610 Medizin und Gesundheit
Refine
Year of publication
- 2020 (867) (remove)
Document Type
- Article (678)
- Doctoral Thesis (103)
- Preprint (66)
- Contribution to a Periodical (10)
- Part of Periodical (6)
- Book (3)
- Master's Thesis (1)
Has Fulltext
- yes (867)
Keywords
- COVID-19 (20)
- inflammation (17)
- SARS-CoV-2 (11)
- quality of life (8)
- Quality of life (7)
- biomarker (7)
- cancer (7)
- macrophage (7)
- obesity (7)
- ADHD (6)
- depression (6)
- MRI (5)
- Machine learning (5)
- immunotherapy (5)
- pain (5)
- polytrauma (5)
- stroke (5)
- ACLF (4)
- EEG (4)
- Epilepsy (4)
- HIV (4)
- Inflammation (4)
- Rare diseases (4)
- Stroke (4)
- TAVI (4)
- aortic stenosis (4)
- autophagy (4)
- bipolar disorder (4)
- bladder cancer (4)
- breast cancer (4)
- cognition (4)
- coronavirus (4)
- cytokines (4)
- drug resistance (4)
- exercise (4)
- portal hypertension (4)
- schizophrenia (4)
- tumor microenvironment (4)
- Abdominal aortic aneurysm (3)
- Aortic stenosis (3)
- Biomarkers (3)
- Cardiovascular magnetic resonance (3)
- Cirrhosis (3)
- DNA methylation (3)
- Diagnostics (3)
- Diagnostik (3)
- Endovascular repair (3)
- Gesundheitsökonomie (3)
- Health economics (3)
- Heart failure (3)
- Human behaviour (3)
- Hypoxia (3)
- Infections (3)
- Macrophages (3)
- Magnetic resonance imaging (3)
- Mortality (3)
- NASH (3)
- Offene Versorgung (3)
- Open repair (3)
- Peri-implantitis (3)
- Postural control (3)
- Register (3)
- Registries (3)
- Registry (3)
- Strength training (3)
- Treatment (3)
- acute-on-chronic liver failure (3)
- apoptosis (3)
- attention (3)
- child (3)
- chimeric antigen receptor (3)
- complications (3)
- cytotoxicity (3)
- epilepsy (3)
- glioblastoma (3)
- glioma (3)
- hippocampus (3)
- integrins (3)
- iron (3)
- machine learning (3)
- macrophages (3)
- mesenchymal stromal cells (3)
- miRNA (3)
- microRNA (3)
- microbiome (3)
- migration (3)
- neuroblastoma (3)
- neurodegeneration (3)
- outcome (3)
- ovarian cancer (3)
- physical activity (3)
- precision medicine (3)
- prevalence (3)
- prevention (3)
- proliferation (3)
- prostate cancer (3)
- proteostasis (3)
- psoriasis (3)
- reactive oxygen species (3)
- sulforaphane (3)
- toxicity (3)
- 3D printing (2)
- 3D rapid prototyping (2)
- AML (2)
- ATP (2)
- Abdominelles Aortenaneurysma (2)
- Alzheimer’s disease (2)
- Artificial intelligence (2)
- Ascites (2)
- Ataxia telangiectasia (2)
- Autism spectrum disorder (2)
- BMI (2)
- Bibliometrics (2)
- Bladder cancer (2)
- Borrelia (2)
- CD19 (2)
- CD44 (2)
- CNN (2)
- Cancer (2)
- Cardiology (2)
- Cerebrospinal fluid (2)
- Children (2)
- Clinical decision support systems (2)
- Cohort studies (2)
- Computer-assisted diagnosis (2)
- Critical care (2)
- DTI (2)
- Database searching (2)
- Datenschutz (2)
- Dementia (2)
- Depression (2)
- Emergency room (2)
- Endoscopy (2)
- Endovaskuläre Behandlung (2)
- Epidemiology (2)
- Erweiterter Suizid (2)
- Europe (2)
- Extended suicide (2)
- Gemeinschaftliche Selbsttötung (2)
- Gene expression (2)
- Gene regulation (2)
- General practice (2)
- Genetics (2)
- Germany (2)
- Glioma (2)
- HIV-1 (2)
- Healthy adults (2)
- Hepatocellular carcinoma (2)
- IDH mutation (2)
- IL-10 (2)
- Immunohistochemistry (2)
- Immunological methods (2)
- Immunologische Methoden (2)
- Immunology (2)
- In vitro (2)
- Klebsiella pneumoniae (2)
- Klinische Ergebnisse (2)
- Knochenersatzmaterial (2)
- Krankheit (2)
- Language (2)
- Lebensqualität (2)
- Liver diseases (2)
- Liver transplantation (2)
- Long-term potentiation (2)
- MSD (2)
- Medical research (2)
- Metaanalysis (2)
- Morbidity (2)
- Morphology (2)
- Multiple sclerosis (2)
- Myocardial perfusion (2)
- NADPH oxidase (2)
- NAFLD (2)
- Neurology (2)
- Neurons (2)
- Notaufnahme (2)
- Object vision (2)
- Outcome (2)
- PCR (2)
- Patient blood management (2)
- Patients (2)
- Pneumonia (2)
- Preventive medicine (2)
- Public health (2)
- Radiomics (2)
- Remuneration (2)
- Seizure (2)
- Suicide pact (2)
- Survey (2)
- Transfusion (2)
- Treatment outcome (2)
- Validation (2)
- Vergütung (2)
- Wearable cardioverter-defibrillator (2)
- Women (2)
- acute lymphoblastic leukemia (2)
- adaptation (2)
- adolescents (2)
- adult (2)
- aging (2)
- alveolar ridge augmentation (2)
- animal experiment (2)
- antiepileptic drugs (2)
- augmentation (2)
- bibliometrics (2)
- biomarkers (2)
- body mass index (2)
- cardiac surgery (2)
- cerebral hemorrhage (2)
- cerebral venous thrombosis (2)
- chemoresistance (2)
- children (2)
- cirrhosis (2)
- cleaning (2)
- clinical studies (2)
- coagulopathy (2)
- combination therapy (2)
- complement (2)
- connective tissue (2)
- continuous performance test (2)
- curcumin (2)
- cystic fibrosis (2)
- cytomegalovirus (2)
- data science (2)
- decompensated liver cirrhosis (2)
- delirium (2)
- dental education (2)
- dental implants (2)
- dental profession (2)
- dentoalveolar surgery (2)
- diabetes mellitus (2)
- direct-acting antivirals (2)
- drug discovery (2)
- elderly (2)
- electroencephalography (2)
- environmental tobacco smoke (2)
- evolution (2)
- fascia (2)
- fibroblasts (2)
- fibrosis (2)
- flow cytometry (2)
- gait analysis (2)
- growth (2)
- hepatic encephalopathy (2)
- hepatocellular carcinoma (2)
- histology (2)
- hyperactivity (2)
- hypoxia (2)
- immunity (2)
- immunosuppression (2)
- impulsivity (2)
- infection (2)
- innate immunity (2)
- integrin (2)
- joint contact forces (2)
- kidney (2)
- liver (2)
- liver cirrhosis (2)
- lung cancer (2)
- lung function (2)
- lymphocytes (2)
- mTOR (2)
- mass spectrometry (2)
- metformin (2)
- mitochondria (2)
- multiple sclerosis (2)
- musculoskeletal disorders (2)
- musculoskeletal modeling (2)
- natural killer cells (2)
- neural oscillations (2)
- neurocognition (2)
- oncology (2)
- oral and maxillofacial surgery (2)
- pancreatic cancer (2)
- patient blood management (2)
- periodontitis (2)
- polygenic risk score (2)
- post-translational modifications (2)
- prognosis (2)
- protein degradation (2)
- protein synthesis (2)
- proteome (2)
- proteomics (2)
- public health (2)
- renal cell carcinoma (2)
- resistance training (2)
- risk factors (2)
- risk prediction (2)
- screening (2)
- sepsis (2)
- severe acute respiratory syndrome coronavirus 2 (2)
- simulation training (2)
- sphingosine 1-phosphate (2)
