Mechanisms of exposure and response prevention in obsessive-compulsive disorder: effects of habituation and expectancy violation on short-term outcome in cognitive behavioral therapy

Background: Exposure and response prevention is effective and recommended as the first choice for treating obsessive-compulsive disorders (OCD). Its mechanisms of action are rarely studied, but two major theories make distinct assumptions: while the emotional processing theory assumes that treatment effects are associated with habituation within and between exposure sessions, the inhibitory learning approach highlights the acquisition of additional associations, implying alternative mechanisms like expectancy violation. The present study aimed to investigate whether process variables derived from both theories predict short-term outcome. Method: In a university outpatient unit, 110 patients (63 female) with OCD received manual-based cognitive-behavioral therapy with high standardization of the first two exposure sessions. Specifically, therapists repeated the first exposure session identically and assessed subjective units of distress as well as expectancy ratings in the course of exposure sessions. Based on these data, individual scores for habituation and distress-related expectancy violation were calculated and used for prediction of both percentage change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and remission status after 20 therapy sessions. Results: In a multiple regression model for percentage change, within-session habituation during the first exposure was a significant predictor, while in a logistic regression predicting remission status, distress-related expectancy violation during the first exposure revealed significance. A path model further supported these findings. Conclusions: The results represent first evidence for distress-related expectancy violation and confirm preliminary findings for habituation, suggesting that both processes contribute to treatment benefits of exposure in OCD, and both mechanisms appear to be independent

Mechanisms of exposure and response prevention in obsessive-compulsive disorder: effects of habituation and expectancy violation on short-term outcome in cognitive behavioral therapy

Background Exposure and response prevention is effective and recommended as the first choice for treating obsessive-compulsive disorders (OCD). Its mechanisms of action are rarely studied, but two major theories make distinct assumptions: while the emotional processing theory assumes that treatment effects are associated with habituation within and between exposure sessions, the inhibitory learning approach highlights the acquisition of additional associations, implying alternative mechanisms like expectancy violation. The present study aimed to investigate whether process variables derived from both theories predict short-term outcome. Method In a university outpatient unit, 110 patients (63 female) with OCD received manual-based cognitive-behavioral therapy with high standardization of the first two exposure sessions. Specifically, therapists repeated the first exposure session identically and assessed subjective units of distress as well as expectancy ratings in the course of exposure sessions. Based on these data, individual scores for habituation and distress-related expectancy violation were calculated and used for prediction of both percentage change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and remission status after 20 therapy sessions. Results In a multiple regression model for percentage change, within-session habituation during the first exposure was a significant predictor, while in a logistic regression predicting remission status, distress-related expectancy violation during the first exposure revealed significance. A path model further supported these findings. Conclusions The results represent first evidence for distress-related expectancy violation and confirm preliminary findings for habituation, suggesting that both processes contribute to treatment benefits of exposure in OCD, and both mechanisms appear to be independent

Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test)

Background In order to validate if the test result of the Chemotherapy Resistance Test (CTR-Test) is able to predict the resistances or sensitivities of tumors in ovarian cancer patients to drugs, the CTR-Test result and the corresponding clinical response of individual patients were correlated retrospectively. Results were compared to previous recorded correlations. Methods The CTR-Test was performed on tumor samples from 52 ovarian cancer patients for specific chemotherapeutic drugs. Patients were treated with monotherapies or drug combinations. Resistances were classified as extreme (ER), medium (MR) or slight (SR) resistance in the CTR-Test. Combination treatment resistances were transformed by a scoring system into these classifications. Results Accurate sensitivity prediction was accomplished in 79% of the cases and accurate prediction of resistance in 100% of the cases in the total data set. The data set of single agent treatment and drug combination treatment were analyzed individually. Single agent treatment lead to an accurate sensitivity in 44% of the cases and the drug combination to 95% accuracy. The detection of resistances was in both cases to 100% correct. ROC curve analysis indicates that the CTR-Test result correlates with the clinical response, at least for the combination chemotherapy. Those values are similar or better than the values from a publication from 1990. Conclusions Chemotherapy resistance testing in vitro via the CTR-Test is able to accurately detect resistances in ovarian cancer patients. These numbers confirm and even exceed results published in 1990. Better sensitivity detection might be caused by a higher percentage of drug combinations tested in 2012 compared to 1990. Our study confirms the functionality of the CTR-Test to plan an efficient chemotherapeutic treatment for ovarian cancer patients

Produção de pigmentos extracelulares por espécies de Fusarium e Aspergillus

The search for substitutes of synthetic dyes has been gaining increasing attention, due to their carcinogenic and allergenic potential. In that sense, the primary focus has been to find sustainable sources, which generate minimal environmental impact during the dyeing process. We aimed to perform a screening on filamentous fungi from genera Fusarium and Aspergillus for biodye extraction. Five species from these genera were fermented in glucose-salts broth and semi-solid potato substrate. Each species was tested in pH 4.6 and 5.6 and incubated under stationary conditions at 20 and 27 °C for 4–6 weeks. The biodye was extracted, concentrated in a rotary evaporator and lyophilized for isolation of its powdered form. Aspergillus parasiticus and A. flavus respectively produced orange and yellow pigments in liquid medium, while Fusarium graminearum produced red pigments in semi-solid substrate. We concluded that the studied fungi are effective biodye producers.Atualmente, a busca para substituir os corantes sintéticos, devido ao seu potencial carcinogênico e aparecimento de reações alérgicas, por fontes sustentáveis, que gerem impactos mínimos ao meio ambiente durante o processo de coloração vêm ganhando destaque. Assim, os objetivos do presente estudo foi realizar uma triagem com fungos filamentosos dos gêneros Fusarium spp. e Aspergillus spp. para extração de biocorante. Um total de cinco espécies pertencentes ao gênero Fusarium e Aspergillus foram fermentados em soluções líquidas de sais-glicose e formulações semissólidas de batata. Cada espécie foi testada em pH 4,6 e 5,6 e incubados sob condições estacionárias a temperatura de 20 e 27°C por 4-6 semanas. O biocorante foi extraído, concentrado em rotaevaporador e liofilizado para sua obtenção em forma de pó. Aspergillus parasiticus e Aspergillus flavus produziram pigmentos alaranjados e amarelos, respectivamente no meio líquido. Fusarium graminearum produziu pigmentos vermelhos em formulação semissólida. Com base nesses resultados foi possível observar que os fungos citados são eficientes produtores de biocorantes

