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Background: Problematic mealtime behaviors and inadequate diet quality are pressing concerns for children with autism spectrum disorder (ASD). This study aimed to evaluate recruitment feasibility and baseline outcomes of the Autism Eats program for children under 3 years with ASD., Methods: Recruitment feasibility was assessed through reach and participation rates. The Healthy Eating Index (HEI-2015) scores were calculated from 3-day food records. Problematic mealtime behaviors were assessed with the Brief Autism Mealtime Behavior Inventory. Parental feeding practices were assessed using the Child Feeding Questionnaire. Anthropometric measurements of children and parents were taken. Weight-for-length percentiles were calculated based on the CDC growth charts. Descriptive statistics, one-sample t-tests, and Spearman's rho correlations were used for data analysis., Results: Of the contacted dyads, 74 % agreed to participate. All 51 enrolled dyads completed baseline survey (100 %), and 98 % completed 3-day food records and anthropometric measurements. Significantly higher problematic mealtime behaviors were observed, compared to the reference (e.g., Total score 55.7 vs. 32.5; p < .001). Children with ASD exhibited lower HEI-2015 scores than national data (e.g., Total score 59 vs. 62). A large proportion of the children (29 %) had a weight-for-length ≥ 95th percentile. Several significant associations were found among mealtime behaviors, diet quality, parental feeding practices, and weight status., Conclusion: Recruitment was highly feasible, and the findings suggest that early nutrition intervention may hold promise in addressing problematic mealtime behaviors and promoting healthier dietary habits in young children with ASD., Clinical Trial Registration: This trial has been registered at www., Clinicaltrials: gov (NCT05194345)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Obesity is a well-known cause of cardiovascular disease and metabolic disorders. Normal-weight obesity, where the body mass index(BMI) is within the normal range but the body fat percentage is high, also adversely impacts cardiovascular and metabolic health. This study explored the effects of whole-body circuit training using a weighted vest on serum resistin, insulin resistance, and cardiovascular disease risk factors in normal-weight obese women., Methods: Thirty-six normal-weight obese women were divided into three groups: Weighted Vest Circuit Training(WVCT)(n = 12), Body Weight Circuit Training(BWCT)(n = 12), and a Control group(CON)(n = 12). Participants in the WVCT and BWCT groups engaged in whole-body circuit training three times per week for eight weeks. Serum resistin, cardiovascular disease risk factors, and insulin resistance were measured before and after the intervention., Results: The study revealed significant and impactful findings. There were substantial improvements in body composition(Skeletal Muscle Mass: +7.5 %, p  = 0.042, d  = 0.80), Serum Resistin(-38.2 %, p  = 0.001, d  = 0.85), insulin resistance(HOMA-IR: 27.1 %, p  < 0.001, d  = 0.88), and a reduction in IL-6 levels(-25.4 %, p  = 0.082, d  = 0.60) in the WVCT group compared to the BWCT and CON groups. The WVCT group outperformed the other groups, demonstrating greater effectiveness in reducing cardiovascular risk factors., Conclusion: These findings have significant implications for healthcare. Whole-body circuit training with weighted vests has effectively improved body composition, reduced serum resistin, and lowered insulin resistance, reducing cardiovascular disease risk factors in normal-weight obese women. These results could inform and enhance the treatment and management of obesity-related cardiovascular and metabolic disorders., (© 2024 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Teachers experience significant stress with 93% reported high levels of stress (Herman et al., 2018), and literature examining teacher stress levels during the COVID-19 pandemic reveals that 30 percent of teachers experience significantly high levels of stress (Silva et al., 2021). Low levels of teacher well-being and higher levels of stress have been linked to punitive behavior management (Jennings & Greenberg, 2009) and lower student academic achievement (Goddard et al., 2000). The aim of the present study is to explore the relationship between