Refine
Year of publication
- 2018 (152) (remove)
Document Type
- Article (104)
- Doctoral Thesis (47)
- Report (1)
Language
- English (152) (remove)
Has Fulltext
- yes (152)
Is part of the Bibliography
- no (152)
Keywords
- - (90)
- climate change (4)
- dendrochronology (3)
- innate immunity (3)
- platelets (3)
- <i>Burkholderia pseudomallei</i> (2)
- Brain-derived neurotrophic factor (2)
- Bürgerkrieg (2)
- CASP model (2)
- China (2)
- Clinical guideline (2)
- Cystitis (2)
- Depression (2)
- Flavivirus (2)
- Fournier’s gangrene (2)
- GWAS (2)
- Germany (2)
- Hyperbaric oxygenation (2)
- Klimawandel (2)
- Morphologic changes (2)
- Necrotizing fasciitis (2)
- Necrotomy (2)
- Obesity (2)
- Plasmaphysik (2)
- Pyelonephritis (2)
- Sepsis (2)
- Sepsis score (2)
- Simulation (2)
- Small animal MRI (2)
- Soft tissue infection (2)
- Staphylococcus aureus (2)
- Streptococcus pneumoniae (2)
- Systematic review (2)
- Therapy (2)
- Urinary tract infection (2)
- Vitamin D (2)
- antibiotics (2)
- antimicrobial peptides (2)
- ascariasis (2)
- bias (2)
- biofilm (2)
- causal inference (2)
- dendroecology (2)
- environment (2)
- helminth (2)
- intestinal nematode (2)
- lectin (2)
- melioidosis (2)
- mendelian randomization (2)
- metabolomics (2)
- microbiota (2)
- phenotypic plasticity (2)
- proteomics (2)
- public awareness (2)
- statistical methods (2)
- tree-ring width (2)
- 1,2,3-benzotriazoles (1)
- 1,2,4-triazoles (1)
- 2,4-diamino-1,3,5-triazines (1)
- 2-imino-2<i>H</i>-chromen-3-yl-1,3,5-triazines (1)
- 2-imino-coumarins (1)
- 2<i>H</i>-chromen-3-yl-1,3,5-triazines (1)
- 2D PAGE (1)
- <i>Clostridiodes difficile</i> (1)
- <i>Hermite</i>-polynomials (1)
- <i>Kolmogorov</i>-backward-equation (1)
- <i>N</i>-acylhydrazones (1)
- <i>N</i>-sulfonylhydrazones (1)
- <i>S. aureus</i> (1)
- ACT-209905 (1)
- AFLP, microsatellite SSR, ITS, DNA isolation (1)
- ATP-binding cassette transporters (1)
- Adaptation (1)
- Africa (1)
- African swine fever virus (1)
- Afrikanische Schweinepest Virus (1)
- Alaska (1)
- Alfvén Waves (1)
- Animal behavior (1)
- Annual rings (1)
- Antioxidans (1)
- Anxiety sensitivity (1)
- Arbovirus (1)
- Asymmetric synthesis (1)
- Austria (1)
- B cell class switch (1)
- B1 B cells (1)
- Bathymodiolus (1)
- Bathymodiolus symbiosis (1)
- Baumgrenze (1)
- Bayley scales (1)
- Benign breast tumours (1)
- Beringung (1)
- Biochemie (1)
- Biomathematik , Bioinformatik (1)
- Blue Intensity (1)
- Bodentemperatur (1)
- Bronchopulmonary dysplasia (1)
- Buche (1)
- CA–Markov (1)
- CD40L (1)
- CFTR Cl (1)
- Cerebral Palsy Kinder (1)
- Cerebral cavernous malformations (1)
- Chemo-enzymatic synthesis (1)
- Chiral amines (1)
- Civil conflicts (1)
- Clade Annotation (1)
- Climate Change (1)
- Cochrane–Orcutt procedure (1)
- Collisions (1)
- Comparative Gene Finding (1)
- Comparative Genomics (1)
- CyberKnife robotic radiosurgery (1)
- Cybermobbing (1)
- Cytochrome P-450 (1)
- DHEAS (1)
- DISQOVER (1)
- DLX proteins (1)
- DNA-microarray (1)
- Deep-sea hydrothermal vents (1)
- Democracy (1)
- Demokratie (1)
- Dendrochronologie (1)
- Diagnosis (1)
- Dispersal (1)
- Doxorubicin (1)
- Dual Decomposition (1)
- EEG (1)
- EMSA (1)
- Ecosystem Dynamics (1)
- Elektrochemischer Sensor (1)
- Entwicklungszusammenarbeit (1)
- Environmental conditions (1)
- Epidemiology (1)
- Evolution (1)
- Evolutionsbiologie , Tierökologie , Sexuelle Selektion , Sexualverhalten (1)
- Fast Particles (1)
- Feldversuch (1)
- Fettsucht (1)
