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
- - (87)
- 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 Biochemie (7)
- Institut für Community Medicine (7)
- Institut für Pharmazie (7)
- Institut für Diagnostische Radiologie und Neuroradiologie (6)
- Institut für Psychologie (6)
- Klinik und Poliklinik für Neurologie (6)
Publisher
- Frontiers Media S.A. (37)
- MDPI (37)
- S. Karger AG (16)
- De Gruyter (5)
- BioMed Central (BMC) (4)
- Akadémiai Kiadó (1)
- Hindawi (1)
- IOP Publishing (1)
- Nature Publishing Group (1)
- SAGE Publications (1)
Species of the genus Wolffia are traditionally used as human food in some of the Asian countries. Therefore, all 11 species of this genus, identified by molecular barcoding, were investigated for ingredients relevant to human nutrition. The total protein content varied between 20 and 30% of the freeze-dry weight, the starch content between 10 and 20%, the fat content between 1 and 5%, and the fiber content was ~25%. The essential amino acid content was higher or close to the requirements of preschool-aged children according to standards of the World Health Organization. The fat content was low, but the fraction of polyunsaturated fatty acids was above 60% of total fat and the content of n-3 polyunsaturated fatty acids was higher than that of n-6 polyunsaturated fatty acids in most species. The content of macro- and microelements (minerals) not only depended on the cultivation conditions but also on the genetic background of the species. This holds true also for the content of tocopherols, several carotenoids and phytosterols in different species and even intraspecific, clonal differences were detected in Wolffia globosa and Wolffia arrhiza. Thus, the selection of suitable clones for further applications is important. Due to the very fast growth and the highest yield in most of the nutrients, Wolffia microscopica has a high potential for practical applications in human nutrition.
Background and Aims: Gastrointestinal stromal tumors (GISTs) are rare malignancies but the most common mesenchymal tumors of the digestive tract. Recent advances in diagnostic imaging and an increasing incidence will confront us more frequently with stromal tumors. This single center study aimed to characterize GIST patients in terms of tumor location, clinical presentation, metastasis formation, as well as associated secondary malignancies. Methods: In a retrospective study, 104 patients with a histologically confirmed diagnosis of GIST, collected between 1993 and 2011, were characterized for several clinical features. Results: The most common GIST location was the stomach (67.6%) followed by the small intestine (16.2%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most frequently reported symptoms whereas about one-third of patients remained clinically asymptomatic (31.6%); 14.4% of patients had either synchronous or metachronous metastases and there was a significant prevalence also in the low risk group. The proportion of secondary malignant associated neoplasms was 31% in our GIST cohort, among which gastrointestinal, genitourinary tumors, and breast cancer were the most prevalent. Conclusion: There was a considerable risk for metastasis formation and the development of secondary neoplasias that should encourage discussion about the appropriate surveillance strategy after surgery for GIST.
Background: Iodine deficiency disorders (IDD) represent a global health threat to individuals and societies. IDD prevention programmes have been introduced in many parts of the world. However, challenges remain, particularly in Europe due to fragmentation and diversity of approaches that are not harmonized. Objectives: This review is dedicated to the public-health impact of IDD prevention programmes. It sums up experiences collected by the EUthyroid consortium so far and provides information on stakeholders that should be involved in actions directed to improve the impact of IDD prevention. Methods: A joint European database for combining registry-based outcome and monitoring data as well as tools for harmonizing study methods were established. Methods for analyzing thyroglobulin from a dried blood spot are available for assessing the iodine status in the general population and at-risk groups. Mother-child cohorts are used for in-depth analysis of the potential impact of mild-to-moderate iodine deficiency on the neurocognitive development of the offspring. A decision-analytic model has been developed to evaluate the long-term effectiveness and cost effectiveness of IDD prevention programmes. Results: EUthyroid has produced tools and infrastructure to improve the quality of IDD monitoring and follows a dissemination strategy targeting policymakers and the general public. There are tight connections to major stakeholders in the field of IDD monitoring and prevention. Conclusions: EUthyroid has taken steps towards achieving a euthyroid Europe. Our challenge is to inspire a greater sense of urgency in both policymakers and the wider public to address this remediable deficit caused by IDD.