teacher emotion and use of evidence-based instructional strategies that promote student success. In this study, 17 first-year teachers completed a novel measurement, inclusive of single-item scales intended to assess feelings of stress, efficacy, and school connectedness, several times a day, each day of the week, for 1 month. The classroom strategies assessment system of evidence-based academic and behavioral instructional strategies was used in weekly teacher observations. Results indicated validity between these single-item scales and established measures of teacher well-being. A positive relationship between teachers' in-the-moment well-being and evidence-based instruction was found, as well as substantial variation in teacher emotional response across days and weeks. Implications and future directions are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Factor mixture modeling (FMM) incorporates both continuous latent variables and categorical latent variables in a single analytic model clustering items and observations simultaneously. After two decades since the introduction of FMM to psychological and behavioral science research, it is an opportune time to review FMM applications to understand how these applications are utilized in real-world research. We conducted a systematic review of 76 FMM applications. We developed a comprehensive coding scheme based on the current methodological literature of FMM and evaluated common usages and practices of FMM. Based on the review, we identify challenges and issues that applied researchers encounter in the practice of FMM and provide practical suggestions to promote well-informed decision making. Lastly, we discuss future methodological directions and suggest how FMM can be expanded beyond its typical use in applied studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Factor mixture modeling (FMM) has been increasingly used in behavioral and social sciences to examine unobserved population heterogeneity. Covariates (e.g., gender, race) are often included in FMM to help understand the formation and characterization of latent subgroups or classes. This Monte Carlo simulation study evaluated the performance of one-step and three-step approaches to covariate inclusion across three scenarios, i.e., correct specification (study 1), model misspecification (study 2), and model overfitting (study 3), in terms of direct covariate effects on factors. Results showed that the performance of these two approaches was comparable when class separation was large and the specification of covariate effect was correct. However, one-step FMM had better class enumeration than the three-step approach when class separation was poor, and was more robust to the misspecification or overfitting concerning direct covariate effects. Recommendations regarding covariate inclusion approaches are provided herein depending on class separation and sample size. Large sample size (1000 or more) and the use of sample size-adjusted BIC (saBIC) in class enumeration are recommended., (© 2022. The Psychonomic Society, Inc.)

Background: Nonoccupational post-exposure prophylaxis (NPEP) is a short course of medication taken to reduce the likelihood of acquiring human immunodeficiency virus (HIV) infection upon exposure. A review of the literature demonstrates an urgent need for an empirically validated instrument that measures detailed knowledge of NPEP among the key population of men who have sex with men (MSM)., Methods: Semi-structured interviews, focus groups, and a cross-sectional survey with a sample of 419 MSM was conducted in 2018 in China to develop and psychometrically evaluate the new instrument, the NPEP Knowledge Scale. Exploratory and confirmatory factor analyses, differential item functioning analyses, and structural equation modeling were conducted using Mplus 7.4., Results: The NPEP Knowledge Scale demonstrated excellent reliability and validity. Cronbach's alpha was 0.903. The range of item R 2 were 0.527-0.969, p's < 0.001. Model estimated inter-item correlations ranged between 0.534 and 0.968. In addition, HIV knowledge, NPEP use, and NPEP knowledge were all significantly correlated., Conclusions: The NPEP Knowledge Scale is suitable for research, program evaluation, and clinical and community services that require using NPEP to minimize the ever-present risk of new HIV infections., (© 2023. The Author(s).)