- sphingosine 1-phosphate receptor (2)
- spinal dural leaks (2)
- stress (2)
- superficial siderosis (2)
- surgery (2)
- survival (2)
- survivin (2)
- thrombosis (2)
- thymus (2)
- transcriptome (2)
- transplantation (2)
- tumor growth (2)
- tumor progression (2)
- von Willebrand factor (2)
- (cardiac) surgery (1)
- 14-3-3 gene family (1)
- 16 segment AHA model (1)
- 16S rRNA sequencing (1)
- 19F MR spectroscopy (1)
- 1H MR spectroscopy (1)
- 2'-deoxyguanosine riboswitch (1)
- 2-hydroxyglutarate (1)
- 2019-nCoV (1)
- 3,4-DCA; biotransformation (1)
- 3-hydroxyanthranilic acid (1)
- 3D printed cell-free scaffold (1)
- 3D-Druck (1)
- 4-fluoroamphetamine (1)
- 9-HODE (1)
- A-FFIP (1)
- A2BP1 (1)
- AAA+ disaggregase (1)
- ABC transporters (1)
- ABCB1 (1)
- ABCC1 (1)
- ACE-Bestimmung (1)
- ADAMTS-13 (1)
- ADAMTS13 (1)
- ADGRE1 (1)
- ADHD differential diagnosis (1)
- ADHS (1)
- AKI (1)
- ALL (1)
- AMH (1)
- AML – acute myeloid leukemia (1)
- ARDS (1)
- ASD-specific (1)
- ASPECTS (1)
- ATP binding (1)
- Abductor pollicis longus (1)
- Ablation (1)
- Abrasion (1)
- Absenteeism (1)
- Absorption modeling (1)
- Abusive head trauma (AHT) (1)
- Access (1)
- Accumulated degree days (1)
- Acellular dermis (1)
- Acoustics (1)
- Action potentials (1)
- Acute HIV infection (1)
- Acute appendicitis (1)
- Acute elbow dislocation (1)
- Acute hospital (1)
- Acute lymphoblastic leukemia (1)
- Acute lymphocytic leukaemia (1)
- Acute-on-chronic subdural hematoma (1)
- Addison’s disease (1)
- Adenosine (1)
- Adherence (1)
- Adipose tissue (1)
- Administrative claims data (1)
- Advanced breast cancer (1)
- Adverse drug reaction (1)
- Afrikanische Schlafkrankheit (1)
- Age determination (1)
- Age determination by skeleton (1)
- Age groups (1)
- Aging (1)
- Albumin ratio (1)
- Algorithms (1)
- Alkaloid (1)
- Allergic rhinitis (1)
- Allgemeinmedizin (1)
- Allogeneic (1)
- Alpha oscillations (1)
- Alzheimer's disease (1)
- Amino acid analysis (1)
- Amisulpride (1)
- Amitriptyline (1)
- Anal cancer (1)
- Anandamide (1)
- Anatomy (1)
- Anderson–Fabry (1)
- Andropogon virginicus (1)
- Angiogenesis (1)
- Angiotensin Converting Enzyme (1)
- Angiotensin-converting enzyme (1)
- Animal model (1)
- Anterior cruciate ligament reconstruction (1)
- Anti-CMV IgG (1)
- Anti-inflammatory (1)
- Anti-rheumatic agents (1)
- Anticholinergic (1)
- Anticoagulant (1)
- Anticoagulant therapy (1)
- Anticoagulants (1)
- Anticoagulation (1)
- Antidepressiva (1)
- Antigens/Peptides/Epitopes (1)
- Antihormone therapy (1)
- Antiviral immune response (1)
- Aortic input function (1)
- Apoptosis (1)
- Appendectomy (1)
- Aquilegia (1)
- Arbeitsgedächtnis (1)
- Arrhythmia syndromes (1)
- Arthroplasty (1)
- Ataxia score (1)
- Athletes (1)
- Atm (1)
- Atrial fibrillation (1)
- Attention deficit (1)
- Auditory cortex (1)
- Auditory midbrain (1)
- Auditory system (1)
- Aufmerksamkeit (1)
- Aufmerksamkeitsleistung (1)
- Autoimmune vasculopathy (1)
- Autologous biomaterial (1)
- Autopsy (1)
- Awareness campaign (1)
- Axiography (1)
- B cells (1)
- B-cell lymphoma (1)
- B-cell receptor (1)
- BAG3 (1)
- BCL6 (1)
- BCX7353 (1)
- BDNF (1)
- BET inhibitor (1)
- BEZ235 (1)
- BFIS (1)
- BG-index (1)
- BIRC5 (1)
- BK channel (1)
- BMC (1)
- BRD4 (1)
- Bacterial abundance (1)
- Bagatelltrauma (1)
- Bakterien (1)
- Bakterientest (1)
- Balloon-expandable TAVI (1)
- Bauchaortenaneurysma (1)
- Bee venom allergy (1)
- Begriffsbestimmung (1)
- Belastung (1)
- Benign enlargement of the subarachnoid spaces (BESS) (1)
- Benign pulmonary diseases (1)
- Benigne Lungenerkrankungen (1)
- Bestimmungsmethoden (1)
- Bestrahlung (1)
- Betriebliche Gesundheitsförderung (1)
- Bewegungsanalyse mit Inertialsensoren (1)
- Bewegungsstörung (1)
- Bildgebung (1)
- BioID (1)
- Bioavailability prediction (1)
- Biomarker (1)
- Biopsy (1)
- Bleeding (1)
- Blocked occlusion (1)
- Blood flow (1)
- Body limbs (1)
- Body measurements (1)
- Body modification (1)
- Body temperature (1)
- Bone defect (1)
- Bone regeneration (1)
- Bone remodelling (1)
- Bone substitute (1)
- Bone tissue engineering (1)
- Brain asymmetry (1)
- Brain injuries (1)
- Brain size I (1)
- Brain structure (1)
- Brain tumor surgery (1)
- Brain tumors (1)
- Brain-stimulus synchrony (1)
- Breast cancer survivers (1)
- Breathing (1)
- Brustkrebs (1)
- Burden (1)
- Burden of illness (1)
- Büroangestellte (1)
- C1 inhibitor (1)
- C2 domain (1)
- CAD/CAM (1)
- CAKUT (1)
- CAR (1)
- CCL2 (1)
- CD107-Assay (1)
- CD3 (1)
- CD34 + cells (1)
- CD4 binding site (1)
- CD41 (1)
- CD49d (1)
- CD62P (1)
- CD8+ T cell (1)
- CDI (1)
- CDK9 (1)
- CEBPD (1)
- CIRS (1)
- CLP (1)
- CMVepidemiology (1)
- COINS (1)
- COMP (1)
- COVID 19 pandemic (1)
- CPT1A (1)
- CRE-dependent transcription (1)
- CRISPR/Cas9 (1)
- CUELA system (1)
- CXCL10 (1)
- CXCR3 (1)
- Callous-unemotional traits (1)
- Calpain (1)
- Cancer check up (1)
- Cancer treatment (1)
- Candida spp (1)
- Cannabidiol (1)
- Capnography (1)
- Cardiac acoustic biomarkers (1)
- Cardiac arrest (1)
- Cardiac masses (1)
- CardioMEMS™ HF system (1)
- Careers (1)
- Caspase-8 (1)
- Cell death and immune response (1)
- Cell staining (1)
- Cell-based therapies (1)
- Cellular neuroscience (1)
- Central nervous system (1)
- Cerebellum (1)
- Cerebral hypoperfusion (1)
- Cerebrovascular disorders (1)
- Checkpoint inhibitor (1)
- Chemoradiation (1)
- Chemoradiotherapy (1)
- Chemotherapie (1)
- Chemotherapy (1)
- Child (1)
- Child abuse (1)
- Child health (1)
- Children and adolescents (1)
- Chimiothérapie (1)
- Chirurgie (1)
- Chromatin accessibility (1)
- Chromatin conformation (1)
- Chronic conditions (1)
- Chronic depression (1)
- Chronic inflammation (1)
- Chronology of disease (1)
- Classification (1)
- Clavien–Dindo classification (1)
- Climate inequity (1)
- Clinical genetics (1)
- Clinical trial (1)
- Clinical trials (1)
- Clostridium (1)
- Clustering coefficients (1)
- Coagulation (1)
- Coagulopathy management (1)
- Cognition (1)
- Cognitive behavioral therapy (1)
- Cognitive impairment (1)
- Cognitive neurology (1)
- Cold hardiness (1)
- Cold tolerance (1)
- Collagen-based biomaterial (1)
- Colonic neoplasms (1)
- Combo® DTS (1)
- Comparators (1)
- Complications (1)
- Compression stocking (1)
- Computed axial tomography (1)
- Computer hardware (1)
- Computer science (1)
