Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Rational Approach to Improve Detergent Efficacy for Membrane Protein Stabilization.

Membrane protein structures are essential for the molecular understanding of diverse cellular processes and drug discovery. Detergents are not only widely used to extract membrane proteins from membranes but also utilized to preserve native protein structures in aqueous solution. However, micelles formed by conventional detergents are suboptimal for membrane protein stabilization, necessitating the development of novel amphiphilic molecules with enhanced protein stabilization efficacy. In this study, we prepared two sets of tandem malonate-derived glucoside (TMG) variants, both of which were designed to increase the alkyl chain density in micelle interiors. The alkyl chain density was modulated either by reducing the spacer length (TMG-Ms) or by introducing an additional alkyl chain between the two alkyl chains of the original TMGs (TMG-Ps). When evaluated with a few membrane proteins including a G protein-coupled receptor, TMG-P10,8 was found to be substantially more efficient at extracting membrane proteins and also effective at preserving protein integrity in the long term compared to the previously described TMG-A13. This result reveals that inserting an additional alkyl chain between the two existing alkyl chains is an effective way to optimize detergent properties for membrane protein study. This new biochemical tool and the design principle described have the potential to facilitate membrane protein structure determination.

Flavobacterium sp. strain GJW24 ameliorates drought resistance in Arabidopsis and Brassica.

Candidate strains that contribute to drought resistance in plants have been previously screened using approximately 500 plant growth-promoting rhizobacteria (PGPR) obtained from Gotjawal, South Korea, to further understand PGPR associated with plant drought tolerance. In this study, a selected PGPR candidate, Flavobacterium sp. strain GJW24, was employed to enhance plant drought tolerance. GJW24 application to Arabidopsis increased its survival rate under drought stress and enhanced stomatal closure. Furthermore, GJW24 promoted Arabidopsis survival under salt stress, which is highly associated with drought stress. GJW24 ameliorated the drought/salt tolerance of Brassica as well as Arabidopsis, indicating that the drought-resistance characteristics of GJW24 could be applied to various plant species. Transcriptome sequencing revealed that GJW24 upregulated a large portion of drought- and drought-related stress-inducible genes in Arabidopsis. Moreover, Gene Ontology analysis revealed that GJW24-upregulated genes were highly related to the categories involved in root system architecture and development, which are connected to amelioration of plant drought resistance. The hyper-induction of many drought/salt-responsive genes by GJW24 in Arabidopsis and Brassica demonstrated that the drought/salt stress tolerance conferred by GJW24 might be achieved, at least in part, through regulating the expression of the corresponding genes. This study suggests that GJW24 can be utilized as a microbial agent to offset the detrimental effects of drought stress in plants.

Foldable Detergents for Membrane Protein Stability.

Detergents are widely used for membrane protein structural study. Many recently developed detergents contain multiple tail and head groups, which are typically connected via a small and branched linker. Due to their inherent compact structures, with small inter-alkyl chain distances, these detergents form micelles with high alkyl chain density in the interiors, a feature favorably associated with membrane-protein stability. A recent study on tandem triazine maltosides (TZMs) revealed a distinct trend; despite possession of an apparently large inter-alkyl chain distance, the TZM-Es were highly effective at stabilizing membrane proteins. Thanks to the incorporation of a flexible spacer between the two triazine rings in the linker region, these detergents are prone to folding into a compact architecture in micellar environments instead of adopting an extended conformation. Detergent foldability represents a new concept of novel detergent design with significant potential for future detergent development.

A Genome-Wide Screen Reveals That Endocytic Genes Are Important for Pma1p Asymmetry during Cell Division in Saccharomyces cerevisiae.

An asymmetry in cytosolic pH between mother and daughter cells was reported to underlie cellular aging in the budding yeast Saccharomyces cerevisiae; however, the underlying mechanism remains unknown. Preferential accumulation of Pma1p, which pumps cytoplasmic protons out of cells, at the plasma membrane of mother cells, but not of their newly-formed daughter cells, is believed to be responsible for the pH increase in mother cells by reducing the level of cytoplasmic protons. This, in turn, decreases the acidity of vacuoles, which is well correlated with aging of yeast cells. In this study, to identify genes that regulate the preferential accumulation of Pma1p in mother cells, we performed a genome-wide screen using a collection of single gene deletion yeast strains. A subset of genes involved in the endocytic pathway, such as VPS8, VPS9, and VPS21, was important for Pma1p accumulation. Unexpectedly, however, there was little correlation between deletion of each of these genes and the replicative lifespan of yeast, suggesting that Pma1p accumulation in mother cells is not the key determinant that underlies aging of mother cells.

