Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol 1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol 1′-hydroxylation, with a Ki value of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50 equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate the in vivo extent of the observed in vitro interactions

Two ways teachers can develop greater harmonious passion

Background Passion is highly prized. The Dualistic Model of Passion provides a general roadmap for how people develop passion, at least under conditions in which they can freely schedule their daily activity, abandon activities they no longer value, and have flexible time to invest as they see fit. But teaching is a different, because many aspects of this activity are fixed and pre-set by circumstances. Recognizing this unique condition of classroom PE teaching, we designed the present investigation to test the merits of two antecedents teachers can utilize to develop greater (harmonious) passion—namely, participate in an autonomy-supportive teaching workshop (Study 1) and incorporate intrinsic instructional goals into their lesson plans (Study 2). Purpose The over-arching purpose was to investigate the potential of two malleable and personally controllable catalysts to greater harmonious teaching passion. Method Study 1 used a randomized control trial. We randomly assigned 104 Korean PE teachers to participate (or not) in an autonomy-supportive teaching (AST) workshop. PE teachers self-reported their harmonious and obsessive passion at the beginning, middle, and end of an academic year. Study 2 used a longitudinal research design and a sample that included both PE and non-PE teachers. These 134 secondary-grade level teachers self-reported their intrinsic instructional goals, autonomy-supportive teaching, and harmonious and obsessive passion across three waves. Results In Study 1, a repeated-measures ANCOVA showed that teachers in the experimental condition, compared to teachers in the control condition, showed a longitudinal increase in autonomy-supportive teaching and harmonious passion and a longitudinal decrease in obsessive passion. A mediation analysis confirmed that participants in the AST workshop experienced greater autonomy-supportive teaching that then explained their greater harmonious passion and lesser obsessive passion. In Study 2, a structural equation modeling analysis showed that adopting intrinsic instructional goals early in the year longitudinally increased harmonious passion (but did not decrease obsessive passion). A mediation analysis confirmed that teachers who more adopted intrinsic instructional goals experienced greater autonomy-supportive teaching that then explained their greater harmonious passion. Conclusion Teachers can gain personal control over their harmonious passion. They can do this through greater autonomy-supportive teaching. And teachers can become more autonomy supportive in two ways: Participate in an expert-provided professional development experience (Study 1) or incorporate intrinsic instructional goals into the delivery of their instruction (Study 2). Additional ways teachers can develop harmonious passion may be possible, so we encourage future research to continue this search with additional samples, such as sport coaches

Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

Insulin and glucagon secretions, and morphological change of pancreatic islets in OLETF rats, a model of type 2 diabetes mellitus.

This study was performed to observe the changes of glucose-related hormones and the morphological change including ultrastructure of the pancreatic islets in the male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose at the 30th (709 plus minus 73 mg.h/dL) and at the 40th week (746 plus minus 87 mg.h/ dL) of age were significantly higher than that at the 10th week (360 plus minus 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 plus minus 0.9 ng.h/mL, increased gradually to 10.8 plus minus 8.3 ng.h/mL at the 30th week, and decreased to 1.8 plus minus 1.2 ng.h/mL at the 40th week. The size of islet was increased at 20th week of age and the distribution of peripheral alpha cells and central beta cells at the 10th and 20th weeks was changed to a mixed pattern at the 40th week. On electron microscopic examination, beta cells at the 20th week showed many immature secretory granules, increased mitochondria, and hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta cell contained scanty intracellular organelles and secretory granules and apoptosis of acinar cell was observed. In conclusion, as diabetes progressed, increased secretion of insulin was accompanied by increases in size of islets and number of beta-cells in male OLETF rats showing obese type 2 diabetes. However, these compensatory changes could not overcome the requirement of insulin according to the continuous hyperglycemia after development of diabetes

Community-dwelling older adults needs and acceptance regarding the use of robot technology to assist with daily living performance

Background The rate of aging in Korea is extremely fast compared to major countries. We examined the key demands of community-dwelling older adults with regard to Connected Active Space technology, which provides tailored assistance with daily living performance through robotic services. Methods This study is based on a mixed-method design, through a quantitative survey (n = 234) first phase, followed by a qualitative study with focus group interviews (n = 23) to explore the needs and acceptance of community-dwelling aged people concerning the application of robot technology in their daily lives. Results The scores concerning the need for and acceptance of robot services to assist daily living performance were high, at 7.2 and 7.9 out of 10 points, respectively. Further, for both needs and acceptance, timely reaction to emergency situations, early detection of emergency situations, help to locate objects, assistance with mobility, and assistance in memory recall were prioritized (in that order). In a thematic analysis of qualitative data from three focus-group interviews, a mismatch between desires and functional capacity was the core characteristic of living as an older person and being a friend and helper was the most desired trait of a robot service. Conclusion Although most of the participants lived independently, they regularly experienced difficulties regarding buying products, transportation, using phones, and preparing meals. If appropriate assistance technology is developed, this population can maintain its independence. Thus, it is necessary to address main needs, including detecting and addressing emergency situations, locating objects, assisting mobility and memory recall, and assisting with daily living performance. New robot services that can be tailored to the functions or abilities of the elderly must be developed based on individually collected information.This work was funded by the Korea Institute of Science & Technology [grant Number: 2E26470–16-099]. The funding body had no role in the design of this study, in collection, analysis and interpretation of data, and in writing the manuscript

Reciprocal Relationship Between Depression and Internet Gaming Disorder in Children: A 12-month Follow-Up of the iCURE Study Using Cross-Lagged Path Analysis