- Computer software (1)
- Computer-aided drug design (1)
- Computers (1)
- Concept paper (1)
- Conduct disorder (1)
- Conduct problems (1)
- Confinement (1)
- Congenital CMVinfection (1)
- Congenital anomalies (1)
- Congenital diaphragmatic hernia (1)
- Connectivity (1)
- Conservative treatment (1)
- Constitution (1)
- Continuous Process Verification (1)
- Control (1)
- Cooperation (1)
- Copy number (1)
- Coronary artery disease (1)
- Coronavirus (1)
- Cortical degeneration (1)
- Cortical thickness (1)
- Cp (1)
- Cpk (1)
- Craniomaxillofacial injuries (1)
- Critical Online Reasoning Assessment (1)
- Critical size (1)
- Croatia (1)
- Crohn's disease (1)
- Crohn’s disease (1)
- CspA (1)
- CspZ (1)
- Curriculum (1)
- Cyp46a1 (1)
- CysLTR1 (1)
- Cysteine‐Rich Domain (CRD) (1)
- Cystic fibrosis (1)
- Cytokines (1)
- Cytomegalovirus (CMV) (1)
- DAMPs (1)
- DBS (1)
- DFNB9 (1)
- DILI (1)
- DNA damage (1)
- DNA damage response (1)
- DNA sequence analysis (1)
- DNase1-seq (1)
- DRG (1)
- DST (1)
- DYRK1A (1)
- Darunavir (1)
- Data processing (1)
- Data protection (1)
- Data science (1)
- Datenverarbeitung (1)
- Decision making (1)
- Decontamination (1)
- Deep vein thrombosis (1)
- Defibrillation (1)
- Dehnen (1)
- Delegation (1)
- Demenz (1)
- Density equalizing mapping (1)
- Density-equalizing mapping (1)
- Dental air (1)
- Dental casts (1)
- Dental implant (1)
- Dental implants (1)
- Dental practice (1)
- Dental students (1)
- Determination method (1)
- Developmental disorders (1)
- Diabetes mellitus (1)
- Diagnosis (1)
- Diagnosis related groups (1)
- Diagnostic algorithm (1)
- Diagnostic error (1)
- Diagnostic markers (1)
- Differential diagnosis (1)
- Diffuse large B-cell lymphoma (1)
- Disabilities (1)
- Disaster victim identification (1)
- Disc herniation (1)
- Diseases (1)
- Disintegration (1)
- Distress screening (1)
- Distribution limits (1)
- Dopamine (1)
- Double suicide (1)
- Double-blind placebo-controlled trial (1)
- Douleur (1)
- Downy mildew (1)
- Dravet syndrome (1)
- Drug permeability (1)
- Drug susceptibility testing (1)
- Dural onlays (1)
- Dysphagia (1)
- Désir d’enfant (1)
- E-NTPDase (1)
- E3 ligase (1)
- EBM (1)
- EEG reference choices (1)
- EGFR (1)
- EGFR pathway (1)
- EGFRvIII mutation (1)
- EGR1-dependent transcription (1)
- ELISA (1)
- EMR1 (1)
- EMT (1)
- EQIP (1)
- ERBB2 (HER2/neu) (1)
- ERK3 (1)
- ES (1)
- ESMO-MCBS (1)
- Early intervention (1)
- Ebola virus (1)
- Echovirus-30 (1)
- Ecto-5'-nucleotidase (1)
- Edoxaban (1)
- Education (1)
- Einstellungen (1)
- Einwilligungsfähigkeit (1)
- Eisenmangel (1)
- Ejection fraction (1)
- Elderly (1)
- Electrical stimulation (1)
- Embryos (1)
- Emergency treatment (1)
- Emotions (1)
- End-of-life decisions (1)
- Endocrinology (1)
- Endometrial carcinoma (1)
- Endometriome (1)
- Endométriomes (1)
- Endothelial cells (1)
- Endothelial protein C receptor (1)
- Endovaskuläre Versorgung (1)
- Endpoints (1)
- Enterobacteriaceae (1)
- Entscheidungsassistenz (1)
- Epidemiological data (1)
- Epidural abscess (1)
- Epigenetics (1)
- Epilepsie (1)
- Episodic memory (1)
- Epstein-Barr virus (1)
- Erdnussallergie (1)
- Ergonomic analysis (1)
- Ergonomie am Arbeitsplatz (1)
- Ergonomische Analyse (1)
- Erregerspektrum der Tonsillitis (1)
- Erwachsene (1)
- Evaluation (1)
- Evidence based medicine (1)
- Evidence-based dentistry (1)
- Evidence-based medicine (1)
- Evidenzbasierte Medizin (1)
- Ewing sarcoma (1)
- Exercise challenge (1)
- Exercise therapy (1)
- Exercise-induced asthma (1)
- Exhaled nitric oxide (1)
- External-/self-assessment (1)
- Eye movements (1)
- Eye tracking (1)
- F4/80 (1)
- F508del homozygous (1)
- FBK-R23 (1)
- FDM (1)
- FET (1)
- FEV1 (1)
- FFF (1)
- FHIR (1)
- FLT3-ITD (1)
- FTMT (1)
- Factor H (1)
- Fasting (1)
- Feedback (1)
- Female subjects (1)
- Ferritinophagy (1)
- Ferroptose (1)
- Ferroptosis (1)
- Fertilität (1)
- Fertilité (1)
- Fibromyalgia (1)
- Finevo (1)
- Fingolimod (1)
- First-line regimen (1)
- Five-Konzept (1)
- Fluid therapy (1)
- Forced expiratory volume in 1 s (1)
- Forensic entomology (1)
- Forensic examination (1)
- Fourier analysis (1)
- Fracture (1)
- Fracture type (1)
- Fragebogenentwicklung (1)
- Fresh frozen plasma (1)
- Functional characterization (1)
- Functional clustering (1)
- Functional mitral regurgitation (1)
- G-CSF (1)
- G-protein-coupled receptors (1)
- G2A receptor (1)
- GABA (1)
- GCN (1)
- GFAP (1)
- GHQ-28 (1)
- GIRD (1)
- GLA deficiency (1)
- GPCR (1)
- GWAS (1)
- Gait analysis (1)
- Gas gangrene (1)
- Gastrocnemius muscles (1)
- Gastroschisis (1)
- Gene expression prediction (1)
- Genetic heart disease (1)
- Genetic syndromes (1)
- Geoffrey Burnstock (1)
- Geographical disparities (1)
- Gerontologie (1)
- Geschichte 1663-1748 (1)
- Geschlecht (1)
- Gesundheit (1)
- Gesundheitsamt (1)
- Gesundheitsberichterstattung (1)
- Gesundheitsbildung (1)
- Gesundheitserziehung (1)
- Gesundheitsförderung (1)
- Gesundheitswissenschaften (1)
- Glioblastom (1)
- Global warming (1)
- Graph theory (1)
- Gray matter volume (1)
- Green Tobacco Sickness (GTS) (1)
- Greenhouse effect (1)
- Guided bone regeneration (GBR) (1)
- Guided tissue regeneration (GTR) (1)
- HADS (1)
- HAE (1)
- HBV filaments (1)
- HBV genotypes (1)
- HBV surface protein (1)
- HCC (1)
- HCC recurrence (1)
- HCV (1)
- HDAC (1)
- HDAC and BET inhibitor (1)
- HDAC inhibitor (1)
- HDAC4 (1)
- HEUS (1)
- HEV (1)
- HFrEF (1)
- HHUSD (1)
- HIBCPP cells (1)
- HIFT (1)
- HILI (1)
- HIV-1 escape restriction (1)
- HLA DQ haplotypes (1)
- HLA class I (1)
- HNSCC (1)
- HOSO (1)
- HRM (1)
- Haematocrit (1)
- Haemodynamic monitoring (1)
- Hausarztmangel (1)
- HbA1c (1)
- HeLa cells (1)
- Health care (1)
- Health care sector (1)
- Health education and awareness (1)
- Health literacy (1)
- Health policy (1)
- Health services (1)
- Healthcare costs (1)
- Healthcare resource utilization (1)
- Health‐related quality of life (1)
- Heat shock protein 27 (1)
- Hematologic malignancies (1)
- Hematoxylin staining (1)
- Hemispheric specialization (1)
- Hemodynamics (1)
- Hepatic encephalopathy (1)
- Hepatitis C virus (1)
- Heregulin (1)
- Heterogeneity (1)
- HiC (1)
- HiChIP (1)
- High oblique sagittal osteotomy (1)
- Hippocampal excitability (1)
- Hippocampus (1)
- Histological analysis (1)
- Histology (1)
