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Publikationen von unseren Experten bei MEDIAN

Die Qualität unserer Leistungen und das wissenschaftliche Engagement unserer zahlreichen Experten spiegelt sich auch in der Vielzahl der Veröffentlichungen in unterschiedlichen Journals und Fachzeitschriften wieder. Verschaffen Sie sich einen Überblick und stöbern Sie in unserer Publikathek. 

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Can biofeedback-based training alleviate fatigue and vigilance performance in fatigued MS patients?

Erscheinung: 2020 / Neuropsychological Rehabilitation

MS related fatigue might be related to autonomous nervous system (ANS) dysfunctions or to inflammation related vagal (hyper-) activation. Consequently, influencing ANS status may lead to relieve of fatigue. We used two opposite biofeedback interventions to either increase sympathetic (“self-alert training”, SAT) or parasympathetic activation (“progressive muscle relaxation”, PMR). We recorded fatigue status of patients before and after a challenging vigilance task, their behavioural performance on this task, their skin conductance response (SCR), and parameters indicating parasympathetic activity concerning heart rate variability (HRV). We repeated these recordings after the biofeedback training sessions. Patients of the SAT group were able to learn to increase their SCR voluntarily. Patients of the PMR group showed increasing parameters indicating parasympathetic modulation of the HRV. The vigilance task increased their feeling of fatigue. However, there was no effect of biofeedback training on either fatigue status or performance on the vigilance task. Our results show that MS patients can learn to change voluntarily their ANS activity using biofeedback instructions based on SCR and this can be used in future studies to test the postulated link between ANS and fatigue. However, in this experimental intervention we were unable to document a relation between ANS activity and fatigue.

Autoren: Schlake HP.

Large diameter hemicraniectomy does not improve long‑term outcome in malignant infarction

Erscheinung: 2020 / Journal of Neurology

Introduction: In malignant cerebral infarction decompressive hemicraniectomy has demonstrated beneficial effects, but the optimum size of hemicraniectomy is still a matter of debate. Some surgeons prefer a large-sized hemicraniectomy with a diameter of more than 14 cm (HC > 14). We investigated whether this approach is associated with reduced mortality and an improved long-term functional outcome compared to a standard hemicraniectomy with a diameter of less than 14 cm (HC ≤ 14). Methods:Patients from the DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY) registry who received hemicraniectomy were dichotomized according to the hemicraniectomy diameter (HC ≤ 14 cm vs. HC > 14 cm). The primary outcome was modified Rankin scale (mRS) score ≤ 4 after 12 months. Secondary outcomes were in-hospital mortality, mRS ≤ 3 and mortality after 12 months, and the rate of hemicraniectomy-related complications. The diameter of the hemicraniectomy was examined as an independent predictor of functional outcome in multivariable analyses. Results: Among 130 patients (32.3% female, mean (SD) age 55 (11) years), the mean hemicraniectomy diameter was 13.6 cm. 42 patients (32.3%) had HC > 14. There were no significant differences in the primary outcome and mortality by size of hemicraniectomy. Rate of complications did not differ (HC ≤ 14 27.6% vs. HC > 14 36.6%, p = 0.302). Age and infarct volume but not hemicraniectomy diameter were associated with outcome in multivariable analyses. Conclusion: In this post-hoc analysis, large hemicraniectomy was not associated with an improved outcome or lower mortality in unselected patients with malignant middle cerebral artery infarction. Randomized trials should further examine whether individual patients could benefit from a large-sized hemicraniectomy.

Autoren: Schultze-Amberger J.

Predicting participation in and success of a concurrent smoking cessation program during inpatient treatment for alcohol dependence

Erscheinung: 2021 / Psychiatria Danubina

Background: Predicting participation in and success of smoking cessation programs in alcohol dependent patients has yielded heterogeneous results. Moreover, these findings have rarely been based on prospective studies from clinical routine settings. Identifying predictors in prospective studies could help to tailor interventions that increase participation and success rates of smoking cessation therapies for these patients at a high risk for alcohol- and smoking-related morbidities and mortalities.Subjects and methods: During inpatient alcohol dependence treatment, 99 nicotine dependent patients were recruited. 73 patients chose to participate in a voluntary smoking cessation program. Interviews and questionnaires were used at baseline and at discharge to assess a large set of variables covering smoking and alcohol related factors, general psychopathology, quality of life and personality traits. Multiple logistic regression models were calculated to predict participation in the smoking cessation program and smoking abstinence at follow-up three months after discharge.Results: Participation in the smoking cessation program was predicted by higher stage of change, higher confidence in abstaining from smoking and lower perceived stress. Successful smoking cessation at follow-up was predicted by higher expectations of negative physical feelings due to smoking and lower expectations of temptations to smoke at baseline, and by lower number of daily smoked cigarettes at discharge.Conclusion: Despite the small sample size, this prospective study gives a first indication of clinically relevant predictors of participation in and success of a smoking cessation program by exploring many previously reported predictors simultaneously. The findings and their implications for treatment allocation and optimization are discussed. 