Aims: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise., Materials and Methods: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%-10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study., Results: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.99% (95% confidence interval -1.24%, -0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p < .0001). Placebo-adjusted mean changes in fasting plasma glucose (-40.1 mg/dl) and body weight (-2.5 kg) at week 24 were statistically significant (p < .0001). In addition, a significant decrease in blood pressure, low-density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high-density lipoprotein cholesterol. No significant increase in treatment-related adverse events was observed for enavogliflozin., Conclusions: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Rising rates of mental health challenges among youths have become a significant concern following the COVID 19 pandemic. Although strong evidence supports the implementation of universal screening as a preventative approach to address unmet mental health concerns, the research is less clear surrounding the use of such data in decision-making processes when significant discrepancies between informants (e.g., students and teachers) exist. The purpose of the study was twofold. First, the study aimed to determine the degree of rater concordance between teachers and students on students' internalizing concerns. The second objective was to determine whether concordance on internalizing behaviors differs across ages/grades and if this differentially impacts distal (i.e., academic) outcomes. Results indicated that teachers and students demonstrated limited agreement on ratings of internalizing behaviors. However, when students and teachers agreed, higher and more positive emotional behaviors were linked to higher reading/math performance. Furthermore, patterns of informant dis/agreement and relationships between internalizing concerns and academic outcomes were similar across grade levels. Implications and areas for future research are discussed., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Autism spectrum disorder (ASD) is a developmental disorder that affects communication and social behaviors. Children with ASD often experience mealtime behavior challenges and selective eating behaviors. They also tend to consume fewer fruits and vegetables and more high-energy dense foods, compared to neurotypical peers. A nutrition intervention was designed to prevent the development of feeding disorders and the long-term negative health impacts associated with poor dietary intake. This randomized controlled trial will evaluate the feasibility and preliminary efficacy of the nutrition education intervention for children with ASD and their parents through the Early Intervention (EI) services. We will recruit EI providers and parent-child dyads (n = 48) from EI programs, and randomly assign them into Autism Eats intervention (n = 24) or enhance usual care (EUC) comparison group (n = 24). The Autism Eats is 10 weekly sessions delivered individually as part of EI, while the EUC group will receive only 1 nutrition education session and then weekly parent handouts. The Autism Eats integrates ASD-specific feeding strategies and behaviorally-focused intervention strategies such as goal setting. Feasibility indicators include reach/participation, attrition, completion, fidelity, compatibility, and qualitative participant feedback. Outcome measures include dietary intakes and mealtime behaviors of children with ASD using 3-day food records and a validated questionnaire, the Brief Autism Mealtime Behavior Inventory (BAMBI). We will examine whether there are differences in children's food intakes, variety, diet quality, and mealtime behaviors between Autism Eats and EUC groups at post-intervention and 5-month follow-up assessment. This study will provide critical data to inform a full-scale randomized controlled trial., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Latent profile analysis (LPA) identifies heterogeneous subgroups based on continuous indicators that represent different dimensions. It is a common practice to measure each dimension using items, create composite or factor scores for each dimension, and use these scores as indicators of profiles in LPA. In this case, measurement models for dimensions are not included and potential noninvariance across latent profiles is not modeled in LPA. This simulation study examined the robustness of LPA in terms of class enumeration and parameter recovery when the noninvariance was unmodeled by using composite or factor scores as profile indicators. Results showed that correct class enumeration rates of LPA were relatively high with small degree of noninvariance, large class separation, large sample size, and equal proportions. Severe bias in profile indicator mean difference was observed with intercept and loading noninvariance, respectively. Implications for applied researchers are discussed., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Patient-specific dose prediction improves the efficiency and quality of radiation treatment planning and reduces the time required to find the optimal plan. In this study, a patient-specific dose prediction model was developed for a left-sided breast clinical case using deep learning, and its performance was compared with that of conventional knowledge-based planning using RapidPlan™., Methods: Patient-specific dose prediction was performed using a contour image of the planning target volume (PTV) and organs at risk (OARs) with a U-net-based modified dose prediction neural network. A database of 50 volumetric modulated arc therapy (VMAT) plans for left-sided breast cancer patients was utilized to produce training and validation