The ezrin-radixin-moesin (ERM) proteins are a family of membrane-associated proteins known to play roles in cell-shape determination as well as in signaling pathways. We have previously shown that amphetamine decreases phosphorylation levels of these proteins in the nucleus accumbens (NAcc), an important neuronal substrate mediating rewarding effects of drugs of abuse. In the present study, we further examined what molecular pathways may be involved in this process. By direct microinjection of LY294002, a PI3 kinase inhibitor, or of S9 peptide, a proposed GSK3β activator, into the NAcc core, we found that phosphorylation levels of ERM as well as of GSK3β in this site are simultaneously decreased. These results indicate that ERM proteins are under the regulation of Akt-GSK3β signaling pathway in the NAcc core. The present findings have a significant implication to a novel signal pathway possibly leading to structural plasticity in relation with drug addiction.
Amphetamine ; Animals ; Glycogen Synthase Kinases ; Humans ; Membrane Proteins ; Microinjections ; Negotiating ; Neurons ; Nucleus Accumbens ; Phosphorylation ; Phosphotransferases ; Plastics ; Proto-Oncogene Proteins c-akt ; Rats ; Reward ; Signal Transduction ; Street Drugs ; Substance-Related Disorders

OBJECTIVE: We aimed to investigate the ability of readout-segmented echo-planar imaging (rs-EPI)-based diffusion tensor imaging (DTI) in assessing the microstructural change of extraocular muscles (EOMs) and optic nerves in patients with thyroid-associated orbitopathy (TAO) as well as in evaluating disease activity.MATERIALS AND METHODS: We enrolled 35 TAO patients and 22 healthy controls (HCs) who underwent pre-treatment rs-EPI-based DTI. Mean, axial, and radial diffusivity (MD, AD, and RD) and fractional anisotropy (FA) of the medial and lateral EOMs and optic nerve for each orbit were calculated and compared between TAO and HC groups and between active and inactive TAO groups. Factors such as age, sex, disease duration, mediation, and smoking history between groups were also compared. Logistic regression analysis was used to evaluate the predictive value of significant variables for disease activity.RESULTS: Disease duration was significantly shorter in active TAOs than in inactive ones (p < 0.001). TAO patients showed significantly lower FA and higher MD, AD, and RD than HCs for both medial and lateral EOMs (p < 0.001), but not the AD value of lateral EOMs (p = 0.619). Active patients had significantly higher FA, MD, and AD than inactive patients for medial EOMs (p < 0.005), whereas only FA differed significantly in the lateral EOMs (p = 0.018). The MD, AD, and RD of optic nerves were significantly lower in TAO patients than HCs (p < 0.05), except for FA (p = 0.129). Multivariate analysis showed that the MD of medial EOMs and disease duration were significant predictors for disease activity. The combination of these two parameters showed optimal diagnostic efficiency for disease activity (area under the curve, 0.855; sensitivity, 68.4%; specificity, 96.9%).CONCLUSION: rs-EPI-based DTI is promising in assessing microstructural changes of EOMs and optic nerves and can help to indicate the disease activity of TAO, especially through the MD of medial EOMs.
Anisotropy ; Diffusion Tensor Imaging ; Diffusion ; Echo-Planar Imaging ; Humans ; Logistic Models ; Multivariate Analysis ; Muscles ; Negotiating ; Optic Nerve ; Orbit ; Sensitivity and Specificity ; Smoke ; Smoking ; Troleandomycin

