternata must be able to synthesize biotin in order to utilize nutrients for growth, colonization and development within the host.

Proper Functions of Peroxisomes Are Vital for Pathogenesis of Citrus Brown Spot Disease Caused by Alternaria alternata.

In addition to the production of a host-selective toxin, the tangerine pathotype of Alternaria alternata must conquer toxic reactive oxygen species (ROS) in order to colonize host plants. The roles of a peroxin 6-coding gene (pex6) implicated in protein import into peroxisomes was functionally characterized to gain a better understanding of molecular mechanisms in ROS resistance and fungal pathogenicity. The peroxisome is a vital organelle involved in metabolisms of fatty acids and hydrogen peroxide in eukaryotes. Targeted deletion of pex6 had no impacts on the biogenesis of peroxisomes and cellular resistance to ROS. The pex6 deficient mutant (Δpex6) reduced toxin production by 40% compared to wild type and barely induce necrotic lesions on citrus leaves. Co-inoculation of purified toxin with Δpex6 conidia on citrus leaves, however, failed to fully restore lesion formation, indicating that toxin only partially contributed to the loss of Δpex6 pathogenicity. Δpex6 conidia germinated poorly and formed fewer appressorium-like structures (nonmelanized enlargement of hyphal tips) than wild type. Δpex6 hyphae grew slowly and failed to penetrate beyond the epidermal layers. Moreover, Δpex6 had thinner cell walls and lower viability. All of these defects resulting from deletion of pex6 could also account for the loss of Δpex6 pathogenicity. Overall, our results have demonstrated that proper peroxisome functions are of vital importance to pathogenesis of the tangerine pathotype of A. alternata.

Mangosteen Concentrate Drink Supplementation Promotes Antioxidant Status and Lactate Clearance in Rats after Exercise.

High-strength or long-duration exercise can lead to significant fatigue, oxidative stress, and muscle damage. The purpose of this study was to examine the effect of mangosteen concentrate drink (MCD) supplementation on antioxidant capacity and lactate clearance in rats after running exercise. Forty rats were divided into five groups: N, non-treatment; C, control; or supplemented with MCD, including M1, M5, and M10 (0.9, 4.5, and 9 mL/day) for 6 weeks. The rats were subjected to 30 min running and exhaustive-running tests using a treadmill. The blood lactate; triglyceride; cholesterol and glucose levels; hepatic and muscular malonaldehyde (MDA) levels; and antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), were analyzed. The results of this study demonstrated that MCD supplementation can increase GPx and CAT activities, alleviate oxidative stress in muscle, and increase lactate clearance, and is thereby beneficial to reduced muscle fatigue after exercise.

The association between tic medication therapy and psychiatric comorbidities among patients with Tourette syndrome: A national population-based study in Taiwan.

BACKGROUND: Tourette syndrome (TS) is often comorbid with attention deficit hyperactivity disorder, obsessive-compulsive disorder, and depression. Medications are the main treatment for TS. Relationships between TS medication therapy and psychiatric comorbidities remain unclear. This study explored the impacts of TS medication on the risk of psychiatric comorbidities using a nationally representative sample of TS in Taiwan. METHODS: Data from National Health Insurance Research Database in Taiwan was used to identify 997,213 children and adolescents aged 6-18 years who had received a diagnosis of TS based on ICD-9-CM codes in 2000-2010. Cox's proportional hazard regression analysis was conducted to estimate the risk of comorbidities among subjects with and without tic medication therapy. RESULTS: We found that in TS patients, a lower risk of psychiatric comorbidities occurred in the tic medication therapy group (p = 0.012) and the crude hazard ratio (HR) was 0.6 (95% confidence interval (CI) = 0.4-0.8, p < 0.001). After adjusting for potential confounders of gender, age, income, level of care, department visited, brain injury, and the number of suicide attempts, the risk of comorbidities was still significantly lower in the tic medication therapy group (adjusted HR = 0.5, 95% CI = 0.3-0.6, p < 0.001). DISCUSSION: One limitation was that we did not include all mediations used to treat psychiatric comorbidities among TS patients. This study found the effectiveness of TS medications on improving psychiatric comorbidities. CONCLUSIONS: Compared to those without medication, medication therapy appears to have a benefit of decreasing the risk of psychiatric comorbidities. Strategies to improve medication regimens should be considered in clinical settings.

