Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease.

BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls. CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease.     

Tunneling nanotubes enable intercellular transfer of MHC class I molecules

Carefully orchestrated intercellular communication is an essential prerequisite for an effective immune response. In recent years tunneling nanotubes (TNT) have emerged as a novel mechanism of cell–cell communication. These long membrane protrusions can establish cytoplasmic continuity between distant cells and enable the exchange of cellular components. In the present study we addressed the question whether these structures can facilitate the intercellular transfer of MHC class I molecules. We found a transmembrane HLA-A2-EGFP but not a soluble HLA-G1s-EGFP fusion protein to be effectively transferred between HeLa cells. Inhibition of actin polymerization significantly reduced the HLA-A2 transfer rate, indicating that transfer is dependent on tunneling nanotubes, whose de novo formation requires actin polymerization. Furthermore, overexpression of the nanotube-inducing protein LST1 promoted transfer of HLA-A2. Moreover, LST1 protein expression is enhanced in antigen presenting cells. Our results indicate that tunneling nanotubes can mediate transfer of MHC class I molecules between distant cells.     

Combinations of Monoclonal Antibodies to Anthrax Toxin Manifest New Properties in Neutralization Assays

Monoclonal antibodies (MAbs) are potential therapeutic agents against Bacillus anthracis toxins, since there is no current treatment to counteract the detrimental effects of toxemia. In hopes of isolating new protective MAbs to the toxin component lethal factor (LF), we used a strain of mice (C57BL/6) that had not been used in previous studies, generating MAbs to LF. Six LF-binding MAbs were obtained, representing 3 IgG isotypes and one IgM. One MAb (20C1) provided protection from lethal toxin (LeTx) in an in vitro mouse macrophage system but did not provide significant protection in vivo. However, the combination of two MAbs to LF (17F1 and 20C1) provided synergistic increases in protection both in vitro and in vivo. In addition, when these MAbs were mixed with MAbs to protective antigen (PA) previously generated in our laboratory, these MAb combinations produced synergistic toxin neutralization in vitro. But when 17F1 was combined with another MAb to LF, 19C9, the combination resulted in enhanced lethal toxicity. While no single MAb to LF provided significant toxin neutralization, LF-immunized mice were completely protected from infection with B. anthracis strain Sterne, which suggested that a polyclonal response is required for effective toxin neutralization. In total, these studies show that while a single MAb against LeTx may not be effective, combinations of multiple MAbs may provide the most effective form of passive immunotherapy, with the caveat that these may demonstrate emergent properties with regard to protective efficacy.     

The neural correlates of emotion-based cognitive control in adults with early childhood behavioral inhibition

The present study is the first to assess whether the neural correlates of cognitive control processes differ in adults with and without a behaviorally inhibited temperament during early childhood. Adults with and without childhood behavioral inhibition completed an emotional conflict task while undergoing functional magnetic resonance imaging scanning. While no group differences in behavior were observed, adults with childhood behavioral inhibition, relative to adults without childhood behavioral inhibition, exhibited greater dorsomedial prefrontal cortex activity during conflict detection and greater putamen activity during conflict adaptation. Lifetime psychopathology predicted behavioral, but not brain-related, differences in conflict adaptation. These data suggest that the brain regions underlying cognitive control processes are differentially influenced by childhood behavioral inhibition, and may be differently related to psychopathology.     

Optimism and the Experience of Pain: A Systematic Review

Abstract

A growing body of literature provides evidence of the health-promoting effects of optimism, including its protective role in acute and chronic pain. Optimists are characterized by positive expectations concerning the future. These positive outcome expectancies lead to more and longer goal-directed efforts and the use of approach coping strategies. No systematic review on the effects of optimism on the experience of pain has so far been conducted. A search in the databases PubMed, Web of Science and PsycInfo, and the scanning of reference lists identified 69 eligible studies. These were categorized according to sample size, participants’ age and sex, design, optimism-pain relation as primary vs. secondary study objective, and level of study/publication quality. Overall percentages of positive, zero, and negative associations between optimism and pain as well as relative frequencies of these associations in the different categories were analyzed. About 70% of the studies showed a positive, i.e., beneficial association between optimism and at least one pain outcome. A larger percentage of beneficial associations was found in studies with experimental designs, in studies with the optimism-pain relation as primary objective, in high-quality studies/publications, and in studies including participants with a higher average age. The review suggests that optimism is associated with less acute and chronic pain, especially since a higher percentage of beneficial associations was found with high study/publication quality and with the primary focus on this relationship. For the moderating role of age, different explanations are proposed. Further research on causal relationships and on optimism-fostering clinical interventions is needed.     

Learning Curve of Speech Recognition

Speech recognition (SR) speeds patient care processes by reducing report turnaround times. However, concerns have emerged about prolonged training and an added secretarial burden for radiologists. We assessed how much proofing radiologists who have years of experience with SR and radiologists new to SR must perform, and estimated how quickly the new users become as skilled as the experienced users. We studied SR log entries for 0.25 million reports from 154 radiologists and after careful exclusions, defined a group of 11 experienced radiologists and 71 radiologists new to SR (24,833 and 122,093 reports, respectively). Data were analyzed for sound file and report lengths, character-based error rates, and words unknown to the SR’s dictionary. Experienced radiologists corrected 6 characters for each report and for new users, 11. Some users presented a very unfavorable learning curve, with error rates not declining as expected. New users’ reports were longer, and data for the experienced users indicates that their reports, initially equally lengthy, shortened over a period of several years. For most radiologists, only minor corrections of dictated reports were necessary. While new users adopted SR quickly, with a subset outperforming experienced users from the start, identification of users struggling with SR will help facilitate troubleshooting and support.     

Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic carcinoma after curative resection

The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand breaks, could serve as an early marker for new lesions in pancreatic cancer. We determined the expression of MRE11, RAD50 and NIBRIN, and their possible prognostic value regarding survival.     

Assessing Adolescent Personality Disorders With the Shedler–Westen Assessment Procedure for Adolescents

This two‐part study describes the development and validation of a method for quantifying adolescent personality pathology using the latest edition of the Shedler–Westen Assessment Procedure for Adolescents (SWAP‐II‐A), an instrument designed to be used by clinically experienced observers. In Study 1, experienced psychologists and psychiatrists described a normative clinical sample of 950 North American patients. Study 2 applied the SWAP‐II‐A in a day treatment setting. Results indicated that SWAP‐II‐A personality disorder (PD) scales evidenced high internal consistency, construct validity with Diagnostic and Statistical Manual of Mental Disorders (5th ed.) symptoms and diagnoses, and concurrent validity with Child Behavior Checklist (CBCL) ratings. Independent observers saw patients similarly, and PD assessments were significantly associated with CBCL scale scores and ward behavior.