Autoren: Frischknecht U., Pätz T., Reinhard I., Dinter C., Kiefer F., Weber Tillmann

Activation of the Glucocorticoid Receptor Rapidly Triggers Calcium-dependent Serotonin Release in vitro

Erscheinung: 2021 / CNS Neuroscience & Therapeutics

Aims: Glucocorticoids rapidly provoke serotonin (5-HT) release in vivo. We aimed to investigate molecular mechanisms of glucocorticoid receptor (GR)-triggered 5-HT release.Methods: Employing 1C11 cells to model 5-HT neurotransmission, immunofluorescence and Pearson's Correlation Coefficient were used to analyze colocalization of GR, 5-HT, vesicle membrane protein synaptotagmin 1 and vesicle dye FM4-64FX. FFN511 and FM4-64FX dyes as well as calcium imaging were used to visualize vesicular 5-HT release upon application of GR agonist dexamethasone, GR antagonist mifepristone and voltage-gated calcium channel (VGCC) inhibitors.Results: GR, 5-HT, synaptotagmin 1 and FM4-64FX showed overlapping staining patterns, with Pearson's Correlation Coefficient indicating colocalization. Similarly to potassium chloride, dexamethasone caused a release of FFN511 and uptake of FM4-64FX, indicating vesicular 5-HT release. Mifepristone, calcium depletion and inhibition of L-type VGCC significantly diminished dexamethasone-induced vesicular 5-HT release.Conclusions: In close proximity to 5-HT releasing sites, activated GR rapidly triggers L-type VGCC-dependent vesicular 5-HT release. These findings provide a better understanding of the interrelationship between glucocorticoids and 5-HT relea

Autoren: Paul N., Raymond J., Lumbreras S., Bartsch D., Weber Tillmann, Lau T

Serotonin deficiency induced after brain maturation rescues consequences of early life adversity

Erscheinung: 2021 / Scientific Reports

Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKO × MS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.

Autoren: Aboagye B., Weber Tillmann, Merdian H. L., Bartsch D., Lesch K. P., Waider J.

Repeated application of the covert shift of attention task improves endogenous but not exogenous attention in patients with unilateral visuospatial inattention

Erscheinung: 2021 / Brain and Cognition

Background: Most neglect treatment studies focus on automatic re-orientation procedures, assuming a deficit in automatic processes. We compare an automatic- and a controlled procedure, using the endogenous and exogenous variants of Posner’s covert shift of attention task. Method: In two experiments, neglect patients and patients with a right hemispherical stroke without neglect performed three blocks of Posner’s covert shift of attention task (Posner Task) on two days. In Study 1 we used endogenous cues, in Study 2, exogenous cues. Results: In the endogenous task, neglect patients improved significantly with valid left-sided cues between block 1 and 2 on Day 1, subsequently showing a plateauing. They also showed a gradual improvement on invalid trials on both days. In the exogenous condition, all participants responded only increasingly faster on trials with a long stimulus onset asynchrony. Practicing on both tasks led to fewer omissions for left-sided targets, minimally in the exogenous and clearly in the endogenous condition. Conclusion: In line with prior neuroanatomical studies, our study shows that practicing an endogenous, but not an exogenous, visuospatial attention task leads to significant improvements in neglect patients, especially for invalid trials, suggesting that neglect treatments based on top-down strategies should be given more attention.

Autoren: Heber-Thieser Ines-Ann

Post-COVID und die Lunge

Erscheinung: 2021 / Respiratory Physiology & Neurobiology

Most people recover completely after an acute infection with the novel corona virus SARS-CoV2. But some people continue to experience symptoms after their recovery. This phenomenon is called post-acute or long-COVID (from week 4 after the infection up to week 12) and persistent post-COVID (symptoms for effects that persist 12 or more weeks after onset). The exact processes that cause long COVID remain unknown. Most of those patients suffer from long-term symptoms of lung damage, including breathlessness, coughing, fatigue and limited ability to exercise. Today, 18 months after the first infections in Europe we have access to the first practical guidelines for the long-/post-COVID syndrome. Further on first prospective studies analysing the incidence of post-COVID are now available. In this review we will discuss some questions about treatment and follow up of patients suffering from pulmonary sequelae after their COVID-19 infection, based on the actual literature.