- Histoplasma qPCR (1)
- History (1)
- Hmox1 (1)
- HoLEP (1)
- Hodgkin lymphoma (1)
- Hodgkin’s lymphoma (1)
- Homicide-suicide (1)
- Homizid-Suizid (1)
- Hospital case volume (1)
- Hospitalization (1)
- House dust mite allergy (1)
- Human (1)
- Human immunodeficiency virus (HIV) (1)
- Hymenoptera venom immunotherapy (1)
- Hyperactivity (1)
- Hyperscanning (1)
- Hyponatremia (1)
- Hypoxia-inducible factor-1α (HIF-1α) (1)
- Höchstrichterliche Rechtsprechung (1)
- ICAM-1 (1)
- ICD (1)
- IDH1 inhibitor (1)
- IDO1 (1)
- IFA (1)
- IFN-γ expression (1)
- IKKε (1)
- IL-1β (1)
- IL-6 (1)
- ISR (1)
- IV iron (1)
- IVD degeneration (IVDD) (1)
- Iatrochemie (1)
- Iatrochemistry (1)
- Identification (1)
- Identifikation (1)
- Identifizierung von Katastrophenopfern (1)
- Idiopathische Dystonie (1)
- IgG (1)
- Image processing (1)
- Image processing (computer-assisted) (1)
- Immune suppression (1)
- Immune system (1)
- Immunomodulatory agents (1)
- Immunotherapy (1)
- Implant osseointegration (1)
- Implementación (1)
- Implementation (1)
- Imrt (1)
- In vivo (1)
- Induced membrane technique (1)
- Inducible nitric oxide synthase (iNOS) (1)
- Induction chemotherapy (1)
- Inertial motion capture (1)
- Infektionen (1)
- Inferior colliculus (1)
- Inflammatory bowel disease (1)
- Inflammatory pattern (1)
- Injury (1)
- Injury Severity Score (ISS) (1)
- Innate immunity (1)
- Integrated Pulmonary Index (1)
- Integration (1)
- IntelliCage (1)
- Intelligence (1)
- Intensive care (1)
- Interferons (1)
- Internet (1)
- Interoperability (1)
- Interposition (1)
- Interstitial pneumonia (1)
- Interview (1)
- Intoxication (1)
- Intoxikation (1)
- Intravenous antibiotic therapy (1)
- Intravenous injections (1)
- Invasive species (1)
- Ireb2 (1)
- Iron (1)
- Isocitrate dehydrogenase (1)
- JNK (1)
- Joint actions (1)
- Joint loading (1)
- Jumping (1)
- K-homology RNA-binding domain (1)
- KOOS IV (1)
- Ki-67/MIB1 (1)
- Ki67 transgenic c‐myc/TGFα mice (1)
- Kidney diseases (1)
- Kidney neoplasm (1)
- Kinder (1)
- Kinderwunsch (1)
- Kinds of diseases (1)
- Kinematic analysis (1)
- Knees (1)
- Kognitive Beeinträchtigungen (1)
- Konzeptpapier (1)
- Krankenhausfallaufkommen (1)
- Krankheitskosten (1)
- Körpermaße (1)
- Körpermodifizierung (1)
- L-DOPA (1)
- LBP (1)
- LIR interaction, (1)
- LPS (1)
- Lactobacillus (1)
- Landarztprogramm (1)
- Langstreckige Knochendefekte (1)
- Language delay (1)
- Late gadolinium enhancement (1)
- Left hemisphere (1)
- Legal considerations (1)
- Legs (1)
- Lennox-Gastaut syndrome (1)
- Leukemia (1)
- Leukämie (1)
- Lipodystrophy (1)
- Liver transplant (1)
- Local IgE (1)
- Local allergic rhinitis (1)
- Locally advanced (1)
- Lockdown (1)
- Loco-regional control (1)
- Long non-coding RNAs (1)
- Longchain polyunsaturated fatty acids (1)
- Loving kindness meditation (1)
- Low-dose ionizing radiation (1)
- Low-dose radiation therapy (1)
- Lower back pain (1)
- Lung cancer (1)
- Lung development (1)
- Lung function (1)
- Lung ultrasound (1)
- Lungenerkrankungen (1)
- Lymph nodes (1)
- Lymphocytes (1)
- Lymphoma (1)
- Lysophosphatidic acids (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MAGGIC score (1)
- MAPK6 (1)
- MCAO (1)
- MHC (1)
- MICA (1)
- MM-121 (1)
- MMP14 (1)
- MODY (1)
- MR-spectroscopy (1)
- MS (1)
- MYC (1)
- Machine learning algorithms (1)
- Machine-learning (1)
- Macroautophagy (1)
- Macrophage polarization (1)
- Malaria (1)
- Mammakarzinom (1)
- Management (1)
- Marker genes (1)
- Market Access (1)
- Masquelet technique (1)
- Mass disaster (1)
- Massenkatastrophe (1)
- Massenspektrometrie (1)
- Master Plan 2020 (1)
- Masterplan 2020 (1)
- Maxillofacial surgery (1)
- Mean erythrocyte volume (1)
- Medical education (1)
- Medical implants (1)
- Medical law (1)
- Medical risk factors (1)
- Medical studies (1)
- Medicinal chemistry (1)
- Medizin (1)
- Medizinrecht (1)
- Medizinstudierende (1)
- Medizinstudium (1)
- Meldepflicht (1)
- Membrane potential (1)
- Memory consolidation (1)
- Memory quality (1)
- Mesenchymal stromal cells (MSC) (1)
- Mesh (1)
- Meta-analysis (1)
- Metabolic diseases (1)
- Metastatic (1)
- Metta (1)
- Michael acceptor (1)
- MicroRNA-181a (1)
- Microbiology (1)
- Microfluidics (1)
- Microglial cells (1)
- Microparticles (1)
- Microphysiological models (1)
- Microstates (1)
- Midwifery (1)
- Mindfulness (1)
- Minimally invasive surgical procedures (1)
- Minor injury (1)
- Mitochondrial dysfunction (1)
- MitraClip (1)
- Mobilization (1)
- Molecular autopsy (1)
- Molecular diagnostic testing (1)
- Molecular neuroscience (1)
- Monetary incentive delay (1)
- Mongolian spot (1)
- Monitoring (1)
- Monocytes (1)
- Morphologie (1)
- Motivational situation (1)
- Motivationslage (1)
- Motor control (1)
- Motor cortex (1)
- Mouse models (1)
- Mucomaix® matrix (1)
- Multidrug-resistance (1)
- Multimedication (1)
- Multimorbidity (1)
- Multiparametric MRI (1)
- Multiplate (1)
- Multiple Sklerose (1)
- Multiple-indication review (1)
- Mundhöhlenkarzinome (1)
- Muscle functions (1)
- Musculoskeletal diseases (1)
- Muskuloskelettale Erkrankungen (1)
- Mutation databases (1)
- Muttermilch (1)
- Mutual information (1)
- Myocardial infarction (MI) (1)
- Myocardial injury (1)
- Myocardial segmentation (1)
- Myonecrosis (1)
- Mφs (1)
- N-glycoproteome (1)
- N2 (1)
- NAFL (1)
- NCOA4 (1)
- NCoR1 (1)
- NDBI (1)
- NF-κB (1)
- NF-κB pathway (1)
- NF-кB (1)
- NIRS (1)
- NK-ZELL-BASIERTER IMMUNTHERAPIE (1)
- NK-ZELLEN (1)
- NKG2D (1)
- NLRP3 inflammasomes (1)
- NMES (1)
- NMR spectroscopy (1)
- NOTCH (1)
- NPH insulin (1)
- NREM sleep (1)
- NS1608 (1)
- NSE (1)
- NTM (1)
- Nachtschattengewächs (1)
- Natural sounds (1)
- Necrotizing fasciitis (1)
- Negative appendectomy rate (1)
- Nek1 (1)
- Neonatal brain damage (1)
- Neonatal surgery outcome (1)
- Nephrectomy (1)
- Nesplora Aquarium (1)
- Network models (1)
- Network motifs (1)
- Neural circuits (1)
- Neural networks (1)
- Neurocognition (1)
- Neurodegeneration (1)
- Neurodevelopmental disorders (1)
- Neuron (1)
- Neuronal plasticity (1)
- Neuropathic pain (1)
- Neurophysiology (1)
- Neuropsychological testing (1)
- Neuropsychology (1)
- Neuroscience (1)
- Neurosurgery (1)
- Neurotransmitter (1)
- Nevus of Ito (1)
- Nevus of Ota (1)
- Next-generation sequencing (1)
