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Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
The two main phytocannabinoids—delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)—have been extensively studied, and it has been shown that THC can induce transient psychosis. At the same time, CBD appears to have no psychotomimetic potential. On the contrary, emerging evidence for CBD's antipsychotic properties suggests that it may attenuate effects induced by THC. Thus, we investigated and compared the effects of THC and CBD administration on emotion, cognition, and attention as well as the impact of CBD pre-treatment on THC effects in healthy volunteers. We performed a placebo-controlled, double-blind, experimental trial (GEI-TCP II; ClinicalTrials.gov identifier: NCT02487381) with 60 healthy volunteers randomly allocated to four parallel intervention groups, receiving either placebo, 800 mg CBD, 20 mg THC, or both cannabinoids. Subjects underwent neuropsychological tests assessing working memory (Letter Number Sequencing test), cognitive processing speed (Digit Symbol Coding task), attention (d2 Test of Attention), and emotional state (adjective mood rating scale [EWL]). Administration of CBD alone did not influence the emotional state, cognitive performance, and attention. At the same time, THC affected two of six emotional categories—more precisely, the performance-related activity and extraversion—, reduced the cognitive processing speed and impaired the performance on the d2 Test of Attention. Interestingly, pre-treatment with CBD did not attenuate the effects induced by THC. These findings show that the acute intake of CBD itself has no effect per se in healthy volunteers and that a single dose of CBD prior to THC administration was insufficient to mitigate the detrimental impact of THC in the given setting. This is in support of a complex interaction between CBD and THC whose effects are not counterbalanced by CBD under all circumstances.
Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.
Background & Aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.
The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.
The experimental area 2 (EAR-2) at CERNs neutron time-of-flight facility (n_TOF), which is operational since 2014, is designed and built as a short-distance complement to the experimental area 1 (EAR-1). The Parallel Plate Avalanche Counter (PPAC) monitor experiment was performed to characterize the beam pro↓le and the shape of the neutron 'ux at EAR-2. The prompt γ-flash which is used for calibrating the time-of-flight at EAR-1 is not seen by PPAC at EAR-2, shedding light on the physical origin of this γ-flash.
Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.
Insects with aquatic life stages can transfer sediment and water pollutants to terrestrial ecosystems, which has been described for metals, polyaromatic hydrocarbons, and polychlorinated chemicals. However, knowledge of the transfer of aquatic micropollutants released by wastewater treatment plants is scarce despite some preliminary studies on their occurrence in riparian spiders. In our study, we address a major analytical gap focusing on the transfer of the micropollutant carbamazepine from the larvae to the adult midges of Chironomus riparius using an optimized QuEChERS extraction method and HPLC–MS/MS applicable to both life stages down to the level of about three individuals. We show that the uptake of carbamazepine by larvae is concentration-dependent and reduces the emergence rate. Importantly, the body burden remained constant in adult midges. Using this information, we estimated the daily exposure of insectivorous tree swallows as terrestrial predators to carbamazepine using the energy demand of the predator and the energy content of the prey. Assuming environmentally relevant water concentrations of about 1 μg/L, the daily dose per kilogram of body weight for tree swallows was estimated to be 0.5 μg/kg/day. At places of high water contamination of 10 μg/L, the exposure may reach 5 μg/kg/day for this micropollutant of medium polarity. Considering body burden changes upon metamorphosis, this study fills the missing link between aquatic contamination and exposure in terrestrial habitats showing that wastewater pollutants can impact birds’ life. Clearly, further analytical methods for biota analysis in both habitats are urgently required to improve risk assessment.