PURPOSE: The purpose of this study was to construct and test a structural equation model on nursing work outcomes based on Youssef and Luthans' positive psychological capital and integrated conceptual framework of work performance.METHODS: This study used a structured questionnaire administered to 340 nurses. Data were analyzed using structural equation modeling.RESULTS: Positive psychological capital showed indirect and direct effects on job satisfaction, retention intention, organizational citizenship behavior, and nursing performance. While, the nursing work environment had direct and indirect effects on job satisfaction and nursing performance, it only had indirect effects on intention to work and organizational citizenship behavior. Additionally, a mediating effect on retention intention and organizational citizenship behavior was found between job satisfaction and nursing performance variables.CONCLUSION: The nursing organization needs to build a supportive work environment and reinforce positive psychological capital to improve nursing performance. Additionally, it needs to actively manage the necessary parameters involved in the stages of job satisfaction, retention intention, nursing performance, and organizational citizenship behavior of nurses. The findings propose the continuous management of nursing personnel based on nurses' attitude outcome, behavioral intention, behavioral outcome, and stage of role performance.
Attitude of Health Personnel ; Intention ; Job Satisfaction ; Negotiating ; Nursing ; Psychology, Industrial ; Task Performance and Analysis ; Work Performance

A male elderly patient came with buccal mucosa swelling associated with tooth 46 and 47. Periapical radiograph confirmed the presence of periapical lesion and narrow root canals on both teeth. Challenging impediments were sensed upon negotiating most of the narrow root canals which were common in elderly patients. Glide path creation involved pre-flaring, K-file bending, watch winding movement, and very gentle strokes. After achieving patency, shaping, cleaning, and sealing phase can be performed.
Aged ; Negotiating

OBJECTIVE: Resilience and impulsivity have opposite effects on depression in stressful situations. This study aimed to investigate the association among resilience, impulsivity, and depression in young males. METHODS: The participants consisted of 429 conscripts who underwent military training over 5 weeks. The surveys included the Connors- Davidson Resilience Scale-Korean version, the Barratt Impulsiveness Scale-11-Revised, and the Center for Epidemiological Studies- Depression Scale. The surveys were administered both before and after training. RESULTS: When simultaneously considering impulsivity and resilience, resilience was not associated with depression. Impulsivity had a complete negative mediating effect on resilience and depressive symptoms. Impulsivity is a significant negative mediating factor for the protective effect of resilience on depression. CONCLUSION: This study recommends considering impulsivity when evaluating the protective role of resilience against depression.
Depression ; Humans ; Impulsive Behavior ; Male ; Military Personnel ; Negotiating

OBJECTIVE: This study aims to examine the parallel multiple mediators of depressive symptoms and sleep quality in the relations between stress and physical health-related quality of life (PHQOL)/mental health-related quality of life (MHQOL) among the women in late pregnancy. METHODS: Of 1120 pregnant women participated in the cross-sectional study which consisted of Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Pittsburgh Sleep Quality Index and MOS 12-item Short Form Health Survey. Parallel multiple mediator models were used to analyze the relations between stress, depressive symptoms, sleep quality and PHQOL/MHQOL. RESULTS: The effect of perceived stress on PHQOL was partially through the indirect path of sleep quality (β=-0.061). But in the model for MHQOL, depressive symptoms and sleep quality played parallel mediators, and the indirect path effect of depressive symptoms (β=-0.179) was higher than sleep quality (β=-0.029). CONCLUSION: The findings contributed to the understanding about the influential mechanism of stress on PHQOL/MHQOL. And it reminded the importance of sleep quality and depressive symptoms for improving QOL in late pregnancy.
Cross-Sectional Studies ; Depression ; Depression, Postpartum ; Female ; Health Surveys ; Humans ; Negotiating ; Pregnancy ; Pregnant Women ; Quality of Life

