MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors

BACKGROUND MicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated. METHODS Tissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets. RESULTS Widespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change. CONCLUSIONS Expression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers

The reporting of statistics in medical educational studies: an observational study

<p>Abstract</p> <p>Background</p> <p>There is confusion in the medical literature as to whether statistics should be reported in survey studies that query an entire population, as is often done in educational studies. Our objective was to determine how often statistical tests have been reported in such articles in two prominent journals that publish these types of studies.</p> <p>Methods</p> <p>For this observational study, we used electronic searching to identify all survey studies published in <it>Academic Medicine </it>and the <it>Journal of General Internal Medicine </it>in which an entire population was studied. We tallied whether inferential statistics were used and whether p-values were reported.</p> <p>Results</p> <p>Eighty-four articles were found: 62 in <it>Academic Medicine </it>and 22 in the <it>Journal of General Internal Medicine</it>. Overall, 38 (45%) of the articles reported or stated that they calculated statistics: 35% in <it>Academic Medicine </it>and 73% in the <it>Journal of General Internal Medicine</it>.</p> <p>Conclusion</p> <p>Educational enumeration surveys frequently report statistical tests. Until a better case can be made for doing so, a simple rule can be proffered to researchers. When studying an entire population (e.g., all program directors, all deans, and all medical schools) for factual information, do not perform statistical tests. Reporting percentages is sufficient and proper.</p

Re-examining the Unified Theory of Acceptance and Use of Technology (UTAUT): Towards a Revised Theoretical Model

YesBased on a critical review of the Unified Theory of Acceptance and Use of Technology (UTAUT), this study first formalized an alternative theoretical model for explaining the acceptance and use of information system (IS) and information technology (IT) innovations. The revised theoretical model was then empirically examined using a combination of meta-analysis and structural equation modelling (MASEM) techniques. The meta-analysis was based on 1600 observations on 21 relationships coded from 162 prior studies on IS/IT acceptance and use. The SEM analysis showed that attitude: was central to behavioural intentions and usage behaviours, partially mediated the effects of exogenous constructs on behavioural intentions, and had a direct influence on usage behaviours. A number of implications for theory and practice are derived based on the findings

The Feasibility of performing resistance exercise with acutely ill hospitalized older adults

BACKGROUND: For older adults, hospitalization frequently results in deterioration of mobility and function. Nevertheless, there are little data about how older adults exercise in the hospital and definitive studies are not yet available to determine what type of physical activity will prevent hospital related decline. Strengthening exercise may prevent deconditioning and Pilates exercise, which focuses on proper body mechanics and posture, may promote safety. METHODS: A hospital-based resistance exercise program, which incorporates principles of resistance training and Pilates exercise, was developed and administered to intervention subjects to determine whether acutely-ill older patients can perform resistance exercise while in the hospital. Exercises were designed to be reproducible and easily performed in bed. The primary outcome measures were adherence and participation. RESULTS: Thirty-nine ill patients, recently admitted to an acute care hospital, who were over age 70 [mean age of 82.0 (SD= 7.3)] and ambulatory prior to admission, were randomized to the resistance exercise group (19) or passive range of motion (ROM) group (20). For the resistance exercise group, participation was 71% (p = 0.004) and adherence was 63% (p = 0.020). Participation and adherence for ROM exercises was 96% and 95%, respectively. CONCLUSION: Using a standardized and simple exercise regimen, selected, ill, older adults in the hospital are able to comply with resistance exercise. Further studies are needed to determine if resistance exercise can prevent or treat hospital-related deterioration in mobility and function

A Concept to Improve Care for People with Dementia

AbstractDementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data.Abstract Dementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data