Ein Update zur "Neuropsychotherapie" und Illustration aus der laufenden Forschung zum Einsatz emotionsfokussierter Vorgehensweisen

Während es fast trivial erscheint, dass erfolgreiche Psychotherapien – also Veränderungen im Erleben und Verhalten – prinzipiell mit funktionellen und strukturellen Veränderungen des Gehirns zusammenhängen, erweist es sich als deutlich anspruchsvoller, spezifischeren Fragestellungen nachzugehen und aus ihnen Implikationen für die Psychotherapie zu abzuleiten: Welche neuronalen Mechanismen sind an psychotherapeutisch relevanten Veränderungen im Erleben und Verhalten beteiligt? Wodurch werden diese neuronalen Wirkmechanismen beeinflusst? Und wie werden diese Erkenntnisse für die Psychotherapie praktisch nutzbar gemacht? Anhand aktueller Forschungsbefunde und konzeptueller Überlegungen in Anlehnung an Grawes “Neuropsychotherapie” wird in diesem Beitrag zu solchen und verwandten Fragen Stellung genommen. Eine laufende Studie an der Schnittstelle zwischen Psychotherapieprozessforschung und Neurowissenschaften illustriert, wie neuronale Wirkmechanismen erforscht und in bestehende psychologisch-psychotherapeutische Theorien eingebunden werden können. Untersucht werden hierbei die Effekte einer emotionsfokussierten Mikrointervention auf das subjektive emotionale Erleben und neurophysiologische Parameter. Solche neuronalen korrelate emotionaler Veränderungsprozesse werden vor dem theoretischen Hintergrund emotionsfokussierter und allgemeiner Psychotherapie interpretiert.

Focus on emotion as a catalyst of memory updating during reconsolidation

We share the idea of Lane et al. that successful psychotherapy exerts its effects through memory reconsolidation. To support it, we add further evidence that a behavioral interference may trigger memory update during reconsolidation. Furthermore, we propose that – in addition to replacing maladaptive emotions – new emotions experienced in the therapeutic process catalyze reconsolidation of the updated memory structure.

Facilitating Emotional Processing: An Experimental Induction of Psychotherapeutically Relevant Affective States

Psychotherapy research has shown that cognitive-affective meaning making is related to beneficial therapy outcomes. This study explores the underlying micro-processes by inducing specific cognitive-affective states and studying their immediate effects on emotional activation, the resolution of interpersonal grievances, and factors related to therapeutic progress, e.g., mastery experiences, clarification of meaning. Participants suffering from interpersonal grievances were randomly assigned to two conditions. A sentence completion task was employed to induce either the expression of emotional distress or cognitive-affective meaning making. Expressive writing was used to deepen processing. Findings of those participants adhering to the induction procedure (n = 85) showed no differences between conditions at baseline. During writing, participants in both conditions were equally emotionally activated. Directly after the writing task, participants in the meaning making condition (n = 50) reported less unresolved interpersonal grievances, and more mastery experiences, but, e.g., not more clarification, compared to those in the emotional expression condition (n = 35). Results suggest that engagement in specific states that promote meaning making of emotional experience facilitates emotional processing and is related to therapeutic benefit.

Capturing socially motivated linguistic change. How the use of gender-fair language afffects support for social initiatives in Austria and Poland.

Gender-fair language consists of the symmetric linguistic treatment of women and men instead of using masculine forms as generics. In this study, we examine how the use of gender-fair language affects readers' support for social initiatives in Poland and Austria. While gender-fair language is relatively novel in Poland, it is well established in Austria. This difference may lead to different perceptions of gender-fair usage in these speech communities. Two studies conducted in Poland investigate whether the evaluation of social initiatives (Study 1: quotas for women on election lists; Study 2: support for women students or students from countries troubled by war) is affected by how female proponents (lawyers, psychologists, sociologists, and academics) are referred to, with masculine forms (traditional) or with feminine forms (modern, gender-fair). Study 3 replicates Study 2 in Austria. Our results indicate that in Poland, gender-fair language has negative connotations and therefore, detrimental effects particularly when used in gender-related contexts. Conversely, in Austria, where gender-fair language has been implemented and used for some time, there are no such negative effects. This pattern of results may inform the discussion about formal policies regulating the use of gender-fair language.

Dose escalated intensity modulated radiotherapy in the treatment of cervical cancer.