Glyco-Steroidal Amphiphiles (GSAs) for Membrane Protein Structural Study.

Integral membrane proteins pose considerable challenges to high resolution structural analysis. Maintaining membrane proteins in their native state during protein isolation is essential for structural study of these bio-macromolecules. Detergents are the most commonly used amphiphilic compounds for stabilizing membrane proteins in solution outside a lipid bilayer. We previously introduced a glyco-diosgenin (GDN) detergent that was shown to be highly effective at stabilizing a wide range of membrane proteins. This steroidal detergent has additionally gained attention due to its compatibility with membrane protein structure study via cryo-EM. However, synthetic inconvenience limits widespread use of GDN in membrane protein study. To improve its synthetic accessibility and to further enhance detergent efficacy for protein stabilization, we designed a new class of glyco-steroid-based detergents using three steroid units: cholestanol, cholesterol and diosgenin. These new detergents were efficiently prepared and showed marked efficacy for protein stabilization in evaluation with a few model membrane proteins including two G protein-coupled receptors. Some new agents were not only superior to a gold standard detergent, DDM (n-dodecyl-ß-d-maltoside), but were also more effective than the original GDN at preserving protein integrity long term. These agents represent valuable alternatives to GDN, and are likely to facilitate structural determination of challenging membrane proteins.

A Randomized Controlled Trial Comparing Neurofeedback and Cognitive-Behavioral Therapy for Insomnia Patients: Pilot Study.

Insomnia is a common disease that negatively affects patients both mentally and physically. While insomnia disorder is mainly characterized by hyperarousal, a few studies that have directly intervened with cortical arousal. This study was conducted to investigate the effect of a neurofeedback protocol for reducing cortical arousal on insomnia compared to cognitive-behavioral treatment for insomnia (CBT-I). Seventeen adults with insomnia, free of other psychiatric illnesses, were randomly assigned to neurofeedback or CBT-I. All participants completed questionnaires on insomnia [Insomnia Severity Index (ISI)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], and dysfunctional cognition [Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16)]. The neurofeedback group showed decreases in beta waves and increases in theta and alpha waves in various areas of the electroencephalogram (EEG), indicating lowered cortical arousal. The ISI and PSQI scores were significantly decreased, and sleep efficiency and sleep satisfaction were increased compared to the pre-treatment scores in both groups. DBAS scores decreased only in the CBT-I group (NF p = 0.173; CBT-I p = 0.012). This study confirmed that neurofeedback training could alleviate the symptoms of insomnia by reducing cortical hyperarousal in patients, despite the limited effect in reducing cognitive dysfunction compared to CBT-I.

[Effects of Early Oral Feeding versus Delayed Oral Feeding on Bowel Function, Gastrointestinal Complications and Surgical Recovery after Cesarean Section under Regional Anesthesia: Systematic Review and Meta-Analysis].

PURPOSE: This study aimed to assess combined effects of early oral feeding after Cesarean section (C/S) under regional anesthesia on bowel function, gastrointestinal complications and surgical recovery. METHODS: A systematic literature search was conducted using KISS, RISS, PubMed, CINAHL, EMBASE, CENTRAL and Google Scholar to identify randomized clinical trials comparing early oral feeding (EOF) with delayed oral feeding (DOF) after C/S. Outcome variables were bowel function and gastrointestinal complications and surgical recovery. Effect size was calculated using weighted mean differences (WMDs) and relative risks (RRs), with 95% confidence intervals (CIs). RESULTS: Seven studies involving 1,911 patients from 568 studies, 7 studies were included in meta-analysis. EOF was significantly associated with shorter time to recover bowel movement compared with DOF (WMD, -2.50; CI, -3.50~-1.50). EOF was not associated with nausea (RR, 1.15; CI, 0.87~1.53) and vomiting (RR, 0.96; CI, 0.65~1.42), but lower incidence of abdominal distension (RR, 0.70; CI, 0.50~0.98). EOF was significantly associated with shorter time to discontinuation of intravenous fluids (WMD, -8.88; 95% CI, -16.65~-1.11) and removal of urinary catheter (WMD, -15.23; CI, -25.62~-4.85). CONCLUSION: This meta-analysis provides evidence that EOF after C/S under regional anesthesia not only accelerates return of bowel function and surgical recovery but also reduces gastrointestinal complications. These results suggest that EOF should be offered to women who have undergone C/S to improve the recovery experience and reduce overall medical costs.