Mangosteen pericarp components alleviate progression of prostatic hyperplasia and mitochondrial dysfunction in rats.

Prostatic hyperplasia, characterized by progressive hyperplasia of glandular and stromal tissues, is the most common proliferative abnormality of the prostate in aging men. A high-fat diet (HFD) usually is a major factor inducing oxidative stress, inflammation, and an abnormal state of the prostate. Mangosteen pericarp powder (MPP) has abundant xanthones which can be antioxidant, anti-inflammatory, and antiproliferative agents. Therefore, the purpose of this study was to research whether MPP supplementation can affect the progression of prostatic hyperplasia. Twenty-four male F344 rats were randomly divided into four groups, including a control group (C), prostatic hyperplasia-induced group (P), prostatic hyperplasia-induced with low-dose MPP group (PL), and induced with high-dose MPP group (PH). The P, PL, and PH groups were given weekly intraperitoneal injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) at 25 mg/kg body weight for 10 weeks, and simultaneously fed an HFD for 24 weeks. Our findings first demonstrated that MPP consumption significantly decreased the prostate weight, serum testosterone and dihydrotestosterone concentrations, protein expression of proliferating cell nuclear antigen, and malondialdehyde levels and ameliorated mitochondrial function in prostatic tissues. These results suggest that MPP supplementation could be used to attenuate the progression of prostatic hyperplasia.

Effectiveness of a modified comprehensive behavioral intervention for tics for children and adolescents with tourette's syndrome: A randomized controlled trial.

AIM: To evaluate the effectiveness of a modified four-session Comprehensive Behavioral Intervention for Tics programme for decreasing tics in children and adolescents with Tourette's syndrome. BACKGROUND: Comprehensive Behavioral Intervention for Tics programme has been shown to decrease tic severity. However, the lack of behaviour therapists in countries, such as in Taiwan, may preclude application of the standard eight-session, 10-week programme. DESIGN: Randomized controlled study. METHODS: Participants aged 6-18 years diagnosed with Tourette's syndrome or chronic tic disorder were recruited from February 2015 through September 2016. Participants in the control and intervention groups (N = 23 each) received the routine care (daily pyridoxine [50 mg] and psychoeducation). The intervention group received additional four behavioural intervention sessions over a 3-month period that included psychoeducation, habit reversal training, relaxation training, and education on tic relapse prevention. The outcome measures, Yale Global Tic Severity Scale scores, were assessed at before and after the completion of programme for both groups and again at 3 months follow-up for the intervention group. The effect of the intervention on severity scores was assessed using a generalized estimated equation. RESULTS: Comparison of scores before and after intervention showed that the intervention significantly decreased the severity of total motor tics (B = -3.28, p < .01) and total tics (B = -5.86, p < .01) as compared with control treatment. YGTSS scores for the intervention group were lower at 3-month follow-up as compared with before treatment or immediately after treatment completion (total tics, p < .001). CONCLUSION: The modified four-session Comprehensive Behavioral Intervention for Tics programme was more effective than routine care for decreasing tic severity in our cohort of 6- to 18-year olds. This improvement was maintained 3 months after intervention. IMPACT: Healthcare providers, including nurses, in countries currently not adopting Comprehensive Behavioral Intervention for Tics programme should be made aware of the positive effects of this modified intervention for Tourette's syndrome.

Effect of Endoplasmic Reticular Stress on Free Hemoglobin Metabolism and Liver Injury.