Caspase Activation Is Required for T Cell Proliferation

Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade. It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity. This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors. We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity. This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval. The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation. These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner

Die psychosozialen Belastungen von jungen Kindern mit kinderpsychiatrischen Störungen

Es wird ein Überblick gegeben über zwei Patientenkollektive von Kindern im Kindergartenalter, die in Regensburg und Landshut teilstationär behandelt wurden. Expansive und Sozialverhaltensstörungen waren in beiden Stichproben am häufigsten, gefolgt von emotional-ängstlichen Störungen und Bindungsstörungen. Risikofaktoren im Sinne psychosozialer Belastungen lagen bei ca. 80% aller Kinder vor. Diese Auffälligkeiten waren in jenen Kategorien häufiger, die innerfamiliäre Faktoren wie abweichende Kommunikationsstrukturen, Unangemessenheit elterlicher Anforderungen,  abweichende Familiensituation und psychische Erkrankung eines weiteren Familienmitglieds bezeichnen

Development of a Novel Valve-Controlled Drug-Elutable Microstent for Microinvasive Glaucoma Surgery: In Vitro and Preclinical In Vivo Studies

Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure–flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drugelutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma

A docking model of key components of the DISC complex: death domain superfamily interactions redefined

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116305/1/feb2s0014579301021627.pd

Caspase-8 binding to cardiolipin in giant unilamellar vesicles provides a functional docking platform for bid

Caspase-8 is involved in death receptor-mediated apoptosis in type II cells, the proapoptotic programme of which is triggered by truncated Bid. Indeed, caspase-8 and Bid are the known intermediates of this signalling pathway. Cardiolipin has been shown to provide an anchor and an essential activating platform for caspase-8 at the mitochondrial membrane surface. Destabilisation of this platform alters receptor-mediated apoptosis in diseases such as Barth Syndrome, which is characterised by the presence of immature cardiolipin which does not allow caspase-8 binding. We used a simplified in vitro system that mimics contact sites and/or cardiolipin-enriched microdomains at the outer mitochondrial surface in which the platform consisting of caspase-8, Bid and cardiolipin was reconstituted in giant unilamellar vesicles. We analysed these vesicles by flow cytometry and confirm previous results that demonstrate the requirement for intact mature cardiolipin for caspase-8 activation and Bid binding and cleavage. We also used confocal microscopy to visualise the rupture of the vesicles and their revesiculation at smaller sizes due to alteration of the curvature following caspase-8 and Bid binding. Biophysical approaches, including Laurdan fluorescence and rupture/tension measurements, were used to determine the ability of these three components (cardiolipin, caspase-8 and Bid) to fulfil the minimal requirements for the formation and function of the platform at the mitochondrial membrane. Our results shed light on the active functional role of cardiolipin, bridging the gap between death receptors and mitochondria

A functional genomics approach reveals suggestive quantitative trait loci associated with combined TLR4 and BCP crystal-induced inflammation and osteoarthritis

Objective: Basic calcium phosphate (BCP) crystals can activate the NLRP3 inflammasome and are potentially involved in the pathogenesis of osteoarthritis (OA). In order to elucidate relevant inflammatory mechanisms in OA, we used a functional genomics approach to assess genetic variation influencing BCP crystal-induced cytokine production. Method: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers who were previously genotyped and stimulated with BCP crystals and/or lipopolysaccharide (LPS) after which cytokines release was assessed. Cytokine quantitative trait locus (cQTL) mapping was performed. For in vitro validation of the cQTL located in anoctamin 3 (ANO3), PBMCs were incubated with Tamoxifen and Benzbromarone prior to stimulation. Additionally, we performed co-localisation analysis of our top cQTLs with the most recent OA meta-analysis of genome-wide association studies (GWAS). Results: We observed that BCP crystals and LPS synergistically induce IL-1β in human PBMCs. cQTL analysis revealed several suggestive loci influencing cytokine release upon stimulation, among which are quantitative trait locus annotated to ANO3 and GLIS3. As functional validation, anoctamin inhibitors reduced IL-1β release in PBMCs after stimulation. Co-localisation analysis showed that the GLIS3 locus was shared between LPS/BCP crystal-induced IL-1β and genetic association with Knee OA. Conclusions: We identified and functionally validated a new locus, ANO3, associated with LPS/BCP crystal-induced inflammation in PBMCs. Moreover, the cQTL in the GLIS3 locus co-localises with the previously found locus associated with Knee OA, suggesting that this Knee OA locus might be explained through an inflammatory mechanism. These results form a basis for further exploration of inflammatory mechanisms in OA.</p