- Nicotine (Nicotiana tabacum/ Nicotiana rustica) (1)
- Nicotinic acetylcholine receptors (1)
- Nikotin (Nicotiana tabacum/ Nicotiana rustica) (1)
- Nikotinerge Acetylcholinrezeptoren (1)
- Nivolumab (1)
- Non-abusive head trauma (NAHT) (1)
- Non-allergic-rhinitis (1)
- Non-apoptotic functions (1)
- Non-clear cell renal cell cancer (1)
- Non-small cell lung cancer (1)
- Non-tuberculous mycobacteria (1)
- Non-vitamin K antagonist oral anticoagulants (1)
- Nordic questionnaire (1)
- Normal distribution (1)
- Normative modeling (1)
- NoxO1 (1)
- Number of platelets (1)
- OGTT (1)
- OR time (1)
- OSA (1)
- OTSC Proctology (1)
- Obduktion (1)
- Obstetrics (1)
- Omphalocele (1)
- Oncology (1)
- Open Access (1)
- Opioids (1)
- Oppositional defant disorder (1)
- Optogenetics (1)
- Oral anticoagulation (1)
- Oral cancer (1)
- Organoids (1)
- Orphan nuclear receptor (1)
- Orthognathic surgery (1)
- Oryctolagus cuniculus (1)
- OspE (1)
- Osteoarthritis (1)
- Osteonecrosis (1)
- Outcomes (1)
- Ovarian cancer treatment (1)
- Ovarielle Reserve (1)
- Ovartoxizität (1)
- Overwintering (1)
- Oxygen (1)
- PARK2 (1)
- PBMC (peripheral blood mononuclear cells) (1)
- PBPK (1)
- PD-1 inhibitor (1)
- PDE inhibition (1)
- PDE‐5‐inhibitor (1)
- PEA-15 (1)
- PHGDH (1)
- PI3K/mTor inhibition (1)
- PKD (1)
- PKD/IC (1)
- PLSC (1)
- PRNT (1)
- PROM (1)
- PRRT2 (1)
- PSA screening (1)
- PSA-Screening (1)
- PV loop (1)
- PWI (1)
- PYGL (1)
- Paediatric trauma patients (1)
- Pain (1)
- Pain sensation (1)
- Palliative care (1)
- Parasympathetic (1)
- Parkinson's disease (1)
- Pathogenesis (1)
- Pathologists (1)
- Patient information materials (1)
- Patient outcome assessment (1)
- Patient reported outcomes (1)
- Patient safety (1)
- Patterns of care (1)
- Peanut allergy (1)
- Pediatric patients (1)
- Peer review (1)
- Pelvic (1)
- Percutaneous endoscopic gastrostomy (1)
- Performance Metrics (1)
- Pericardial effusion (1)
- Pericarditis (1)
- Periodontitis grades B and C (1)
- Periprocedural anticoagulation (1)
- Perrault syndrome (1)
- Persistent depressive disorder (1)
- Pgrmc1 (1)
- Phalangeal fractures (1)
- Pharma Management (1)
- Pharmaceutical (1)
- Pharmacology (1)
- Phase I clinical trial (1)
- Phase II trial (1)
- Phase rotors (1)
- Phenotypic plasticity (1)
- Philemon and Baucis (1)
- Philemon und Baucis (1)
- Phosphoproteome (1)
- Phylogeny (1)
- Physical activity (1)
- Physician-assisted suicide (1)
- Physicians (1)
- Pim-1 (1)
- Plantagearbeiter (1)
- Plantation workers (1)
- Plasma transfusion (1)
- Plasma usage (1)
- Platelet-rich fibrin (1)
- Polygenic risk score (1)
- Polypharmacy (1)
- Polysomnography (1)
- Polytrauma (1)
- Portal hypertension (1)
- Portal veins (1)
- Post mortem interval (1)
- Posture (1)
- Pp (1)
- Ppk (1)
- Praktisches Jahr (1)
- PreS1 deletion (1)
- Preclinical drug development (1)
- Prediction (1)
- Premotor cortex (1)
- Pressure distribution (1)
- Pressure measuring plate (1)
- Prevalence (1)
- Prevention (1)
- Pre‐Ligand Assembly Domain (PLAD) (1)
- Primary breast lymphoma (1)
- Primary care (1)
- Primary health care (1)
- Probability density (1)
- Probability distribution (1)
- Procalcitonin (1)
- Procedural skills (1)
- Process Capability (1)
- Process Performance (1)
- Process Validation (1)
- Professions (1)
- Progestatifs synthétiques (1)
- Prostata-specific antigen (1)
- Prostataspezifisches Antigen (1)
- Prostate cancer (1)
- Protease inhibitor therapy (1)
- Proteasome inhibitor (1)
- Protestantism (1)
- Prototypes (1)
- Präanalytik (1)
- Prävention (1)
- Pseudoprogression (1)
- Psycho-oncology (1)
- Psychological stress (1)
- Psychologische Beeinträchtigung (1)
- Psychology (1)
- Psychopharmaka (1)
- Psychosocial impact (1)
- Pteridine (1)
- Pulmonary edema (1)
- Pulmonary embolism (1)
- Pulmonary hypertension (1)
- Pulmonary hypoplasia (1)
- QOL (1)
- Qb-Test (1)
- QbTest® (1)
- Qualitative research (1)
- Quality Control (1)
- Quality indicators (1)
- Qualitätsindikatoren (1)
- Quantitative (q)T2 mapping (1)
- Quantitative magnetic resonance imaging (1)
- Quantitative research (1)
- Quantra (1)
- Quarantine (1)
- Questionnaire (1)
- Questionnaires (1)
- Quinolones (1)
- R406 (1)
- RAS (1)
- RBC (1)
- RBFOX1 (1)
- RDoC (1)
- RIPK1 (1)
- RNA chaperone (1)
- RNA structures (1)
- RNA therapeutics (1)
- RNAseq analysis (1)
- RRMS (1)
- RUCAM (1)
- RULA (1)
- Radiation exposure (1)
- Radical cystectomy (1)
- Radiotherapy (1)
- Radiothérapie (1)
- Ramadan (1)
- Randomised trial (1)
- Randomized controlled trial (1)
- Randomized controlled trials (1)
- Randomized trial (1)
- Rapid diagnostic test (1)
- Ratgeber (1)
- Real-time phase contrast (1)
- Rechtliche Würdigung (1)
- Rectal cancer (1)
- Reference values (1)
- Referenzwerte (1)
- Refractory ALL (1)
- Refractory AML (1)
- RegJoint™ (1)
- Regeneration (1)
- Regret (1)
- Regulatory Affairs (1)
- Relaxometrie (1)
- Reliability (1)
- Renal replacement therapy (1)
- Rescue medication (1)
- Research & Development (1)
- Research investment (1)
- Respiration (1)
- Respiratory distress syndrome (1)
- Resting-state (1)
- Retinal diseases (1)
- Retinoic acid (1)
- Retrospective studies (1)
- Return to work (1)
- Review (1)
- Reward (1)
- Rezidiv (1)
- Rhabdomyosarkom (1)
- Rheumatoid arthritis (1)
- Right hemisphere (1)
- Risk factors (1)
- Risk-stratification (1)
- Robotik (1)
- Roussel Uclaf Causality Assessment Method (1)
- Roux-en-Y gastric bypass (1)
- Running (1)
- Rush protocol (1)
- Récidive (1)
- Réserve ovarienne (1)
- S100b (1)
- S1P lyase (1)
- S1P receptors (1)
- S1P1–5 (1)
- S1PR4 (1)
- SARS‐CoV‐2 (1)
- SCA2 (1)
- SCN5A (1)
- SEAP (1)
- SENP (1)
- SF-36 (1)
- SIDS (1)
- SIRS (1)
- SKI II (1)
- SLC20A1 (1)
- SLUG (1)
- SMAD (1)
- SNORD95 (1)
- SPC (1)
- SPSS (1)
- STAT3 (1)
- SUMO (1)
- Safety (1)
- Sarcoidosis (1)
- Sarcomas (1)
- Sarkoidose (1)
- Saudi Arabia (1)
- Scaffold (1)
- Schlaganfall (1)
- Schmerz (1)
- Schädel-MRT (1)
- Seattle heart failure model (1)
- Second donation (1)
- Secular trend (1)
- Selbstmordpakt (1)
- Self-expandable TAVI (1)
- Seltene Erkrankungen (1)
- Semitendinosus tendon autograft (1)
- Senescence (1)
- Sensorimotor processing (1)
- Sepsis (1)
- Seribantumab (1)
- Serin (1)
- Serious injured children (1)
- Seroconverter (1)
- Seroprevalence (1)
- Serum biomarker (1)
