Valproatverordnungen bei Mädchen und Frauen im gebärfähigen Alter in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Aufgrund des teratogenen Potenzials von Valproat wurden die Empfehlungen zur Risikoaufklärung und Verordnung bei...     

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient’s response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.     

Depression,psychological distress,and quality of life in patients with cardioverter defibrillator with or without cardiac resynchronization therapy

Congestive heart failure is frequent and leads to reduced exercise capacity, reduced quality of life (QoL), and depression in many patients. Cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD) offer therapeutic options and may have an impact on QoL and depression. This study was performed to evaluate physical and mental health in patients undergoing ICD or combined CRT/ICD-implantation (CRT-D). Echocardiography, spiroergometry, and psychometric questionnaires [Beck Depression Inventory, General World Health Organization Five Well-being Index (WHO-5), Brief Symptom Inventory and 36-item Short Form (SF-36)] were obtained in 39 patients (ICD: 17, CRT-D: 22) at baseline and 6-month follow-up (FU) after device implantation. CRT-D patients had a higher NYHA class and broader left bundle branch block than ICD patients at baseline. At FU, ejection fraction (EF), peak oxygen uptake, and NYHA class improved significantly in CRT-D patients but remained unchanged in ICD patients. Patients with CRT-D implantation showed higher levels of depressive symptoms, psychological distress, and impairment in QoL at baseline and FU compared to ICD patients. These impairments remained mostly unchanged in all patients after 6 months. Overall, these findings imply that there is a need for careful assessment and treatment of psychological distress and depression in ICD and CRT-D patients in the course of device implantation as psychological burden seems to persist irrespective of physical improvement.     

Homeostatic regulation of CD8+ T cells after antigen challenge in the absence of Fas (CD95)

The role of Fas in the homeostatic regulation of CD8⁺ T cells after antigen challenge was analyzed in the murine model of lymphocytic choriomeningitis virus (LCMV) infection. Mice homozygous for the lpr mutation and carrying T cell receptor (TCR) αβ transgenes specific for the LCMV glycoprotein peptide aa 33–41 in the context of H-2D^b were used. Five main results emerged: first, development of lymphadenopathy and of CD4⁻CD8⁻ double-negative B220⁺ T cells in lpr mice was not inhibited by the αβ TCR transgenes; second, tolerance induction and peripheral deletion of CD8⁺ T cells induced by LCMV glycoprotein peptide injection was independent of Fas expression; third, clonal down-regulation of Fas-deficient TCR-transgenic CD8⁺ T cells after acute LCM virus infection was identical to the decline of transgenic T cells expressing Fas; fourth, in vivo activated CD8⁺ effector T cells from TCR transgenic and TCR-lpr/lpr mice were equally susceptible to activation-induced cell death in vitro; and fifth, transgenic effector T cells from lpr/lpr mice were cleared in the declining phase of the immune response in vivo without giving rise to CD4⁻CD8⁻ double-negative T cells. Taken together, these data suggest that the homeostatic regulation of CD8⁺ T cells after antigen challenge in vivo is regulated by mechanisms that do not require Fas.     

Challenges and satisfaction in Cardiothoracic Surgery Residency Programmes: insights from a Europe-wide survey

Open in a separate window OBJECTIVESThe increasing complexity of surgical patients and working time constraints represent challenges for training. In this study, the European Association for Cardio-Thoracic Surgery Residents’ Committee aimed to evaluate satisfaction with current training programmes across Europe. METHODSWe conducted an online survey between October 2018 and April 2019, completed by a total of 219 participants from 24 countries.RESULTSThe average respondent was in the fourth or fifth year of training, mostly on a cardiac surgery pathway. Most trainees follow a 5–6-year programme, with a compulsory final certification exam, but no regular skills evaluation. Only a minority are expected to take the examination by the European Board of Cardiothoracic Surgery. Participants work on average 61.0 ± 13.1 h per week, including 27.1 ± 20.2 on-call. In total, only 19.7% confirmed the implementation of the European Working Time Directive, with 42.0% being unaware that European regulations existed. Having designated time for research was reported by 13.0%, despite 47.0% having a postgraduate degree. On average, respondents rated their satisfaction 7.9 out of 10, although 56.2% of participants were not satisfied with their training opportunities. We found an association between trainee satisfaction and regular skills evaluation, first operator experience and protected research time.CONCLUSIONSOn average, residents are satisfied with their training, despite significant disparities in the quality and structure of cardiothoracic surgery training across Europe. Areas for potential improvement include increasing structured feedback, research time integration and better working hours compliance. The development of European guidelines on training standards may support this.     

A mutation update on the LDS‐associated genes TGFB2/3 and SMAD2/3

The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor‐β (TGF‐β) receptors (TGFBR1 and TGFBR2) were described to cause LDS, hereby leading to impaired TGF‐β signaling. More recently, TGF‐β ligands, TGFB2 and TGFB3, as well as intracellular downstream effectors of the TGF‐β pathway, SMAD2 and SMAD3, were shown to be involved in LDS. This emphasizes the role of disturbed TGF‐β signaling in LDS pathogenesis. Since most literature so far has focused on TGFBR1/2, we provide a comprehensive review on the known and some novel TGFB2/3 and SMAD2/3 mutations. For TGFB2 and SMAD3, the clinical manifestations, both of the patients previously described in the literature and our newly reported patients, are summarized in detail. This clearly indicates that LDS concerns a disorder with a broad phenotypical spectrum that is still emerging as more patients will be identified. All mutations described here are present in the corresponding Leiden Open Variant Database.     

Warming and Salt Intrusion Affect Microcystin Production in Tropical Bloom-Forming Microcystis

The Vietnamese Mekong Delta is predicted to be one of the regions most impacted by climate change, causing increased temperature and salinity in inland waters. We hypothesized that the increase in temperature and salinity may impact the microcystin (MC) production of two Microcystis strains isolated in this region from a freshwater pond (strain MBC) and a brackish water pond (strain MTV). The Microcystis strains were grown at low (27 °C), medium (31 °C), high (35 °C) and extremely high (37 °C) temperature in flat photobioreactors (Algaemist). At each temperature, when cultures reached a stable state, sea salt was added to increase salinity to 4‰, 8‰, 12‰ and 16‰. MC concentrations and cell quota were reduced at high and extremely high temperatures. Salinity, in general, had comparable effects on MC concentrations and quota. At a salinity of 4‰ and 8‰, concentrations of MC per mL of culture and MC cell quota (based on chlorophyll, dry-weight and particle counts) were higher than at 0.5‰, while at the highest salinities (12‰ and 16‰) these were strongly reduced. Strain MBC produced five MC variants of which MC-RR and MC-LR were most abundant, followed by MC-YR and relatively low amounts of demethylated variants dmMC-RR and dmMC-LR. In strain MTV, MC-RR was most abundant, with traces of MC-YR and dmMC-RR only in cultures grown at 16‰ salinity. Overall, higher temperature led to lower MC concentrations and cell quota, low salinity seemed to promote MC production and high salinity reduced MC production. Hence, increased temperature and higher salinity could lead to less toxic Microcystis, but since these conditions might favour Microcystis over other competitors, the overall biomass gain could offset a lower toxicity.     

New and emerging technologies for genetic toxicity testing

The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow‐up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow‐up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.