- Flight ability (1)
- Flug (1)
- Foreign aid (1)
- Fourier analysis (1)
- Friedensvertrag (1)
- GAPDH, ALDH (1)
- GHG emissions (1)
- GPU computing (1)
- Gastrointestinal oncology (1)
- Gastrointestinal stromal tumor (1)
- Gastrointestinal symptoms (1)
- Gastrointestinal tract (1)
- Gene Structure Prediction (1)
- Genetic counselling (1)
- Genetic diversity (1)
- Genome Annotation (1)
- Genotyping (1)
- Glazitektonik (1)
- Global South regional policy (1)
- Global change (1)
- Glutaredoxin (1)
- Glutaredoxine (1)
- Glutathion (1)
- Glutathione (1)
- Glycoprotein B (1)
- Graphen (1)
- Greifvögel (1)
- Gyro-kinetic Theory (1)
- HACA (1)
- HCMV (1)
- HCO (1)
- HEV (1)
- HIT (1)
- Hangzhou International Airport (1)
- Heat-flux (1)
- Hepatitis-E-Virus , Polymerase-Kettenreaktion , Microarray , West-Nil-Virus , Flaviviren , RNS-Viren , Genotypisierung (1)
- Herpesviren (1)
- Heterostrukturen (1)
- Himalayan Silver Fir (<i>Abies spectabilis</i>), Nepal Himalaya (1)
- Hirninfarkt (1)
- Hyperventilation (1)
- IDD in pregnant women (1)
- IL-10 (1)
- Ili River delta (1)
- Imaging features (1)
- Impfstoff (1)
- Individual phenotype (1)
- Integrins (1)
- Interoception (1)
- Interozeption (1)
- Intrastate conflicts (1)
- Intraventricular hemorrhage (1)
- Iodine (1)
- Iodine deficiency disorders (1)
- Ionthruster (1)
- Isopropylamine (1)
- JSNZ (1)
- Jahresring (1)
- Juniperus communis (1)
- Kinetic simulation (1)
- Komplexes Plasma (1)
- Konfliktregelung (1)
- Korrespondenzprinzip (1)
- LAVH (1)
- LPS (1)
- LUCC (1)
- Lagrangian Relaxation (1)
- Lake Balkhash (1)
- Landformanalyse (1)
- Landsat (1)
- Lemnaceae (1)
- LiDAR (1)
- Local adaptation (1)
- Lord's Resistance Army (1)
- Low temperature plasma (1)
- Lycaena tityrus (1)
- Lymphozyt (1)
- MTIP planning (1)
- Machtteilungsregierungen (1)
- Magnetismus (1)
- Master-Gleichung (1)
- Mathematik (1)
- Mediation (1)
- Medienbildung (1)
- Mediennutzungsethik (1)
- Membranfusion (1)
- Metastasis (1)
- Middle East (1)
- Mikrobiologie (1)
- Minimally invasive diagnostics (1)
- Mitochondrium (1)
- Mixed methods (1)
- Molecular biology (1)
- Molecular genetics (1)
- Molekularbiologie (1)
- Molekularbiologie, Genotypisierung, Genetische Diversität (1)
- Molybdenum (1)
- Molybdopterin (1)
- Monitoring IDD (1)
- Monte Carlo (1)
- Movement (1)
- NF-Y (1)
- Neurodevelopmental outcome (1)
- Neuroimmunologie (1)
- Nichtlineare Dynamik (1)
- OCT1 (1)
- Optomechanik (1)
- Oral health, Cerebral palsy, Children, Prevention (1)
- Orale Gesundheit (1)
- Osmoregulation (1)
- Outcomes research (1)
- Overview (1)
- Oxidativer Stress (1)
- Oxidoreduktase (1)
- P300 (1)
- PCLake (1)
- PD-L1 (1)
- PEI,PDADMA,PSS,surface forces,atomic force microscopy, colloidal probe (1)
- PF4 (1)
- Parkinson's disease (1)
- Partial migration (1)
- Pediatric (1)
- Permissive hypercapnia (1)
- Picea glauca (1)
- Plasma (1)
- Plasma , Plasmaphysik , Tokamak , Stellarator , Magnetohydrodynamik , Kinetische Theorie , Simulation , Alfvén-Welle , Energiereiches Teilchen (1)
- Plasma Physics (1)
- Plastizität (1)
- Political Economy (1)
- Politische Ökonomie (1)
- Polyphenole (1)
- Potamopyrgus antipodarum (1)
- Power-Sharing (1)
- Prevalence (1)
- Prevention (1)
- Profilbilanzierung (1)
- Protein engineering (1)
- Proteine (1)
- Proteomanalyse (1)
- Pt(II) complexes (1)
- Pterin (1)
- Quantenoptik (1)
- Quantenpunkt (1)
- RT-qPCR (1)
- Rabies (1)
- Rabies virus (1)
- Radikalfänger (1)
