Developing a tool for identifying high-risk employers for inspection.

BACKGROUND: Workers' Compensation Board (WCB) data and other information are sometimes used to calculate an 'Occupational Health and Safety (OHS) index' as a way of identifying businesses considered 'high risk' to be inspected as part of enforcement work. However, no evidence on the validity of this index exists. AIMS: To evaluate the performance of the Alberta OHS index, a 'score' based largely on WCB claims data, and to see if an index calculated using different information could perform better. METHODS: Data from the Alberta Compliance Management Information System database, 2011-2015, and WCB claim database, 2007-2014, were retrieved. Issuing 'stop work' or 'stop use' orders in inspections was defined as a proxy of high-risk outcome. The performance of the current and a modified OHS index were assessed using receiver operating characteristics (ROC) and regression analyses. RESULTS: In large employers, neither the current nor the modified OHS index was particularly effective in identifying 'high risk' employers with the area under the ROC curve (AROC) of 0.55 (95% confidence interval [CI] 0.52-0.57; P < 0.001) and 0.59 (95% CI 0.57-0.62; P < 0.001), respectively. In small employers, neither index seemed very effective with an AROC of 0.54 (95% CI 0.53-0.56; P < 0.001) and 0.55 (95% CI 0.53-0.56; P < 0.001), respectively. These results were consistent in subgroup analyses of assignments without specific initiatives, both in large and small employers. CONCLUSIONS: Neither the current nor a modified OHS index seemed to effectively identify high-risk employers. Heterogeneous results in large and small employers suggest that approaches to different-sized employers are appropriate.

Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer.

Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference. Using methyl-DNA immunoprecipitation coupled with microarray analysis, we found that the protein tyrosine phosphatase receptor type R (PTPRR) was silenced through DNMT3B-mediated methylation in the cervical cancer. PTPRR inhibited p44/42 MAPK signaling, the expression of the transcription factor AP1, human papillomavirus (HPV) oncogenes E6/E7 and DNMTs. The methylation status of PTPRR increased in cervical scrapings (n=358) in accordance with disease severity, especially in invasive cancer. Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer.

Kidney-targeting Smad7 gene transfer inhibits renal TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways, and improves diabetic nephropathy in mice.

AIMS/HYPOTHESIS: The TGF-ß/MAD homologue (SMAD) and nuclear factor κB (NF-κB) signalling pathways have been shown to play a critical role in the development of renal fibrosis and inflammation in diabetic nephropathy. We therefore examined whether targeting these pathways by a kidney-targeting Smad7 gene transfer has therapeutic effects on renal lesions in the db/db mouse model of type 2 diabetes. METHODS: We delivered Smad7 plasmids into the kidney of db/db mice using kidney-targeting, ultrasound-mediated, microbubble-inducible gene transfer. The histopathology, ultrastructural pathology and pathways of TGF-ß/SMAD2/3-mediated fibrosis and NF-κB-dependent inflammation were evaluated. RESULTS: In this mouse model of type 2 diabetes, Smad7 gene therapy significantly inhibited diabetic kidney injury, compared with mice treated with empty vectors. Symptoms inhibited included: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulo-interstitial collagen matrix abundance and renal inflammation, including Inos (also known as Nos2), Il1b and Mcp1 (also known as Ccl2) upregulation, as well as macrophage infiltration; and (3) podocyte and endothelial cell injury as demonstrated by immunohistochemistry and/or electron microscopy. Further study demonstrated that the improvement of type 2 diabetic kidney injury by overexpression of Smad7 was associated with significantly inhibited local activation of the TGF-ß/SMAD and NF-κB signalling pathways in the kidney. CONCLUSIONS/INTERPRETATION: Our results clearly demonstrate that kidney-targeting Smad7 gene transfer may be an effective therapy for type 2 diabetic nephropathy, acting via simultaneous modulation of the TGF-ß/SMAD and NF-κB signalling pathways.

A rare case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary.

Clear cell carcinomas and endometrioid carcinomas are associated with endometriosis. The association of clear cell carcinomas with mucinous lesions has only been reported infrequently, and with mucinous cystadenoma has been rarely reported. This is the second reported case of the coexistence of ovarian clear cell carcinoma, mucinous cystadenoma, and endometriosis in the same ovary. A 57-year-old woman presented with lower abdominal pain for three weeks. Ultrasonography revealed a 16 x 14 x 10 cm mass in the left ovary with solid and cystic components. Hysterectomy and bilateral salpingo-oophorectomy were performed. Histopathological examination of the left ovary revealed the presence of clear cell carcinoma, mucinous cystadenoma, and endometriosis. Continuity between the areas of mucinous epithelium and clear cell carcinoma were noted; this may suggest that clear cell carcinoma may arise from endometriosis or mucinous cystic tumors.

Acute interstitial nephritis with prominent eosinophil infiltration.