- Sex (1)
- Sharp injuries (1)
- Shoulder injury (1)
- Shoulder luxation (1)
- Sialic acid (1)
- Sialinsäure (1)
- Side effects (1)
- Signal intensity (1)
- Signs and symptoms (1)
- Single-Molecule Localization Microscopy (SMLM) (1)
- Slc11a2 (1)
- Slc25a37 (1)
- Sleep (1)
- Sleep deprivation (1)
- Smac mimetic (1)
- Small molecules (1)
- Social brain (1)
- Social differences (1)
- Social information processing (1)
- Social participation (1)
- Socio-economic analysis (1)
- Socioeconomic analysis (1)
- Socioeconomic indices (1)
- Soft tissue infection (1)
- Software tools (1)
- Solanaceae (1)
- Sozialwissenschaften (1)
- Speech (1)
- Spine fractures (1)
- Spinocerebellar ataxia type 2 (1)
- Sports and exercise medicine (1)
- Stage at presentation (1)
- Standard dataset (1)
- Standard reference values (1)
- Standard value (1)
- State of Control (1)
- Statisitcal Control (1)
- Statisitcal Process Control Chart (1)
- Statistical data (1)
- Status epilepticus (1)
- Stem cell (1)
- Stereoelektroenzephalographie (1)
- Stereotaxie (1)
- Sterols (1)
- Stiffness (1)
- Streptokokken (1)
- Striatum (1)
- Stroke genetics (1)
- Störfaktoren (1)
- Sub-segmentation (1)
- Sub-zero exposure (1)
- Sudden death (1)
- Sudden infant death syndrome (1)
- Sunitinib (1)
- Supported Decision-making (1)
- Supreme court ruling (1)
- Surgeons (1)
- Surgery (1)
- Surgical and invasive medical procedures (1)
- Surgical therapy (1)
- Surveys (1)
- Suspension (1)
- Swallowing (1)
- Syllables (1)
- Sympathetic (1)
- Symptome (1)
- Synaptic plasticity (1)
- Synaptic transmission (1)
- Synthetische Gestagene (1)
- Systematic reviews (1)
- Szientometrie (1)
- Säkularer Trend (1)
- T cell receptor (1)
- T cells (1)
- T-Zellen (1)
- T-cell receptor (1)
- T-tubule system (1)
- T1 and T2 mapping (1)
- T2 (1)
- TAMs (1)
- TAPSE (1)
- TBK1 (1)
- TBSS (1)
- TDM (1)
- TGF-beta (1)
- TGF-β (1)
- TGFβ (1)
- TGR(mREN2)27 (1)
- THV (1)
- TLR2/6 (1)
- TRIMs (1)
- TRPA1 (1)
- TSC22D3 (1)
- TVT (1)
- Tabakkonsum (1)
- Tagging (1)
- Tamponade (1)
- Target validation (1)
- Targeted sequencing (1)
- Temsirolimus (1)
- Tendon incontinence repair (1)
- Tendon transplantation (1)
- Tendons (1)
- Tennis player (1)
- Terminology (1)
- Test assay (1)
- Tfrc (1)
- Therapie (1)
- Therapies (1)
- Therapy (1)
- Thrombotic thrombocytopenic purpura (1)
- Thrombozytenkonzentrat (1)
- Thrombozytentransfusion (1)
- Thumb carpometacarpal joint osteoarthritis (1)
- Tissue engineering (1)
- Tocilizumab (1)
- Todesart (1)
- Toll-like receptor (1)
- Tonsillitis (1)
- Torque (1)
- Total hip arthroplasty (1)
- Touchscreen (1)
- Toxicité ovarienne (1)
- Training history (1)
- Transcatheter Aortic Valve Implantation (1)
- Transcription regulation (1)
- Transcriptional regulatory elements (1)
- Transcriptome analysis (1)
- Transfusion practice (1)
- Transfusionszwischenfall (1)
- Transgenic mice (1)
- Transitional cell carcinoma (1)
- Translation proteomics (1)
- Transportation (1)
- TraumaRegister DGU® (TR-DGU) (1)
- Treatment costs (1)
- Treatment effectiveness (1)
- Treatment modification (1)
- Treatment rates (1)
- Treg (1)
- Treg cell (1)
- Trend Analysis (1)
- Trypanosoma brucei (1)
- Tumor marker (1)
- Tumor microenvironment (1)
- Tumormarker (1)
- Tumormikromilieu (1)
- Type 2 diabetes (1)
- Type of death (1)
- ULK4 (1)
- UPPS (1)
- USP28 (1)
- UV/Vis spectroscopy (1)
- Ubiquitin (1)
- Ubiquitin ligase (1)
- Ubiquitinome (1)
- Ulcerative colitis (1)
- Ultra-rush protocol (1)
- Umfrage (1)
- Unc-51-like kinase (1)
- Uncertainty (1)
- Undergraduate education (1)
- Undergraduates (1)
- Unfälle (1)
- Upper body posture (1)
- Urothelial cancer (1)
- VHH (1)
- VIGALL (1)
- VIM (1)
- VLA4 (1)
- Vascular endothelial growth factor (VEGF) (1)
- Veins (1)
- Venous thromboembolism (1)
- Ventricular arrhythmia (1)
- Ventricular arrhythmias (1)
- Vespid venom allergy (1)
- Videorasterstereography (1)
- Viral infection (1)
- Vmem (1)
- Volume therapy (1)
- Volumetrie (1)
- Volunteer donor (1)
- Vorsorgeuntersuchung (1)
- Voxel-based morphometry (VBM) (1)
- Watertight Dural closure (1)
- Wearable cardioverter‐defibrillator (1)
- Western diet (1)
- Winter survival (1)
- Wissenschaftstheorie (1)
- Workplace ergonomics (1)
- Wound care (1)
- Wound healing (1)
- Wounds (1)
- Wundversorgung (1)
- YM155 (1)
- YWHAE (1)
- YWHAZ (1)
- Year of practical training (1)
- Yellow fluorescent protein (1)
- Zink (1)
- [18F]FET PET (1)
- abnormality detection (1)
- abuse (1)
- abuso (1)
- academic medicine (1)
- acetylation (1)
- acetylcholine (1)
- acetylcholinesterase (1)
- acid dentine lysate (1)
- acidosis (1)
- acoustic emission (1)
- acquired drug resistance (1)
- actin dynamics (1)
- action sounds (1)
- action-effect association (1)
- activated clotting time measurement (1)
- activities of daily life (1)
- activity-based benefits (1)
- acupuncture (1)
- acute coronary syndromes (1)
- acute decompensation (1)
- acute decompensation of cirrhosis (1)
- acute kidney injury (1)
- acute myeloid leukaemia (1)
- acute respiratory distress syndrome (1)
- acute-on-chronic liver failure (ACLF) (1)
- acute‐on‐chronic liver failure (1)
- adaptive cardiac remodelling (1)
- adaptive immunity (1)
- adenovirus (1)
- adhesion (1)
- adiabatic saturation (1)
- adipose-derived mesenchymal stem/stromal cells (1)
- adjuvante Krebstherapie (1)
- adolescentes (1)
- adoptive cancer immunotherapy (1)
- adrenoceptors (1)
- adult and elderly patients (1)
- advanced care planning (1)
- adverse events (1)
- aerobic exercise (1)
- affective disorder (1)
- affective disorders (1)
- affinity purification (1)
- aftercare structures (1)
- age (1)
- aggressiveness (1)
- air flow (1)
- alcohol use disorder (1)
- alcoholic hepatitis (1)
- algorithm (1)
- alirocumab (1)
- alkaloid (1)
- allergy (1)
- allocation (1)
- allogeneic donor (1)
- allogeneic hematopoietic stem cell transplantation (1)
- alpha power (1)
- alpha-galactosidase A deficiency (1)
- alpharetroviral vector (1)
- alternative matrices (1)
- alternative oxidase (1)
- amblyopia (1)
- amino acid PET (1)
- amlexanox (1)
- amyloid beta-peptides (1)
- amyotrophic lateral sclerosis (ALS) (1)
- anaemia walk-in clinic (1)
- anal cancer (1)
- anemia (1)
- angiography (1)
- angiokeratoma diffuse (1)
- animal (1)
- animal model (1)