PURPOSE Standard dose of external beam radiotherapy seems to be insufficient for satisfactory control of loco-regionally advanced cervical cancer. Aim of our study is to evaluate the outcome as well as early and chronic toxicities in patients with loco-regionally advanced cervical cancer, treated with dose escalated intensity modulated radiotherapy (IMRT) combined with cisplatin chemotherapy. MATERIAL AND METHODS Thirty-nine patients with cervical carcinoma FIGO stage IB2 - IVA were treated with curative intent between 2006 and 2010. The dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Primary tumors < 4 cm in diameter (n = 6; 15.4 %) received an external beam radiotherapy (EBRT) boost of 5.4 Gy, primary tumors > 4 cm in diameter (n = 33; 84.6 %) received an EBRT boost of 9 Gy. Patients with positive lymph nodes detected with (18)FDG-PET/CT (n = 22; 56.4 %) received a boost to a total dose of 59.4 - 64.8 Gy. The para-aortic region was included in the radiation volume in 8 (20.5 %) patients and in 5 (12.8 %) patients the para-aortic macroscopic lymph nodes received an EBRT boost. IMRT was followed with a 3D planned high dose rate intrauterine brachytherapy given to 36 (92.3 %) patients with a total dose ranging between 15-18 Gy in three fractions (single fraction: 4-6.5 Gy). Patients without contraindications (n = 31/79.5 %) received concomitantly a cisplatin-based chemotherapy (40 mg/kg) weekly. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0). RESULTS Mean overall survival for the entire cohort was 61.1 months (±3.5 months). Mean disease free survival was 47.2 months (±4.9 months) and loco-regional disease free survival was 55.2 months (±4.4 months). 65 % of patients developed radiotherapy associated acute toxicities grade 1, ca. 30 % developed toxicities grade 2 and just two (5.2 %) patients developed grade 3 toxicities, one acute diarrhea and one acute cystitis. 16 % of patients had chronic toxicities grade 1, 9 % grade 2 and one patient (2.6 %) toxicities grade 3 in the form of vaginal dryness. CONCLUSION Dose escalated IMRT appears to have a satisfactory outcome with regards to mean overall survival, disease free and loco-regional disease free survival, whereas the treatment-related toxicities remain reasonably low.

Reducing women’s lack of fit with leadership? Effects of the wording of job advertisements

Linguistic forms which refer to individuals impact mental representations of these individuals: When masculine generics are used, women tend to be cognitively underrepresented, whereas feminine–masculine word pairs are associated with a higher cognitive inclusion of women. The present research investigates whether linguistic forms affect women’s perceived lack of fit with leadership positions, which is particularly pronounced for high-status leadership positions. In a hiring-simulation experiment (N = 363), we tested the effects of different linguistic forms used in German-language job advertisements: (1) masculine forms (e.g., Geschäftsführer, ‘CEO, masc.’); (2) masculine forms with (m/f) (e.g., Geschäftsführer (m/w), ‘CEO, masc. (m/f)’); and (3) word pairs (e.g., Geschäftsführerin/Geschäftsführer, ‘CEO, fem./CEO, masc.’). The job ads announced either a high- or low-status leadership position. Results showed that female applicants were perceived to fit less well with the high-status position than male applicants when either the masculine or the masculine form with (m/f) was used––even though they were perceived to be equally competent. However, female and male applicants were perceived as fitting the high-status leadership position similarly well when word pairs were used.

Recommendations from GEC ESTRO Breast Cancer Working Group (I): Target definition and target delineation for accelerated or boost Partial Breast Irradiation using multicatheter interstitial brachytherapy after breast conserving closed cavity surgery

OBJECTIVE The aim was to develop a delineation guideline for target definition for APBI or boost by consensus of the Breast Working Group of GEC-ESTRO. PROPOSED RECOMMENDATIONS Appropriate delineation of CTV (PTV) with low inter- and intra-observer variability in clinical practice is complex and needs various steps as: (1) Detailed knowledge of primary surgical procedure, of all details of pathology, as well as of preoperative imaging. (2) Definition of tumour localization before breast conserving surgery inside the breast and translation of this information in the postoperative CT imaging data set. (3) Calculation of the size of total safety margins. The size should be at least 2 cm. (4) Definition of the target. (5) Delineation of the target according to defined rules. CONCLUSION Providing guidelines based on the consensus of a group of experts should make it possible to achieve a reproducible and consistent definition of CTV (PTV) for Accelerated Partial Breast Irradiation (APBI) or boost irradiation after breast conserving closed cavity surgery, and helps to define it after selected cases of oncoplastic surgery.

Interobserver variations of target volume delineation in multicatheter partial breast brachytherapy after open cavity surgery

PURPOSE To investigate interobserver variations of target volume delineations in accelerated partial breast irradiation with multicatheter brachytherapy (BT) and to assess the impact of guidelines on consistency of contouring. METHODS AND MATERIALS A contouring study with two phases in interstitial accelerated partial breast irradiation after open cavity surgery was conducted by the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology Breast Cancer Working Group. Contours of cavity and planning target volume (PTV) on preimplant and postimplant CT images were delineated. In Phase 1, nine radiation oncologists defined the target volumes of 5 patients, whereas in Phase 2, four observers draw the contours of 4 patients applying guidelines. In Phase 1, experience in breast BT after open cavity surgery was assessed. The delineations were compared between Phase 1 and Phase 2, the impact of guidelines was assessed, and cavity visualization score was related to consistency of delineations. RESULTS Significant interobserver variability in delineations of lumpectomy cavity and PTV was observed among the participants. Observers with BT experience after open cavity surgery outlined the cavity and PTV more consistently (conformity indexgen: 0.52 vs. 0.48 and 0.59 vs. 0.55 for preimplant and postimplant cavities). For all volumes, the mean Vmax/Vmin was 2.2 vs. 2.8. Having used guidelines all conformity indices increased significantly. For cavity, the increase was 14% and 11%, whereas for the PTV, 28% and 17% on the preimplant and postimplant CT images, respectively. A strong correlation was found between consistency of contours and cavity visualization score. CONCLUSIONS Simple guidelines on defining the lumpectomy cavity significantly increased the consistency of contouring. Reliable consistency of target volume definition can be expected only for good cavity visibility.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Eliciting the mitochondrial unfolded protein response via NAD(+) repletion reverses fatty liver disease