Cyclo-(l-Phe-l-Pro), a Quorum-Sensing Signal of Vibrio vulnificus, Induces Expression of Hydroperoxidase through a ToxR-LeuO-HU-RpoS Signaling Pathway To Confer Resistance against Oxidative Stress.

Vibrio vulnificus, an opportunistic human pathogen, produces cyclo-(l-Phe-l-Pro) (cFP), which serves as a signaling molecule controlling the ToxR-dependent expression of innate bacterial genes, and also as a virulence factor eliciting pathogenic effects on human cells by enhancing intracellular reactive oxygen species levels. We found that cFP facilitated the protection of V. vulnificus against hydrogen peroxide. At a concentration of 1 mM, cFP enhanced the level of the transcriptional regulator RpoS, which in turn induced expression of katG, encoding hydroperoxidase I, an enzyme that detoxifies H2O2 to overcome oxidative stress. We found that cFP upregulated the transcription of the histone-like proteins vHUα and vHUß through the cFP-dependent regulator LeuO. LeuO binds directly to upstream regions of vhuA and vhuB to enhance transcription. vHUα and vHUß then enhance the level of RpoS posttranscriptionally by stabilizing the mRNA. This cFP-mediated ToxR-LeuO-vHUαß-RpoS pathway also upregulates genes known to be members of the RpoS regulon, suggesting that cFP acts as a cue for the signaling pathway responsible for both the RpoS and the LeuO regulons. Taken together, this study shows that cFP plays an important role as a virulence factor, as well as a signal for the protection of the cognate pathogen.

Reliability and Validity of the Korean Translation of Quantitative Checklist for Autism in Toddlers: A Preliminary Study.

OBJECTIVES: We aimed to assess the test-retest reliability, internal consistency, and validity of the Korean version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT). METHODS: The Korean version of the Q-CHAT and the Korean version of the Child Behavior Checklist (CBCL) 1.5-5 were completed by parents of 24 toddlers and preschoolers with autism spectrum disorder (ASD) and 80 unselected toddlers and preschoolers. Parents of the ASD group also completed the Social Communication Questionnaire (SCQ), and Childhood Autism Rating Scale (CARS) scores were obtained from medical records. RESULTS: The ASD group scored higher on the Q-CHAT than the unselected group. The Cronbach's alpha coefficient of the Q-CHAT was 0.658, and test-retest reliability was calculated to be 0.836. The estimated area under the curve was 0.793. The total scores of the Q-CHAT in the ASD group demonstrated significant positive correlations with findings regarding pervasive development problems in the CBCL, SCQ, and CARS. A total score of 33.5 may be a useful cutoff point to use when identifying toddlers at risk of ASD. CONCLUSION: The Korean version of the Q-CHAT has good reliability and validity and can be used as a screening tool in order to identify toddlers and preschool children at risk of ASD.

Performance of APACHE IV in Medical Intensive Care Unit Patients: Comparisons with APACHE II, SAPS 3, and MPM0 III.

BACKGROUND: In this study, we analyze the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE IV, Simplified Acute Physiology Score (SAPS) 3, and Mortality Probability Model (MPM)0 III in order to determine which system best implements data related to the severity of medical intensive care unit (ICU) patients. METHODS: The present study was a retrospective investigation analyzing the discrimination and calibration of APACHE II, APACHE IV, SAPS 3, and MPM0 III when used to evaluate medical ICU patients. Data were collected for 788 patients admitted to the ICU from January 1, 2015 to December 31, 2015. All patients were aged 18 years or older with ICU stays of at least 24 hours. The discrimination abilities of the three systems were evaluated using c-statistics, while calibration was evaluated by the Hosmer-Lemeshow test. A severity correction model was created using logistics regression analysis. RESULTS: For the APACHE IV, SAPS 3, MPM0 III, and APACHE II systems, the area under the receiver operating characteristic curves was 0.745 for APACHE IV, resulting in the highest discrimination among all four scoring systems. The value was 0.729 for APACHE II, 0.700 for SAP 3, and 0.670 for MPM0 III. All severity scoring systems showed good calibrations: APACHE II (chi-square, 12.540; P=0.129), APACHE IV (chi-square, 6.959; P=0.541), SAPS 3 (chi-square, 9.290; P=0.318), and MPM0 III (chi-square, 11.128; P=0.133). CONCLUSIONS: APACHE IV provided the best discrimination and calibration abilities and was useful for quality assessment and predicting mortality in medical ICU patients.

