Sequelae of early trauma from a neurobiological perspective

Childhood trauma is one of the most well-established risk factors for the development of mental disorders. Due to the availability of new technologies, we are now beginning to understand how early trauma gets under the skin and exerts a sustained influence on various domains of psychological functioning and health. In the present review we will first briefly summarize what is currently known about the neurobiological effects of childhood trauma. We will then consider genetic and epigenetic factors as possible mechanisms mediating the biological embedding of childhood trauma.Der Zusammenhang zwischen frühen Traumatisierungen in der Kindheit und einem erhöhten psychischen Erkrankungsrisiko ist in der Fachliteratur seit Langem gut belegt. Erst in den letzten Jahren beginnen wir aufgrund technologischer Fortschritte zu verstehen, wie frühe Traumatisierungen körperlich niedergeschrieben werden und sich so ein Leben lang auf verschiedene Aspekte unseres Verhaltens und Erlebens auswirken können. In der vorliegenden Übersicht wird zunächst der aktuelle Erkenntnisstand zu den neurobiologischen Auswirkungen von Kindheitstraumata kurz zusammengefasst. Danach werden genetische und epigenetische Faktoren als mögliche Mechanismen der biologischen Einbettung betrachtet

Prediction of slope instabilities due to deep-seated gravitational creep

International audienceDeep-seated gravitational creep in rock slopes, rock-flow or sackung is a special category of mass-movement, in which long-lasting small-scale movements prevail. The prime causes of these mass movements in the Alpine area seem to have been glacial retreat at ~15000 a B.P. Many sackung stabilize and some undergo the transition to rapid sliding. This paper concentrates on four mass-movements in crystalline complexes of the Austrian Alps which have been investigated for aspects of deep-seated gravitational creep and prediction of the transition to rapid sliding. The present-day extent of the creeping or sliding of the rock mass has been modelled by a process of progressive, stress induced damage. Subcritical crack growth has been assumed to control this process and also the velocity of the mass movement. A sliding surface and decreasing Coulomb stress at this surface as a function of slip is a precondition for instability. The development of the four examples has been modelled successfully by a rotational slider block model and the conception of subcritical crack growth and progressive smoothing of the sliding surface. The interrelations between velocity, pore water pressure, seismic activity and the state of the sliding surface have been derived. Finally we discuss how the hypothesis inherent in the models presented could be validated and used for prediction

Antiferromagnetically coupled CoFeB/Ru/CoFeB trilayers

This work reports on the magnetic interlayer coupling between two amorphous CoFeB layers, separated by a thin Ru spacer. We observe an antiferromagnetic coupling which oscillates as a function of the Ru thickness x, with the second antiferromagnetic maximum found for x=1.0 to 1.1 nm. We have studied the switching of a CoFeB/Ru/CoFeB trilayer for a Ru thickness of 1.1 nm and found that the coercivity depends on the net magnetic moment, i.e. the thickness difference of the two CoFeB layers. The antiferromagnetic coupling is almost independent on the annealing temperatures up to 300 degree C while an annealing at 350 degree C reduces the coupling and increases the coercivity, indicating the onset of crystallization. Used as a soft electrode in a magnetic tunnel junction, a high tunneling magnetoresistance of about 50%, a well defined plateau and a rectangular switching behavior is achieved.Comment: 3 pages, 3 figure

Rational hemochromatosis therapy with erythrocytapheresis under low doses of erythropoietin

