The direct effect of lipopolysaccharide on an isolated heart is different from the effect on cardiac myocytes in vitro.

Introduction: Lipopolysaccharide (LPS) is widely used to induce experimental animals. However, its effects on cardiac contraction is controversial. Although LPS probably induces its influence in vivo both directly and indirectly, we focused on the direct effects of LPS in this report. Material and methods: Isolated ventricular myocytes mounted on a Langendorff apparatus were perfused with LPS. The changes in cultured H9c2 cells incubated with LPS over a 3-h exposure were compared with the changes after a 24-h incubation. Apoptosis was identified using flow cytometry and Western blotting. The mRNA levels were also determined. Results: LPS directly stimulated cardiac contractility at low doses, although it produced inhibition at higher doses. The TLR4-coupled JAK2/STAT3 pathway was identified in H9c2 cells after LPS treatment, with an increase in intracellular calcium levels. LPS dose-dependently activated hypertrophic signals in H9c2 cells and induced apoptosis at the high dose. However, apoptosis was observed in H9c2 cells after a 24-h exposure to LPS, even at low doses. This observation appears to be associated with the level of paracrine cytokines. Changes in H9c2 cells by LPS were diminished by NPS2390, an inhibitor of the calcium-sensing receptor (CaSR). LPS also promoted CaSR mRNA expression in H9c2 cells, which may be unrelated to the changes in cytokine expression influenced by an inflammasome inhibitor. Conclusions: In contrast to the isolated hearts, LPS activated hypertrophic signals prior to apoptotic signals in cardiac cells. Thus, LPS injury appears to be associated with CaSR, which was not markedly influenced by an inflammasome inhibitor.

Thymoquinone activates imidazoline receptor to enhance glucagon-like peptide-1 secretion in diabetic rats.

Introduction: Thymoquinone (TQ) is one of the principal bioactive ingredients proven to exhibit anti-diabetic effects. Recently, glucagon-like peptide-1 (GLP-1) has been found to be involved in antidiabetic effects in rats. The aim of this study was to evaluate the mediation of GLP-1 in the antidiabetic effect of TQ and to understand the possible mechanisms. Material and methods: NCI-H716 cells and CHO-K1 cells were used to investigate the effects of TQ on GLP-1 secretion in vitro. In type 1 diabetic rats, the changes in plasma glucose and GLP-1 levels were evaluated with TQ treatment. Results: The direct effect of TQ on imidazoline receptors (I-Rs) was identified in CHO-K1 cells overexpressing I-Rs. Additionally, in the intestinal NCI-H716 cells that may secrete GLP-1, TQ treatment enhanced GLP-1 secretion in a dose-dependent manner. However, these effects of TQ were reduced by ablation of I-Rs with siRNA in NCI-H716 cells. Moreover, these effects were inhibited by BU224, the imidazoline I2 receptor (I-2R) antagonist. In diabetic rats, TQ increased plasma GLP-1 levels, which were inhibited by BU-224 treatment. Functionally, TQ-attenuated hyperglycemia is also evidenced through GLP-1 using pharmacological manipulations. Conclusions: This report demonstrates that TQ may promote GLP-1 secretion through I-R activation to reduce hyperglycemia in type-1 diabetic rats.

Psychophysiological factors as predictors of second language writing achievement in a computer-based test.

Sleep quality, personality, and cognitive load potentially increase second language writing (SLW) anxiety and subsequently affect SLW achievement. This study investigates the predictions of sleep quality, personality (social inhibition/ negative affectivity), and cognitive load (content/ computer) toward SLW anxiety and achievement in a computer-based test. Participants included 172 voluntary undergraduates majoring in English as foreign language. SLW anxiety in a computer-based test, sleep disturbance, personality and cognitive load was assessed with the SLW Anxiety Inventory, Pittsburg Sleep Quality Index, Type-D Personality, and cognitive load questionnaires. A structural equation modeling approach was applied to examine the interdependence among the observed variables. An adequate-fit SLW anxiety model was built (X2 = 6.37, df = 6, p = 0.383, NFI = 0.97, CFI = 1.00, RMSEA = 0.02; R-squared multiple correlations: SLW anxiety in a computer-based test = 0.19, computer-based SLW achievement = 0.07). The structural model showed that sleep disturbance (+0.17), social inhibition personality (+0.31), and computer-induced cognitive load (+0.16) were significant predictors of SLW anxiety in a computer-based test. Subsequently, SLW anxiety in a computer-based test (-0.16) and computer-induced cognitive load (-0.16) were significant negative predictors of computer-based SLW achievement.

GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats.

Background: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia. Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9-39 (Ex 9-39) were separately administered to TQ- or vehicle-treated diabetic rats. Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9-39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects. Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.

Bevacizumab Dose Affects the Severity of Adverse Events in Gynecologic Malignancies.

