Integrated Expression Profiling and Genome-Wide Analysis of ChREBP Targets Reveals the Dual Role for ChREBP in Glucose-Regulated Gene Expression

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator

Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Cross-cultural adaptation and validation of the Depression, Anxiety and Stress Scale-21 (DASS-21) in the Korean working population

In this study, we developed a new Korean translation for the shortened version of the Depression, Anxiety, and Stress Scale (DASS-21) and examined its psychometric properties in a Korean working population.To develop a new Korean version of the DASS-21 and test its psychometric properties specific to the Korean working population.The DASS-21 was translated to the Korean language in accordance with scientific guidelines for cross-cultural adaptation. A total of 228 general workers from Korea then completed the newly translated version of the DAS S-21 and its psychometric properties were evaluated.Most of the questionnaire items were correctly loaded on the proposed scales of the original questionnaire. Excellent internal consistency and measurement consistency over a one week interval were obtained for all scales (Cronbach's alpha; 0.87, 83, and 83, and ICC (2, 1); 0.84, 0.94, and 0.89 for depression, anxiety and stress scales, respectively). All three scales were negatively associated with the level of life satisfaction (p

Cross-cultural adaptation and validation of the Latack Coping Scale in the general working population in Korea

BACKGROUND: Currently, there are no assessment tools for measuring coping strategies for stress at work in the Korean language. OBJECTIVE: The purpose of this study was to translate the Latack Coping Scale to workplace stress into Korean and examine its psychometric properties in a Korean working population. METHODS: Translation of the the Latack Coping Scale was performed according to the scientific guidelines for cross-cultural adaptation. Two hundred and forty one general workers in Korea completed the new Korean version of the Latack Coping Scale as well as the Type D Personality Scale-14 (negative affectivity). Psychometric properties (reliability and validity) were evaluated. RESULTS: Factor analysis yielded a model that was consistent with the originally proposed subscales of the questionnaire. Good to excellent internal consistency and measurement consistency over a one week interval were obtained for five subscales (Cronbach's alpha; 0.61 to 0.86 and ICC (2.2); 0.80 to 0.87). Escape coping scales were positively associated with Type D personality while control coping scales were negatively associated with Type D personality. CONCLUSIONS: This Korean version of the Latack Coping Scale has shown excellent validity and reliability in the Korean working population. Organizations investigating work stress and coping methods in Korean workers can use this instrument with confidence

Are Measures of Postural Behavior Using Motion Sensors in Seated Office Workers Reliable?

Objective: In this study, the reliability of measures of upper body postural behavior (head, thorax, neck, and arm) during sustained office work was evaluated. Background: Although there has been a substantial body of research examining the technical aspects of posture measurement in office workers using motion sensors, there is a paucity of literature examining whether posture-related behaviors are actually consistent among office workers in the field on different days and times. Method: Thirty one office workers performed their usual work for three, 1-hr sessions (two morning sessions and one afternoon session) while wearing wireless motion sensors. Reliability coefficients of the derived measures of postural behavior were calculated. Results: Most (30/31) of the postural behavior measures demonstrated modest to excellent reliability (ICC 2.1: 0.48–0.84). Reliability appeared to be mildly affected by factors such as the time of day recordings were taken and variations in desk setups. Conclusion: The findings suggest these measures may be a reliable method for evaluating postural behavior in the office work environment in future studies. Application: Postural measurement using a technical motion sensor described an acceptable reliability to be used for risk assessment in the workplace. Consideration of assessment time and desk setting would increase the accuracy of postural measurement

Job strain and psychological distress in office workers: The role of coping

BACKGROUND: Work-related psychosocial factors such as job strain are thought to contribute to elevated psychological stress in office workers. One factor that may impact the relationship between job strain and psychological distress is the individual's coping resources.OBJECTIVE: The purpose of this study is to examine the interaction effect of coping resources on the relationship between job strain and psychological distress in office workers.METHODS: 220 office workers in Australia and Korea completed the Job Content Questionnaire (to evaluate job strain and social support at work), the Depression, Anxiety, and Stress Scale, (DASS-21, a measure of psychological distress), and the Coping with Job Stress Scale to assess control and escape coping. Hierarchical regression analyses were executed to examine the interaction and moderating effect of coping resources.RESULTS: Job strain had a direct positive relationship with all three domains of psychological distress. The relationship between job strain and depression was positively moderated by escape coping, but negatively moderated by social support. Use of higher levels of escape coping predicted higher levels of depression and anxiety symptoms when higher levels of job strain were perceived.CONCLUSIONS: Findings suggest there may be a direct relationship between job strain and psychological distress in office workers. This relationship, however, may be moderated by the office workers coping resources (coping strategies and social support). It is suggested that the evaluation of coping might be a key consideration in the elements of the assessment of psychological distress in office workers