Objectives: Previous studies have reported an association between Internet gaming disorder (IGD) and depression, but the directionality of the relationship remains unclear. Therefore, we examined the reciprocal relationship between level of depressive symptoms and IGD among children in a longitudinal study. Methods: Research panels for this study consisted of 366 elementary-school students in the iCURE study. All participants were current Internet users, so they could be considered an at-risk population for IGD. Self-reported severity of IGD features and level of depression were assessed by the Internet Game Use-Elicited Symptom Screen and Children’s Depression Inventory, respectively. Follow-up assessment was completed after 12 months. We fitted cross-lagged structural equation models to investigate the association between the two variables at two time points contemporaneously. Results: The cross-lagged analysis revealed that level of depression at baseline significantly predicted severity of IGD features at the 12-month follow-up (β = 0.15, p = .003). Severity of IGD features at baseline also significantly predicted level of depression at the 12-month follow-up (β = 0.11, p = .018), controlling for possible confounding factors. Conclusions: The cross-lagged path analysis indicates a reciprocal relationship between severity of IGD features and level of depressive symptoms. Understanding the reciprocal relationship between depressive symptoms and severity of IGD features can assist in interventions to prevent both conditions. These findings provide theoretical support for prevention and remediation plans for IGD and depressive symptoms among children

Separatrix modes in weakly deformed microdisk cavities

Optical modes in deformed dielectric microdisk cavities often show an unexpected localization along unstable periodic ray orbits. We reveal a new mechanism for this kind of localization in weakly deformed cavities. In such systems the ray dynamics is nearly integrable and its phase space contains small island chains. When increasing the deformation the enlarging islands incorporate more and more modes. Each time a mode comes close to the border of an island chain (separatrix) the mode exhibits a strong localization near the corresponding unstable periodic orbit. Using an EBK quantization scheme taking into account the Fresnel coefficients we derive a frequency condition for the localization. Observing far field intensity patterns and tunneling distances, reveals small differences in the emission properties. © 2017 Optical Society of America.1

Attentional state-synchronous peripheral electrical stimulation during action observation induced distinct modulation of corticospinal plasticity after stroke

IntroductionBrain computer interface-based action observation (BCI-AO) is a promising technique in detecting the user's cortical state of visual attention and providing feedback to assist rehabilitation. Peripheral nerve electrical stimulation (PES) is a conventional method used to enhance outcomes in upper extremity function by increasing activation in the motor cortex. In this study, we examined the effects of different pairings of peripheral nerve electrical stimulation (PES) during BCI-AO tasks and their impact on corticospinal plasticity.Materials and methodsOur innovative BCI-AO interventions decoded user's attentive watching during task completion. This process involved providing rewarding visual cues while simultaneously activating afferent pathways through PES. Fifteen stroke patients were included in the analysis. All patients underwent a 15 min BCI-AO program under four different experimental conditions: BCI-AO without PES, BCI-AO with continuous PES, BCI-AO with triggered PES, and BCI-AO with reverse PES application. PES was applied at the ulnar nerve of the wrist at an intensity equivalent to 120% of the sensory threshold and a frequency of 50 Hz. The experiment was conducted randomly at least 3 days apart. To assess corticospinal and peripheral nerve excitability, we compared pre and post-task (post 0, post 20 min) parameters of motor evoked potential and F waves under the four conditions in the muscle of the affected hand.ResultsThe findings indicated that corticospinal excitability in the affected hemisphere was higher when PES was synchronously applied with AO training, using BCI during a state of attentive watching. In contrast, there was no effect on corticospinal activation when PES was applied continuously or in the reverse manner. This paradigm promoted corticospinal plasticity for up to 20 min after task completion. Importantly, the effect was more evident in patients over 65 years of age.ConclusionThe results showed that task-driven corticospinal plasticity was higher when PES was applied synchronously with a highly attentive brain state during the action observation task, compared to continuous or asynchronous application. This study provides insight into how optimized BCI technologies dependent on brain state used in conjunction with other rehabilitation training could enhance treatment-induced neural plasticity

Alcohol induces cell proliferation via hypermethylation of ADHFE1 in colorectal cancer cells

BACKGROUND: The hypermethylation of Alcohol dehydrogenase iron containing 1 (ADHFE1) was recently reported to be associated with colorectal cancer (CRC) differentiation. However, the effect of alcohol on ADHFE1 hypermethylation in CRC is still unclear. METHODS: The methylation status and expression levels of ADHFE1 were investigated in primary tumor tissues and adjacent normal tissues of 73 patients with CRC, one normal colon cell line, and 4 CRC cell lines (HT-29, SW480, DLD-1, and LoVo) by quantitative methylation-specific polymerase chain reaction (QMSP) and real-time reverse transcription polymerase chain reaction (real time PCR), respectively. The effect of alcohol on the methylation status of ADHFE1 was analyzed in HT-29, SW480, DLD-1, and CCD18Co cells using QMSP, real-time PCR, immunoblot, and cell proliferation assay. RESULTS: ADHFE1 was hypermethylated in 69 of 73 CRC tissues (95%) compared to adjacent normal tissues (p < 0.05). The mRNA expression of ADHFE1 was significantly reduced in CRC compared to adjacent normal tissues (p < 0.05) and its expression was decreased in the alcohol consumption group (p < 0.05). ADHFE1 was hypermethylated and its expression was decreased in 4 CRC cell lines compared with normal colon cell line. Alcohol induced hypermethylation of ADHFE1, decreased its expression, and stimulated cell proliferation of HT-29, SW480, and DLD-1cells. CONCLUSION: These results demonstrate that the promoter hypermethylation of ADHFE1 is frequently present in CRC and alcohol induces methylation-mediated down expression of ADHFE1 and proliferation of CRC cells