Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-κB activation

BACKGROUND: Osteopontin (OPN), a secreted phosphoglycoprotein, has been strongly associated with tumor progression and aggressive cancers. MDA-MB-435 cells secrete very high levels of OPN. However metastasis-suppressed MDA-MB-435 cells, which were transfected with breast cancer metastasis suppressor 1 (BRMS1), expressed significantly less OPN. BRMS1 is a member of mSin3-HDAC transcription co-repressor complex and has been shown to suppress the metastasis of breast cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1 regulates OPN expression. RESULTS: The search for a BRMS1-regulated site on the OPN promoter, using luciferase reporter assays of the promoter deletions, identified a novel NF-κB site (OPN/NF-κB). Electrophoretic mobility shift assays and chromatin immunoprecipitations (ChIP) confirmed this site to be an NF-κB-binding site. We also show a role of HDAC3 in suppression of OPN via OPN/NF-κB. CONCLUSION: Our results show that BRMS1 regulates OPN transcription by abrogating NF-κB activation. Thus, we identify OPN, a tumor-metastasis activator, as a crucial downstream target of BRMS1. Suppression of OPN may be one of the possible underlying mechanisms of BRMS1-dependent suppression of tumor metastasis

A national survey on the patterns of treatment of inflammatory bowel disease in Canada

BACKGROUND: There is a general lack of information on the care of inflammatory bowel disease (IBD) in a broad, geographically diverse, non-clinic population. The purposes of this study were (1) to compare a sample drawn from the membership of a national Crohn's and Colitis Foundation to published clinic-based and population-based IBD samples, (2) to describe current patterns of health care use, and (3) to determine if unexpected variations exist in how and by whom IBD is treated. METHODS: Mailed survey of 4453 members of the Crohn's and Colitis Foundation of Canada. The questionnaire, in members stated language of preference, included items on demographic and disease characteristics, general health behaviors and current and past IBD treatment. Each member received an initial and one reminder mailing. RESULTS: Questionnaires were returned by 1787, 913, and 128 people with Crohn's disease, ulcerative colitis and indeterminate colitis, respectively. At least one operation had been performed on 1159 Crohn's disease patients, with risk increasing with duration of disease. Regional variation in surgical rates in ulcerative colitis patients was identified. 6-Mercaptopurine/Azathioprine was used by 24% of patients with Crohn's disease and 12% of patients with ulcerative colitis (95% CI for the difference: 8.9% – 15%). In patients with Crohn's disease, use was not associated with gender, income or region of residence but was associated with age and markers of disease activity. Infliximab was used by 112 respondents (4%), the majority of whom had Crohn's disease. Variations in infliximab use based on region of residence and income were not seen. Sixty-eight percent of respondents indicated that they depended most on a gastroenterologist for their IBD care. There was significant regional variation in this. However, satisfaction with primary physician did not depend on physician type (for example, gastroenterologist versus general practitioner). CONCLUSION: This study achieved the goal of obtaining a large, geographically diverse sample that is more representative of the general IBD population than a clinic sample would have been. We could find no evidence of significant regional variation in medical treatments due to gender, region of residence or income level. Differences were noted between different age groups, which deserves further attention

ISAAC, a framework for integrated safety analysis of functional, geometrical and human aspects

International audienceThis paper aims at presenting methods and tools that are developed in the ISAAC project (Improvement of Safety Activities on Aeronautical Complex Systems, www.isaac-fp6.org), a European Community funded project, to support the safety assessment of complex embedded systems. The ISAAC methodology proposes to base as much of the safety analyses as is feasibly possible on simulable and formally verifiable system models that include fault models and can be shared both by safety and design engineers. On one hand, tools were developed to support safety assessment of Simulink, SCADE, Statemate, NuSMV and AltaRica models. On the other hand, formal models are coupled with additional models to address the problems of common cause analysis and human error analysis

Interprofessional Education: An evaluation of a joint learning workshop for podiatry and pharmacy students

"Interprofessional Education occurs when two or more professionals learn with, from and about each other to improve collaboration and the quality of care" (CAIPE 2002). Interprofessional education forms part of the Standards for the Initial Education and Training of Pharmacists. Working with and understanding the role of another profession has been shown to positively impact on the quality of care of the patient. Following positive pharmacy student feedback from visits to podiatry clinics an interprofessional learning workshop with case - based scenarios was developed. These were based on patients with high risk medical conditions that would impact on the work of both professions. Data from the feedback forms was evaluated and analysed to determine whether the workshop increased knowledge of the British National Formulary (BNF), the prescribing process and gave an insight in to the role of other healthcare professionals. We discuss how the student’s learning has been enhanced by the contribution of another professional group. The workshop was positively received. Students were observed working together discussing the patients’ conditions and issues relating to their care. This initially revolved around the students’ area of knowledge; however, as the session progressed it became apparent that the students were learning with, from and about each other for the benefit of patient care

