Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma

The production of prostaglandins is regulated by cyclooxygenases (COXs), which also have a role in tumour development and progression in various human malignancies, including cholangiocarcinoma. Limited information is available of the correlation of COX-2 protein expression and prognosis in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to determine the clinical significance of COX-2 expression in ICC. In addition the correlation of COX-2 expression and apoptosis/proliferation was analysed. COX-2 expression was determined immunohistochemically in 62 resected ICCs. Proliferation was assessed using Ki67-immunohistochemistry, and apoptosis was measured with the TdT-mediated dUTP nick-end-labelling technique. COX-2 was identified as an independent prognostic factor (P = 0.028) in resected ICC by survival analysis. High levels of COX-2 expression were found to be associated both with reduced apoptosis and increased proliferation of tumour cells. This study demonstrates the independent prognostic value of the COX-2 expression in resected ICC, thus, offering a potential additional adjuvant therapeutic approach with COX-2 inhibitors

Determinants of SARS-CoV-2 receptor gene expression in upper and lower airways

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.</p

Determinants of expression of SARS-CoV-2 entry-related genes in upper and lower airways.

Funder: Dutch Research Council (NWO)Funder: Cancer Research UK Cambridge CentreFunder: ATS Foundation/Boehringer Ingelheim Pharmaceuticals Inc. Research FellowshipFunder: The Netherlands Ministry of Spatial Planning, Housing, and the EnvironmentFunder: Chan Zuckerberg InitiativeFunder: The Netherlands Ministry of Health, Welfare, and SportFunder: Longfonds Junior FellowshipFunder: Cambridge BioresourceFunder: The Netherlands Organization for Health Research and DevelopmentFunder: Cambridge NIHR Biomedical Research CentreFunder: Parker B. Francis FellowshipFunder: China Scholarship Counci

Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk

INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use. METHODS: We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project. RESULTS: No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power. CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer

Are social norms associated with smoking in French university students? A survey report on smoking correlates

<p>Abstract</p> <p>Background</p> <p>Knowledge of the correlates of smoking is a first step to successful prevention interventions. The social norms theory hypothesises that students' smoking behaviour is linked to their perception of norms for use of tobacco. This study was designed to test the theory that smoking is associated with perceived norms, controlling for other correlates of smoking.</p> <p>Methods</p> <p>In a pencil-and-paper questionnaire, 721 second-year students in sociology, medicine, foreign language or nursing studies estimated the number of cigarettes usually smoked in a month. 31 additional covariates were included as potential predictors of tobacco use. Multiple imputation was used to deal with missing values among covariates. The strength of the association of each variable with tobacco use was quantified by the inclusion frequencies of the variable in 1000 bootstrap sample backward selections. Being a smoker and the number of cigarettes smoked by smokers were modelled separately.</p> <p>Results</p> <p>We retain 8 variables to predict the risk of smoking and 6 to predict the quantities smoked by smokers. The risk of being a smoker is increased by cannabis use, binge drinking, being unsupportive of smoke-free universities, perceived friends' approval of regular smoking, positive perceptions about tobacco, a high perceived prevalence of smoking among friends, reporting not being disturbed by people smoking in the university, and being female. The quantity of cigarettes smoked by smokers is greater for smokers reporting never being disturbed by smoke in the university, unsupportive of smoke-free universities, perceiving that their friends approve of regular smoking, having more negative beliefs about the tobacco industry, being sociology students and being among the older students.</p> <p>Conclusion</p> <p>Other substance use, injunctive norms (friends' approval) and descriptive norms (friends' smoking prevalence) are associated with tobacco use.</p> <p>University-based prevention campaigns should take multiple substance use into account and focus on the norms most likely to have an impact on student smoking.</p

Contributing Factors to Operating Room Delays Identified from an Electronic Health Record: A Retrospective Study

The operating room (OR) is considered a major cost center and revenue generator for hospitals. Multiple factors contribute to OR delays and impact patient safety, patient satisfaction scores, and hospital financial performance. Reducing OR delays allows better utilization of OR resources and staffing and improves patient satisfaction while decreasing operating costs. Accurate scheduling can be the basis to achieve these goals. The objective of this initial study was to identify factors not normally documented in the electronic health record (EHR) that may contribute to or be indicators of OR delays. Materials and Methods. A retrospective data analysis was performed analyzing 67,812 OR cases from 12 surgical specialties at a small university medical center from 2010 through the first quarter of 2017. Data from the hospital’s EHR were exported and subjected to statistical analysis using Statistical Analysis System (SAS) software (SAS Institute, Cary, NC). Results. Statistical analysis of the extracted EHR data revealed factors that were associated with OR delays including, surgical specialty, preoperative assessment testing, patient body mass index, American Society of Anesthesiologists (ASA) physical status classification, daily procedure count, and calendar year. Conclusions. Delays hurt OR efficiency on many levels. Identifying those factors may reduce delays and better accommodate the needs of surgeons, staff, and patients thereby leading to improved patient’s outcomes and patient satisfaction. Reducing delays can decrease operating costs and improve the financial position of the operating theater as well as that of the hospital. Anesthesiology teams can play a key role in identifying factors that cause delays and implementing mitigating efficiencies