- Range shift (1)
- Reaktive Sauerstoffspezies (1)
- Recurrence (1)
- Relativistische Quantenmechanik (1)
- Rotbuche (1)
- S. aureus (1)
- SNP (1)
- STED microscopy (1)
- Salztoleranz (1)
- Schamethik (1)
- Schlaganfall induzierte Immunschwäche (1)
- Schmetterling (1)
- Schnecke (1)
- Schweinekrankheit (1)
- Sexting (1)
- Shrubs (1)
- Sinlge port (1)
- Sozialität (1)
- Sphingosine-1-Phosphate (1)
- Spinnen (1)
- Spintronik (1)
- Starch (1)
- Stark gekoppelte Systeme (1)
- Stellarator (1)
- Stickland reactions (1)
- Streutheorie (1)
- Stärke (1)
- T cell maturation (1)
- Teilzug (1)
- Theodoxus fluviatilis (1)
- Thiole (1)
- Thioredoxine (1)
- Third-party intervention (1)
- Thrombospondin (1)
- Tierphysiologie (1)
- Tierseuche (1)
- Tokamak (1)
- Tollwut (1)
- Tollwutvirus (1)
- Transaminases (1)
- Two component systems (1)
- Uganda (1)
- Uncoupling (1)
- VEEV (1)
- Vascular malformation (1)
- Vegetation Ecology (1)
- Verbreitung (1)
- Vietnam (1)
- Virologie (1)
- Virus (1)
- Virus evolution (1)
- Vogelzug (1)
- WNV (1)
- Waldgrenze (1)
- Waldökologie (1)
- Waldökosystem (1)
- Weichselvereisung (1)
- Weißfichte (1)
- Winter (1)
- Yeast (1)
- Zitterbewegung (1)
- Zoonose (1)
- [Fe-S] Cluster (1)
- absolute (1)
- adaptation (1)
- adaptive immunity (1)
- age (1)
- agroecosystems (1)
- airport cases (1)
- alanine scanning (1)
- alcohol risk drinking (1)
- alexithymia (1)
- amino acids (1)
- anaerobic metabolism (1)
- animal (1)
- anti-GD<sub>2</sub> immunotherapy (1)
- anticoagulants (1)
- anticonvulsants (1)
- antiseptic stewardship (1)
- aquaporins (1)
- aquatic plants (1)
- arable wild plants (1)
- arid river basins (1)
- arm (1)
- arm ability training (1)
- asymmetric synthesis (1)
- asymptotic expansion (1)
- atomic force microscopy (1)
- attention (1)
- autoimmunity (1)
- autoregressive conditional heteroskedasticity (1)
- averaging (1)
- bacterial meningitis (1)
- beech (1)
- big-fish-little-pond-effect (1)
- bile acids (1)
- binding force (1)
- binding land-use plan (1)
- biocide (1)
- biodiversity offsets (1)
- biomanipulation (1)
- blood–brain barrier (1)
- boreal forest (1)
- brain stimulation (1)
- brownfields (1)
- cancer therapy (1)
- carbon–carbon lyase (1)
- carboplatin (1)
- catalytic activity (1)
- ch14.18/CHO (1)
- chaperones (1)
- chromoplexy (1)
- chromosomal translocations (1)
- chromosome conformation capture (1)
- chronic pancreatitis (1)
- chronotypes (1)
- cisplatin (1)
- climate elasticity (1)
- climate regime (1)
- climate sensitivity (1)
- climate signal age effects (1)
- climate variability (1)
- climate warming (1)
- climate-growth relationships (1)
- climate–growth relationships (1)
- cloud removal (1)
- cognition (1)
- cognitive control (1)
- colonization (1)
- combination assay (1)
- comorbidity (1)
- complement dependent cytotoxicity (1)
- composite ridges (1)
- computational fluid dynamics (1)
- concussion (1)
- corridor development strategies (1)
- coumarins (1)
- counterfactual analysis (1)
- criterial (1)
- cross-reactivity (1)
- cross-resistance (1)
- cross-tolerance (1)
- crystallized intelligence (1)
- cutaneous T-cell lymphoma (1)
- cyberbullying (1)
- damage-associated molecular patterns (1)
- deep sequencing (1)
- dehydroepiandrosterone (1)
- dendritic cells (1)
- diffusion tensor imaging (1)
- diffusion tractography (1)
- diffusion weighted imaging (1)
- digital elevation models (1)
- dual task (1)
- duckweed (1)
- ductal closure (1)
- ductal epithelium (1)