A community- based hepatitis B linkage-to-care program: a case study on Asian Americans chronically infected with hepatitis B virus.

BACKGROUND: Hepatitis B is an important disease of ethnic disparity which affects Asian Americans and other minority populations disproportionately. Despite the high prevalence of hepatitis B in Asian Americans, many of them remain unscreened and untreated. A majority of the individuals chronically infected with hepatitis B virus (HBV) are not linked to care, for instance, due to a lack of culturally competent programs. There are many serious barriers preventing linkage to care (LTC), including personal, socio-cultural, and economic issues. The purpose of this study was to evaluate various barriers affecting LTC and to investigate the role and efficacy of a community-based Patient Navigator (PN) program in expediting LTC and in improving health outcomes for hepatitis B patients in a high risk population. METHODS: A total of 45 individuals chronically infected with HBV were identified through community screening events and were subsequently linked to patient navigators (PN), who then arranged for the patients to have a medical evaluation with a provider of their choice in their communities. The navigators kept detailed records of the patients' progress towards goal, and planned follow up visits for each patient. A self-report questionnaire was employed to assess patients' demographics, history of HBV infection, and barriers in accessing health care. Specifically, the levels of importance of the barriers due to language, culture, financial reasons were assessed. RESULTS: The study revealed that 38 of the 45 HBV infected individuals knew about their infection status from previous screening. Forty two out of 45 HBV infected individuals were linked to care within a 12 month period, demonstrating a high linkage rate. Most significant barriers identified were language and finance, followed by cultural barrier and others. CONCLUSION: There are specific barriers to accessing adequate care for the patients affected by chronic hepatitis B (CHB) in Korean American community. The implementation of a PN program in conjunction with the community network of health care providers may help to overcome the barriers and facilitate LTC in hepatitis B.

Glucose Levels in Culture Medium Determine Cell Death Mode in MPP(+)-treated Dopaminergic Neuronal Cells.

We previously demonstrated that 1-methyl-4-phenylpyridinium (MPP(+)) causes caspase-independent, non-apoptotic death of dopaminergic (DA) neuronal cells. Here, we specifically examined whether change of glucose concentration in culture medium may play a role for determining cell death modes of DA neurons following MPP(+) treatment. By incubating MN9D cells in medium containing varying concentrations of glucose (5~35 mM), we found that cells underwent a distinct cell death as determined by morphological and biochemical criteria. At 5~10 mM glucose concentration (low glucose levels), MPP(+) induced typical of the apoptotic dell death accompanied with caspase activation and DNA fragmentation as well as cell shrinkage. In contrast, MN9D cells cultivated in medium containing more than 17.5 mM (high glucose levels) did not demonstrate any of these changes. Subsequently, we observed that MPP(+) at low glucose levels but not high glucose levels led to ROS generation and subsequent JNK activation. Therefore, MPP(+)-induced cell death only at low glucose levels was significantly ameliorated following co-treatment with ROS scavenger, caspase inhibitor or JNK inhibitor. We basically confirmed the quite similar pattern of cell death in primary cultures of DA neurons. Taken together, our results suggest that a biochemically distinct cell death mode is recruited by MPP(+) depending on extracellular glucose levels.

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012.

BACKGROUND: Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. METHODS: New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. RESULTS: The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ≥35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ≥50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. CONCLUSIONS: Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00341601.

Teaching skills to use a computer mouse in preschoolers with developmental disabilities: shaping moving a mouse and eye-hand coordination.

We taught seven preschoolers with developmental disabilities to point-and-click with a computer mouse. The computer-based training program consisted of three parts, based on a task analysis of the behavioral prerequisites to point-and-click. Training 1 was designed to shape moving the mouse. Training 2 was designed to build eye-hand coordination by teaching the children to move the on-screen cursor onto specific items on the screen. Training 3 was designed to teach pressing and releasing the mouse button. An instructor provided prompts and blocking to facilitate skill acquisition. A multiple baseline design across participants was used to evaluate the effectiveness of the training program. The results showed that all participants learned to point-and-click after exposure to the training program.

Serum pro-hepcidin could reflect disease activity in patients with rheumatoid arthritis.

The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28< or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.

Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial.

