The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind randomized controlled trial in alcohol use disorder

Background: Alcohol Use Disorder is a highly prevalent mental disorder which puts a severe burden on individuals, families, and society. The treatment of Alcohol Use Disorder is challenging and novel and innovative treatment approaches are needed to expand treatment options. A promising neuroscience-based intervention method that allows targeting cortical as well as subcortical brain processes is real-time functional magnetic resonance imaging neurofeedback. However, the efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a clinical setting is hitherto unclear and will be assessed in the Systems Biology of Alcohol Addiction (SyBil-AA) neurofeedback study. Methods: N = 100 patients with Alcohol Use Disorder will be randomized to 5 parallel groups in a single-blind fashion and receive real-time functional magnetic resonance imaging neurofeedback while they are presented pictures of alcoholic beverages. The groups will either downregulate the ventral striatum, upregulate the right inferior frontal gyrus, negatively modulate the connectivity between these regions, upregulate, or downregulate the auditory cortex as a control region. After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks, participants will be followed up monthly for a period of 3 months and relapse rates will be assessed as the primary outcome measure. Discussion: The results of this study will provide insights into the efficacy of real-time functional magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use Disorder as well as in the involved brain systems. This might help to identify predictors of successful neurofeedback treatment which could potentially be useful in developing personalized treatment approaches. Trial registration: The study was retrospectively registered in the German Clinical Trials Register (trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111–1181-4218) on May 10th, 2016

Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein 2 (rhBMP-2). A pilot study in dogs

The aim of the present study was to investigate bone formation to recombinant human bone morphogenetic protein-2 (rhBMP-2)-biocoated and rhBMP-2-nonbiocoated titanium implants after implantation in dogs. Implantation of sand-blasted and acid-etched (C), chromosulfuric acid surface-enhanced (CSA), and rhBMP-2-biocoated CSA [BMP-A: noncovalently immobilized rhBMP-2 (596 ng/cm(2)), BMP-B: covalently immobilized rhBMP-2 (819 ng/cm(2))] implants was performed in both the mandible and tibia of dogs. After 4 weeks of healing, the percentage of direct bone to implant contact (BIC) and the induced bone density (BD) at a distance of less than and greater than 1 mm adjacent to each implant was assessed. Histomorphometric analysis of implants inserted in the mandible and tibia revealed that BIC values appeared to be highest in the BMP-B group, followed by BMP-A, CSA, and C. BD as measured at a distance of <1 mm revealed obvious differences between groups: BMP-B>BMP-A>CSA>C. However, no differences between groups were observed at a distance of >1 mm. Within the limits of the present study, it may be concluded that rhBMP-2 immobilized by covalent and noncovalent methods on CSA-treated implant surfaces seemed to be stable and promoted direct bone apposition in a concentration-dependant manner

Comparative Analysis of Mesenchymal Stem Cell Cultivation in Fetal Calf Serum, Human Serum, and Platelet Lysate in 2D and 3D Systems

In vitro two-dimensional (2D) and three-dimensional (3D) cultivation of mammalian cells requires supplementation with serum. Mesenchymal stem cells (MSCs) are widely used in clinical trials for bioregenerative medicine and in most cases, in vitro expansion and differentiation of these cells are required before application. Optimized expansion and differentiation protocols play a key role in the treatment outcome. 3D cell cultivation systems are more comparable to in vivo conditions and can provide both, more physiological MSC expansion and a better understanding of intercellular and cell-matrix interactions. Xeno-free cultivation conditions minimize risks of immune response after implantation. Human platelet lysate (hPL) appears to be a valuable alternative to widely used fetal calf serum (FCS) since no ethical issues are associated with its harvest, it contains a high concentration of growth factors and cytokines and it can be produced from expired platelet concentrate. In this study, we analyzed and compared proliferation, as well as osteogenic and chondrogenic differentiation of human adipose tissue-derived MSCs (hAD-MSC) using three different supplements: FCS, human serum (HS), and hPL in 2D. Furthermore, online monitoring of osteogenic differentiation under the influence of different supplements was performed in 2D. hPL-cultivated MSCs exhibited a higher proliferation and differentiation rate compared to HS- or FCS-cultivated cells. We demonstrated a fast and successful chondrogenic differentiation in the 2D system with the addition of hPL. Additionally, FCS, HS, and hPL were used to formulate Gelatin-methacryloyl (GelMA) hydrogels in order to evaluate the influence of the different supplements on the cell spreading and proliferation of cells growing in 3D culture. In addition, the hydrogel constructs were cultivated in media supplemented with three different supplements. In comparison to FCS and HS, the addition of hPL to GelMA hydrogels during the encapsulation of hAD-MSCs resulted in enhanced cell spreading and proliferation. This effect was promoted even further by cultivating the hydrogel constructs in hPL-supplemented media