A longitudinal evaluation of risk factors and interactions for the development of nonspecific neck pain in office workers in two cultures

Objective: To identify risk factors for the development of interfering neck pain in office workers including an examination of the interaction effects between potential risk factors.BackgroundThe 1-year incidence of neck pain in office workers is reported as the highest of all occupations. Identifying risk factors for the development of neck pain in office workers is therefore a priority to direct prevention strategies.Methods: Participants included 214 office workers without neck pain from two cultures. A battery of measures evaluating potential individual and workplace risk factors were administered at baseline, and the incidence of interfering neck pain assessed monthly for 12 months. Survival analysis was used to identify relationships between risk factors and the development of interfering neck pain. Results: One-year incidence was 1.93 (95% CI [1.41, 2.64]) per 100 person months. Factors increasing the risk of developing interfering neck pain were older age, female gender, increased sitting hours, higher job strain, and stress. A neutral thorax sitting posture, greater cervical range of motion and muscle endurance, and higher physical activity were associated with a decreased risk of neck pain. The effects of some risk factors on the development of neck pain were moderated by the workers' coping resources. Conclusion: Multiple risk factors and interactions may explain the development of neck pain in office workers. Therefore, plans for preventing the development of interfering neck pain in office workers should consider multiple individual and work-related factors with some factors being potentially more modifiable than others

Economic burden of patients living with heart disease in the last years of life in Australia:a retrospective analysis using linked data

Aims: People living with heart disease are at elevated risk of hospitalisation during the last years of their life. The aim of this study was to describe hospitalisation-related usage patterns, and associated cost burden, for patients living with heart disease in the last six years of their life.Methods and results: The study was an observational cohort study, using routinely collected and linked data from hospital admission, ED presentation and death registry data in Queensland, Australia. The study sample included 1000 randomly selected patients who died in 2017 due to any cause who had been living with heart disease for at least the prior six years. The two main outcomes of interest in this study were cost of hospital admissions (HA) and cost of emergency department presentation (ED) in the last six years before death. Total cost was calculated as a sum of direct and overhead costs from each of the hospital presentations.The mean HA per patient in the sixth year, second year and last year prior to death was 5.3, 6.6, and 7.5, respectively, with a similar pattern observed for ED presentations. The associated costs per patient from HA followed a similar trajectory increasing gradually from $17,711 in the sixth year to$26,658 in the second last year prior to death. A similar pattern was observed for ED presentation costs.Conclusion: The large increase cost in the last year of life was primarily attributable to higher treatment cost per hospital admission at end of life

Workplace-Based Interventions for Neck Pain in Office Workers: Systematic Review and Meta-Analysis

At present, there is no consolidated evidence for workplace-based interventions for the prevention and reduction of neck pain in office workers.The purpose of this review was to investigate the effectiveness of workplace-based interventions for neck pain in office workers.MEDLINE, PEDro, CINAHL, and CENTRAL were searched for trials published since inception and before May 31, 2016.Randomized controlled trials (RCTs) were considered when they met the following criteria: population consisted of office workers, intervention(s) was performed at the workplace, outcome measures included neck and/or neck/shoulder pain intensity and incidence/prevalence, and comparator groups included no/other intervention.Data were extracted by 1 reviewer using predefined data fields and checked by a second reviewer. Risk of bias was assessed by 2 independent reviewers using the 2015 Cochrane Back and Neck Group guidelines. Evidence quality was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.Twenty-seven RCTs were included. There was moderate-quality evidence that neck/shoulder strengthening exercises and general fitness training were effective in reducing neck pain in office workers who were symptomatic, although the effect size was larger for strengthening exercises. Greater effects were observed with greater participation in exercise. Ergonomic interventions were supported by low-quality evidence.Data could not be obtained from some studies for meta-analysis and assessment of risk of bias. Reporting bias might have been present because only studies in the English language were included.Workplace-based strengthening exercises were effective in reducing neck pain in office workers who were symptomatic, and the effect size was larger when the exercises were targeted to the neck/shoulder. Future RCTs of ergonomic interventions targeted at office workers who are symptomatic are required. More research on neck pain prevention is warranted