Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

Background  

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.     

Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

Background  

Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy.     

Out-of-the-Blue: Depressive Symptoms are Associated with Deficits in Processing Inferential Expectancy-Violations Using a Novel Cognitive Rigidity Task

Rigid cognition is frequently cited as a plausible maintenance or risk factor for depression. However, most performance-based measures of cognitive rigidity associated with depression offer poor ecological validity, produce mixed findings, and afford little in the way of therapeutic application. In order to establish a more useful and relevant performance-based measure of cognitive rigidity in depression, we developed a novel task that probes a rigidity process using stimuli highly relevant to the level of construal, the thematic content, and the rhetorical mode of depressotypic thinking. The task consists of a set of narrative vignettes that contain an expectancy-violation that is incompatible with an initially-established interpretation. As hypothesized, depressive symptoms were associated with reduced ability to update interpretations. This finding was independent of the valence of the expectancy-violation (i.e., was not merely a negativity bias), and was significant after controlling for basic set-shifting ability, intelligence measures, working memory, and other potential confounds. The novel Contingent Inference Task is a promising approach that may probe a more ecologically and etiologically relevant form of cognitive rigidity in depression than other related performance-based rigidity tasks. This rigidity process may underlie the persistence of biased beliefs in depression, and represent a new therapeutic target.     

Redefining the Practice of Peer Review Through Intelligent Automation Part 1: Creation of a Standardized Methodology and Referenceable Database

Conventional peer review practice is compromised by a number of well-documented biases, which in turn limit standard of care analysis, which is fundamental to determination of medical malpractice. In addition to these intrinsic biases, other existing deficiencies exist in current peer review including the lack of standardization, objectivity, retrospective practice, and automation. An alternative model to address these deficiencies would be one which is completely blinded to the peer reviewer, requires independent reporting from both parties, utilizes automated data mining techniques for neutral and objective report analysis, and provides data reconciliation for resolution of finding-specific report differences. If properly implemented, this peer review model could result in creation of a standardized referenceable peer review database which could further assist in customizable education, technology refinement, and implementation of real-time context and user-specific decision support.     

Isolated Double Gastric Perforation in Blunt Abdominal Trauma—a Case Report

Blunt abdominal trauma mostly results from motor vehicle accidents, recreational accidents, falls or assaults with commonly injured internal organs being the spleen, liver, retroperitoneum, small bowel, kidneys, bladder, colorectal, diaphragm and pancreas. Gastric rupture is quite uncommon. Isolated gastric perforations following blunt trauma to the abdomen are mostly seen in paediatric patients. It is uncommon in adult patients and even rarer is the occurrence of double gastric perforations. We report here with a case of isolated double gastric perforation in a 24-year-old male patient following vehicular accident.     

Evaluation and Comparison of Charcot’s Triad and Tokyo Guidelines for the Diagnosis of Acute Cholangitis

Reliability of Charcot’s triad has long been questioned. Tokyo Guidelines committee published Tokyo Guidelines in 2007 and 2013. The aim of this study was to retrospectively examine the patients who had been treated with the diagnosis of acute cholangitis and evaluate 2007–2013 Tokyo criteria and Charcot’s triad. The files of the patients with acute cholangitis in a referral center were examined retrospectively. All patients were classified and evaluated according to 2007 and 2013 Tokyo criteria and Charcot’s triad; and results were compared. It was detected that 51.7 % of patients who did not meet Charcot’s triad were in definitive diagnosis group of both Tokyo criteria. Kappa value was calculated as 0.404 in the analysis of consistency between two Tokyo criteria. Two patients who had features sufficient to objectively make the diagnosis of acute cholangitis failed to meet the Tokyo criteria 2007 or 2013. Charcot’s triad is not sensitive and specific enough in the diagnosis of acute cholangitis. Revision of Tokyo 2007 criteria caused a change in the diagnostic status of 15 % of the patients. It is remarkable that kappa value can hardly be considered as a sign of moderate agreement between two Tokyo guidelines. Tokyo criteria should be supported and updated.