Xeno-Free In Vitro Cultivation and Osteogenic Differentiation of hAD-MSCs on Resorbable 3D Printed RESOMER

The development of alloplastic resorbable materials can revolutionize the field of implantation technology in regenerative medicine. Additional opportunities to colonize the three-dimensionally (3D) printed constructs with the patient’s own cells prior to implantation can improve the regeneration process but requires optimization of cultivation protocols. Human platelet lysate (hPL) has already proven to be a suitable replacement for fetal calf serum (FCS) in 2D and 3D cell cultures. In this study, we investigated the in vitro biocompatibility of the printed RESOMER® Filament LG D1.75 materials as well as the osteogenic differentiation of human mesenchymal stem cells (hMSCs) cultivated on 3D printed constructs under the influence of different medium supplements (FCS, human serum (HS) and hPL). Additionally, the in vitro degradation of the material was studied over six months. We demonstrated that LG D1.75 is biocompatible and has no in vitro cytotoxic effects on hMSCs. Furthermore, hMSCs grown on the constructs could be differentiated into osteoblasts, especially supported by supplementation with hPL. Over six months under physiological in vitro conditions, a distinct degradation was observed, which, however, had no influence on the biocompatibility of the material. Thus, the overall suitability of the material LG D1.75 to produce 3D printed, resorbable bone implants and the promising use of hPL in the xeno-free cultivation of human MSCs on such implants for autologous transplantation have been demonstrated

Fluorinated musk fragrances : the CF2 group as a conformational bias influencing the odour of civetone and (R)-muscone

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council (ERC). The authors acknowledge the EPSRC National Mass Spectrometry Facility (Swansea). M.Y. thanks the China Scholarship Council for financial support. D.O'H. thanks the Royal Society for a Wolfson Research Merit Award.The difluoromethylene (CF2) group has a strong tendency to adopt corner over edge locations in aliphatic macrocycles. In this study, the CF2 group has been introduced into musk relevant macrocyclic ketones. Nine civetone and five muscone analogues have been prepared by synthesis for structure and odour comparisons. X-ray studies indeed show that the CF2 groups influence ring structure and they give some insight into the preferred ring conformations, triggering a musk odour as determined in a professional perfumery environment. The historical conformational model of Bersuker and co-workers for musk fragrance generally holds, and structures that become distorted from this consensus, by the particular placement of the CF2 groups, lose their musk fragrance and become less pleasant.PostprintPeer reviewe

Begleitevaluation der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete: zweiter Zwischenbericht

Mit der Begleitevaluation der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete sollen wissenschaftlich fundierte Erkenntnisse über die Inanspruchnahme, Umsetzung und Wirkungen der wesentlichen Instrumente der aktiven Arbeitsmarktpolitik im SGB II und SGB III zur Förderung der Integration von Geflüchteten in Ausbildung und Arbeit gewonnen werden. Dabei werden auch Kontextfaktoren wie z. B. die regionalen Rahmenbedingungen sowie die Bedeutung der Sprachförderung in den Blick genommen. Zielgrößen sind neben Fortschritten auf dem Weg in Ausbildung und Arbeit auch Fortschritte bei Dimensionen sozialer Teilhabe, die gute Frühindikatoren für eine erst später erfolgende Arbeitsmarktintegration von Geflüchteten darstellen. Dieser Zwischenbericht dokumentiert den bis zum 31. Oktober 2019 erreichten Projektfortschritt und präsentiert empirische Befunde auf Grundlage der bis zu diesem Zeitpunkt verfügbaren umfangreichen projektspezifischen Datenbasis

