Plos One
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Safe from harm: learned, instructed, and symbolic generalization pathways of human threat-avoidance.
Avoidance of threatening or unpleasant events is usually an adaptive behavioural strategy. Sometimes, however, avoidance can become chronic and lead to impaired daily functioning. Excessive threat-avoidance is a central diagnostic feature of anxiety disorders, yet little is known about whether avoidance acquired in the absence of a direct history of conditioning with a fearful event differs from directly learned avoidance. ⋯ Three groups were then tested with a learned CS+ and CS- (learned group), instructed CS+ (instructed group), and generalized CS+ (derived group) presentations. Results showed similar levels of avoidance behaviour and threat-belief ratings about the likelihood of shock across each of the three pathways despite the different mechanisms by which they were acquired. Findings have implications for understanding the aetiology of clinical avoidance in anxiety.
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Ischemia-reperfusion injury following cardiopulmonary resuscitation (CPR) is associated with a systemic inflammatory response, resulting in post-resuscitation disease. In the present study we investigated the response of the pleiotropic inflammatory cytokine macrophage migration inhibitory factor (MIF) to CPR in patients admitted to the hospital after out-of-hospital cardiac arrest (OHCA). To describe the magnitude of MIF release, we compared the blood levels from CPR patients with those obtained in healthy volunteers and with an aged- and gender-matched group of patients undergoing cardiac surgery with the use of extracorporeal circulation. ⋯ MIF shows a rapid and pronounced increase following CPR, hence allowing a very early assessment of the inflammatory response. Further studies are warranted in larger patient groups to determine the prognostic significance of MIF.
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Here we show that bortezomib induces effective proteasome inhibition and accumulation of poly-ubiquitinated proteins in diffuse large B-cell lymphoma (DLBCL) cells. This leads to induction of endoplasmic reticulum (ER) stress as demonstrated by accumulation of the protein CHOP, as well as autophagy, as demonstrated by accumulation of LC3-II proteins. Our data suggest that recruitment of both ubiquitinated proteins and LC3-II by p62 directs ubiquitinated proteins, including I-κBα, to the autophagosome. ⋯ Importantly, the combination of proteasome and autophagy inhibitors showed synergy in killing DLBCL cells. In summary, bortezomib-induced autophagy confers relative DLBCL cell drug resistance by eliminating I-κBα. Inhibition of both autophagy and the proteasome has great potential to kill apoptosis-resistant lymphoma cells.
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Randomized Controlled Trial
PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck.
Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. ⋯ These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck.
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Since September 2005, the International Committee of Medical Journal Editors (ICMJE) has required that randomised controlled trials (RCTs) are prospectively registered in a publicly accessible database. After registration, a trial registration number (TRN) is assigned to each RCT, which should make it easier to identify future publications and cross-check published results with associated registry entries, as long as the unique identification number is reported in the article. ⋯ Our results show that further promotion and implementation of trial registration and accurate reporting of TRN is still needed. This might be helped by inclusion of the TRN as an item on the CONSORT checklist.