- annual bleeding rate (1)
- anti-chronic myeloid leukemia (1)
- anti-diabetes (1)
- anti-inflammatory agents (1)
- anti-inflammatory drug (1)
- anti-inflammatory effects (1)
- anti-skin aging (1)
- anti-tumor activity (1)
- antibiotic treatment (1)
- antibody tests (1)
- anticoagulation (1)
- antigen (1)
- antigen processing and presentation (1)
- antigenic variation (1)
- antigens of infectious origin (1)
- antioxidant defense (1)
- antioxidants (1)
- antireflux surgery (1)
- antiresorptive agents (1)
- antiseizure (1)
- antiviral (1)
- antiviral peptide (1)
- anxiety disorder (1)
- aprotinin (1)
- aptamers (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- arousal (1)
- artesunate (ART) (1)
- artificial intelligence (1)
- ascites (1)
- aspiration (1)
- aspirin (1)
- asthma (1)
- asthma phenotypes (1)
- astrogliosis (1)
- asymptomatic (1)
- ataxia telangiectasia (1)
- athletes (1)
- atopy (1)
- attention module (1)
- attention-deficit/hyperactivity disorder (1)
- atypical MAPK kinase (1)
- auditory cortex (1)
- auditory fMRI (1)
- auditory prediction (1)
- auditory processing (1)
- autism (1)
- autism spectrum disorder (1)
- autograft (1)
- autoimmune diabetes (1)
- autoimmune polyglandular syndrome type 2 (1)
- autoimmune thyroiditis (1)
- autoreactivity (1)
- back pain diagnosis (1)
- bacteria (1)
- bacterial translocation (1)
- balloon pulmonary angioplasty (1)
- barbell training (1)
- basal insulin (1)
- behavioral adverse events (1)
- benchmark standards (1)
- berotralstat (1)
- biglycan (1)
- bio imaging (1)
- bio-enabling formulations (1)
- bioactive lipids (1)
- bioavailability (1)
- biobank (1)
- biological maturation (1)
- bioluminescence (1)
- biomarker study (1)
- biopsy naïve (1)
- bipolare Störung (1)
- bladder cancer (BCa) (1)
- bladder exstrophy-epispadias complex (1)
- blinatumomab (1)
- blood (1)
- blood flow recovery (1)
- blood flow restriction (1)
- blood loss (1)
- blood pressure (1)
- blood transfusion (1)
- blood-brain barrier (1)
- blood-cerebrospinal fluid barrier (1)
- body dysmorphic disorder (1)
- body plethysmography (1)
- bone healing (1)
- bone marrow (1)
- bone marrow mononuclear cells (1)
- bone tissue regeneration (1)
- brain (1)
- brain anatomy (1)
- brain function (1)
- brain metastases (1)
- brain shift (1)
- brain tumor (1)
- brain-derived neurotrophic factor (1)
- brainstem (1)
- broad-range qPCR (1)
- broadly neutralizing antibodies (1)
- bronchiolitis obliterans syndrome (1)
- buccal mucosal graft urethroplasty (1)
- bundle (1)
- butyrylcholinesterase (1)
- bypass (1)
- cART (1)
- cBioPortal (1)
- cHL (1)
- caesarean scar (1)
- caesarean section (1)
- calcium handling (1)
- calcium-sensor (1)
- cancer associated fibroblasts (1)
- cancer immunobiology (1)
- cancer information (1)
- cancer specific survival (1)
- candidemia (1)
- canine cancer (1)
- cannabidiol (1)
- cannabinoids (1)
- cannabis (1)
- capsaicin (1)
- carbapenem resistance (1)
- carbapenemase (1)
- carcinoma (1)
- cardiac (1)
- cardiac I/R injury (1)
- cardiac ischaemia‐reperfusion (1)
- cardiac magnetic (1)
- cardiac rehabilitation (1)
- cardiomyopathy (1)
- cardiothoracic surgery (1)
- career promotion (1)
- cartilage oligomeric matrix protein (1)
- catheter (1)
- cell and focal adhesion (1)
- cell death (1)
- cell motility (1)
- cell proliferation (1)
- cell survival (1)
- cell-free expression (1)
- cells (1)
- cellular immunology (1)
- cellular reaction (1)
- cellular therapy (1)
- central nervous system (1)
- ceramides (1)
- cerebellum (1)
- cerumen (1)
- cervical cancer (1)
- cetuximab-bevacizumab therapy sequence (1)
- changes immune activation (1)
- chaperones (1)
- chelation therapy (1)
- chemokine receptor 4 (1)
- chemokines (1)
- chemoprotection (1)
- chemotaxis (1)
- chemotherapeutics-treated (1)
- chemotherapy (1)
- chest trauma (1)
- children and adolescents (1)
- chloroplasts (1)
- cholestasis (1)
- cholesterol (1)
- cholinesterase (1)
- chronic coronary artery disease (1)
- chronic illness (1)
- chronic inflammation (1)
- chronic kidney disease (1)
- chronic liver disease (1)
- chronic low back pain (1)
- chronic metabolic acidosis (1)
- chronic myeloid leukemia (1)
- chronic thromboembolic pulmonary hypertension (1)
- chronic total occlusion (1)
- chronische Niereninsuffizienz (1)
- chronische metabolische Azidose (1)
- circulation (1)
- cisplatin resistance (1)
- cisplatin sensitivity (1)
- classical Hodgkin lymphoma (1)
- clinical (1)
- clinical benefit (1)
- clinical history (1)
- clinical immunology (1)
- clinical pathways (1)
- clinical study (1)
- clinically important restrictions and symptoms (1)
- cloacal malformation (1)
- clock genes (1)
- clopidogrel (1)
- clustering (1)
- co-crystallization (1)
- coagulation (1)
- cochlear implant (1)
- coffee (1)
- cognitive aging (1)
- cognitive decline (1)
- coherence (1)
- collagen type I (1)
- collagen-based matrix (1)
- collateral growth (1)
- colon carcinoma (1)
- colorectal cancer (1)
- colorectal cancer (CRC) (1)
- combined therapy (1)
- common genetic variation (1)
- common variants (1)
- comparative oncology (1)
- comparative pathology (1)
- competition fear (1)
- complement; patients (1)
- complex IV (1)
- computational biology (1)
- computational neuroimaging (1)
- computed tomography (1)
- computer vision (1)
- computer-aided diagnosis (1)
- computer-assisted (1)
- conduct disorder (1)
- confidence (1)
- consolidation treatment (1)
- contact heat evoked potentials (CHEPS) (1)
- contamination (1)
- contralateral delay activity (1)
- coping (1)
- coronary artery bypass surgery (1)
- coronary artery disease (1)
- coronavirus disease 2019 (1)
- cortex (1)
- cortex, gray matter (1)
- cortical folding (1)
- cortisol (1)
- cost-of-illness (1)
- covalent drugs (1)
- covalent inhibitors (1)
- cranberry (1)
- crepitation (1)
- crepitus (1)
- critical care (1)
- cross fitness (1)
- cryogenic electron microscopy (1)
- cyclin Y (1)
- cyclooxygenase 2 (1)
- cyclophosphamide (1)
- cytarabin (1)
- cytokine gene expression (1)
- cytokine storm (1)
- cytokine-induced killer cells (1)
- cytotoxic lymphocytes (1)
- dapagliflozin (1)
- data projection (1)
- day clinic (1)
- debris (1)
- decision making (1)
- decision support systems (1)
- decision-making (1)
- declaration of tobacco ingredients (1)