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal-Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria.

Primary Ewing Family of Tumor Arising in the Ovary: A Case Report.

Ewing sarcoma and peripheral primitive neuroectodermal tumor constitute the Ewing family of tumors (EFT). EFTs primarily arising in the ovary are extremely rare. We report the case of a 22-yr-old nulliparous woman with a primary EFT in the ovary that initially presented as a 3-cm teratoma-like ovarian tumor, with rapid progression to a 15-cm-sized tumor with liver metastasis in 3 mo. The patient underwent suboptimal debulking surgery and salvage chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide. In conclusion, primary EFT in the ovary is extremely rare with highly aggressive behavior and poor outcome for metastatic disease. Demonstration of EWSR1 rearrangement, observed in a variety of soft tissue tumors, is very helpful in the diagnosis of EFT when interpreted on the basis morphology and immunohistochemistry.

Risk Factors of Hypersensitivity to Carboplatin in Patients with Gynecologic Malignancies.

We evaluated the prevalence of and risk factors for hypersensitivity reactions related to carboplatin, which is commonly used to treat gynecological malignancies. All women with pathologically documented ovarian, fallopian tube, or primary peritoneal cancer treated with carboplatin alone or a carboplatin-based combination chemotherapy regimen at a single hospital between January 2006 and December 2013 were retrospectively recruited. We analyzed the incidence, characteristics, risk factors, management, and outcomes of carboplatin-related hypersensitivity reactions among these patients. Among 735 eligible women, 75 (10.2%) experienced a total of 215 carboplatin-related hypersensitivity reaction events. The annual incidence of carboplatin-related hypersensitivity reactions gradually increased from 0.88% in 2006 to 5.42% in 2013. The incidence of carboplatin-related hypersensitivity was higher in patients with advanced stage disease (P < 0.001, Kruskal-Wallis test), serous and mixed histological types (P = 0.003, Kruskal-Wallis test), malignant ascites (P = 0.009, chi-square test), and history of other drug allergy (P < 0.001, chi-square test). Compared to women without hypersensitivity reactions, women who experienced hypersensitivity reactions had a significantly greater median cycle number (12 vs. 6, P < 0.001, independent sample t-test) and dose (6,816 vs. 3,844 mg, P < 0.001, independent sample t-test). The cumulative incidence of carboplatin-related hypersensitivity reactions dramatically increased with >8 cycles or dose >3,500 mg. Therefore, disease severity, histological type, malignant ascites, past drug allergies, and cumulative carboplatin dose are risk factors for carboplatin-related hypersensitivity reactions. Such reactions could potentially be reduced or prevented by slowing the infusion rate and using a desensitization protocol involving anti-allergy medications.

Computer-Detected Attention Affects Foreign Language Listening but Not Reading Performance.

No quantitative study has explored the influence of attention on learning English as a foreign language (EFL). This study investigated whether computer-detected attention is associated with EFL reading and listening and reading and listening anxiety. Traditional paper-based English tests used as entrance examinations and tests of general trait anxiety, reading, listening, reading test state anxiety, and listening test state anxiety were administered in 252 Taiwan EFL college students who were divided into High Attention (Conners' Continuous Performance Test, CPT < 50) and Low Attention (CPT ≥ 50) groups. No differences were found between the two groups for traditional paper-based English tests, trait anxieties, general English reading anxiety scales, and general English listening anxiety scales. The Low Attention group had higher test state anxiety and lower listening test scores than the High Attention group, but not in reading. State anxiety during listening tests for EFL students with computer-detected low attention tendency was elevated and their EFL listening performance was affected, but those differences were not found in reading.

Effects of audio-visual aids on foreign language test anxiety, reading and listening comprehension, and retention in EFL learners.

This study examined the effects of audio-visual aids on anxiety, comprehension test scores, and retention in reading and listening to short stories in English as a Foreign Language (EFL) classrooms. Reading and listening tests, general and test anxiety, and retention were measured in English-major college students in an experimental group with audio-visual aids (n=83) and a control group without audio-visual aids (n=94) with similar general English proficiency. Lower reading test anxiety, unchanged reading comprehension scores, and better reading short-term and long-term retention after four weeks were evident in the audiovisual group relative to the control group. In addition, lower listening test anxiety, higher listening comprehension scores, and unchanged short-term and long-term retention were found in the audiovisual group relative to the control group after the intervention. Audio-visual aids may help to reduce EFL learners' listening test anxiety and enhance their listening comprehension scores without facilitating retention of such materials. Although audio-visual aids did not increase reading comprehension scores, they helped reduce EFL learners' reading test anxiety and facilitated retention of reading materials.

Revealing topological superconductivity in extended quantum spin Hall Josephson junctions.

