Neuroprotection effects of kynurenic acid-loaded micelles for the Parkinson's disease models.

Anti-glutamatergic agents may have neuroprotective effects against excitotoxicity that is known to be involved in the pathogenesis of Parkinson's disease (PD). One of these agents is kynurenic acid (KYNA), a tryptophan metabolite, which is an endogenous N-methyl-D-aspartic acid (NMDA) receptor antagonist. However, its pharmacological properties of poor water solubility and limited blood-brain barrier (BBB) permeability rules out its systemic administration in disorders affecting the central nervous system. Our aim in the present study was to investigate the neuroprotective effects of KYNA-loaded micelles (KYNA-MICs) against PD in vitro and in vivo. Lipid-based micelles (MICs) in conjunction with KYNA drug delivery have the potential to enhance the penetration of therapeutic drugs into a diseased brain without BBB obstacles. KYNA-MICs were characterized by particle size (105.8 ± 12.1 nm), loading efficiency (78.3 ± 4.23%), and in vitro drug release (approximately 30% at 24 h). The in vitro experiments showed that KYNA-MICs effectively reduced 2-fold protein aggregation. The in vivo studies revealed that KYNA was successfully delivered by 5-fold increase in neurotoxin-induced PD brains. The results showed significant enhancement of KYNA delivery into brain. We also found that the KYNA-MICs exhibited several therapeutic effects. The KYNA-MICs reduced protein aggregation of an in vitro PD model, ameliorated motor functions, and prevented loss of the striatal neurons in a PD animal model. The beneficial effects of KYNA-MICs are probably explained by the anti-excitotoxic activity of the treatment's complex. As the KYNA-MICs did not induce any appreciable side-effects at the protective dose applied to a chronic PD mouse model, our results demonstrate that KYNA provides neuroprotection and attenuates PD pathology.

Assessment System for Predicting Maximal Safe Range for Heel Height by Using Force-Sensing Resistor Sensors and Regression Models.

Women often wear high-heeled shoes for professional or esthetic reasons. However, high-heeled shoes can cause discomfort and injury and can change the body's center of gravity when maintaining balance. This study developed an assessment system for predicting the maximal safe range for heel height by recording the plantar pressure of participants' feet by using force-sensing resistor (FSR) sensors and conducting analyses using regression models. Specifically, 100 young healthy women stood on an adjustable platform while physicians estimated the maximal safe height of high-heeled shoes. The collected FSR data combined with and without personal features were analyzed using regression models. The experimental results showed that the regression model based on the pressure data for the right foot had better predictive power than that based on data for the left foot, regardless of the module. The model with two heights had higher predictive power than that with a single height. Furthermore, adding personal features under the condition of two heights afforded the best predictive effect. These results can help wearers choose maximal safe high-heeled shoes to reduce injuries to the bones and lower limbs.

Sample size determination for comparing accuracies between two diagnostic tests under a paired design.

With the progressive technology, many medical researches are aimed to develop diagnostic tests that can detect diseases faster and accurately. The assessment of the accuracy of the diagnostic test for classifying two groups is through the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). When a paired design is considered, the sample size determination requires the information about two AUC estimates and the corresponding variance and covariance of two AUC estimators. This paper derives the nonparametric estimators of the variance and covariance of two AUC estimators. The result is used to derive the sample size formula when the paired sample is planned. Since most of the results do not have a closed form, numerical results are provided under various scenarios.

Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy.

BACKGROUND: Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT. METHODS: We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3-6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage). RESULTS: Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03-4.08), T2 (OR, 2.08; 95% CI, 1.05-4.01), and T3 (OR, 3.94; 95% CI, 1.44-10.79) were independent predictors of death or disability at 90 days. CONCLUSION: Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.

Exploring the Outcomes and Satisfaction of Automated Physiological Monitoring Systems Among Nurses.

Vital signs are central to the assessment of physiologic functions of patients and must be included in the electronic health record. The purpose of this retrospective and cross-sectional design study was to evaluate use of-and satisfaction with-automated physiological monitoring systems. Usage data from a hospital database were analyzed 3, 6, and 12 months after implementation of the automated system (June 2018 to May 2019). In addition, questionnaires were completed by 168 nurses, and 20 nurses were interviewed between August/September 2020 and October/November 2020, respectively. Results revealed that usage frequency of automated physiological monitoring devices increased steadily with user familiarity. Although respondents indicated general satisfaction with the devices, system downtime, sufficiency of the battery charge, and data transmission speed were identified as needing correction to smooth workflow and boost work efficiency. Although most interviewees considered devices easy to use, some mentioned transmission speed of the gateway, scanner sensitivity, and accuracy of the ear thermometer as needing improvement. For nurses to use automated physiological monitoring devices fully, a user-friendly design in functions and features is vital, and in-service training and a streamlined workflow are recommended to facilitate technology adoption.