- early competencies (1)
- echocardiography (1)
- ecology (1)
- ecosystem dynamics (1)
- education (1)
- embodied cognition (1)
- embodiment (1)
- empathy (1)
- entry (1)
- environmental offsets (1)
- epidemiology (1)
- epilepsy (1)
- epileptic encephalopathies (1)
- epithelial fluid secretion (1)
- ethics of media use (1)
- ethics of shame (1)
- eutrophication (1)
- experimental pancreatitis (1)
- experimental plant ecology (1)
- expression (1)
- fagus sylvatica (1)
- fatty acids (1)
- fetal and adult neurogenesis (1)
- fisheries (1)
- flow tank (1)
- fluid intelligence (1)
- forest ecology (1)
- forest understory vegetation (1)
- free amino acids (1)
- fusion loops (1)
- gH/gL complex (1)
- genetic adaptation (1)
- genomics (1)
- genotyping (1)
- geometric morphometrics (1)
- gestural-verbal association (1)
- glacier skiing (1)
- glacitectonics (1)
- glioblastoma multiforme (1)
- global production networks (1)
- glutaredoxins (1)
- gradient-design field experiment (1)
- granuloma (1)
- greenfields (1)
- gross tumor volume optimization (1)
- habituation (1)
- health risk behaviors (1)
- healthcare (1)
- heat-shock proteins (1)
- heparin- and antibody-induced thrombocytopenia (1)
- heparins (1)
- herpesvirus (1)
- high-ability tracked students (1)
- high-frequency heart rate variability (1)
- homoarginine (1)
- host-symbiont (1)
- humanized mice (1)
- hybrid molecules (1)
- hydrazones (1)
- hydrological regimes (1)
- ibuprofen (1)
- image reconstruction (1)
- imagery (1)
- immune evasion (1)
- immunogenicity (1)
- impact mitigation regulation (1)
- implied volatility surface (1)
- in vitro anticancer activity (1)
- in vitro antitumor activity (1)
- inactivity (1)
- incidence (1)
- individual academic self-concept (SESSKO) (1)
- individual based (1)
- indoleamine 2,3-dioxygenase (1)
- indomethacin (1)
- infants (1)
- infection (1)
- inflammation (1)
- infrastructure (1)
- inner urban development (1)
- insurance claims (1)
- interactions (1)
- invasive (1)
- iodine deficiency disorders (1)
- iron surrogates (1)
- isoprenoid degradation (1)
- jep Gene (1)
- katalytische Aktivität (1)
- knowledge-is-power (1)
- kynurenine pathway (1)
- lake restoration. nutrient load reduction (1)
- land conversion (1)
- land use change (1)
- landcover reconstruction (1)
- language disorders (1)
- language processing (1)
- levetiracetam (1)
- light-sheet imaging (1)
- linear discriminant analyses (1)
- lipoprotein (1)
- lipoprotein profiling (1)
- locus coeruleus (1)
- long-term infusion (1)
- longitudinal (1)
- luciferase reporter gene assay (1)
- lung metastases (1)
- lymphocyte trafficking (1)
- mTHPC (1)
- mass spectrometry (1)
- mast cell (1)
- matrix metalloproteinase (1)
- maximum latewood density (1)
- mechanism (1)
- media education (1)
- medical assistants (1)
- membrane fusion (1)
- mental representations (1)
- mental rotation (1)
- mental transformations (1)
- metabolic interactions (1)
- metabolism (1)
- methyltryptophan (1)
- micro-site (1)
- mineral soil (1)
- mixed model (1)
- mode comparison (1)
- monoterpene (1)
- mortality (1)
- mouse model (1)
- mucosal immunity (1)
- mucus (1)
- multiphoton imaging (1)
- multitasking (1)
- myeloid-derived suppressor cells (1)
- myxomycetes (1)
- near-hand space (1)
- neuroactive steroids (1)
- neuroblastoma (1)
- neuropsychiatric diseases (1)
- night shift work (1)
- no-net-loss (1)
- non-small cell lung cancer (1)
- norepinephrine (1)