PURPOSE: Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer. METHODS: We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m(2) (day 1 and 8) and oxaliplatin 100 mg/m(2) (day 1), every 3 weeks. RESULTS: Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4-25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1-6.5, 95% CI) and median overall survival was 8.3 months (5.8-10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%). CONCLUSIONS: The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs.

A multicenter phase II study of gemcitabine and S-1 combination chemotherapy in patients with unresectable pancreatic cancer.

PURPOSE: To confirm the efficacy and toxicity of gemcitabine and S-1 combination chemotherapy when used as a first-line therapy in patients with unresectable pancreatic cancer. METHODS: Patients with locally advanced or metastatic or recurrent pancreatic adenocarcinoma, which was histologically or cytologically proven, with at least one measurable lesion were eligible for the study. Gemcitabine at a dose of 1,000 mg/m2 was intravenously given over 30 min on days 1 and 8, while S-1 at a dose of 40 mg/m2 was orally given twice daily from day 1 to 14, and the cycle was repeated every 3 weeks. The objective response rate, which was assessed according to RECIST criteria, was the primary end point. RESULTS: A total of 38 patients were enrolled between June 2006 and June 2007. The median number of treatment courses was 5.5 (range 1-22). Thirty-four patients were evaluable for response. Although no complete response was seen, partial responses were achieved in 11 patients, resulting in an overall response rate of 32% [95% confidence interval (CI) 17-48%]. The median response duration was 6.0 months (95% CI 4.6-8.3 months), the median time-to-progression was 5.4 months (95% CI 2.9-8.0 months), and the median overall survival was 8.4 months (95% CI 5.7-11.1 months). The major grade 3/4 hematologic toxicities were neutropenia (39.5%), leukopenia (15.8%), thrombocytopenia (2.6%), and anemia (7.9%). The major grade 3/4 non-hematologic toxicities included anorexia (10.5%), stomatitis (2.6%), rash (7.9%), fatigue (7.9%) and hyperbilirubinemia (5.3%). CONCLUSIONS: Gemcitabine and S-1 combination chemotherapy was effective and tolerable in patients with unresectable pancreatic cancer.

Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B.

We have shown previously that hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. Most solid tumors contain hypoxic components and overexpression of cyclin D1. The purpose of the present study was to investigate the molecular mechanism by which momilactone B exerts its inhibitory effects on breast cancer cells. Momilactone B, extracted from Korean rice hulls, suppressed hypoxia-induced increases in phospho-STAT5, STAT5b, cyclin D1, and cdk4 protein levels in human breast cancer cells. STAT5b expression was inhibited by siRNA experiments leading to decreased cyclin D1. The effects of momilactone B on cell growth and apoptosis-related gene expression were investigated in breast cancer cells under hypoxic conditions (2% O2). Bax and p21 expression was found to be up-regulated, whereas ppRb and bcl-2 were down-regulated in momilactone B-treated cells under hypoxic conditions. However, the p53 protein level did not change. Flow cytometry with Annexin-FITC staining showed that the number of apoptotic cells increased in hypoxic cells treated with momilactone B compared with untreated hypoxic cells. Furthermore, caspase activity increased upon treatment with momilactone B under hypoxic conditions. These results indicate that momilactone B inhibits the growth of breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through STAT5b and a caspase-3 dependent pathway. We suggest that momilactone B accelerates hypoxia-induced apoptosis of human breast cancer cells through STAT5b, and may represent an effective chemopreventive or therapeutic agent against breast cancer.

Stimulus-stimulus pairing and subsequent mand acquisition of children with various levels of verbal repertoires.

Effects of a stimulus-stimulus pairing procedure on the subsequent acquisition of mand operants were investigated. An attempt was made to shape novel sounds that emerged through the pairing procedure into a mand. Six children, aged two to five years, with moderate to severe language and communication delays, participated. Two conditions were used following the pairing condition: postpairing and direct reinforcement. The emergence of mands was compared across these conditions. An additional analysis was made of the relation between participants' baseline verbal repertoires and the effects of the pairing and the emergence of mands. Results indicate the possibility of stimulus control from a stimulus-stimulus pairing to mand as shown in two of the participants who had demonstrated high rates of vocal play and low to no verbal repertoire prior to this study. Target vocal sounds during postpairing and direct reinforcement condition remained at zero to low levels for participants with high verbal repertoire and little vocal play, warranting future studies on relations between the pre-existing verbal repertoire and the effectiveness of stimulus-stimulus pairing.