Hepatitis C Virus Induces the Cannabinoid Receptor 1

BACKGROUND: Activation of hepatic CB(1) receptors (CB(1)) is associated with steatosis and fibrosis in experimental forms of liver disease. However, CB(1) expression has not been assessed in patients with chronic hepatitis C (CHC), a disease associated with insulin resistance, steatosis and metabolic disturbance. We aimed to determine the importance and explore the associations of CB(1) expression in CHC. METHODS: CB(1) receptor mRNA was measured by real time quantitative PCR on extracted liver tissue from 88 patients with CHC (genotypes 1 and 3), 12 controls and 10 patients with chronic hepatitis B (CHB). The Huh7/JFH1 Hepatitis C virus (HCV) cell culture model was used to validate results. PRINCIPAL FINDINGS: CB(1) was expressed in all patients with CHC and levels were 6-fold higher than in controls (P<0.001). CB(1) expression increased with fibrosis stage, with cirrhotics having up to a 2 fold up-regulation compared to those with low fibrosis stage (p<0.05). Even in mild CHC with no steatosis (F0-1), CB(1) levels remained substantially greater than in controls (p<0.001) and in those with mild CHB (F0-1; p<0.001). Huh7 cells infected with JFH-1 HCV showed an 8-fold upregulation of CB(1), and CB(1) expression directly correlated with the percentage of cells infected over time, suggesting that CB(1) is an HCV inducible gene. While HCV structural proteins appear essential for CB(1) induction, there was no core genotype specific difference in CB(1) expression. CB(1) significantly increased with steatosis grade, primarily driven by patients with genotype 3 CHC. In genotype 3 patients, CB(1) correlated with SREBP-1c and its downstream target FASN (SREBP-1c; R=0.37, FASN; R=0.39, p<0.05 for both). CONCLUSIONS/SIGNIFICANCE: CB(1) is up-regulated in CHC and is associated with increased steatosis in genotype 3. It is induced by the hepatitis C virus

A Daily Diary Approach to the Examination of Chronic Stress, Daily Hassles and Safety Perceptions in Hospital Nursing

Purpose: Stress is a significant concern for individuals and organisations. Few studies have explored stress, burnout and patient safety in hospital nursing on a daily basis at the individual level. This study aimed to examine the effects of chronic stress and daily hassles on safety perceptions, the effect of chronic stress on daily hassles experienced and chronic stress as a potential moderator. Method: Utilising a daily diary design, 83 UK hospital nurses completed three end-of-shift diaries, yielding 324 person days. Hassles, safety perceptions and workplace cognitive failure were measured daily, and a baseline questionnaire included a measure of chronic stress. Hierarchical multivariate linear modelling was used to analyse the data. Results: Higher chronic stress was associated with more daily hassles, poorer perceptions of safety and being less able to practise safely, but not more workplace cognitive failure. Reporting more daily hassles was associated with poorer perceptions of safety, being less able to practise safely and more workplace cognitive failure. Chronic stress did not moderate daily associations. The hassles reported illustrate the wide-ranging hassles nurses experienced. Conclusion: The findings demonstrate, in addition to chronic stress, the importance of daily hassles for nurses’ perceptions of safety and the hassles experienced by hospital nurses on a daily basis. Nurses perceive chronic stress and daily hassles to contribute to their perceptions of safety. Measuring the number of daily hassles experienced could proactively highlight when patient safety threats may arise, and as a result, interventions could usefully focus on the management of daily hassles

Making Sense of the Environment: The Role of Perceived Effectiveness

This manuscript develops and explores two ideas: (1) that perceptions of environmental uncertainty are after-the-fact rationalizations used by decision makers to explain strong or weak effectiveness assessments, and (2) that different contexts motivate different sense-making outcomes. The findings, based on a sample of senior decision makers from 34 firms in two industries, suggest that assessments of effectiveness and perceptions of environmental uncertainty are related through decision makers' sense-making efforts. The manuscript also addresses the limitations and implications of these results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67487/2/10.1177_001872679304600503.pd

The contingent effect of social networks on organizational commitment: A comparison of instrumental and expressive ties in a multinational high-technology company

10.1525/sop.2010.53.4.479Sociological Perspectives534479-50