datasets. The dose prediction deep neural network (DpNet) feature weights of the previously learned convolution layers were applied to the test on a cohort of 10 test sets. With the same patient data set, dose prediction was performed for the 10 test sets after training in RapidPlan. The 3D dose distribution, absolute dose difference error, dose-volume histogram, 2D gamma index, and iso-dose dice similarity coefficient were used for quantitative evaluation of the dose prediction., Results: The mean absolute error (MAE) and one standard deviation (SD) between the clinical and deep learning dose prediction models were 0.02 ± 0.04%, 0.01 ± 0.83%, 0.16 ± 0.82%, 0.52 ± 0.97, - 0.88 ± 1.83%, - 1.16 ± 2.58%, and - 0.97 ± 1.73% for D 95% , D mean in the PTV, and the OARs of the body, left breast, heart, left lung, and right lung, respectively, and those measured between the clinical and RapidPlan dose prediction models were 0.02 ± 0.14%, 0.87 ± 0.63%, - 0.29 ± 0.98%, 1.30 ± 0.86%, - 0.32 ± 1.10%, 0.12 ± 2.13%, and - 1.74 ± 1.79, respectively., Conclusions: In this study, a deep learning method for dose prediction was developed and was demonstrated to accurately predict patient-specific doses for left-sided breast cancer. Using the deep learning framework, the efficiency and accuracy of the dose prediction were compared to those of RapidPlan. The doses predicted by deep learning were superior to the results of the RapidPlan-generated VMAT plan., (© 2021. The Author(s).)

Although collecting data from multiple informants is highly recommended, methods to model the congruence and incongruence between informants are limited. Bauer and colleagues suggested the trifactor model that decomposes the variances into common factor, informant perspective factors, and item-specific factors. This study extends their work to the trifactor mixture model that combines the trifactor model and the mixture model. This combined approach allows researchers to investigate the common and unique perspectives of multiple informants on targets using latent factors and simultaneously take into account potential heterogeneity of targets using latent classes. We demonstrate this model using student self-rated and teacher-rated academic behaviors ( N = 24,094). Model specification and testing procedures are explicated in detail. Methodological and practical issues in conducting the trifactor mixture analysis are discussed., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Factor mixture modeling (FMM) has been increasingly used to investigate unobserved population heterogeneity. This study examined the issue of covariate effects with FMM in the context of measurement invariance testing. Specifically, the impact of excluding and misspecifying covariate effects on measurement invariance testing and class enumeration was investigated via Monte Carlo simulations. Data were generated based on FMM models with (1) a zero covariate effect, (2) a covariate effect on the latent class variable, and (3) covariate effects on both the latent class variable and the factor. For each population model, different analysis models that excluded or misspecified covariate effects were fitted. Results highlighted the importance of including proper covariates in measurement invariance testing and evidenced the utility of a model comparison approach in searching for the correct specification of covariate effects and the level of measurement invariance. This approach was demonstrated using an empirical data set. Implications for methodological and applied research are discussed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: In China, non-occupational post-exposure prophylaxis (nPEP) is not a conventional service yet and nPEP related studies are very few. Recently, China's 13th Five Year Action Plan for HIV/AIDS Containment and Prevention examines the feasibility of including nPEP as one of the national strategies for HIV prevention. However, there is a concern that nPEP use might exacerbate high-risk sexual activities. In order to facilitate a research-based policy making of routinizing nPEP services, the current study examined potential effects of nPEP use on condom use and number of sexual partners among Chinese men who have sex with men (MSM) ., Methods: A cross-sectional survey was conducted in two cities of China in November and December 2018. Descriptive analyses of participants' sociodemographic and behavioral characteristics were conducted using SPSS 24.0. Mplus 7.4 was used to conduct confirmatory factor analysis and structural equation modeling., Results: The sample included 419 Chinese MSM with a mean age of 28.04 (SD = 9.71). Participants reported more positive anticipation of their own behaviors than other MSM's behaviors regarding condom use and number of sexual partners if nPEP were to be routinized in China. About 60% of participants reported discrepancies between anticipated individual and population behaviors as a potential result of routinization of nPEP services. Anticipated individual behavioral change was positively related to age and duration of residence in the current city, and negatively related to education. Anticipated population behavioral change was positively related to age. Anticipated behavioral discrepancy was positively related to being ethnic minority and never married., Conclusions: These findings identify a high-risk subgroup of MSM, who reported they would use condoms less and/or have more sexual partners when nPEP becomes available. This subgroup of MSM might benefit from targeted health interventions. Moreover, there is a clear discrepancy between anticipated individual and population behavioral changes regarding future routinization of nPEP services, suggesting incorporating nPEP services as a means of community development for MSM.