Der vorliegende Band dokumentiert die Erhebungsinstrumente der dritten Phase des BilWiss-Forschungsprogramms BilWiss-UV1 ("Ertrag und Entwicklung des universitären bildungswissenschaftlichen Wissens - Validierung eines Kompetenztests für Lehrkräfte") zu wissenschaftlichen Zwecken. Ziel dieser letzten Projektphase ist die Weiterentwicklung und Verbesserung des in den Vorgängerprojekten "BilWiss" und "BilWiss-Beruf" entwickelten Kompetenztests zur Erfassung des bildungswissenschaftlichen Wissens bei Lehramtsstudierenden und -absolvent(inn)en. Dieses Skalenhandbuch dokumentiert ausschlieÿlich den im Rahmen von BilWiss-UV erhobenen Studierendenlängsschnitt (LSII) der vorwiegend der Frage nachgeht, inwieweit sich bildungswissenschaftliches Wissen als Folge der Instruktion im Lehramtsstudium verändert. Ziel des Studierendenlängsschnittes ist es, eine Verteilung der Studierenden über den kompletten Studienverlauf abzubilden, da davon ausgegangen wird, dass je nach Fortschritt im Studium ein unterschiedlicher Bildungswissenschaftlicher Wissensstand zu erwarten ist. Das Projekt wird im Rahmen des BMBF-Förderprogramms "KoKoHS - Kompetenzmodelle und Instrumente der Kompetenzerfassung im Hochschulsektor-Validierung und methodische Innovationen" gefördert. Das Forschungsprogramm ist ein Verbundprojekt der Goethe-Universität Frankfurt (Prof. Dr. Mareike Kunter, Koordination), der Universität Duisburg-Essen (Prof. Dr. Detlev Leutner) sowie der Technischen Universität München (Prof. Dr. Tina Seidel). Das gesamte Programm zielt darauf ab, zu untersuchen, inwieweit angehende Lehrkräfte durch das Studium der Bildungswissenschaften unterstützt werden, mit den vielfältigen Herausforderungen ihres Berufs professionell umzugehen. Die zentrale Annahme dabei ist, dass konzeptuelles Wissen über bildungswissenschaftliche Inhalte die professionelle Entwicklung im Vorbereitungsdienst und im Berufseinstieg unterstützt. Die Grundhypothese des Projekts lautet: Bildungswissenschaftliche Inhalte und Zusammenhänge stellen einen begrifflichen Rahmen dar, den Lehrkräfte benötigen, um Unterrichts- und Schulereignisse angemessen zu interpretieren, zu reflektieren und so für die eigene Kompetenzentwicklung zu nutzen. Die in der Studie eingesetzten Instrumente sollen öffentlich für wissenschaftliche Zwecke zugänglich gemacht werden und sind vor allem als Hilfestellung für die Arbeit mit dem Längsschnittdatensatz anzusehen. Bereits veröffentlicht unter ISBN: 978-3-00-055380-6 finden Sie die Erhebungsinstrumente der Projektphasen des BilWiss-Forschungsprogramms von 2009-2016. Weiterführende Informationen zum theoretischen Ansatz der Studie und Ergebnissen der Studie können der Internetseite http://www.bilwiss.uni-frankfurt.de sowie den im Literaturverzeichnis aufgeführten Publikationen entnommen werden.