Quantum spin Hall-superconductor hybrids are promising sources of topological superconductivity and Majorana modes, particularly given recent progress on HgTe and InAs/GaSb. We propose a new method of revealing topological superconductivity in extended quantum spin Hall Josephson junctions supporting "fractional Josephson currents." Specifically, we show that as one threads magnetic flux between the superconductors, the critical current traces an interference pattern featuring sharp fingerprints of topological superconductivity-even when noise spoils parity conservation.

Poor sleep quality measured by polysomnography in non-obese asthmatic children with or without moderate to severe obstructive sleep apnea.

BACKGROUND: The co-effect of asthma and obstructive sleep apnea (OSA) on sleep quality among children remained unclear. OBJECTIVE: To compare sleep quality and emotional/behavioral problems among asthmatic and non-asthmatic children with or without moderate to severe obstructive sleep apnea. METHOD: An AHI-range-matched BMI-range-matched cross-sectional design was used to examine polysomnographic evaluation and emotional/behavioral problems in 102 non-obese children aged between 6 and 12 years old, categorized as with or without asthma and sleep disordered breathing. RESULTS: Asthmatic children in AHI ≤ 5/h group revealed a significantly longer sleep latency, a greater leg movement index (LMI), and a lower ratio of slow wave sleep compared with non-asthmatic AHI ≤ 5/h group. Compared with non-asthmatic AHI > 5/h group, asthmatic children displayed a higher ratio of REM sleep, sleep stage 1 and 2, a lower ratio of slow wave sleep, as well as a greater respiratory arousal index and LMI. There was no significant difference in emotional/behavior problems among groups. CONCLUSION: Sleep disturbance exists in asthmatic children with or without moderate to severe obstructive sleep apnea. Non-obese asthmatic children had less slow wave sleep compared with non-asthmatic children. We might recommend that sleep quality could be noticed and evaluated in children with asthma.

Electrical manipulation of Majorana fermions in an interdigitated superconductor-ferromagnet device.

We show that a topological phase supporting Majorana fermions can form in a two-dimensional electron gas (2DEG) adjacent to an interdigitated superconductor-ferromagnet structure. An advantage of this setup is that the 2DEG can induce the required Zeeman splitting and superconductivity from a single interface, allowing one to utilize a wide class of 2DEGs including the surface states of bulk InAs. We demonstrate that the interdigitated device supports a robust topological phase when the finger spacing λ is smaller than half of the Fermi wavelength λ(F). In this regime, the electrons effectively see a "smeared" Zeeman splitting and pairing field despite the interdigitation. The topological phase survives even in the opposite limit λ > λ(F)/2, although with a reduced bulk gap. We describe how to electrically generate a vortex in this setup to trap a Majorana mode, and predict an anomalous Fraunhofer pattern that provides a sharp signature of chiral Majorana edge states.

Effects of computer-based immediate feedback on foreign language listening comprehension and test-associated anxiety.

This study investigated the effects of immediate feedback on computer-based foreign language listening comprehension tests and on intrapersonal test-associated anxiety in 72 English major college students at a Taiwanese University. Foreign language listening comprehension of computer-based tests designed by MOODLE, a dynamic e-learning environment, with or without immediate feedback together with the state-trait anxiety inventory (STAI) were tested and repeated after one week. The analysis indicated that immediate feedback during testing caused significantly higher anxiety and resulted in significantly higher listening scores than in the control group, which had no feedback. However, repeated feedback did not affect the test anxiety and listening scores. Computer-based immediate feedback did not lower debilitating effects of anxiety but enhanced students' intrapersonal eustress-like anxiety and probably improved their attention during listening tests. Computer-based tests with immediate feedback might help foreign language learners to increase attention in foreign language listening comprehension.

Vanished gender differences of cardiometabolic risk factors after matching the apnea hypopnea index at postmenopausal age.

BACKGROUND: Sleep-disordered breathing (SDB) and cardiometabolic risk factors are male prevalent. OBJECTIVE: This study investigated whether gender differences remained prominent after matching for the apnea hypopnea index (AHI) and postmenopause. METHODS: In a retrospective analysis of 350 eligible SDB patients, female patients were matched with male patients of the same age and body mass index (BMI) (age-BMI-matched [nAHImt]; n = 102 pairs) or were matched with male patients of the same age, BMI, and AHI (age-BMI-AHI-matched [AHImt]; n = 66 pairs). The nAHImt or AHImt patients were further separated into junior and senior subgroups. RESULTS: In the nAHImt/junior group, women had shorter neck circumferences, better sleep architecture, and lower AHI, Epworth Sleepiness Scale (ESS) score, blood pressure (BP), total cholesterol (TC), triglyceride (TG), and uric acid (UA) than nAHImt/junior men. In the AHImt/junior group, women had shorter neck circumferences, lower waist/hip ratios, ESS, BP, TG, and UA than AHImt junior men. In the nAHImt/senior group, women had lower AHI, neck circumferences, waist/hip ratios, diastolic BP, and UA than men. In contrast, in the AHImt/senior group, most cardiometabolic parameters were similar between women and men. After further matching for the AHI, many elements of gender differences disappeared. CONCLUSIONS: Compared with AHImt men, women had lower UA, TG, BP, and daytime sleepiness before menopause, but gender differences became indistinguishable postmenopause. We suggested that matching sleep quality or adjusting AHI would be noteworthy and required for studying gender differences.

