Increase in CD230 (cellular prion protein) fluorescence on blood lymphocytes in bovine spongiform encephalopathy–infected nonhuman primates

BACKGROUND: The cellular prion protein (PrP^c) plays a central role in prion diseases such as variant Creutzfeldt‐Jakob disease. This disease can be transmitted by blood transfusion. However, the exact kinetics of blood infectivity and the blood fraction carrying infectivity have not yet been identified. STUDY DESIGN AND METHODS: Simian PrP^c epitopes were mapped by flow cytometry using monoclonal antibodies (MoAbs). A whole blood/no wash protocol was established, validated, and applied to investigate peripheral blood cell–associated PrP^c expression profiles in bovine spongiform encephalopathy (BSE)‐infected cynomolgus monkeys and age‐/sex‐matched controls. In addition, physiologic expression patterns on blood cells and in lymphoid tissues were determined. RESULTS: In BSE‐infected macaques, blood lymphocyte–associated PrP^c fluorescence gradually increased years before the onset of clinical signs (p_{F test} < 0.0001). The increase in fluorescence intensity was detectable with MoAb 12F10, whereas we failed to detect an increase with 3F4. In parallel, plasma concentrations of soluble CD230 also increased. Centrifugation of lymphocytes almost completely eliminated differences between infected and noninfected animals, most likely caused by a partial loss in cell‐associated CD230 into the plasma supernatant. CONCLUSION: Blood lymphocytes from asymptomatically infected as well as diseased macaques were characterized by increased CD230 fluorescence, and phosphatidylinositol‐phospholipase C–resistant PrP molecules contributed at least partially to this increase. Conformational changes within PrP^c molecules may be the underlying mechanism for the increased PrP^c fluorescence. This cell‐associated phenomenon contributed at least partially to an increase in soluble plasma‐derived PrP^c levels. It is not yet known whether these changes reflect infectivity.     

LEXICALISATION IN SPEECH PRODUCTION: EVIDENCE FROM FORM RELATED WORD SUBSTITUTIONS IN APHASIA

One of the major empirical sources of theories of speech production are speech errors in normal speakers. Speech errors occurring during lexicalisation of a concept to be expressed can result in whole-word substitutions that are target related in form and/ or meaning or can appear as nonword productions (neologism). Similar error phenomena have been reported for aphasic patients. The present study describes the aphasic, HZ, who produced mainly form-related word substitutions and neologisms in several single-word processing tasks (picture naming, repetition, and reading aloud). In picture naming, meaning-related substitutions also occurred as well as substitutions that were related both in meaning and form (mixed errors). Three hypotheses of the origin of formal errors were tested: the full interactive activation hypothesis postulating meaning-form interactions, the lexical (form) retrieval hypothesis, and the post-lexical phonological encoding hypothesis. HZ's performance on repetition and reading aloud (tests showed no mixed errors and no effects of imageability and of target frequency on formal errors) failed to support the predictions of the first two hypotheses. However, the phonological encoding hypotheses (enriched by a comprehensionbased editor) could also not account for the data (e.g. for some task-specific asymmetries in the error pattern). Instead, an attempt is made to account for formal and mixed errors by construing word form encoding as an interactively organised component within a two-stage model of lexicalisation. Formal errors are traced back to interactions between lexical forms and sublexical phonological information during the second stage of lexicalisation. Mixed errors occur when lexical forms of the target's semantic competitors are involved in word form encoding.     

Retrospective analysis of clinical outcomes in bilateral cleft lip and palate patients after secondary alveolar bone grafting and premaxilla osteotomy,using a new dento-maxillary scoring system