An emerging body of research has investigated the relationship between helping (as a type of organizational citizenship behaviour) and emotional exhaustion (as an aspect of employee health). Research has demonstrated a significant relationship between helping and emotional exhaustion, but the theoretical arguments for the causal direction vary across studies. Specifically, some researchers have conceptualized helping as an outcome of emotional exhaustion, while others have regarded helping as a predictor of emotional exhaustion. This lack of theoretical clarity in directionality hinders the field's ability to summarize existing empirical findings cohesively and elucidate theoretical mechanisms. Therefore, this study attempts to clarify the theoretical directionality between helping and emotional exhaustion using four waves of data collected at 6-month intervals. Autoregressive cross-lagged analyses with auto-correlations revealed that more helping was associated with less future emotional exhaustion from Wave 1 to Wave 2, but from Wave 2 to Wave 3, the directionality reversed, as less emotional exhaustion significantly predicted more future helping, and from Wave 3 to Wave 4, both prediction directions were no longer significant. The findings suggest that helping and emotional exhaustion reciprocally affect each other, though the reciprocal pattern may disappear across time. The present study sheds light on the theoretical relationship between helping and emotional exhaustion, and provides theoretical and practical implications., (© 2020 John Wiley & Sons, Ltd.)

Background: Simulation education is a learning method for improving self-efficacy and critical thinking skills. However, not much study has been done on how to use it for education on emergency cardiac arrest situations, for which a multidisciplinary team approach is required., Objectives: This study investigated the effects of simulation education on nursing students' self-efficacy and critical thinking skills in emergency cardiac arrest situations., Design: A quasi-experimental research approach with a crossover design was used to compare two types of simulation instruction methods., Participants and Setting: This study was conducted with 76 nursing students divided into two groups by order of instruction methods, in November and December 2016., Methods: Both groups of participants experienced a simulation lesson based on the same emergency scenario. Group A first completed a roleplay of an emergency cardiac arrest situation in a clinical setting, while Group B first listened to a lecture on the procedure. After ten days, Group A repeated the simulation exercise after listening to the lecture, while Group B completed the simulation exercise after the roleplay. The students' self-efficacy and critical thinking skills were measured using a questionnaire before and after each session., Results: In the first session, self-efficacy and critical thinking skills scores increased greatly from pretest to posttest for Group A in comparison to Group B; no statistically significant difference was found between the two groups. In the second session, Group B showed a significant increase between pretest and posttest, while Group A showed no significant difference., Conclusions: Conducting the simulation exercise after the roleplay was a more effective teaching method than conducting it after the lecture. Moreover, having the nursing students assume various roles in realistic roleplay situations combined with simulation exercises led to a deeper understanding of clinical situations and improved their self-efficacy and critical thinking skills., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: We previously reported the partial effectiveness of imatinib (also known as STI571, Glivec, or Gleevec) on anaplastic thyroid cancer (ATC) cells. Imatinib is a selective tyrosine kinase inhibitor that has been used for various types of cancer treatments. Recently, several reports have demonstrated that imatinib enhanced the sensitivity of cancer cells to other anticancer drugs. In this study, therefore, we investigated whether imatinib enhances the antitumor activity of docetaxel in ATC cells., Methods: Two ATC cell lines, FRO and KTC-2, were treated with imatinib and/or docetaxel. Cell survival assay and flow cytometry for annexin V were used to assess the induction of apoptosis. Changes of pro- and antiapoptotic factors were determined by Western blot. Nuclear factor-κB (NF-κB) activity was measured by DNA-binding assay. Tumor growth was also investigated in vivo., Results: The combined treatment significantly enhanced apoptosis compared with single treatment. ATC cells themselves expressed high levels of antiapoptotic factors, X-linked inhibitor of apoptosis (XIAP), and survivin. The treatment with docetaxel alone further increased their expressions; however, the combined treatment blocked the inductions. Although imatinib alone had no effect on NF-κB background levels, combined treatment significantly suppressed the docetaxel-induced NF-κB activation. Further, the combined administration of the drugs also showed significantly greater inhibitory effect on tumor growth in mice xenograft model., Conclusions: Imatinib enhanced antitumor activity of docetaxel in ATC cells. Docetaxel seemed to induce both pro- and antiapoptotic signaling pathways in ATC cells, and imatinib blocked the antiapoptotic signal. Thus, docetaxel combined with imatinib emerges as an attractive strategy for the treatment of ATC.