Sleep-disordered breathing, behavior, and academic performance in Taiwan schoolchildren.

OBJECTIVE: The behaviors of children may be affected by sleep-disordered breathing (SDB). This study adopts a cross-sectional approach to investigate the relationship between the sleep apneas-hypopneas index during sleep and the behavioral and academic performance of schoolchildren in Taiwan. METHODS: A total of 138 children (85 boys and 53 girls), ages 6-11, were recruited from two elementary schools to participate in this study. Overnight polysomnographic examinations in hospital were performed to assess sleep quality, including total sleep time, arousal index, apneas-hypopneas index, desaturation index, and lowest oxygen saturation, as well as the percentage of total sleep time spent in rapid eye movement, stage 1, stage 2, stage 3, and stage 4. The children's parents and teachers were required to complete a Chinese version of the Child Behavior Checklist and Teacher's Report Form to assess child behavior and academic achievement. RESULTS: Compared with children without SDB (apneas-hypopneas index ≤1), those with severe SDB (apneas-hypopneas index >15) exhibited more irregular behavioral performance in somatic complaints (odds ratio (OR) = 9.43; 95% confidence interval (CI) = 1.04-85.71) and attention (OR = 9.95; 95% CI = 1.02-97.00). However, different severities of SDB groups did not show significant associations in academic performance. CONCLUSION: Our study suggests that children with severe SDB may predispose to somatic complaints and attention problems so that sleep examination or medical intervention might be provided at an early age in these children.

Effects of tocotrienol-rich fraction on exercise endurance capacity and oxidative stress in forced swimming rats.

The present study aimed to examine the effects of tocotrienol-rich fraction (TRF) on exercise endurance and oxidative stress in forced swimming rats. Rats fed on isocaloric diet were orally given 25 (TRF-25) and 50 (TRF-50) mg/kg of TRF, or 25 mg/kg D-alpha-tocopherol (T-25) whilst the control group received only the vehicle for 28 days, followed by being forced to undergo swimming endurance tests, with measurements taken of various biochemical parameters, including blood glucose, lactate and urea nitrogen, glycogen, total antioxidant capacity, antioxidant enzymes, thiobarbituric acid-reactive substances (TBARS), and protein carbonyl. Results showed that the TRF-treated animals (268.0 +/- 24.1 min for TRF-25 and 332.5 +/- 24.3 min for TRF-50) swam significantly longer than the control (135.5 +/- 32.9 min) and T-25-treated (154.1 +/- 36.4 min) animals, whereas there was no difference in the performance between the T-25 and control groups. The TRF-treated rats also showed significantly higher concentrations of liver glycogen, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as of muscle glycogen and SOD than the control and the T-25-treated animals, but lower levels in blood lactate, plasma and liver TBARS, and liver and muscle protein carbonyl. Taken together, these results suggest that TRF is able to improve the physiological condition and reduce the exercise-induced oxidative stress in forced swimming rats.

Dehydroepiandrosterone sulfate linked to physiologic response against hot spring immersion.

The steroid dehydroepiandrosterone sulfate (DHEA-S) is associated with longevity and adaptation against external stress in humans. The aim of the study was to investigate the acute effect of a 30-min hot spring immersion at 41 degrees C on insulin resistance measures of 16 male subjects, in relation to DHEA-S level. To elucidate the role of DHEA-S in the coping against the heat stress, all subjects were evenly divided into lower and upper halves according to their baseline DHEA-S concentrations. The levels of glucose, insulin, blood pressure, and stress hormones (growth hormone, testosterone, and cortisol) in both groups were compared before and after hot spring immersion. The result shows that hot spring immersion significantly increased heart rate and reduced diastolic blood pressure, both of which were paralleled with a drop of DHEA-S concentration. Homeostasis model assessment for insulin resistance (HOMA-IR) and area under curve of glucose (GAUC) of oral glucose tolerance test were significantly increased by the hot spring immersion only in the Low DHEA-S group. Likewise, hot spring immersion caused an opposing effect on cortisol changes for the Low and High DHEA-S groups (+95% vs. -33%, p<0.05), respectively. In conclusion, hot spring bathing induced insulin resistance confined only to those Low DHEA-S individuals. This response may be associated with a stress response such as increased cortisol levels.