Evaluation of relevant clinical outcomes in patients with bilateral cleft lip and palate (BCLP) after secondary aveolar bone grafting (SABG) and premaxilla osteotomy (PMO), through the use of a new scoring system.Data were collected retrospectively from all patients with BCLP who were operated on between 2004 and 2014, at the end of follow-up. The treatment protocol consisted of SABG + PMO in patients aged between 9 and 13 years. At the end of follow-up, the following parameters were scored: (un)interrupted dental arch, skeletal sagittal relationship, bone height using the Bergland/Abyholm criteria, and the presence of postoperative fistula. These parameters were combined to produce a dento-maxillary scoring system, giving a final score between 1 and 10. For statistical analysis, the independent t-test was used.Of 55 children, 45 were suitable for analysis. The mean age at time of surgery was 12.0 years (8.9–16.4 yrs), and the mean follow-up time was 11.7 years (5.8–15.8 yrs). The average number of surgeries executed under general anesthesia was 6 (range: 3–11). The average dento-maxillary score in this patient cohort was 7.6 (1–10; median: 8). Among these patients, 31 had an uninterrupted dental arch; the average Bergland/Abyholm score was 2.07; 30 patients exhibited an Angle class I incisor relationship; and, in 38 cases, the oronasal communication was closed after SABG + PMO treatment. A significant effect of fistulas was seen on dento-maxillary score (p = 0.001). Specifically, a significant effect of fistulas was seen on interrupted dental arch (p = 0.002) and on Bergland/Abyholm score (p = 0.037).The proposed dento-maxillary scoring system is a straightforward tool that can be used to describe and analyze the amount of dento-maxillary rehabilitation at the end of the treatment. Persistence of oronasal fistulas in patients with BCLP has a significant impact on interruption of the dental arch, and can influence dental results at the end of the second decade.     

An Improved Integration Scheme for Mode-Coupling-Theory Equations

Within the mode-coupling theory (MCT) of the glass transition, we reconsider the numerical schemes to evaluate the MCT functional. Here we propose nonuniform discretizations of the wave number, in contrast to the standard equidistant grid,in order to decrease the number of grid points without losing accuracy. We discuss indetail how the integration scheme on the new grids has to be modified from standardRiemann integration. We benchmark our approach by solving the MCT equations numerically for mono-disperse hard disks and hard spheres and by computing the criticalpacking fraction and the nonergodicity parameters. Our results show that significantimprovements in performance can be obtained employing a nonuniform grid.     

Methodenintegration in Beratung und Psychotherapie

The article in the journal “Zeitschrift für Psychodrama und Soziometrie” discusses the question as to how methods can be satisfactorily integrated in psychotherapy and counselling. The author shows how the process of integration takes place in a field of tension between continuous differentiation and integration. The view of integration presented contrasts with unreflected eclecticism. The attempt is also made to describe valid integrators that practitioners can employ to make fruitful use of new experiences and knowledge for their therapeutic interventions. A further perspective throws light on phenomena of the implicit knowledge acquired and utilized by practitioners in the course of their careers.     

Neurobiological correlates of problem gambling in a quasi-realistic blackjack scenario as revealed by fMRI

In the present study we obtained functional magnetic resonance imaging (fMRI) data in occasional gamblers (OG) and problem gamblers (PG) during a quasi-realistic blackjack game. We focused on neuronal correlates of risk assessment and reward processing. Participants had to decide whether to draw or not to draw a card in a high-risk or low-risk blackjack situation. We assumed PG would show differences in prefrontal and ventral striatal brain regions in comparison to OG during risk assessment and due to the winning or losing of money. Although both groups did not differ in behavioral data, blood oxygen level dependent (BOLD) signals in PG and OG significantly differed in thalamic, inferior frontal, and superior temporal regions. Whereas PG demonstrated a consistent signal increase during high-risk situations and a decrease in low-risk situations, OG presented the opposite pattern. During reward processing as derived from contrasting winning vs. losing situations, both PG and OG groups showed an enhancement of ventral striatal and posterior cingulate activity. Furthermore, PG demonstrated a distinct fronto-parietal activation pattern which has been discussed to reflect a cue-induced addiction memory network which was triggered by gambling-related cues.     

Cost Effectiveness of Intrathecal Therapy for Pain

Successful management of chronic cancer and nonmalignant pain remains a challenge to clinicians, and cost effectiveness is an important consideration for clinical decision making. Although the oral route was previously considered the optimal method of chronic opioid administration, emerging evidence demonstrates a therapeutic advantage to intrathecal opioid delivery compared to alternative modalities. Intrathecal drug delivery uses an implantable drug infusion system to deliver very low doses of opioids and other analgesics directly into the intrathecal space. Although the initial costs of surgical implantation of an intrathecal pump appear to be substantial, maintenance costs of intrathecal drug delivery over time are significantly lower than other routes of administration, including oral and intravenous drug delivery. Cost analyses of alternate routes of opioid administration indicate that intrathecal delivery is the most cost-effective route of opioid administration for patients who require long-term management of cancer (≥ 3–6 months) or nonmalignant pain (≥ 11–22 months).