FTS and 2-DG induce pancreatic cancer cell death and tumor shrinkage in mice

The Ras inhibitor S-trans-trans farnesylthiosalicylic acid (FTS) inhibits active Ras, which controls cell proliferation, differentiation, survival, and metabolism. FTS also inhibits HIF1α expression in cancer cells, leading to an energy crisis. The synthetic glucose analog 2-deoxy-D-glucose (2-DG), which inhibits glycolysis, is selectively directed to tumor cells that exhibit increased glucose consumption. The 2-DG enters tumor cells, where it competes with glucose for glycolytic enzymes. In cancer models, as well as in human phase 1 trials, 2-DG inhibits tumor growth without toxicity. We postulated that under normoxic conditions, tumor cells treated with FTS would be more sensitive than normal cells to 2-DG. We show here that combined treatment with FTS and 2-DG inhibited cancer cell proliferation additively, yet induced apoptotic cell death synergistically both in vitro and in vivo. The induced apoptosis was inferred from QVD-OPH inhibition, an increase in cleaved caspase 3, and loss of survivin. FTS and 2-DG when combined, but not separately, also induced an increase in fibrosis of the tumor tissue, chronic inflammation, and tumor shrinkage. Overall, these results suggest a possible new treatment of pancreatic tumors by the combined administration of FTS and 2-DG, which together induce pancreatic tumor cell death and tumor shrinkage under non-toxic conditions

Auditory presentation and synchronization in Adobe Flash and HTML5/JavaScript Web experiments

Substantial recent research has examined the accuracy of presentation durations and response time measurements for visually presented stimuli in Web-based experiments, with a general conclusion that accuracy is acceptable for most kinds of experiments. However, many areas of behavioral research use auditory stimuli instead of, or in addition to, visual stimuli. Much less is known about auditory accuracy using standard Web-based testing procedures. We used a millisecond-accurate Black Box Toolkit to measure the actual durations of auditory stimuli and the synchronization of auditory and visual presentation onsets. We examined the distribution of timings for 100 presentations of auditory and visual stimuli across two computers with difference specs, three commonly used browsers, and code written in either Adobe Flash or JavaScript. We also examined different coding options for attempting to synchronize the auditory and visual onsets. Overall, we found that auditory durations were very consistent, but that the lags between visual and auditory onsets varied substantially across browsers and computer systems

Carpal tunnel syndrome and the use of computer mouse and keyboard: A systematic review

<p>Abstract</p> <p>Background</p> <p>This review examines evidence for an association between computer work and carpal tunnel syndrome (CTS).</p> <p>Methods</p> <p>A systematic review of studies of computer work and CTS was performed. Supplementary, longitudinal studies of low force, repetitive work and CTS, and studies of possible pathophysiological mechanisms were evaluated.</p> <p>Results</p> <p>Eight epidemiological studies of the association between computer work and CTS were identified. All eight studies had one or more limitation including imprecise exposure and outcome assessment, low statistical power or potentially serious biases. In three of the studies an exposure-response association was observed but because of possible misclassification no firm conclusions could be drawn. Three of the studies found risks below 1. Also longitudinal studies of repetitive low-force non-computer work (n = 3) were reviewed but these studies did not add evidence to an association. Measurements of carpal tunnel pressure (CTP) under conditions typically observed among computer users showed pressure values below levels considered harmful. However, during actual mouse use one study showed an increase of CTP to potentially harmful levels. The long term effects of prolonged or repeatedly increased pressures at these levels are not known, however.</p> <p>Conclusion</p> <p>There is insufficient epidemiological evidence that computer work causes CTS.</p

Cancer Survivors’ Social Context in the Return to Work Process:Narrative Accounts of Social Support and Social Comparison Information

Purpose: Returning to work is a process that is intertwined with the social aspects of one’s life, which can influence the way in which that person manages their return to work and also determines the support available to them. This study aimed to explore cancer patients’ perceptions of the role of their social context in relation to returning to work following treatment. Methods: Twenty-three patients who had received a diagnosis of either urological, breast, gynaecological, or bowel cancer participated in semi-structured interviews examining general perceptions of cancer, work values and perceptions of the potential impact of their cancer diagnosis and treatment on work. Interviews were analysed using the iterative process of Framework Analysis. Results: Two superordinate themes emerged as influential in the return to work process: Social support as a facilitator of return to work (e.g. co-workers’ support and support outside of the workplace) and Social comparison as an appraisal of readiness to return to work (e.g. comparisons with other cancer patients, colleagues, and employees in other organisations or professions). Conclusions: Two functions of the social context of returning to work after cancer were apparent in the participants’ narrative: the importance of social support as a facilitator of returning to work and the utilisation of social comparison information in order to appraise one’s readiness to return to work. The role of social context in returning to work has largely been absent from the research literature to date. The findings of this study suggest that social support and social comparison mechanisms may have a significant impact on an individual’s successful return to the workplace

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years