The association between total serum isomers of per- and polyfluoroalkyl substances, lipid profiles, and the DNA oxidative/nitrative stress biomarkers in middle-aged Taiwanese adults.

Per- and polyfluoroalkyl substances (PFAS) have been widely used in consumer products. In vitro and animal studies have demonstrated that exposure to perfluorooctanoic acid (PFOA) and/or perfluorooctane sulfonate (PFOS) increases oxidative/nitrative stress. Recent studies have also found that isomers of PFOA/PFOS may have unique biological effects on clinical parameters. However, the correlation between PFOA/PFOS isomers and markers of oxidative/nitrative stress has never been investigated in the general population. In the current study, 597 adult subjects (ages between 22 and 63 years old) were enrolled from a control group of a case-control study entitled "Work-related risk factors and coronary heart disease". We investigated the correlation between the serum isomers of PFOA/PFOS, lipid profiles, and the urine compounds 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NO2Gua) in these participants. There were 519 men and 78 women with a mean age of 45.8 years. Linear PFOA levels were positively correlated with serum low density lipoprotein cholesterol (LDL-C), small dense LDL, and triglyceride, and linear PFOS levels were positively correlated with LDL-C and HDL-C in multiple linear regression analyses. After controlling for potential confounders, the mean levels of 8-OHdG and 8-NO2Gua significantly increased across the quartiles of linear PFOS in multiple linear regression analyses. When both the 8-OHdG and 8-NO2Gua levels were above the 50th percentile, the odds ratio (OR) of higher levels of LDL-C (>75th percentile) with one unit increase in ln linear PFOS level was the highest (OR 3.15 (95% CI = 1.45-6.64), P = 0.003) in logistic regression models. In conclusion, serum linear PFOA/PFOS were correlated with lipid profiles, and linear PFOS was associated with urine oxidative/nitrative stress biomarkers. The positive correlation between linear PFOS and LDL-C was more marked when concentrations of urine oxidative/nitrative stress biomarkers were elevated. Further studies are needed to elucidate the causal relationships among PFAS isomers, lipid profiles, and oxidative/nitrative stress.

A five-year longitudinal study of the relation between end-stage kidney disease as the outcomes.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are required to undergo consecutive time-based blood and biochemical tests to determine the progression of the disease according to changes in their blood and biochemical data. This study employed a random intercept model to investigate whether time-based blood and biochemical data present any notable clinical meaning that can be used to track disease progression. METHODS: This study conducted a retrospective analysis on the dialytic data of 148 patients with ESKD, who received hemodialysis between January 2005 and December 2015. The patients were all at least 20 years old, and the data used included patient demographic information and results for at least 60 blood and biochemical tests. A random intercept model was used to analyze the relationships among blood and biochemical test results, explanatory variables of patient comorbidities, and time. RESULTS: The age range of patients was between 33 and 98 years, with an average of 66.1 years and those over 65 years old comprising 51.3% (n = 76) of the total. Furthermore, hypertension was found to be the most common comorbidity among patients (87.2%, n = 129), followed by anemia (48.6%, n = 72), diabetes (47.3%, n = 70), dyslipidemia (19.6%, n = 29), and peptic ulcer (19.6%, n = 29). Coronary atherosclerotic heart disease is a comorbidity that can serve as a strong and independent marker for prognosis in patients with ESKD. Serum creatinine level can serve as an alternative indicator because patients with ESKD and comorbid diabetes may exhibit increased creatinine levels. CONCLUSIONS: The results of a parameter estimation for longitudinal data analysis suggested that comorbidity and time were critical variables influencing blood and biochemical test results. Furthermore, WBC and HBC, HCT, albumin, protein, and creatinine levels were recognized as variables of critical significance. The results obtained in this study indicate that multimorbidity increases the treatment burden on patients, leading to polypharmacy. For this reason, comprehensive care and treatment of ESKD cannot rely solely on data from one single time point; instead, longitudinal analysis and other data that can affect patient prognosis must also be considered.

