The Euromarket in the face of change

Financial innovations are currently displacing traditional methods of Euro-currency financing, while in Germany and Japan there is talk of establishing international free banking zones along American lines. What are the reasons for these developments and how are they affecting the Euromarket

A novel Troponin I mutation associated with severe restrictive cardiomyopathy—a case report of a 27-year-old woman with fatigue

Background: Restrictive cardiomyopathy is rare and heterogeneous in origin, clinical manifestation, and prognosis. Familial forms have, amongst others, been associated with mutations in the TNNI3 gene. We present a case of familial restrictive cardiomyopathy associated with a novel TNNI3 mutation including longitudinal follow-up. Case summary: A 27-year-old woman was evaluated for fatigue in the context of a family history of sudden cardiac death. Echocardiography was normal except for mild left atrial dilatation. Focused genetic screening, limited to the most common genes associated with cardiomyopathy, was unremarkable in 2006. In biopsy, mild inflammatory cardiomyopathy was diagnosed, and the patient was discharged. Thirteen years later, rapid clinical deterioration occurred in the context of new-onset atrial fibrillation (AF). Echocardiography now showed gross bi-atrial dilatation and evidence of diastolic dysfunction. Based on haemodynamic tracings during angiography, a diagnosis of restrictive cardiomyopathy was made. In 2018, next-generation sequencing revealed the hitherto undescribed Troponin I variant Lys193Glu in a functionally critical domain. Haemodynamic stabilization was achieved by pulmonary vein isolation. Until now, the patient remains symptom free under diuretic treatment. Discussion: Diagnosis of restrictive cardiomyopathy is complicated by often oligosymptomatic early presentation and a diverse clinical picture. Thorough medical and family history and early invasive haemodynamic tracing are indispensable in diagnosis. Therapy-refractory AF should raise suspicion. Reporting of longitudinal follow-up cases is essential to better understand the early symptoms, development, and prognosis of this rare disease. Broad genetic testing in unclear cases has become more available and affordable and should be considered early in the diagnostic workflow

Stellungnahme zu den Sektorkonzepten der Bundesregierung zu Grundbildung, Berufliche Bildung und Hochschulbildung

Das Bundesministerium für Wirtschaftliche Zusammenarbeit und Entwicklung hat 1992/93 drei Sektorkonzepte zur Förderung der Entwicklungszusammenarbeit im Bildungsbereich in Neufassungen herausgegeben: zur Grundbildung, zur beruflichen Bildung und zum Hochschulwesen. Die Kommission "Bildungsforschung mit der Dritten Welt" hat die in diesen Sektorkonzepten niedergelegten Vorstellungen und Vorschläge erörtert. Die Verfasser haben Überlegungen auf der Basis dieser Diskussionen in der Absicht einer kritischen Politikberatung erarbeitet. Zunächst wird zu den einzelnen Sektorkonzepten Stellung genommen, dann folgen einige grundsätzliche Bemerkungen zu allen drei Papieren. (DIPF/Orig.

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

How are social stressors at work related to well-being and health? A systematic review and meta-analysis

Background: Social relationships are crucial for well-being and health, and considerable research has established social stressors as a risk for well-being and health. However, researchers have used many different constructs, and it is unclear if these are actually different or reflect a single overarching construct. Distinct patterns of associations with health/well-being would indicate separate constructs, similar patterns would indicate a common core construct, and remaining differences could be attributed to situational characteristics such as frequency or intensity. The current meta-analysis therefore investigated to what extent different social stressors show distinct (versus similar) patterns of associations with well-being and health. Methods: We meta-analysed 557 studies and investigated correlations between social stressors and outcomes in terms of health and well-being (e.g. burnout), attitudes (e.g. job satisfaction), and behaviour (e.g. counterproductive work behaviour). Moderator analyses were performed to determine if there were differences in associations depending on the nature of the stressor, the outcome, or both. To be included, studies had to be published in peer-reviewed journals in English or German; participants had to be employed at least 50% of a full-time equivalent (FTE). Results: The overall relation between social stressors and health/well-being was of medium size (r = -.30, p < .001). Type of social stressor and outcome category acted as moderators, with moderating effects being larger for outcomes than for stressors. The strongest effects emerged for job satisfaction, burnout, commitment, and counterproductive work behaviour. Type of stressor yielded a significant moderation, but differences in effect sizes for different stressors were rather small overall. Rather small effects were obtained for physical violence and sexual mistreatment, which is likely due to a restricted range because of rare occurrence and/or underreporting of such intense stressors. Conclusions: We propose integrating diverse social stressor constructs under the term "relational devaluation" and considering situational factors such as intensity or frequency to account for the remaining variance. Practical implications underscore the importance for supervisors to recognize relational devaluation in its many different forms and to avoid or minimize it as far as possible in order to prevent negative health-related outcomes for employees

