Search results for "610 Medicine & health"
showing 10 items of 627 documents
Mutant HRAS as novel target for MEK and mTOR inhibitors.
2015
HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an imp…
Automatic Processing of Changes in Facial Emotions in Dysphoria: A Magnetoencephalography Study
2018
It is not known to what extent the automatic encoding and change detection of peripherally presented facial emotion is altered in dysphoria. The negative bias in automatic face processing in particular has rarely been studied. We used magnetoencephalography (MEG) to record automatic brain responses to happy and sad faces in dysphoric (Beck’s Depression Inventory ≥ 13) and control participants. Stimuli were presented in a passive oddball condition, which allowed potential negative bias in dysphoria at different stages of face processing (M100, M170, and M300) and alterations of change detection (visual mismatch negativity, vMMN) to be investigated. The magnetic counterpart of the vMMN was el…
Unilateral Maximal Isometric Hex Bar Pull Test : Within-Session Reliability and Lower Body Force Production in Male and Female Freeski Athletes
2021
The aim of the study was to (1) assess the within-session reliability of a unilateral isometric hex bar pull (UIHBP) maximal voluntary contraction (MVC) test and, (2) determine unilateral isometric absolute peak force (PFabs) and relative peak force (PF) values in freeski athletes. Twenty-one male and eight female academy to national team freeskiers performed the novel UIHBP MVC task on a force plate and PFabs and relative PF were assessed (1000 Hz). Within-session measures of PFabs offered high reliability on left and right limbs for males (ICC = 0.91–0.94, CV = 2.6–2.2%) and females (ICC = 0.94–0.94, CV = 1.4–1.6%), while relative PF measures showed good to high reliability in both left a…
Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition.
2021
Abstract Direct oral anti–activated factor X and antithrombin agents have largely replaced vitamin K antagonists as the standard of care in treatment of venous thromboembolism. However, gaps in efficacy and safety persist, notably in end‐stage renal disease, implantable heart valves or assist devices, extracorporeal support of the circulation, and antiphospholipid syndrome. Inhibition of coagulation factor XI (FXI) emerges as a promising new therapeutic target. Antisense oligonucleotides offer potential advantages as a prophylactic or therapeutic modality, with one dose‐finding trial in orthopedic surgery already published. In addition, monoclonal antibodies blocking activation and/or activ…
Online prevention programmes for university students: stakeholder perspectives from six European countries
2021
Abstract Background Students beginning university are at a heightened risk for developing mental health disorders. Online prevention and early intervention programmes targeting mental health have the potential to reduce this risk, however, previous research has shown uptake to be rather poor. Understanding university stakeholders’ (e.g. governing level and delivery staff [DS] and students) views and attitudes towards such online prevention programmes could help with their development, implementation and dissemination within university settings. Methods Semi-structured interviews, focus groups and online surveys were completed with staff at a governing level, university students and DS (i.e.…
Is diabetes the cost to pay for a greater cardiovascular prevention?
2010
The recent JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) trial is another study providing evidence about the effectiveness of statin therapy in reducing cardiovascular risk. Yet, in this study significantly higher glycated hemoglobin levels and incidence rates of diabetes were observed in persons treated with rosuvastatin than the placebo group. It should be noted that adverse effects on glucose metabolism have already been reported, albeit rarely, in previous trials with statins. Although the exact mechanisms involved are unknown, it seems that statins may deteriorate glycemic control by decreasing different metabolites,…
The effects of ezetimibe on LDL-cholesterol: quantitative or qualitative changes ?
2009
Ezetimibe represents the first of a new class of agents, the cholesterol absorption inhibitors, able to reduce low-density lipoproteins (LDL)-cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. To-date all the data regarding the efficacy of ezetimibe comes from the studies of its lipid-lowering power. Yet, recent findings from the ENHANCE study on atherosclerosis progression showed that the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL-cholesterol levels was present. Therefore, we cannot exclude that e…
Atherogenic dyslipidemia and oxidative stress: a new look
2009
Although results from in vitro studies and clinical trials demonstrate strong associations between oxidative stress and cardiovascular risk, to date still no convincing data are available to suggest that treatment with antioxidants might reduce vascular events. Oxidative modifications of low-density lipoproteins (LDL) represent an early stage of atherosclerosis, and small, dense LDL are more susceptible to oxidation than larger, more buoyant particles. Oxidized LDL are independent predictors of subclinical and clinical atherosclerosis. Recent studies suggested that novel therapeutic strategies may take into account the removal of such particles from circulation. Future research is required …
The differential effects of thiazolidindiones on atherogenic dyslipidemia in type 2 diabetes: what is the clinical significance?
2008
Diabetic dyslipidemia is typically characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol and a concomitant increase in atherogenic small dense low-density lipoproteins. Thiazolidindiones are able to lower the levels of fasting glucose and glycated hemoglobin significantly by improving insulin sensitivity, as well as improving some aspects of diabetic dyslipidemia: total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol tend to increase while triglycerides are generally decreased.This paper reviewed the effects of pioglitazone and rosiglitazone on atherogenic diabetic dyslipidemia, in particular on sma…