Die Hämochromatose zählt mit einer Häufigkeit von 1 : 200 – 1 : 400 zu den häufigsten Erbkrankheiten. Sie ist charakterisiert durch eine vermehrte Eisenaufnahme und Eisenspeicherung im Gewebe und verschiedenen Organen. Ohne adäquate Behandlung führt die Erkrankung zu Organschäden und zum Tode. Daher ist es das Ziel einer Therapie der Hämochromatose, den Eisenüberschuss so rasch wie möglich mindestens auf einen physiologischen Wert zu reduzieren. Zurzeit besteht die Standardtherapie der Hämochromatose aus der regelmäßigen Durchführung von Aderlässen. Dieses Verfahren ist jedoch langwierig, oft nicht gut verträglich und bleibt durch Entwicklung einer Anämie limitiert. Diese Schwierigkeiten lassen sich vermutlich durch eine Kombinationstherapie mittels Erythrozytapherese und Erythropoetin vermeiden. In der vorliegenden Arbeit wurden die Ergebnisse von 20 unselektierten Patienten (18 Männer und 2 Frauen, 36 – 71 Jahre) mit Hämochromatose retrospektiv analysiert. Alle Patienten unterzogen sich einer Behandlung mittels Erythrozytapherese (2 – 38 x 400-500 ml) und Erythropoetingaben, um die Hämoglobinkonzentration stabil zu halten. Davor hatten 14 von diesen Patienten die Behandlung mittels Aderlass aufgrund von Unverträglichkeit abgebrochen. Alle Patienten tolerierten die Behandlung sehr gut und keiner der Patienten entwickelte eine klinisch relevante Nebenwirkung, die eine Fortführung der Therapie limitieren könnte. Während sich die Hämoglobinkonzentration nicht wesentlich veränderte, ließ sich die Ferritinkonzentration bei allen Patienten, die die Therapie fortführten, rasch weitgehend normalisieren. Bei zwei Patienten konnte die Therapie aufgrund einer weiten Anreise nicht bis zur Normalisierung der Ferritinwerte durchgeführt werden. Abgesehen von den Gelenkbeschwerden bei 8 Patienten, bildeten sich alle anderen Symptome der Hämochromatose zurück. Somit stellt die Erythrozytapherese oder auch die Aderlasstherapie in Kombination mit Erythropoetingaben eine sinnvolle Alternative zur herkömmlichen Aderlasstherapie dar. Die Therapie wird von den Patienten eher bevorzugt und es lassen sich unter Berücksichtigung des Zeitaufwandes, der Arbeitsausfalltage, der Verwendung von Erythropoetin-Biosimilars und zum Teil auch der entnommenen Blutkonserven Kosten eher einsparen.Summary: Hereditary hemochromatosis with an incidence of 1:200 – 1:400 is the most common hereditary disease. It is characterized by increased iron absorption and deposition in various organs, leading to organ damage and even death. To date, phlebotomy (bloodletting) is the standard therapy of iron- overload in hemochromatosis. However, this treatment is long lasting, frequently intolerable and/or remains limited due the development of significant anemia. All these difficulties might be overcome by a combination therapy using erythropoietin preparations and erythrocytapheresis. Here, we demonstrate the results of 20 treated patients (18 male and 2 females; age 36-71 years) with primary hemochromatosis. All patients underwent a treatment regiment using a combination of erythrocytapheresis (2 – 38 x 400 – 500 ml) and erythropoietin administration to keep hemoglobin concentration largely constant during observation. Prior to this treatment, 14 of the 20 patients had discontinued phlebotomy due to intolerability. All 20 patients tolerated the new treatment very well, and significant side effects were not observed in a single patient. While hemoglobin values did not significantly changed, ferritin concentration decreased to normal levels in all cases who did not stop treatment. Two patients were unable to continue treatment due to the long distance between their residence and the medical practice. Apart from symptoms related to arthritis in 8 patients, all other symptoms related to hemochromatosis were abolished. In total, the costs including those related to time and working days of affected patients, the use of biosimilars instead of erythropoietin and, at least in part, the use of the collected blood units as normal units might be rather lower than those caused by phlebotomy. Thus it can be concluded that erythrocytapheresis or phlebotomy combined with controlled administration of erythropoietin biosimilars is the most rapid, effective and tolerable therapy in patients with significant hemochromatosis

Tissue distribution of 5-hydroxymethylcytosine and search for active demethylation intermediates.

5-Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an intermediate of an active demethylation process, which could involve further oxidation of the hydroxymethyl group to a formyl or carboxyl group followed by either deformylation or decarboxylation. Here, we use an ultra-sensitive and accurate isotope based LC-MS method to precisely determine the levels of hmC in various mouse tissues and we searched for 5-formylcytosine (fC), 5-carboxylcytosine (caC), and 5-hydroxymethyluracil (hmU) as putative active demethylation intermediates. Our data suggest that an active oxidative mC demethylation pathway is unlikely to occur. Additionally, we show using HPLC-MS analysis and immunohistochemistry that hmC is present in all tissues and cell types with highest concentrations in neuronal cells of the CNS

Simulation of magnetic active polymers for versatile microfluidic devices

We propose to use a compound of magnetic nanoparticles (20-100 nm) embedded in a flexible polymer (Polydimethylsiloxane PDMS) to filter circulating tumor cells (CTCs). The analysis of CTCs is an emerging tool for cancer biology research and clinical cancer management including the detection, diagnosis and monitoring of cancer. The combination of experiments and simulations lead to a versatile microfluidic lab-on-chip device. Simulations are essential to understand the influence of the embedded nanoparticles in the elastic PDMS when applying a magnetic gradient field. It combines finite element calculations of the polymer, magnetic simulations of the embedded nanoparticles and the fluid dynamic calculations of blood plasma and blood cells. With the use of magnetic active polymers a wide range of tunable microfluidic structures can be created. The method can help to increase the yield of needed isolated CTCs