- oil palm plantation (1)
- optical imaging analyses (1)
- osmoregulation (1)
- osmotolerance (1)
- overfishing (1)
- overweight (1)
- oxaliplatin (1)
- oxidoreductase (1)
- pain (1)
- palynology (1)
- pancreas (1)
- patent ductus arteriosus (1)
- pediatric thrombosis (1)
- peptidases (1)
- peptide sharing (1)
- peripersonal space (1)
- peritoneal B cells (1)
- photodynamic therapy (1)
- physiological responses (1)
- phytosterols (1)
- pig (1)
- plant traits (1)
- plasticity (1)
- poaching (1)
- podocyte nephropathy (1)
- pollen accumulation rates (1)
- pollen productivity estimates (1)
- poly(hydroxyalkanoates) (1)
- polycrystalline gold (1)
- population-based (1)
- post-translational modifications (1)
- pregnenolone sulfate (1)
- preterm infant (1)
- prevalence (1)
- principal component analyses (1)
- production-integrated compensation (1)
- promoter (1)
- protection (1)
- protein (1)
- protein synthesis (1)
- proteins (1)
- psychological refractory period (PRP) (1)
- pyramidal tract integrity (1)
- quinolines (1)
- radical polishing (1)
- radiometric interpolation (1)
- reactivation (1)
- recruitment curve steepness (1)
- redox regulation (1)
- regime shift (1)
- rehabilitation (1)
- ring-opening reactions (1)
- rubber plantation (1)
- rule changes (1)
- salinity (1)
- salivary alpha-amylase (1)
- secondary plantmetabolites (1)
- seizure (1)
- self assembled monolayer (1)
- serial block-face scanning electron microscopy (SBFSEM) (1)
- serious adverse reaction (1)
- sex (1)
- sexting (1)
- smoking (1)
- snail (1)
- snow cover manipulation (1)
- social (1)
- social cognition (1)
- social interaction (1)
- soil organic carbon stock (1)
- solute carriers (1)
- spatial analysis (1)
- spatial cognition (1)
- spectral matching (1)
- sphingosine-1-phosphate (S1P) (1)
- starvation (1)
- statistical analysis (1)
- stereotactic body radiation therapy (1)
- stream ecology (1)
- stroke (1)
- structure (1)
- structured illumination microscopy (1)
- subacute stroke (1)
- summer skiing (1)
- superresolution microscopy (1)
- surface forces (1)
- symbiosis (1)
- synergism (1)
- synthesis (1)
- tVNS (1)
- temporal dynamics (1)
- temporal fitting (1)
- terahertz emission spectroscopy (1)
- terahertz transmission spectroscopy (1)
- thrombosis (1)
- tiling, self-similarity, fractal, aperiodic, iterated function system (1)
- toxin formation (1)
- training (1)
- transfusion (1)
- tree growth–climate correlation (1)
- tree size (1)
- tree-growth patterns (1)
- treeline (1)
- treeline ecotone (1)
- tropical forest conversion (1)
- tuberculosis (1)
- ultrafast spincaloritronics (1)
- ultrafast spintronics (1)
- upper limb motor function (1)
- urine normalization (1)
- vagus nerve (1)
- vegetation history (1)
- venous thromboembolism (1)
- vent (1)
- viral diagnosis (1)
- viral infections (1)
- virulence (1)
- vocational education and training (1)
- volatility (1)
- voxel-based morphometry (1)
- white spruce (1)
- winter ecology (1)
- women’s’ health (1)
- wood anatomy (1)
- β-amino acid (1)
- β-phenylalanine ethyl ester (1)
- ω-transaminase (1)
Institute
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (15)
- Institut für Physik (10)
- Kliniken und Polikliniken für Innere Medizin (8)
- Abteilung für Mikrobiologie und Molekularbiologie (7)
- Institut für Chemie und Biochemie (7)
- Institut für Community Medicine (7)
- Institut für Pharmazie (7)
- Institut für Diagnostische Radiologie (6)
- Institut für Psychologie (6)