With no approved pharmacological treatment, non-alcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic NAD(+) levels driving reductions in hepatic mitochondrial content, function and ATP levels, in conjunction with robust increases in hepatic weight, lipid content and peroxidation in C57BL/6J mice. In an effort to assess the effect of NAD(+) repletion on the development of steatosis in mice, nicotinamide riboside (NR), a precursor for NAD(+) biosynthesis, was given to mice concomitant, as preventive strategy (NR-Prev), and as a therapeutic intervention (NR-Ther), to a HFHS diet. We demonstrate that NR prevents and reverts NAFLD by inducing a SIRT1- and SIRT3-dependent mitochondrial unfolded protein response (UPR(mt) ), triggering an adaptive mitohormetic pathway to increase hepatic β-oxidation and mitochondrial complex content and activity. The cell-autonomous beneficial component of NR treatment was revealed in liver-specific Sirt1 KO mice (Sirt1(hep-/-) ), while Apolipoprotein E-deficient (Apoe(-/-) ) mice challenged with a high-fat high-cholesterol diet (HFC), affirmed the use of NR in other independent models of NAFLD. CONCLUSION Our data warrant the future evaluation of NAD(+) boosting strategies to manage the development or progression of NAFLD. This article is protected by copyright. All rights reserved.

Leptomeningeal contrast enhancement and blood-CSF barrier dysfunction in aseptic meningitis

OBJECTIVE To investigate the blood-CSF barrier (BCSFB) dysfunction in aseptic meningitis. METHODS In our case series of 14 patients with acute aseptic meningitis, we compared MRI characteristics with CSF findings. RESULTS Contrast enhancement in the sulcal space in a leptomeningeal pattern was visualized in 7 patients with BCSFB dysfunction categorized as moderate to severe as evidenced by the CSF/serum albumin ratio (Qalb) but was not present in those with mild or no barrier disturbance (p = 0.001). The Qalb as a marker for the leakiness of the BCSFB and, more indirectly, of the blood-brain barrier (BBB) was positively correlated with the incidence of leptomeningeal contrast enhancement seen on postcontrast fluid-attenuated inversion recovery (FLAIR) MRI (p = 0.003). Patients with a more pronounced brain barrier dysfunction recovered more slowly and stayed longer in the hospital. CONCLUSIONS The severity of meningeal BBB disturbance can be estimated on postcontrast FLAIR MRI, which may be of diagnostic value in patients with aseptic meningitis.

Reduced serum chemerin in patients with more severe liver cirrhosis

Chemerin is a well-established modulator of immune cell function and its serum levels are induced in inflammatory diseases. Liver cirrhosis is associated with inflammation which is aggravated by portal hypertension. The objective of this study was to evaluate whether chemerin is induced in patients with more severe liver cirrhosis and portal hypertension. Chemerin has been measured by ELISA in the portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 45 patients with liver cirrhosis. Chemerin is higher in HVS compared to PVS in accordance with our recently published finding. SVS, HVS and PVS chemerin decline in patients with more advanced liver injury defined by the CHILD-PUGH score. Hepatic chemerin has been determined in a small cohort and is similarly expressed in normal and cirrhotic liver. MELD score and serum markers of liver and kidney function do not correlate with chemerin. There is a positive correlation of chemerin in all compartments with Quick prothrombin time and of SVS chemerin with systolic blood pressure. PVS chemerin is induced in patients with modest/massive ascites but this does not translate into higher HVS and SVS levels. Chemerin is not associated with variceal size. Reduction of portal pressure by transjugular intrahepatic portosystemic shunt does not affect chemerin levels. These data show that low chemerin in patients with more severe liver cirrhosis is associated with reduced Quick prothrombin time.

Erika Mann im Schweizer Exil. Die "Pfeffermüllerin" und das intellektuelle Unternehmen

Die Intellektuellengeschichte hat den Fokus bislang weitgehend auf männliche Intellektuelle gelegt und die Kategorie "Geschlecht" nicht fruchtbar gemacht. Sie hat ausserdem das Exil als Ursache und Kontext von intellektuellem Eingreifen unzureichend in Rechnung gestellt. Sie hat es schliesslich versäumt, die materiellen Voraussetzungen und Interessen für intellektuelles Engagement zu problematisieren. Der Aufsatz geht diesen Fragen anhand von Erika Manns Exil in der Schweiz nach.