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.

Diagnostic evaluation of papillary lesions of the breast on core biopsy.

The management of asymptomatic intraductal papillary lesions of the breast diagnosed on core biopsy poses a challenge for patients and clinicians, as the distinction between common benign lesions and atypical or malignant varieties may be difficult without formal excision. The aim of this study was to determine whether a combination of histopathologic and biomarker features could be used to accurately identify benign papillary lesions on core biopsy. An inclusive group of 127 excised papillary lesions was characterized by detailed histopathologic review and immunohistochemical staining for the basal markers cytokeratin 5/6 (CK5/6) and P63 and the proliferation marker Ki67. Comparison of benign, atypical, and malignant lesions revealed that the combination of broad, sclerotic fibrovascular cores, and epithelial CK5/6 staining was most commonly seen in benign papillomas. Ki67 staining revealed striking intralesional heterogeneity, but there was no difference between the high scores of benign, atypical, or malignant lesions (P=0.173). In a non-overlapping set of 42 cases, a binary classifier specifying benign lesions on the basis of thick fibrovascular cores and epithelial CK5/6 staining on core biopsy gave an overall misclassification rate of 4/42 (10%) when compared with the final excision diagnosis. Misclassified cases included 2/27 lesions ultimately diagnosed as benign and 2/2 atypical papillomas. All malignant lesions (n=13) were correctly assigned. The combined assessment of fibrovascular core thickness and CK5/6 staining on core biopsy distinguished benign from malignant papillary lesions, but did not separate benign from atypical cases. This approach may form a useful addition to the clinicopathologic evaluation of papillary lesions of the breast.

A class discovery and class prediction approach to histopathological classification of mammographic screen detected columnar cell lesions of the breast.

AIMS: Columnar cell lesions (CCLs) of the breast have been increasingly recognised in biopsies taken to investigate mammographic screen detected microcalcification. The aim of this study was to identify distinct CCL subtypes by systematic analysis of histopathology. METHODS: Hierarchical cluster analysis was performed based on the profile of histopathological features in 102 screen detected CCLs. Features assessed included nuclear morphology, acinar dilatation, epithelial cell hyperplasia, cell crowding, apical snout formation and intraluminal secretion. The stability of this classification was tested in an independent cohort of 32 cases. RESULTS: The histopathology of screen detected CCLs was extremely variable. Hierarchical cluster analysis identified two subclasses: Class 1 (34/102, 33%) characterised by absence of nuclear atypia and less pronounced hyperplasia; and Class 2 (68/102, 67%) that were generally more atypical. Ki-67 scores were significantly lower for Class 1 CCLs (p < 0.001). In the independent cohort of 32 cases, Class 1 cases were clearly distinguished from Class 2, indicating that these were stable phenotypes amongst screen detected CCLs. CONCLUSIONS: The histopathological features of CCLs diagnosed at screening are extremely heterogeneous. Using a systematic approach, we have devised a broad classification system that delineates a category of less atypical CCLs that could form a basis for future studies.

Overcoming the challenges of providing clinical/practice education.

The responsibility of educating increasing numbers of students presents major challenges for nursing education. The Canadian Association of Schools of Nursing (CASN) established a task force to examine the issues and barriers associated with provision of clinical/practice education for nursing students and to assist in the development of national guidelines for practice education. In this article, the authors present key findings and recommendations resulting from a literature review, a survey of member schools and a national forum on clinical practice education. All schools of nursing are encouraged to continue to develop innovative ways of providing practice experience to meet growing demands.