Primary dysmenorrhea is a common gynecological complaint among young women that is related to an autonomic nervous system (ANS) disturbance. Acupuncture is one of several therapeutic approaches for primary dysmenorrhea, since it can modulate ANS function. The heart rate variability (HRV) parameters such as high frequency (HF), low frequency (LF) and LF/HF ratio are generally accepted tools to assess ANS activity. The purpose of this study was to investigate the effects of acupuncture applied at Hegu (LI4) and Sanyinjiao (SP6) points on HRV of women with primary dysmenorrhea during the late luteal phase. The experimental design was a crossover and patient-blinded procedure. All subjects participated in Sham (SA) and Real Acupuncture (RA) procedure, separated by one month, in a crossover sequence. The participants included 38 women (mean age 22.3 years; weight 53.8 kg; height 162.6 cm). HRV measurement was 15 min before and 15 min after an acupuncture procedure. The RA procedure was performed at two bilateral acupoints, but needles were inserted subcutaneously to the acupuncture points for the SA procedure. The RA induced a significant decrease in LF/HF ratio and a significant increase in the HF power, while SA treatment caused a significant increase only in the HF power. Manual acupuncture at bilateral acupoints of LI4 and SP6 may play a role in dysmenorrhea treatment with autonomic nervous system involvement.

Recently, we demonstrated that pro-inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 played a critical role in cisplatin-induced cochlear injury and that flunarizine, known as a T-type Ca(2+) channel antagonist, induced a cytoprotective effect against cisplatin cytotoxicity in HEI-OC1 cells by the activation of NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) cascade through PI3K-Akt signaling but calcium-independent pathway. We report here that flunarizine markedly attenuates cisplatin-induced pro-inflammatory cytokine secretion and their messenger RNA transcription as well as cisplatin cytotoxicity through the activation of Nrf2/HO-1 and downregulation of NF-kappaB. In HEI-OC1 cells, overexpression of Nrf2/HO-1 by gene transfer or pharmacological approaches attenuated cisplatin-induced cytotoxicity and pro-inflammatory cytokine production. On the contrary, inhibition of Nrf2/HO-1 signaling by pharmacological inhibitors or specific small interfering RNAs significantly abolished the beneficial effects of flunarizine. Flunarizine also attenuated cisplatin-mediated MAPK activation and pharmacological inhibition of MAPKs, especially MEK1/ERK, blocked cisplatin-induced NF-kappaB activation in HEI-OC1 cells. Furthermore, WT-Nrf2 overexpression effectively blocked MAPK activation after cisplatin exposure. Finally, orally administrated Sibelium, the trade name of flunarizine, suppressed the increase of pro-inflammatory cytokines by cisplatin in both serum and cochleas of mice, whereas it increased HO-1 expression in cochleas. These results indicate that flunarizine induces a protective effect against cisplatin ototoxicity through the downregulation of NF-kappaB by Nrf2/HO-1 activation and the resulting inhibition of pro-inflammatory cytokine production in vitro and in vivo.