Begleitevaluation der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete: Schlussbericht

Dieser Schlussbericht präsentiert wissenschaftliche Erkenntnisse über Umsetzung, Inanspruchnahme, Wirkungen und Wirtschaftlichkeit der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete. Es werden die Fragen beantwortet, wie effektiv und effizient die zentralen Maßnahmen der Arbeitsförderung in den Rechtskreisen SGB II und SGB III für Personen im Kontext von Fluchtmigration im Hinblick auf ihre Arbeitsmarktintegration und soziale Teilhabe sind, und welche Faktoren, wie etwa Sprachförderung und individuelle und lokale Kontextfaktoren, die Maßnahmenwirksamkeit verstärken oder hemmen. Die kausalanalytisch angelegte Auswertung administrativer Daten wird durch die Untersuchung von Befragungsdaten und eine umfassende Implementationsanalyse ergänzt. Aus den empirischen Erkenntnissen abgeleitete Handlungsempfehlungen geben schließlich Impulse, um die Organisation, Prozesse und Rahmenbedingungen der arbeitsmarktpolitischen Integrationsmaßnahmen für Geflüchtete so zu gestalten, dass ihre positiven Wirkungen weiter verstärkt werden können.This final report presents findings on the implementation, utilization, effects and economic efficiency of labor market integration measures for refugees. It answers the questions of how effective and efficient the central employment measures of SGB II and SGB III are for refugee migrants with regard to their labor market integration and social participation, and which factors, such as language support and individual and local context factors, strengthen or inhibit the effectiveness of the measures. The causal analysis of administrative data is complemented by the examination of survey data and a comprehensive implementation analysis. Finally, policy recommendations derived from the empirical findings provide impulses for designing the organization, processes and framework conditions of labor market integration measures for refugees in such a way that their positive effects can be further enhanced

Hypnosis and top-down regulation of consciousness

Hypnosis is a unique form of top-down regulation in which verbal suggestions are capable of eliciting pronounced changes in a multitude of psychological phenomena. Hypnotic suggestion has been widely used both as a technique for studying basic science questions regarding human consciousness but also as a method for targeting a range of symptoms within a therapeutic context. Here we provide a synthesis of current knowledge regarding the characteristics and neurocognitive mechanisms of hypnosis. We review evidence from cognitive neuroscience, experimental psychopathology, and clinical psychology regarding the utility of hypnosis as an experimental method for modulating consciousness, as a model for studying healthy and pathological cognition, and as a therapeutic vehicle. We also highlight the relations between hypnosis and other psychological phenomena, including the broader domain of suggestion and suggestibility, and conclude by identifying the most salient challenges confronting the nascent cognitive neuroscience of hypnosis and outlining future directions for research on hypnosis and suggestion

Downregulation of testicular function in the goat by altrenogest

BACKGROUND: The present study investigated whether the administration of the progestin altrenogest provides noninvasive, temporary, and reversible suppression of gonadal function in the goat as a potential alternative to chirurgical castration, which is related with irreversibility, risks of complications till death of the animal and welfare issues. Eight sexually mature Peacock goats were randomly divided into two groups. The experimental group was administered altrenogest (0.088 mg/kg) orally once daily for 7 weeks. The remaining four goats received an oral glucose solution and served as the control group. After completing the administration period, the reversibility of the medication was evaluated for another 7 weeks (observation phase). The treatment effects were assessed by clinical examination; ultrasound examination of the testes, including one-dimensional grayscale analysis, blood testosterone levels, analysis of semen parameters and libido. At the end of the observation period, the animals were castrated and the testicles were examined histologically. RESULTS: Altrenogest treatment had no significant effect on the physical development of the goats, the sonographic appearance of the testes, the gray values measured in the ultrasound images, or the blood testosterone levels. The effects of treatment on the testicular and semen parameters varied widely in the experimental animals; the testicle volume was significantly lower and the number of pathologically altered sperm in the ejaculate was significantly higher in treated animals. CONCLUSION: These findings indicate that daily altrenogest administration at a dose of 0.088 mg/kg does not reliably suppress gonadal function in the goat