AIMS: Acute interstitial nephritis (AIN) is common, but prominent eosinophil infiltration in patients with acute interstitial nephritis is rare. The possible etiologies, predisposing factors and treatment of such patients are the subjects of this study. METHODS: one patient was reported from our medical center; nine more patients with similar findings were reviewed from the literature. Suspected offending drugs, clinical presentations, predisposing factors and patient outcomes after therapy were recorded. RESULTS: A case of clam extract-associated acute interstitial nephritis with prominent eosinophil infiltration was reported. Ten cases including ours were analyzed. A variety of drugs was thought to be causative. In all, 7 of the 10 patients had a preexisting nephrotic syndrome, and eosinophilia was found in 6. Bone marrow biopsy was not performed in most cases and only available for 2 patients including ours. 9 patients treated with steroids had good responses but 1 patient died despite treatment. CONCLUSIONS: Acute interstitial nephritis with prominent eosinophil infiltration can be caused by a great diversity of drugs, which can include clam extract tablets. A preexisting nephrotic syndrome seemed to be a predisposing factor for this condition. This disease rarely led to fatality and most patients responded well to steroid therapy.

Significance of blood-tinged post-nasal drip in paranasal sinus disease.

OBJECTIVES: Blood-tinged post-nasal drip is a rare manifestation of paranasal sinus disease. Although the presence of such a symptom would intuitively prompt suspicion of malignancy, no previously published study has addressed this issue. METHODS: One hundred and ninety-three patients with paranasal sinus lesions, who had undergone endoscopic sinus surgery for treatment or biopsy, were prospectively recruited. Their clinical information was collected and analysed. RESULTS: In patients without blood-tinged post-nasal drip, 177/181 (97.8 per cent) had chronic paranasal sinusitis and fungal sinusitis. However, in patients who presented with this symptom, six of 12 (50 per cent) were diagnosed with other conditions. The difference was statistically significant (Fisher's exact test, two tails, p < 0.001). In patients with blood-tinged post-nasal drip, diagnoses other than chronic paranasal sinusitis and fungal sinusitis were found more frequently in older males. CONCLUSION: The chance of diagnoses other than the usual sinusitis increased significantly in patients with paranasal sinus diseases who presented with blood-tinged post-nasal drip, especially in older males.

Increasing expression of fascin in renal cell carcinoma associated with clinicopathological parameters of aggressiveness.

AIM: To determine whether higher expression of fascin, an actin-bundling protein associated with motility, in conventional renal cell carcinoma (RCC) is associated with more advanced stages of the disease. METHODS: Immunohistochemical analysis of fascin expression was performed in tissue microarrays of 108 RCCs including 55 clear cell RCCs (CRCCs), 39 CRCCs with granular cell differentiation (GRCCs), 8 CRCCs with sarcomatoid differentiation (SRCCs) and 6 metastatic RCCs. RESULTS: The expression of fascin was undetectable in normal renal tubules of all control cases. However, among the 108 RCC cases, fascin immunoreactivity was seen on the cell membrane and cytoplasm. The average immunostaining score for fascin was 128/400 in grade I, 170/400 in grade II, 207/400 in grade III, and 323/400 in grade IV RCC. The average immunostaining score of fascin was 187/400 for stage T1, 205/400 for stage T2, 288/400 for stage T3, and 355/400 for stage T4 cases of RCCs. Higher fascin scores in RCC were significantly correlated with higher T and N stages and nuclear grade. In addition, the fascin scores in GRCC (368+/-19) and SRCC (263+/-21) were significantly higher than in CRCC (95+/-18). CONCLUSIONS: Our findings demonstrate for the first time that increased expression of fascin is associated with clinicopathological parameters of aggressiveness in patients with RCC. Fascin may be a novel biomarker for diagnosis and treatment of RCC.

The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy.

In animal models of IgA nephropathy, the inevitable endogenous immune response to passively administered antigens alone or in complex with specific IgA mask the exact role each might play in pathogenesis. To delineate the role the immune response might play, we have developed a passive model with exclusive IgA-immune complex-mediated nephropathy in B-cell-deficient (BCD) mice. Glomerular IgA immune deposits were induced by administration of purified IgA antiphosphorylcholine and the specific pneumococcal C-polysaccharide (PnC) antigen daily for 2 weeks into BCD and wild-type (WT) mice. In BCD mice IgA+PnC deposits induced severe glomerular injury and renal dysfunction. In contrast, WT mice developed intense glomerular IgG and IgM and C3 co-deposits of the IgA+PnC with significantly less renal injury. Cytofluorometric analysis revealed that PnC induced in BCD, but not in WT, a rapid and dramatic increase in number of activated CD3(+)/CD69(+) T-cell population. The nuclear factor-kappa B (NF-kappaB) transcription factor was activated early and progressively increased in response to glomerular IgA+PnC deposits. These results suggest that nephritogenic IgA+PnC immune deposits induce glomerular and renal dysfunction through activation of the NF-kappaB. This inflammatory pathway is modulated by the endogenous cellular and antibody response to the antigen affecting the course of IgA nephropathy progression.

Extraskeletal Ewing's sarcoma of the scalp.

Extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour (EES/PNET) is a rare disease entity. Scalp EES/PNET has been reported rarely. We report a case of an 11-year-old boy who had painful and rapidly growing subcutaneous nodes over the scalp and neck. The final diagnosis was EES/PNET after biopsy and immunohistochemical assay. The patient underwent surgical excision, chemotherapy and radiotherapy with a dose of 2000 cGy. Now he has been free of disease for two years. Early awareness and treatment of this rare disease, and wide resection followed by chemotherapy and radiotherapy might improve patients' long-term survival.