Histamine 2 Receptor Agonism and Histamine 4 Receptor Antagonism Ameliorate Inflammation in a Model of Psoriasis

Psoriasis is a chronic inflammatory skin disorder characterized by hyperproliferative keratinocytes and immune cell infiltration into the skin, often accompanied by itch. Histamine, acting via histamine 1–4 receptors, is known to modulate immune responses in the skin and to induce itch. The aim of this study was to test the role of histamine 2 receptors and histamine 4 receptors in the imiquimod-induced psoriasis-like skin inflammation model. BALB/c mice were treated intraperitoneally with amthamine (histamine 2 receptor agonist), JNJ-39758979 (histamine 4 receptor antagonist), a combination of both, or vehicle twice daily in a preventive manner. Imiquimod was applied once daily onto the back skin for 10 consecutive days. Stimulation of histamine 2 receptors and blockade of histamine 4 receptors ameliorated imiquimod-induced skin inflammation. The combination of amthamine and JNJ-39758979 reduced skin inflammation even more pronounced, diminished epidermal hyperproliferation, and inhibited spontaneous scratching behaviour. A combination of histamine 2 receptor agonist and histamine 4 receptor antagonists could represent a new strategy for the treatment of psoriasis

Riboflavin synthase of Schizosaccharomyces pombe. Protein dynamics revealed by (19)F NMR protein perturbation experiments

BACKGROUND: Riboflavin synthase catalyzes the transformation of 6,7-dimethyl-8-ribityllumazine into riboflavin in the last step of the riboflavin biosynthetic pathway. Gram-negative bacteria and certain yeasts are unable to incorporate riboflavin from the environment and are therefore absolutely dependent on endogenous synthesis of the vitamin. Riboflavin synthase is therefore a potential target for the development of antiinfective drugs. RESULTS: A cDNA sequence from Schizosaccharomyces pombe comprising a hypothetical open reading frame with similarity to riboflavin synthase of Escherichia coli was expressed in a recombinant E. coli strain. The recombinant protein is a homotrimer of 23 kDa subunits as shown by sedimentation equilibrium centrifugation. The protein sediments at an apparent velocity of 4.1 S at 20°C. The amino acid sequence is characterized by internal sequence similarity indicating two similar folding domains per subunit. The enzyme catalyzes the formation of riboflavin from 6,7-dimethyl-8-ribityllumazine at a rate of 158 nmol mg(-1 )min(-1 )with an apparent K(M )of 5.7 microM. (19)F NMR protein perturbation experiments using fluorine-substituted intermediate analogs show multiple signals indicating that a given ligand can be bound in at least 4 different states. (19)F NMR signals of enzyme-bound intermediate analogs were assigned to ligands bound by the N-terminal respectively C-terminal folding domain on basis of NMR studies with mutant proteins. CONCLUSION: Riboflavin synthase of Schizosaccharomyces pombe is a trimer of identical 23-kDa subunits. The primary structure is characterized by considerable similarity of the C-terminal and N-terminal parts. Riboflavin synthase catalyzes a mechanistically complex dismutation of 6,7-dimethyl-8-ribityllumazine affording riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. The (19)F NMR data suggest large scale dynamic mobility in the trimeric protein which may play an important role in the reaction mechanism

Wasp controls oriented migration of endothelial cells to achieve functional vascular patterning

Endothelial cell migration and proliferation are essential for the establishment of a hierarchical organization of blood vessels and optimal distribution of blood. However, how these cellular processes are coordinated remains unknown. Here, using the zebrafish trunk vasculature we show that in future veins endothelial cells proliferate more than in future arteries and migrate preferentially towards neighboring arteries. In future arteries endothelial cells show a biphasic migration profile. During sprouting cells move away from the dorsal aorta, during remodelling cells stop or move towards the feeding aorta. The final morphology of blood vessels is thus established by local proliferation and oriented cell migration to and from neighboring vessels. Additionally, we identify WASp to be essential for this differential migration. Loss of WASp leads to irregular distribution of endothelial cells, substantially enlarged veins and persistent arteriovenous shunting. Mechanistically, we report that WASp drives the assembly of junctional associated actin filaments and is required for junctional expression of PECAM-1. Together, our data identify that functional vascular patterning in the zebrafish trunk utilizes differential cell movement regulated by junctional actin, and that interruption of differential migration may represent a pathomechanism in vascular malformations

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation

Background. Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. Methods. We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. Results. Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 ± 17) than standard patients (29 ± 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). Conclusion. We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reaction