Slow versus standard up-titration of paroxetine for the treatment of depression in cancer patients: a pilot study

Objectives  

This study aimed to compare the tolerability and efficacy of two different titrations of paroxetine (slow and standard) in a population of cancer patients with depression.     

Development of an Enzyme-Linked Immunosorbent Assay Using a Recombinant LigA Fragment Comprising Repeat Domains 4 to 7.5 as an Antigen for Diagnosis of Equine Leptospirosis

Leptospira immunoglobulin (Ig)-like (Lig) proteins are a novel family of surface-associated proteins in which the N-terminal 630 amino acids are conserved. In this study, we truncated the LigA conserved region into 7 fragments comprising the 1st to 3rd (LigACon1-3), 4th to 7.5th (LigACon4-7.5), 4th (LigACon4), 4.5th to 5.5th (LigACon4.5–5.5), 5.5th to 6.5th (LigACon5.5–6.5), 4th to 5th (LigACon4-5), and 6th to 7.5th (LigACon6-7.5) repeat domains. All 7 recombinant Lig proteins were screened using a slot-shaped dot blot assay for the diagnosis of equine leptospirosis. Our results showed that LigACon4-7.5 is the best candidate diagnostic antigen in a slot-shaped dot blot assay. LigACon4-7.5 was further evaluated as an indirect enzyme-linked immunosorbent assay (ELISA) antigen for the detection of Leptospira antibodies in equine sera. This assay was evaluated with equine sera (n = 60) that were microscopic agglutination test (MAT) negative and sera (n = 220) that were MAT positive to the 5 serovars that most commonly cause equine leptospirosis. The indirect ELISA results showed that at a single serum dilution of 1:250, the sensitivity and specificity of ELISA were 80.0% and 87.2%, respectively, compared to those of MAT. In conclusion, an indirect ELISA was developed utilizing a recombinant LigA fragment comprising the 4th to 7.5th repeat domain (LigACon4-7.5) as a diagnostic antigen for equine leptospirosis. This ELISA was found to be sensitive and specific, and it yielded results that concurred with those of the standard MAT.     

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.     

Alien motor phenomena: A window on to agency

Introduction. Alien motor phenomena arise in neurological and psychiatric contexts and are likely to implicate several distributed brain systems. Method. A selective literature review, focusing on cognitive neurobiological accounts of alien/anarchic limb, somatoparaphrenia, and delusions of alien control (passivity phenomena); supplemented by an account of the cognitive neuroanatomy of action and agency (subjective sense of causation) in the normal state. Results. Alien motor phenomena reflect impairments of agency through at least two mechanisms. (1) A disinhibition of “lower” motor centres giving rise to relatively stereotypic and contextually inappropriate motor routines (as emerge following medial frontal and corpus callosal lesions). (2) A disturbance of the perception of self-initiated movement, so that control of movement (causation) is attributed to an alien entity (phenomena associated with right parietal lobe lesions, focal epilepsy, and hyperactivity in acute schizophrenia). Conclusion. Whereas alien/anarchic limb dysfunction may be relatively easily explained in cognitive neurobiological terms, a comprehensive account of alien control will require further empirical ingenuity. Current models invoke disturbed feed-forward mechanisms, imitation, and the sense of another's agency (“nonself attribution”).     

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.