An electronic transition of the AlC2 radical (C2v structure) has been observed using laser-induced fluorescence spectroscopy. The molecule was prepared in a supersonic expansion by ablation of an aluminum rod in the presence of acetylene gas. A spectrum was recorded in the 451-453 nm region and assigned to the C 2B2-X 2A1 system (T0 = 22,102.7 cm(-1)) based on a rotational analysis and agreement with calculated molecular parameters and excitation energies. Ab initio results obtained using couple cluster methods are in accord with previous theoretical work which concludes that ground-state AlC2 possesses a T-shaped C2v 2A1 geometry, with the linear 2Sigma+ AlCC isomer 0.70 eV higher in energy. A fit of the experimental spectrum yields rotational constants in the ground and electronically excited states that are in reasonable agreement with the calculated values: A'' = 1.7093(107), B'' = 0.4052(50), C'' = 0.3228(49) cm(-1) for the X 2A1 state, and A' = 1.5621(137), B' = 0.4028(46), C' = 0.3201(54) cm(-1) for C 2B2. Variation in individual fluorescence lifetimes suggests that the emitting C 2B2 state undergoes rovibronic mixing with lower lying electronic states.

The ototoxicity of cisplatin, a widely used chemotherapeutic agent, involves a number of mechanisms, including perturbation of redox status, increase in lipid peroxidation, and formation of DNA adducts. In this study, we demonstrate that cisplatin increased the early immediate release and de novo synthesis of proinflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, through the activation of ERK and NF-kappaB in HEI-OC1 cells, which are conditionally immortalized cochlear cells that express hair cell markers. Both neutralization of proinflammatory cytokines and pharmacologic inhibition of ERK significantly attenuated the death of HEI-OC1 auditory cells caused by cisplatin and proinflammatory cytokines. We also observed a significant increase in the protein and mRNA levels of proinflammatory cytokines in both serum and cochleae of cisplatin-injected rats, which was suppressed by intraperitoneal injection of etanercept, an inhibitor of TNF-alpha. Immunohistochemical studies revealed that TNF-alpha expression was mainly located in the spiral ligament, spiral limbus, and the organ of Corti in the cochleae of cisplatin-injected rats. NF-kappaB protein expression, which overlapped with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling-positive signal, was very strong in specific regions of the cochleae, including the organ of Corti, spiral ligament, and stria vascularis. These results indicate that proinflammatory cytokines, especially TNF-alpha, play a central role in the pathophysiology of sensory hair cell damage caused by cisplatin.

A new approach has been developed for the purpose of measuring the electronic transitions to bound exited states for cations that have been collisionally relaxed to low vibrational and rotational temperatures. This has been used to obtain the first gas phase electronic spectra of the protonated polyacetylenes using a two-color ion-photodissociation approach. Specifically, the origin bands in the B (1)A(1)<-- X(1)A(1) transitions of HC(6)H(2) (+) and HC(8)H(2) (+) (C(2v) geometry) were observed at 26,403.3 and 21,399.8 cm(-1). Data on such cooled systems allow a direct comparison between laboratory and astrophysical measurements.