Elevated soluble (s) CD163 and free hemoglobin (Hb) levels predict fatty liver progression; however, the molecular mechanisms underlying Hb metabolism and liver injury remain undefined. We investigated the effects of endoplasmic reticular (ER) stress on red blood cell (RBC) rheology and free Hb recycling pathways. ER stress was induced in Sprague-Dawley rats by an intraperitoneal injection of tunicamycin (TM) (50, 100, and 200 µg/100 g body weight (BW)) or an intravenous injection of Hb (5 mg/100 g BW). A TM injection increased sCD163 levels, attenuated free Hb uptake, and maintained RBC aggregability. An Hb injection increased serum LVV-hemorphin-7 and total bilirubin levels, but this effect was suppressed by TM. A Western blot analysis showed that ER stress suppressed Hb degradation in the liver through downregulation of globin degradation proteins cathepsin D and glyoxalase-1, as well as heme degradation protein heme oxyganase-1 and keap-1 expression. An ER stress activator also increased the translocation of nuclear factor (NF)-κB (p65) and nuclear factor-erythroid 2-related factor 2 (Nrf2) to nuclei. In conclusion, ER stress triggers ineffective Hb metabolism via altering globin and heme iron degradation pathways. Inability to recycle and metabolize free Hb may underlie the association between iron dysfunction and liver injury.

Resveratrol Can Be Stable in a Medium Containing Fetal Bovine Serum with Pyruvate but Shortens the Lifespan of Human Fibroblastic Hs68 Cells.

This study is aimed at developing a method that can inhibit resveratrol (Res) degradation in Dulbecco's modified Eagle medium (DMEM) and at evaluating the effects of Res on the replicative lifespan of Hs68 cells. We hypothesized that Res can extend the lifespan of Hs68 cells if we can inhibit the oxidative degradation of Res in the medium. We found that the addition of ≥5 U/mL SOD to the medium could completely inhibit Res degradation in DMEM. Fetal bovine serum (FBS) contained 29.3 ± 1.1 U/mL of SOD activity. FBS could prevent Res degradation in the medium through SOD activity and Res-FBS interaction, but the regular FBS concentration (i.e., 10% FBS) exhibited an insufficient ability to completely inhibit Res degradation. We found that pyruvate (1 mM) could potentiate SOD to scavenge superoxide at approximately 2.2-fold. Thus, 10% FBS combined with pyruvate (1 mM) could completely inhibit Res degradation. When Res was not degraded, it still shortened the lifespan of Hs68 cells. Overall, the proposed method involving 10% FBS combined with pyruvate (1 mM) could completely prevent Res degradation. However, in contrast to our hypothesis, Res could induce the shortening of the lifespan of Hs68 cells. The stability of Res analogs (i.e., oxy-Res and acetyl-Res) in the medium and their effects on the lifespan of Hs68 cells were also investigated.

Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti-apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In Vivo.

BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. RESULTS: Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION: Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo.

Curcumin supplementation ameliorated vascular dysfunction and improved antioxidant status in rats fed a high-sucrose, high-fat diet.

Vascular endothelial dysfunction is a potential risk factor for cardiovascular disease. This study evaluated the effect of curcumin on factors associated with vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The experiment included 2 animal feeding phases. In the first feeding phase, male Sprague-Dawley rats were randomly divided into 2 groups: the control group (n = 8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks, the HSF group was randomly divided into 3 subgroups: the O group (n = 8) continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR, cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and glutathione peroxidase activities were increased in the OA group, while CAT levels were enhanced in the OC group. In conclusion, this study showed that curcumin supplementation and diet modification can inhibit HSF diet-induced vascular dysfunction potentially by enhancing NO production and antioxidant enzyme activities, thereby suppressing inflammation and oxidative damage in the vascular endothelium.

Item Response Theory Models for Ipsative Tests With Multidimensional Pairwise Comparison Items.

There is re-emerging interest in adopting forced-choice items to address the issue of response bias in Likert-type items for noncognitive latent traits. Multidimensional pairwise comparison (MPC) items are commonly used forced-choice items. However, few studies have been aimed at developing item response theory models for MPC items owing to the challenges associated with ipsativity. Acknowledging that the absolute scales of latent traits are not identifiable in ipsative tests, this study developed a Rasch ipsative model for MPC items that has desirable measurement properties, yields a single utility value for each statement, and allows for comparing psychological differentiation between and within individuals. The simulation results showed a good parameter recovery for the new model with existing computer programs. This article provides an empirical example of an ipsative test on work style and behaviors.