Based on the latest gnomAD dataset, the prevalence of symptomatic hereditary cerebral cavernous malformations (CCMs) prone to cause epileptic seizures and stroke-like symptoms was re-evaluated in this review and calculated to be 1:5,400-1:6,200. Furthermore, state-of-the-art molecular genetic analyses of the known CCM loci are described which reach an almost 100% mutation detection rate for familial CCMs if whole genome sequencing is performed for seemingly mutation-negative families. An update on the spectrum of CCM1, CCM2, and CCM3 mutations demonstrates that deep-intronic mutations and submicroscopic copy-number neutral genomic rearrangements are rare. Finally, this review points to current guidelines on genetic counselling, neuroimaging, medical as well as neurosurgical treatment and highlights the formation of active patient organizations in various countries.
Background: Levels or fluctuations in the partial pressure of CO<sub>2</sub> (PCO<sub>2</sub>) may affect outcomes for extremely low birth weight infants. Objectives: In an exploratory analysis of a randomized trial, we hypothesized that the PCO<sub>2</sub> values achieved could be related to significant outcomes. Methods: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO<sub>2</sub>. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ<sup>2</sup> test, and the Fisher exact test as well as by multiple logistic regression. Results: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO<sub>2</sub>. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO<sub>2</sub>). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO<sub>2</sub> (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). Conclusions: Birth weight and respiratory morbidity, as measured by MAP × FiO<sub>2</sub>, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO<sub>2</sub>. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.
The glioblastoma multiforme (GBM) not only presents the most common tumor of the central nervous system in adults, it is also the most aggressive brain tumor. Although patients suffering from GBM standardly receive a combination of multiple treatments including surgery, radiotherapy and chemotherapy, its prognosis is still poor with a median survival time of only 12-15 months. Therefore, new and effective treatment methods are urgently needed.
A signaling molecule which is both involved in proliferation, migration and invasion of a broad range of healthy and malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). Previous studies have confirmed that sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) is involved in the regulation of proliferation, invasion, metastasis, vascular maturation and angiogenesis of GBM cells, and is closely related to the occurrence and development of tumors. Thus, ACT-209905 (provided by Actelion Pharmaceuticals) as a selective S1PR1 modulator was applied to gain insights into the molecular processes activated by S1PR1 in GBM cells using two human (LN18, U87MG) and one murine (GL261) GBM cell line.
In our in vitro cell viability analyses, we found that ACT-209905 significantly reduced viability of LN18 cells in a concentration dependent manner. A combined administration of ACT-209905 with S1PR2 inhibitors (Compound 16, Compound 16ME – both provided by ONO Pharmaceuticals, and JTE-013 – commercially available) showed a stronger effect than the single administration demonstrating that both S1PR1 and S1PR2 are involved in growth of GBM cells and may interact with each other. Our results also demonstrated that ACT-209905 can induce apoptosis in GBM cells since caspase 3 activity was induced by the S1PR1 modulator which might therefore play an important role in inhibiting the proliferation of GBM cells. Further, we found a significant inhibitory effect of ACT-209905 on the migration and invasion of LN18 and U87MG GBM cells arguing for a participation of S1PR1 signaling in migration and invasion of GBM cells, too. Stimulation of S1P receptors results in the activation of several kinases such as AKT1 and ERK1/2, correspondingly our immunoblot analyses showed a strong activation of both kinases by S1P which was reduced by ACT-209905 in LN18 cells but not in GL261 cells suggesting that different pathways are activated by S1P in these GBM cell lines. Further studies have to be performed to clarify the role of AKT1 and ERK1/2 in the inhibitory effects of ACT-209905 on GBM proliferation, migration and invasion.
Currently, GBM stem cells are discussed as a reason for resistance against the radiochemotherapy and the recurrence of the tumor. Our immunoblot analyses showed that Nestin and CD133, two marker proteins for GBM stem cells, were higher expressed in GBM cells treated with ACT-209905 compared to control or S1P treated LN18 cells. Further investigations in the future might contribute to the elucidation of an involvement of the S1P receptors in the stem cell behavior of GBM cells. Paradoxically to the up-regulation of CD133 and Nestin by ACT-209905, treatment of LN18 stem-like neurospheres with ACT-209905 showed a significant cytotoxic effect of the compound which was even more pronounced in the stem-like neurosphere cells compared to the adherent parental LN18 cells.
Overall, the studies of this work improve our understanding of the complex mechanisms of S1P signaling in GBM cells and might drive the development of its pharmacological modulation as a new therapeutic principle in GBM. Furthermore, an extended knowledge about the molecular effects of ACT-209905 on GBM cells will broaden the understanding for possible future applications and clinical indications.