Depression leads the higher personal and socio-economical burden within psychiatric disorders. Despite the fact that over 40 antidepressants (ADs) are available, suboptimal response still poses a major challenge and is thought to be partially a result of genetic variation. Pharmacogenetics studies the effects of genetic variants on treatment outcomes with the aim of providing tailored treatments, thereby maximizing efficacy and tolerability. After two decades of pharmacogenetic research, variants in genes coding for the cytochromes involved in ADs metabolism (CYP2D6 and CYP2C19) are now considered biomarkers with sufficient scientific support for clinical application, despite the lack of conclusive cost/effectiveness evidence. The effect of variants in genes modulating ADs mechanisms of action (pharmacodynamics) is still controversial, because of the much higher complexity of ADs pharmacodynamics compared to ADs metabolism. Considerable progress has been made since the era of candidate gene studies: the genomic revolution has made possible to assess genetic variance on an unprecedented scale, throughout the whole genome, and to analyze the cumulative effect of different variants. The results have revealed key information on the biological mechanisms mediating ADs effect and identified hypothetical new pharmacological targets. They also paved the way for future availability of polygenic pharmacogenetic panels to predict treatment outcome, which are expected to explain much higher variance in ADs response compared to CYP2D6 and CYP2C19 only. As the demand and availability of AD pharmacogenetic testing is projected to increase, it is important for clinicians to keep abreast of this evolving area to facilitate informed discussions with their patients.
Antidepressive Agents ; Biomarkers ; Clinical Coding ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2D6 ; Cytochromes ; Depression ; Genetic Variation ; Genome ; Humans ; Metabolism ; Negotiating ; Pharmacogenetics ; Precision Medicine ; Treatment Outcome

This study investigated the effect of emotional stability (ES) on insomnia through anxiety in preoperative patients with cataracts. Fifty-four subjects completed a self-questionnaire that included the Insomnia Severity Index (ISI), the International Personality Item Pool (IPIP) for ES, and the Hospital Anxiety and Depression scale (HADS). Pathway analysis was performed to analyze the mediating effects of ES, the anxiety subscale scores of the HADS, and the ISI scores. The low-ES group exhibited an insomnia severity that was significantly higher than that of the high-ES group (p=0.048). According to the pathway analysis, the significant indirect effect of ES on the ISI scores was mediated by the scores on the anxiety subscale of the HADS. Cataract patients with low ES waiting to undergo surgery have a high risk of experiencing insomnia due to anxiety. Before surgery, it is essential to identify patients’ personality characteristics and provide appropriate intervention.
Anxiety ; Cataract ; Depression ; Humans ; Negotiating ; Sleep Initiation and Maintenance Disorders

OBJECTIVE: The relationship among chronic fatigue, depressive symptoms, and post-traumatic stress symptoms (PTSSs) among Middle East respiratory syndrome (MERS) survivors is poorly understood. METHODS: Of 148 survivors who consented to be registered and underwent assessments at 12 months (T1) and 18 months (T2) after the MERS outbreak, 72 (48.65%) were evaluated for chronic fatigue, depressive symptoms, and PTSSs based on the Impact of Event ScaleRevised (IES-R), the Patient Health Questionnaire-9 (PHQ-9), and the Fatigue Severity Scale (FSS). Data from 52 subjects, who completed both assessments, were analyzed using a regression-based serial multiple mediation model (PROCESS Model 6). RESULTS: Bootstrap analyses indicated no direct effects of T1 FSS on T2 IES-R but significant positive indirect effects of T1 FSS on T2 IESR through T1 PHQ-9 and T2 PHQ-9 (B=2.1601, SE=1.3268, 95% confidence interval=0.4250–6.1307). In other words, both T1 PHQ-9 and T2 PHQ-9 fully mediated the relationship between T1 FSS and T2 IES. CONCLUSION: Chronic fatigue 12 months after MERS had indirect effects on prolonged PTSSs 18 months after MERS via persisting depression in MERS survivors. This finding supports the need to promote interventional programs for emerging infectious disease survivors with chronic fatigue to reduce depression and prevent prolonged PTSSs.
Communicable Diseases, Emerging ; Coronavirus Infections ; Depression ; Fatigue ; Humans ; Middle East ; Negotiating ; Survivors

PURPOSE: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT). MATERIALS AND METHODS: We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. RESULTS: qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. CONCLUSION: Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1. Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.
Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Epithelial-Mesenchymal Transition ; Humans ; Luciferases ; MicroRNAs ; Negotiating ; Neoplasm Metastasis ; Prognosis ; Real-Time Polymerase Chain Reaction