Urinary heavy metals, DNA methylation, and subclinical atherosclerosis.

PURPOSE: Lead (Pb) or cadmium (Cd) exposure has been linked to atherosclerosis. Co-exposure of these two heavy metals often occurs in humans. Recent evidence has indicated a crucial role of DNA methylation in atherosclerosis, while Pb or Cd exposure has also been shown to alter DNA methylation. However, it is still unknown whether DNA methylation plays a role in the pathological mechanism of these two heavy metals in atherosclerosis. APPROACH AND RESULTS: We enrolled 738 participants (12-30 years) to investigate the association among concentrations of urine Pb or Cd, the 5mdC/dG value (a global DNA methylation marker) and the carotid intima-media thickness (CIMT). When each heavy metal was modeled separately, the results showed urine Pb and Cd concentrations were positively associated with the 5mdC/dG value and CIMT, respectively. When the two heavy metals were analyzed in the same model, urinary Pb concentrations were positively associated with the 5mdC/dG value and CIMT, while urinary Cd concentrations were only positively associated with the CIMT. When Pb and Cd are simultaneously considered in the same logistic regression model, the odds ratios (OR) of thicker CIMT (greater than 75th percentile) with one unit increase in ln-Pb level was 1.67 (95% C.I. = 1.17-2.46, P = 0.005) when levels of 5mdC/dG were above 50th percentile, which is higher than 5mdC/dG bellow the 50th percentile (OR = 1.50 (95% C.I. = 0.96-2.35), P = 0.076). In structural equation model (SEM), Pb or Cd levels are directly associated with CIMT. Moreover, Pb or Cd had an indirect association with CIMT through the 5mdC/dG. When we considered Pb and Cd together, Pb levels had a direct association with CIMT and an indirect association with CIMT through the 5mdC/dG value, while Cd only had a direct association with CIMT. CONCLUSIONS: Our findings imply that Pb and Cd exposure might be associated with subclinical atherosclerosis, and global DNA methylation might mediate Pb-associated subclinical atherosclerosis in this young population. Future effort is necessary to elucidate the causal relationship.

Using Nursing Information and Data Mining to Explore the Factors That Predict Pressure Injuries for Patients at the End of Life.

This study investigated the association between patient characteristics and the occurrence of pressure injuries for patients at the end of life. A retrospective study was conducted using data collected from 2062 patients at the end of life between January 2007 and October 2015. In addition to demographic data and pressure injury risk assessment scale scores, injury history, disease type, and length of hospitalization were revealed as the major independent variables for predicting the occurrence of pressure injuries. Both χ tests and t tests were employed for binary variable analysis, and logistic regression was used to conduct multivariate analysis. Classification models were formulated through decision tree analysis, backpropagation neural network, and support vector machine algorithms. The rules obtained using the decision tree algorithm were analyzed and interpreted. The accuracy rate, sensitivity, and specificity of the decision tree, backpropagation neural network, and support vector machine algorithms were 77.15%, 79.54%, and 74.76%; 78.12%, 81.37%, and 74.85%; and 79.32%, 81.03%, and 78.75%, respectively. The predictive factors, ranked in order of importance, were history of pressure injuries, without cancer, excretion, activity/mobility, and skin condition/circulation. These were the primary shared risk factors among the four models used in this study.

Correction to: Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors.

In the original publication, the values provided for the isoflavone and glucosinolate intake variables were incorrectly labeled in Table 1. The correct values of 6.3 mg/day for isoflavone intake, and 20.4 mg/day and 50.1 mg/day for glucosinolate intake are provided in this erratum.

Dietary intake of soy and cruciferous vegetables and treatment-related symptoms in Chinese-American and non-Hispanic White breast cancer survivors.