Prognostic utility of sestamibi lung uptake does not require adjustment for stress-related variables: A retrospective cohort study

BACKGROUND: Increased (99m)Tc-sestamibi stress lung-to-heart ratio (sLHR) has been shown to predict cardiac outcomes similar to pulmonary uptake of thallium. Peak heart rate and use of pharmacologic stress affect the interpretation of lung thallium uptake. The current study was performed to determine whether (99m)Tc-sestamibi sLHR measurements are affected by stress-related variables, and whether this in turn affects prognostic utility. METHODS: sLHR was determined in 718 patients undergoing (99m)Tc-sestamibi SPECT stress imaging. sLHR was assessed in relation to demographics, hemodynamic variables and outcomes (mean follow up 5.6 ± 1.1 years). RESULTS: Mean sLHR was slightly greater in males than in females (P < 0.01) and also showed a weak negative correlation with age (P < 0.01) and systolic blood pressure (P < 0.01), but was unrelated to stress method or heart rate at the time of injection. In patients undergoing treadmill exercise, sLHR was also positively correlated with peak workload (P < 0.05) but inversely with double product (P < 0.05). The combined explanatory effect of sex, age and hemodynamic variables on sLHR was less than 10%. The risk of acute myocardial infarction (AMI) or death increased by a factor of 1.7–1.8 for each SD increase in unadjusted sLHR, and was unaffected by adjustment for sex, age and hemodynamic variables (hazard ratios 1.6–1.7). The area under the ROC curve for the unadjusted sLHR was 0.65 (95% CI 0.59–0.71, P < 0.0001) and was unchanged for the adjusted sLHR (0.65, 95% CI 0.61–0.72, P < 0.0001). CONCLUSION: Stress-related variables have only a weak effect on measured sLHR. Unadjusted and adjusted sLHR provide equivalent prognostic information for prediction of AMI or death

An exploratory study of the impacts of gambling on affected others accessing a social service

Problem gambling affects many people beyond the problem gambler themselves. Help-seeking is relatively rare among affected others, especially those in lower socioeconomic communities. However, these affected others are sometimes in contact with other support agencies. The present research interviewed 10 people seeking support through a social agency who reported being affected by someone else’s gambling. Data from semi-structured interviews were analysed using an inductive descriptive approach to identify three themes: 1) This is ugly; 2) It affects everything; and 3) I just do it by myself. The results highlight the normality of harmful gambling across generations, the lack of any positive aspects to gambling for affected others, and the impacts on families and children. Specific gambling-related help seeking remains rare, however the opportunity to provide support, information and advice on approaches to coping to affected others as they contact social services is highlighted

What is behind smoker support for new smokefree areas? National survey data

BACKGROUND: Some countries have started to extend indoor smokefree laws to cover cars and various outdoor settings. However, policy-modifiable factors around smoker support for these new laws are not well described. METHODS: The New Zealand (NZ) arm of the International Tobacco Control Policy Evaluation Survey (ITC Project) derives its sample from the NZ Health Survey (a national sample). From this sample we surveyed adult smokers (n = 1376). RESULTS: For the six settings considered, 59% of smokers supported at least three new completely smokefree areas. Only 2% favoured smoking being allowed in all the six new settings. Support among Maori, Pacific and Asian smokers relative to European smokers was elevated in multivariate analyses, but confidence intervals often included 1.0.Also in the multivariate analyses, "strong support" by smokers for new smokefree area laws was associated with greater knowledge of the second-hand smoke (SHS) hazard, and with behaviours to reduce SHS exposure towards others. Strong support was also associated with reporting having smokefree cars (aOR = 1.68, 95% CI = 1.21 - 2.34); and support for tobacco control regulatory measures by government (aOR = 1.63, 95% CI = 1.32 - 2.01). There was also stronger support by smokers with a form of financial stress (not spending on household essentials). CONCLUSIONS: Smokers from a range of population groups can show majority support for new outdoor and smokefree car laws. Some of these findings are consistent with the use of public health strategies to support new smokefree laws, such as enhancing public knowledge of the second-hand smoke hazard