The CD99 gene encodes two distinct transmembrane proteins by alternative splicing of its transcript. To examine the effects of two CD99 isoforms on the invasive phenotypes of breast cancer cells, MDA-MB-231 and MCF-7 human breast cancer cell lines were stably transfected with CD99 cDNAs encoding the major wild-type form (type I) or a minor splice variant (type II). As a result, expression of CD99 type II, but not type I, markedly elevated the motility, binding to fibronectin, MMP-9 expression, and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. In MDA-MB-435 breast cancer cells expressing both CD99 type I and type II, invasion-related cellular activities were inhibited by the transfection of small interfering RNA (siRNA) targeted to CD99 type II. Meanwhile, CD99 type II-induced MMP-9 expression in MDA-MB-231 cells was shown to be mediated by the binding of AP-1 factors to the MMP-9 gene promoter. Gel shift assay revealed that ligation of CD99 type II with antibody resulted in the binding of JunD to the AP-1 site of the MMP-9 promoter region. Initiation of CD99 type II signaling by antibody ligation increased expression of JunD and FosB AP-1 factors, along with phosphorylation of Src, Akt, p38 MAPK, ERK, and JNK. Knockdown of JunD and FosB by siRNA transfection abolished the positive effects of CD99 type II on the motility and MMP-9 expression of MDA-MB-231 cells. Increased expression of JunD and FosB as well as elevated cell motility and MMP-9 expression by CD99 type II ligation were also abrogated by inhibitors, dominant-negative forms, and siRNAs for Akt1, ERK1/2, and JNK1 but not for p38 MAPK. These results suggest that expression of a splice variant of CD99 contributes to the invasive ability of human breast cancer cells by up-regulating AP-1-mediated gene expression through the Akt-dependent ERK and JNK signaling pathways.

(+)-(18-crown-6)-tetracarboxylic acid (18C6H4) has been known as a highly efficient chiral selector for resolving primary amine enantiomers in capillary electrophoresis (CE). We investigated the chiral separation of gemifloxacin using 18C6H4 in analytical counter-current chromatography (CCC). The separation conditions for CE, including the binding constant, pH, and run buffer constituents, provided a helpful guideline for chiral CCC. A successful separation of gemifloxacin enantiomers could be achieved using a two-phase solvent system composed of 1-butanol-ethyl-acetate-bis(2-hydroxyethyl)aminotris(hydroxymethyl)methane acetate buffer with a small amount of 18C6H4. The hydrophobicity of the solvent system and the 18C6H4 concentration were varied to optimize the chiral separation.

The pure rotational spectrum of the ethyl radical (C2H5) has been detected for the first time with the Fourier transform millimeter-wave spectrometer. The ethyl radical is produced by discharging the C2H5I gas diluted in Ar. The 1(01)-0(00) rotational transition of the ethyl radical is observed in the frequency range from 43,680 to 43,780 MHz. The observed spectrum shows a very complicated pattern of the fine and hyperfine structures of a doublet radical with the nuclear spins of five protons. The fine and hyperfine components are assigned with the aid of measurements of the Zeeman splittings. As a result, the 22 lines are ascribed to the transitions in the ground vibronic state (A2"). The rotational constant, the spin-rotation interaction constant, and hyperfine interaction constants are determined by the least-squares fit. The Fermi contact term of the alpha-proton is determined to be -64.1654 MHz in the gas phase, indicating that the structure of the -CH2 is essentially planar. The present rotational spectroscopic study further supports that the methyl group of the ethyl radical can be regarded as a nearly free internal rotor with a low energy barrier. A few unassigned lines still remain, which may be vibrational satellites of the internal rotation mode., (Copyright 2004 American Institute of Physics)

Earlier report showed that expression of a splice variant of CD99 transmembrane protein increases invasive ability of human breast cancer cells. Cell motility was also significantly enhanced by the CD99 splice variant expression. In an effort to identify the cellular components that mediate a signal transduction pathway triggered by the CD99 splice variant, known signal path inhibitors were examined for their effects on the motility of the CD99 splice variant-transfected MDA-MB-231 breast cancer cells. Phenylarsine oxide, an inhibitor of phosphatase specific for focal adhesion kinase, and PP1, an inhibitor of src kinase family, significantly suppressed motility of the cells. Among different types of src transfectant clones generated, kinase-negative mutant src transfectant cells were 80% less motile than the mock cells transfected with an empty-vector, while v-src and c-src transfectants exhibited cell motility levels at or slightly above the mock transfectant. These results suggest that src and focal adhesion kinase mediate the intracellular signaling pathway of a CD99 splice variant for the induction of motility of human breast cancer cells.