PURPOSE: This project was undertaken to examine the association between dietary intake of soy or cruciferous vegetables and breast cancer treatment-related symptoms among Chinese-American (CA) and Non-Hispanic White (NHW) breast cancer survivors. METHODS: This cross-sectional study included 192 CA and 173 NHW female breast cancer survivors (stages 0-III, diagnosed between 2006 and 2012) recruited from two California cancer registries, who had completed primary treatment. Patient-reported data on treatment-related symptoms and potential covariates were collected via telephone interviews. Dietary data were ascertained by mailed questionnaires. The outcomes evaluated were menopausal symptoms (hot flashes, night sweats, vaginal dryness, vaginal discharge), joint problems, fatigue, hair thinning/loss, and memory problems. Associations between soy and cruciferous vegetables and symptoms were assessed using logistic regression. Analyses were further stratified by race/ethnicity and endocrine therapy usage (non-user, tamoxifen, aromatase inhibitors). RESULTS: Soy food and cruciferous vegetable intake ranged from no intake to 431 and 865 g/day, respectively, and was higher in CA survivors. Higher soy food intake was associated with lower odds of menopausal symptoms (≥ 24.0 vs. 0 g/day, OR 0.51, 95% CI 0.25, 1.03), and fatigue (≥ 24.0 vs. 0 g/day, OR 0.43, 95% CI 0.22, 0.84). However, when stratified by race/ethnicity, associations were statistically significant in NHW survivors only. Compared with low intake, higher cruciferous vegetable intake was associated with lower odds of experiencing menopausal symptoms (≥ 70.8 vs. < 33.0 g/day, OR 0.50, 95% CI 0.25, 0.97) in the overall population. CONCLUSIONS: In this population of breast cancer survivors, higher soy and cruciferous vegetable intake was associated with less treatment-related menopausal symptoms and fatigue.

Novel tests for evaluating two ROC curves under paired samples.

Disease prevention is important and can be accomplished by developing diagnostic tests. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) are used to assess the accuracy of diagnostic tests. The assessment for the superiority between evaluating two diagnostic tests is needed when comparing two diagnostic tests. Existing tests are constructed by comparing two AUCs under the paired samples. Nevertheless, it is problematic when two ROC curves are crossing. This article proposes a test that takes into account the possible correlation between pairs. Simulations are conducted to evaluate the feasibility of the test.

CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer.

BACKGROUND/PURPOSE: Lung cancer is a heterogeneous disease with varied outcomes. Molecular markers are eagerly investigated to predict a patient's treatment response or outcome. Previous studies used frozen biopsy tissues to identify crucial genes as prognostic markers. We explored the prognostic value of peripheral blood (PB) molecular signatures in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Peripheral blood mononuclear cell (PBMC) fractions from patients with advanced NSCLC were applied for RNA extraction, cDNA synthesis, and real-time polymerase chain reaction (PCR) for the expression profiling of eight genes: DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4, and ZNF264. Proportional hazard (PH) models were constructed to evaluate the association of the eight expressing genes and multiple clinical factors [e.g., sex, smoking status, and Charlson comorbidity index (CCI)] with overall survival. RESULTS: One hundred and forty-one patients with advanced NSCLC were enrolled. They included 109 (77.30%) patients with adenocarcinoma, 12 (8.51%) patients with squamous cell carcinoma, and 20 (14.18%) patients with other pathological lung cancer types. A PH model containing two significant survival-associated genes, CPEB4 and IRF4, could help in predicting the overall survival of patients with advanced stage NSCLC [hazard ratio (HR) = 0.48, p < 0.0001). Adding multiple clinical factors further improved the prediction power of prognosis (HR = 0.33; p < 0.0001). CONCLUSION: Molecular signatures in PB can stratify the prognosis in patients with advanced NSCLC. Further prospective, interventional clinical trials should be performed to test if gene profiling also predicts resistance to chemotherapy.

Joint model of multiple longitudinal measures and a binary outcome: An application to predict orthostatic hypertension for subacute stroke patients.

Stroke patients with orthostatic hypertensive responses that are one of the blood pressure regulation problems can easily fall down while doing rehabilitation, which may result in prolonged hospitalization and delayed treatment and recovery. This may result in increasing the medical cost and burden. In turn, developing a diagnostic test for the orthostatic hypertension (OH) is clinically important for patients who are suffering from stroke. Clinically, a patient needs to have a tilt testing that requires measuring the change of blood pressures and heart rate at all angles to determine whether a stroke patient has OH. It takes lots of time and effort to perform the test. Assuming there exist measurement errors when obtaining the blood pressures and heart rate at all angles, this paper proposes using multiple mixed-effect models to obtain the true trajectories of these measurements, which take into account the measurement error and the possible correlation among multiple measurements, and a logistic regression uses these true trajectories at a given time and other fixed-effect covariates as predictors to predict the status of OH. The joint likelihood function is derived to estimate parameters and the area under the receiver operating characteristics curve is used to estimate the predictive power of the model. Monte Carlo simulations are performed to evaluate the feasibility of the proposed methods. Also, the proposed model is implemented in the real data and provides an acceptable predictive power.