Der vorliegende Band dokumentiert die Erhebungsinstrumente der dritten Phase des BilWiss-Forschungsprogramms BilWiss-UV1 ("Ertrag und Entwicklung des universitären bildungswissenschaftlichen Wissens - Validierung eines Kompetenztests für Lehrkräfte"), zu wissenschaftlichen Zwecken. Das Projekt wird im Rahmen des BMBF-Förderprogramms "KoKoHS - Kompetenzmodelle und Instrumente der Kompetenzerfassung im Hochschulsektor-Validierung und methodische Innovationen" gefördert. Das Forschungsprogramm ist ein Verbundprojekt der Goethe-Universität Frankfurt (Prof. Dr. Mareike Kunter, Koordination), der Universität Duisburg-Essen (Prof. Dr. Detlev Leutner) sowie der Technischen Universität München (Prof. Dr. Tina Seidel). Das gesamte Programm zielt darauf ab, zu untersuchen, inwieweit angehende Lehrkräfte durch das Studium der Bildungswissenschaften unterstützt werden, mit den vielfältigen Herausforderungen ihres Berufs professionell umzugehen. Die zentrale Annahme dabei ist, dass konzeptuelles Wissen über bildungswissenschaftliche Inhalte die professionelle Entwicklung im Vorbereitungsdienst und im Berufseinstieg unterstützt. Die Grundhypothese des Projekts lautet: Bildungswissenschaftliche Inhalte und Zusammenhänge stellen einen begrifflichen Rahmen dar, den Lehrkräfte benötigen, um Unterrichts- und Schulereignisse angemessen zu interpretieren, zu reflektieren und so für die eigene Kompetenzentwicklung zu nutzen. Für die seit 2009 bestehende Längsschnittstichprobe der Vorgängerprojekte BilWiss und BilWiss-Beruf fand Mitte des Jahres 2017 der fünfte MZP statt. Alle Teilnehmer(innen), die sich zur Teilnahme an weiteren Befragungen bereit erklärt hatten, wurden per Email kontaktiert und zur Teilnahme an der Onlineumfrage eingeladen. Es konnten 136 Personen erneut befragt werden, davon sind 124 derzeit aktiv als Lehrkraft im Schuldienst tätig (120 Lehrkräfte in Vollzeit). Im Rahmen des fünften Messzeitpunktes wurde neben Fragebogenskalen zum professionellen Verhalten, auch die im Rahmen von Meilenstein 3 entwickelte Verhaltenscheckliste eingesetzt. Durch deren Einsatz konnte ermittelt werden, dass nahezu alle der befragten Lehrkräfte Sonderfunktionen im Schuldienst übernehmen. Um einige wenige Beispiele herauszugreifen: Es sind 7 befragte Lehrkräfte in der Stufenkoordination beschäftigt, 111 Lehrer(innen) sind Klassenleitung. Als Mentor(in) engagieren sich 34 Personen und ebenfalls 34 Lehrer(innen) kooperieren mit außerschulischen Partnern. Die Durchführung des Observers wurde vom Standort München administriert und betreut. Ende des Jahres 2018 fand schlieÿlich der sechste und letzte Messzeitpunkt als Onlineerhebung statt. Bei der Bearbeitung standen neben der aktuellen beruflichen Situation auch das Erleben und das professionelle Verhalten im Lehrerberuf im Fokus. Zur Erfassung der Professional Vision in Elternberatungssituationen wurde das in 2017 entwickelte Videotool eingesetzt. Ergänzend wurde der Szenariotest zur Elternberatungskompetenz in einer Kurzversion eingesetzt (Bruder, Keller, Klug & Schmitz, 2011). Zur Erfassung des proaktiven Engagements in der Schulentwicklung wurde auch bei diesem Messzeitpunkt die Verhaltenscheckliste eingesetzt. Zur Erfassung der diagnostischen Kompetenz wurde ein neu entwickelter Vignetten-Test eingesetzt. Insgesamt konnten im Online-Fragebogen (inkl. Videotool, Szenariotest, Verhaltenscheckliste und diagnostischen Fallvignetten) 68 Personen befragt werden, davon sind 56 derzeit aktiv als Lehrkraft im Schuldienst tätig (51 Lehrkräfte in Vollzeit). Die in der Studie eingesetzten Instrumente sollen öffentlich für wissenschaftliche Zwecke zugänglich gemacht werden und sind vor allem als Hilfestellung für die Arbeit mit dem Längsschnittdatensatz anzusehen. Bereits veröffentlicht unter ISBN: 978-3-00-055380-6 finden Sie die Erhebungsinstrumente der Projektphasen des BilWiss-Forschungsprogramms von 2009-2016. Weiterführende Informationen zum theoretischen Ansatz der Studie und Ergebnissen der Studie können der Internetseite http://www.bilwiss.uni-frankfurt.de sowie den im Literaturverzeichnis aufgeführten Publikationen entnommen werden.