Autoren: Schüller Per Otto

Increased network centrality of the anterior insula in early abstinence from alcohol

Erscheinung: 2021 / Addiction Biology

Abnormal resting-state functional connectivity, as measured by functional magnetic resonance imaging (MRI), has been reported in alcohol use disorders (AUD), but findings are so far inconsistent. Here, we exploited recent developments in graph-theoretical analyses, enabling improved resolution and fine-grained representation of brain networks, to investigate functional connectivity in 35 recently detoxified alcohol dependent patients versus 34 healthy controls. Specifically, we focused on the modular organization, that is, the presence of tightly connected substructures within a network, and on the identification of brain regions responsible for network integration using an unbiased approach based on a large-scale network composed of more than 600 a priori defined nodes. We found significant reductions in global connectivity and region-specific disruption in the network topology in patients compared with controls. Specifically, the basal brain and the insular–supramarginal cortices, which form tightly coupled modules in healthy subjects, were fragmented in patients. Further, patients showed a strong increase in the centrality of the anterior insula, which exhibited stronger connectivity to distal cortical regions and weaker connectivity to the posterior insula. Anterior insula centrality, a measure of the integrative role of a region, was significantly associated with increased risk of relapse. Exploratory analysis suggests partial recovery of modular structure and insular connectivity in patients after 2 weeks. These findings support the hypothesis that, at least during the early stages of abstinence, the anterior insula may drive exaggerated integration of interoceptive states in AUD patients with possible consequences for decision making and emotional states and that functional connectivity is dynamically changing during treatment.

Autoren: Weil Georg

Obesity – An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances

Erscheinung: 29. 9. 2021 / Biomolecules

Obesity represents a major public health problem with a prevalence increasing at an alarming rate worldwide. Continuous intensive efforts to elucidate the complex pathophysiology and improve clinical management have led to a better understanding of biomolecules like gut hormones, antagonists of orexigenic signals, stimulants of fat utilization, and/or inhibitors of fat absorption. In this article, we will review the pathophysiology and pharmacotherapy of obesity including intersection points to the new generation of antidiabetic drugs. We provide insight into the effectiveness of currently approved anti-obesity drugs and other therapeutic avenues that can be explored.  Keywords: obesity; diabetes mellitus; anti-obesity drugs; obesity metabolism; energy balance

Autoren: Gjermeni Erind, Kirstein Anna S., Kolbig Florentine, Kirchhof Michael, Bundalian Linnaeus, Katzmann Julius L., Laufs U., Blüher Matthias, Garten Antje, Le Duc Diana

Phenotype-tissue expression and exploration (PTEE) resource facilitates the choice of tissue for RNA-seq-based clinical genetics studies

Erscheinung: 2021 / BMC Genomics

Background: RNA-seq emerges as a valuable method for clinical genetics. The transcriptome is “dynamic” and tissue-specific, but typically the probed tissues to analyze (TA) are different from the tissue of interest (TI) based on pathophysiology.Results: We developed Phenotype-Tissue Expression and Exploration (PTEE), a tool to facilitate the decision about the most suitable TA for RNA-seq. We integrated phenotype-annotated genes, used 54 tissues from GTEx to perform correlation analyses and identify expressed genes and transcripts between TAs and TIs. We identified skeletal muscle as the most appropriate TA to inquire for cardiac arrhythmia genes and skin as a good proxy to study neurodevelopmental disorders. We also explored RNA-seq limitations and show that on-off switching of gene expression during ontogenesis or circadian rhythm can cause blind spots for RNA-seq-based analyses.Conclusions: PTEE aids the identification of tissues suitable for RNA-seq for a given pathology to increase the success rate of diagnosis and gene discovery. PTEE is freely available at bioinf.eva.mpg.de/PTEE

Autoren: Velluva Akhil, Radtke Maximilian, Horn Susanne, Popp Bernt, Platzer Konrad, Gjermeni Erind, Lin Chen-Ching, Lemke Johannes R. , Garten Antje, Schöneberg Torsten, Blüher Matthias, Abdou Jamra Rami, Le Duc Diana

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