- Klinik und Poliklinik für Neurologie (6)
Publisher
- MDPI (37)
- Frontiers Media S.A. (33)
- S. Karger AG (16)
- BioMed Central (BMC) (4)
- Frontiers (4)
- De Gruyter (3)
- De Gruyter Oldenbourg (2)
- Akadémiai Kiadó (1)
- Hindawi (1)
- IOP Publishing (1)
In classical models of tumorigenesis, the accumulation of tumor promoting chromosomal aberrations is described as a gradual process. Next-generation sequencing-based methods have recently revealed complex patterns of chromosomal aberrations, which are beyond explanation by these classical models of karyotypic evolution of tumor genomes. Thus, the term chromothripsis has been introduced to describe a phenomenon, where temporarily and spatially confined genomic instability results in dramatic chromosomal rearrangements limited to segments of one or a few chromosomes. Simultaneously arising and misrepaired DNA double-strand breaks are also the cause of another phenomenon called chromoplexy, which is characterized by the presence of chained translocations and interlinking deletion bridges involving several chromosomes. In this study, we demonstrate the genome-wide identification of chromosomal translocations based on the analysis of translocation-associated changes in spatial proximities of chromosome territories on the example of the cutaneous T-cell lymphoma cell line Se-Ax. We have used alterations of intra- and interchromosomal interaction probabilities as detected by genome-wide chromosome conformation capture (Hi-C) to infer the presence of translocations and to fine-map their breakpoints. The outcome of this analysis was subsequently compared to datasets on DNA copy number alterations and gene expression. The presence of chained translocations within the Se-Ax genome, partly connected by intervening deletion bridges, indicates a role of chromoplexy in the etiology of this cutaneous T-cell lymphoma. Notably, translocation breakpoints were significantly overrepresented in genes, which highlight gene-associated biological processes like transcription or other gene characteristics as a possible cause of the observed complex rearrangements. Given the relevance of chromosomal aberrations for basic and translational research, genome-wide high-resolution analysis of structural chromosomal aberrations will gain increasing importance.
The present study seeks to determine potential associations between viral infections and neuropsychiatric diseases. To address this issue, we investigated the peptide commonalities between viruses that have been related to psychiatric and neurological disorders—such as rubella, human immunodeficiency virus, and herpesviruses—and human distal-less homeobox (DLX) proteins expressed in developing brain—namely, DLX1, DLX2, DLX5, and DLX6. Peptide matching analyses revealed a high degree of pentapeptide sharing. From an immunological perspective, this overlap is relevant because pentapeptides are endowed with immunogenicity and antigenicity—that is, they are immune determinants. Moreover, infection-induced immune cross-reactions might have functional, spatial, and temporal implications related to the functions and expression patterns of DLX1 and DLX5 in the fetal and adult human brain. In sum, our data support the hypothesis that viral infections may be linked to neuropsychiatric diseases through autoimmune cross-reactions caused by molecular mimicry between viral proteins and brain-specific DLX self-antigens.