Evaluating Urine Cytology Slide Digitization Efficiency: A Comparative Study Using an Artificial Intelligence-Based Heuristic Scanning Simulation and Multiple Z-Plane Scanning.

INTRODUCTION: Digitizing cytology slides presents challenges because of their three-dimensional features and uneven cell distribution. While multi-Z-plane scan is a prevalent solution, its adoption in clinical digital cytopathology is hindered by prolonged scanning times, increased image file sizes, and the requirement for cytopathologists to review multiple Z-plane images. METHODS: This study presents heuristic scan as a novel solution, using an artificial intelligence (AI)-based approach specifically designed for cytology slide scanning as an alternative to the multi-Z-plane scan. Both the 21 Z-plane scan and the heuristic scan simulation methods were used on 52 urine cytology slides from three distinct cytopreparations (Cytospin, ThinPrep, and BD CytoRich™ [SurePath]), generating whole-slide images (WSIs) via the Leica Aperio AT2 digital scanner. The AI algorithm inferred the WSI from 21 Z-planes to quantitate the total number of suspicious for high-grade urothelial carcinoma or more severe cells (SHGUC+) cells. The heuristic scan simulation calculated the total number of SHGUC+ cells from the 21 Z-plane scan data. Performance metrics including SHGUC+ cell coverage rates (calculated by dividing the number of SHGUC+ cells identified in multiple Z-planes or heuristic scan simulation by the total SHGUC+ cells in the 21 Z-planes for each WSI), scanning time, and file size were analyzed to compare the performance of each scanning method. The heuristic scan's metrics were linearly estimated from the 21 Z-plane scan data. Additionally, AI-aided interpretations of WSIs with scant SHGUC+ cells followed The Paris System guidelines and were compared with original diagnoses. RESULTS: The heuristic scan achieved median SHGUC+ cell coverage rates similar to 5 Z-plane scans across three cytopreparations (0.78-0.91 vs. 0.75-0.88, p = 0.451-0.578). Notably, it substantially reduced both scanning time (137.2-635.0 s vs. 332.6-1,278.8 s, p < 0.05) and image file size (0.51-2.10 GB vs. 1.16-3.10 GB, p < 0.05). Importantly, the heuristic scan yielded higher rates of accurate AI-aided interpretations compared to the single Z-plane scan (62.5% vs. 37.5%). CONCLUSION: We demonstrated that the heuristic scan offers a cost-effective alternative to the conventional multi-Z-plane scan in digital cytopathology. It achieves comparable SHGUC+ cell capture rates while reducing both scanning time and image file size, promising to aid digital urine cytology interpretations with a higher accuracy rate compared to the conventional single (optimal) plane scan. Further studies are needed to assess the integration of this new technology into compatible digital scanners for practical cytology slide scanning.

Comparative evaluation of slide scanners, scan settings, and cytopreparations for digital urine cytology.

Background: Acquiring well-focused digital images of cytology slides with scanners can be challenging due to the 3-dimensional nature of the slides. This study evaluates performances of whole-slide images (WSIs) obtained from 2 different cytopreparations by 2 distinct scanners with 3 focus modes. Methods: Fourteen urine specimens were collected from patients with urothelial carcinoma. Each specimen was equally divided into 2 portions, prepared with Cytospin and ThinPrep methods and scanned for WSIs using Leica (Aperio AT2) and Hamamatsu (NanoZoomer S360) scanners, respectively. The scan settings included 3 focus modes (default, semi-auto, and manual) for single-layer scanning, along with a manual focus mode for 21 Z-layers scanning. Performance metrics were evaluated including scanning success rate, artificial intelligence (AI) algorithm-inferred atypical cell numbers and coverage rate (atypical cell numbers in single or multiple Z-layers divided by the total atypical cell numbers in 21 Z-layers), scanning time, and image file size. Results: The default mode had scanning success rates of 85.7% or 92.9%, depending on the scanner used. The semi-auto mode increased success to 92.9% or 100%, and manual even further to 100%. However, these changes did not affect the standardized median atypical cell numbers and coverage rates. The selection of scanners, cytopreparations, and Z-stacking influenced standardized median atypical cell numbers and coverage rates, scanning times, and image file sizes. Discussion: Both scanners showed satisfactory scanning. We recommend using semi-auto or manual focus modes to achieve a scanning success rate of up to 100%. Additionally, a minimum of 9-layer Z-stacking at 1 µm intervals is required to cover 80% of atypical cells. These advanced focus methods do not impact the number of atypical cells or their coverage rate. While Z-stacking enhances the AI algorithm's inferred quantity and coverage rates of atypical cells, it simultaneously results in longer scanning times and larger image file sizes.

Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial.

BACKGROUND: Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT. METHODS: First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre-post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group. RESULTS: This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre-post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded. CONCLUSIONS: For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.

Improvement in antioxidant activity, angiotensin-converting enzyme inhibitory activity and in vitro cellular properties of fermented pepino milk by Lactobacillus strains containing the glutamate decarboxylase gene.

BACKGROUND: The purpose of this study was to evaluate the functional potential of fermented pepino extract (PE) milk by Lactobacillus strains containing the glutamate decarboxylase (GAD) gene. Three Lactobacillus strains were selected, including L. brevis BCRC 12310, L. casei BCRC 14082 and L. salivarius subsp. salivarius BCRC 14759. The contents of free amino acids, total phenolics content, total carotenoids and the associated functional and antioxidant abilities were analyzed, including angiotensin-converting enzyme (ACE) inhibition activity, 1,1-diphenyl-2-picylhydrazyl (DPPH) radical-scavenging ability and oxygen radical absorbance capacity (ORAC). Cell proliferation of fermented PE milk was also evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RESULTS: Compared to the unfermented PE, fermented PE milk from Lactobacillus strains with the GAD gene showed higher levels of total phenolics, γ-aminobutyric acid, ACE inhibitory activity, DPPH, and ORAC. The viability of human promyelocytic leukemia cells (HL-60) determined by the MTT method decreased significantly when the cells were incubated with the PE and the fermented PE milk extracts. CONCLUSION: The consumption of fermented PE milk from Lactobacillus strains with the GAD gene is expected to benefit health. Further application as a health food is worthy of investigation. © 2012 Society of Chemical Industry.

Gene-Function-Based Clusters Explore Intricate Networks of Gene Expression of Circulating Tumor Cells in Patients with Colorectal Cancer.

Colorectal cancer (CRC) is a complex disease characterized by dynamically deregulated gene expression and crosstalk between signaling pathways. In this study, a new approach based on gene-function-based clusters was introduced to explore the CRC-associated networks of gene expression. Each cluster contained genes involved in coordinated regulatory activity, such as RAS signaling, the cell cycle process, transcription, or translation. A retrospective case-control study was conducted with the inclusion of 119 patients with histologically confirmed colorectal cancer and 308 controls. The quantitative expression data of 15 genes were obtained from the peripheral blood samples of all participants to investigate cluster-gene and gene-gene interactions. DUSP6, MDM2, and EIF2S3 were consistently selected as CRC-associated factors with high significance in all logistic models. CPEB4 became an insignificant factor only when combined with the clusters for cell cycle processes and for transcription. The CPEB4/DUSP6 complex was a prerequisite for the significance of MMD, whereas EXT2, RNF4, ZNF264, WEE1, and MCM4 were affected by more than two clusters. Intricate networks among MMD, RAS signaling factors (DUSP6, GRB2, and NF1), and translation factors (EIF2S3, CPEB4, and EXT2) were also revealed. Our results suggest that limited G1/S transition, uncontrolled DNA replication, and the cap-independent initiation of translation may be dominant and concurrent scenarios in circulating tumor cells derived from colorectal cancer. This gene-function-based cluster approach is simple and useful for revealing intricate CRC-associated gene expression networks. These findings may provide clues to the metastatic mechanisms of circulating tumor cells in patients with colorectal cancer.

Misspecification of a binary dependent variable in the logistic model controlling for the repeated longitudinal measures.

Many medical applications are interested to know the disease status. The disease status can be related to multiple serial measurements. Nevertheless, owing to various reasons, the binary outcome can be measured incorrectly. The estimators derived from the misspecified outcome can be biased. This paper derives the complete data likelihood function to incorporate both the multiple serial measurements and the misspecified outcome. Owing to the latent variables, EM algorithm is used to derive the maximum-likelihood estimators. Monte Carlo simulations are conducted to compare the impact of misspecification on the estimates. A retrospective data for the recurrence of atrial fibrillation is used to illustrate the usage of the proposed model.