Recent research suggests that the P3b may be closely related to the activation of the locus coeruleus-norepinephrine (LC-NE) system. To further study the potential association, we applied a novel technique, the non-invasive transcutaneous vagus nerve stimulation (tVNS), which is speculated to increase noradrenaline levels. Using a within-subject cross-over design, 20 healthy participants received continuous tVNS and sham stimulation on two consecutive days (stimulation counterbalanced across participants) while performing a visual oddball task. During stimulation, oval non-targets (standard), normal-head (easy) and rotated-head (difficult) targets, as well as novel stimuli (scenes) were presented. As an indirect marker of noradrenergic activation we also collected salivary alpha-amylase (sAA) before and after stimulation. Results showed larger P3b amplitudes for target, relative to standard stimuli, irrespective of stimulation condition. Exploratory post hoc analyses, however, revealed that, in comparison to standard stimuli, easy (but not difficult) targets produced larger P3b (but not P3a) amplitudes during active tVNS, compared to sham stimulation. For sAA levels, although main analyses did not show differential effects of stimulation, direct testing revealed that tVNS (but not sham stimulation) increased sAA levels after stimulation. Additionally, larger differences between tVNS and sham stimulation in P3b magnitudes for easy targets were associated with larger increase in sAA levels after tVNS, but not after sham stimulation. Despite preliminary evidence for a modulatory influence of tVNS on the P3b, which may be partly mediated by activation of the noradrenergic system, additional research in this field is clearly warranted. Future studies need to clarify whether tVNS also facilitates other processes, such as learning and memory, and whether tVNS can be used as therapeutic tool.
Arm Ability Training (AAT) has been specifically designed to promote manual dexterity recovery for stroke patients who have mild to moderate arm paresis. The motor control problems that these patients suffer from relate to a lack of efficiency in terms of the sensorimotor integration needed for dexterity. Various sensorimotor arm and hand abilities such as speed of selective movements, the capacity to make precise goal-directed arm movements, coordinated visually guided movements, steadiness, and finger dexterity all contribute to our “dexterity” in daily life. All these abilities are deficient in stroke patients who have mild to moderate paresis causing focal disability. The AAT explicitly and repetitively trains all these sensorimotor abilities at the individual's performance limit with eight different tasks; it further implements various task difficulty levels and integrates augmented feedback in the form of intermittent knowledge of results. The evidence from two randomized controlled trials indicates the clinical effectiveness of the AAT with regard to the promotion of “dexterity” recovery and the reduction of focal disability in stroke patients with mild to moderate arm paresis. In addition, the effects have been shown to be superior to time-equivalent “best conventional therapy.” Further, studies in healthy subjects showed that the AAT induced substantial sensorimotor learning. The observed learning dynamics indicate that different underlying sensorimotor arm and hand abilities are trained. Capacities strengthened by the training can, in part, be used by both arms. Non-invasive brain stimulation experiments and functional magnetic resonance imaging data documented that at an early stage in the training cortical sensorimotor network areas are involved in learning induced by the AAT, yet differentially for the tasks trained. With prolonged training over 2 to 3 weeks, subcortical structures seem to take over. While behavioral similarities in training responses have been observed in healthy volunteers and patients, training-induced functional re-organization in survivors of a subcortical stroke uniquely involved the ipsilesional premotor cortex as an adaptive recruitment of this secondary motor area. Thus, training-induced plasticity in healthy and brain-damaged subjects are not necessarily the same.
Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy.
Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity).
Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The “Test d'Evaluation des Membres Supérieurs de Personnes Âgées” (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living.
Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA).
Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.
Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson's Disease in Germany?
(2018)
Epidemiological aspects of Parkinson's disease (PD), co-occurring diseases and medical healthcare utilization of PD patients are still largely elusive. Based on claims data of 3.7 million statutory insurance members in Germany in 2015 the prevalence and incidence of PD was determined. PD cases had at least one main hospital discharge diagnosis of PD, or one physician diagnosis confirmed by a subsequent or independent diagnosis or by PD medication in 2015. Prevalence of (co-)occurring diseases, mortality, and healthcare measures in PD cases and matched controls were compared. In 2015, 21,714 prevalent PD cases (standardized prevalence: 511.4/100,000 persons) and 3,541 incident PD cases (standardized incidence: 84.1/100,000 persons) were identified. Prevalence of several (co-)occurring diseases/complications, e.g., dementia (PD/controls: 39/13%), depression (45/22%), bladder dysfunction (46/22%), and diabetes (35/31%), as well as mortality (10.7/5.8%) differed between PD cases and controls. The annual healthcare utilization was increased in PD cases compared to controls, e.g., regarding mean ± SD physician contacts (15.2 ± 7.6/12.2 ± 7.3), hospitalizations (1.3 ± 1.8/0.7 ± 1.4), drug prescriptions (overall: 37.7 ± 24.2/21.7 ± 19.6; anti-PD medication: 7.4 ± 7.4/0.1 ± 0.7), assistive/therapeutic devices (47/30%), and therapeutic remedies (57/16%). The standardized prevalence and incidence of PD in Germany as well as mortality in PD may be substantially higher than reported previously. While frequently diagnosed with co-occurring diseases/complications, such as dementia, depression, bladder dysfunction and diabetes, the degree of healthcare utilization shows large variability between PD patients. These findings encourage a rethinking of the epidemiology and healthcare utilization in PD, at least in Germany. Longitudinal studies of insurance claims data should further investigate the individual and epidemiological progression and healthcare demands in PD.
Objectives: We aimed to update the 2010 evidence- and consensus-based national clinical guideline on the diagnosis and management of uncomplicated urinary tract infections (UTIs) in adult patients. Materials and Methods: An interdisciplinary group consisting of 17 representatives of 12 medical societies and a patient representative was formed. Systematic literature searches were conducted in MEDLINE, EMBASE, and the Cochrane Library to identify literature published in 2010–2015. Results: We provide 75 recommendations and 68 statements in the updated evidence- and consensus-based national clinical guideline. The diagnostics part covers practical recommendations on cystitis and pyelonephritis for each defined patient group. Clinical examinations, as well as laboratory testing and microbiological pathogen assessment, are addressed. Conclusion: In accordance with the global antibiotic stewardship initiative and considering new insights in scientific research, we updated our German clinical UTI guideline to promote a responsible antibiotic use and to give clear hands-on recommendations for the diagnosis and management of UTIs in adults in Germany for healthcare providers and patients.
Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).
Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.
Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.
Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.
Mast cells reside on and near the cerebral vasculature, the predominant site of pneumococcal entry into the central nervous system (CNS). Although mast cells have been reported to be crucial in protecting from systemic bacterial infections, their role in bacterial infections of the CNS remained elusive. Here, we assessed the role of mast cells in pneumococcal infection in vitro and in vivo. In introductory experiments using mouse bone marrow-derived mast cells (BMMC), we found that (i) BMMC degranulate and release selected cytokines upon exposure to Streptococcus pneumoniae, (ii) the response of BMMC varies between different pneumococcal serotypes and (iii) is dependent on pneumolysin. Intriguingly though, apart from a slight enhancement of cerebrospinal fluid (CSF) pleocytosis, neither two different mast cell-deficient Kit mutant mouse strains (WBB6F1-KitW/Wv and C57BL/6 KitW-sh/W-sh mice) nor pharmacologic mast cell stabilization with cromoglycate had any significant impact on the disease phenotype of experimental pneumococcal meningitis. The incomplete reversal of the enhanced CSF pleocytosis by local mast cell engraftment suggests that this phenomenon is caused by other c-Kit mutation-related mechanisms than mast cell deficiency. In conclusion, our study suggests that mast cells can be activated by S. pneumoniae in vitro. However, mast cells do not play a significant role as sentinels of pneumococcal CSF invasion and initiators of innate immunity in vivo.