- decorin (1)
- deep fascia (1)
- deep mutational scanning (1)
- deep sedation (1)
- deferred treatment (1)
- delayed auditory feedback (1)
- delayed treatment (1)
- demineralized bone matrix (1)
- dendritic cells (1)
- dental assistants (1)
- dental emergency treatment (1)
- dentin adhesives (1)
- dentist (1)
- dentistry (1)
- dentists (1)
- depressive symptoms clusters (1)
- detoxification (1)
- deubiquitinating enzyme (1)
- development (1)
- diabetes (1)
- diabetes therapy (1)
- diagnosis (1)
- diagnostic algorithm (1)
- diagnostic test (1)
- diet (1)
- differential scanning fluorimetry (1)
- differentiation (1)
- diffusion tensor imaging (1)
- digital pathology (1)
- dihydroceramide (1)
- disease modelling (1)
- disease models (1)
- dislocation (1)
- distress (1)
- diuretics (1)
- docking studies (1)
- dog study (1)
- donor safety (1)
- drug abstinence (1)
- drug delivery (1)
- drug‐resistant epilepsy (1)
- drug–drug interaction (DDI) (1)
- dual BET/HDAC inhibitor (1)
- dual antiplatelet therapy (1)
- dysbiosis (1)
- dysferlin (1)
- dysferlinopathy (1)
- dysphagia (1)
- e-Health (1)
- e-health (1)
- e-scooter (1)
- eHealth (1)
- early detection (1)
- early myocardial damage (EMD) (1)
- early recognition (1)
- economic burden (1)
- effect mechanism (1)
- effectiveness (1)
- efficacy (1)
- effort (1)
- eight disorders (1)
- elderly patients (1)
- electric scooter (1)
- electroencephalography (EEG), EEG reference choices, event-related potentials (ERP), independent component analysis (ICA), pain research, contact heat evoked potentials (CHEPS) (1)
- electrolytic cleaning (1)
- electromyostimulation (1)
- electron transport chain (1)
- electronic adherence measurement (1)
- electrophilic fatty acids (1)
- elimination rate constant (1)
- embolization (1)
- emergence (1)
- empagliflozin (1)
- encoding (1)
- end of life care (1)
- endocannabinoids (1)
- endolysosomal system (1)
- endometrial cancer (1)
- endothelial cells (1)
- engagement (1)
- enterovirus (1)
- eph receptor tyrosin kinase family (1)
- ephrins (1)
- epidemics (1)
- epidemiology (1)
- epidermal growth factor receptor (1)
- epididymitis (1)
- epigenetic (1)
- epigenetics (1)
- epileptic encephalopathy (1)
- episodic memory (1)
- epithelial cells (1)
- epithelial-to-mesenchymal transition (EMT) (1)
- epithelial‐mesenchymal transition (1)
- epitope mapping (1)
- erectile dysfunction (1)
- ergonomics (1)
- erythropoietin (EPO) (1)
- escape mutations (1)
- essential tremor (1)
- ethyl pyruvate (1)
- euthymic (1)
- event logs (1)
- event-related potentials (1)
- event-related potentials (ERP) (1)
- everolimus (1)
- ex vivo model (1)
- ex-Gaussian analysis (1)
- executive function (1)
- exercise on prescription (1)
- exercise therapy (1)
- exercise treatment (1)
- exertion (1)
- experimental human pain models (1)
- experimental pain models (1)
- expertise (1)
- exposure (1)
- extensively drug-resistant (1)
- external fixation (1)
- external joint moments (1)
- extracellular matrix (1)
- extraction socket healing (1)
- extraversion (1)
- extremity (1)
- eye-tracking (1)
- fMRI (1)
- fMRT (1)
- face inversion effect (1)
- facial nerve functional outcome (1)
- factor VIII (FVIII) (1)
- familial infantile epilepsy (1)
- fasting (1)
- fatigue (1)
- feeder cells (1)
- femoral artery ligation (1)
- fenfluramine (1)
- ferric carboxymaltose (1)
- fibromodulin (1)
- fingolimod (1)
- fixation (1)
- focal cortical dysplasia (1)
- focal seizures (1)
- force transmission (1)
- formalin-fixed paraffin-embedded (FFPE) samples (1)
- fourth (1)
- fractional anisotropy (1)
- fractionation (1)
- fracture (1)
- fragile-X-associated tremor-ataxia syndrome (1)
- fragment-based design (1)
- fragment-based drug design (1)
- free gingival graft (1)
- frontal cortex (1)
- fronto-temporal lobar dementia (1)
- fronto-temporal-lobar-dementia (1)
- fully human (1)
- fumonisin B1 (1)
- functional connectivity (1)
- functional coupling (1)
- functional genetics (1)
- functional imaging (1)
- fundoplication (1)
- furcation involvement (1)
- further education (1)
- fusion (1)
- gap junction protein alpha 4-genotype (1)
- gas chromatography-mass spectrometry (1)
- gastric surgery (1)
- gastrocnemius (1)
- gastroesophageal reflux (1)
- gender (1)
- gender difference (1)
- gene regulation (1)
- gene therapy (1)
- genetic diversity (1)
- genetic generalized epilepsy (1)
- genetic phenotypes (1)
- genetic polymorphisms (1)
- genetic predisposition (1)
- genome-wide association study (1)
- geriatric patients (1)
- geriatrischer Ultraschall (1)
- germ cell tumors (1)
- glioblastoma cells (1)
- glucose (1)
- glucose metabolism (1)
- glycosaminoglycan (1)
- graft (1)
- graph theory (1)
- grey matter volume (1)
- growth inhibition (1)
- gyrification (1)
- haematologic malignancies (1)
- haemophilia A (1)
- haemophilic arthropathy (1)
- haemostasis (1)
- harmine (1)
- health care (1)
- health-related quality of life (1)
- healthcare workers (1)
- healthy subjects (1)
- hearing nerve (1)
- heat stress (1)
- hemadsorption (1)
- hematoma (1)
- hematopoietic stem and progenitor cells (1)
- heme-regulated inhibitory kinase (1)
- hemiplegic migraine (1)
- hemispherotomy (1)
- hemodynamic (1)
- hemodynamic instability (1)
- hemophilia A (1)
- hemorrhage (1)
- hemorrhagic transformation (1)
- hepatic fibrosis (1)
- hepatic stellate cells (1)
- hepatitis C virus (1)
- hepatitis C virus (HCV) (1)
- hepatitis E (1)
- hepatocellular cancer (1)
- hepatocyte nuclear factor 4α (1)
- herb induced liver injury (1)
- hereditary angioedema (1)
- hereditary dystopic lipidosis (1)
- herpes simplex virus (1)
- hiPSC (1)
- high dimensional complex data (1)
- high surgical risk (1)
- high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (1)
- high-throughput nucleotide sequencing (1)
- high-throughput screening (1)
- higher education (1)
- high‐mobility group box‐1 (HMGB1) (1)
- hip joint (1)
- histological outcomes (1)
- histological technic (1)
- histomorphometry (1)
- histone modifications (1)
- histoplasmosis (1)
- home-based (1)
- homeostasis (1)
- hospitalization (1)
- host-pathogen interaction (1)
- huCAR19 (1)
- human decellularized dermis (1)
- human genomics (1)
- human lymph node (1)
- human sera (1)
- humanized mice (1)
- humanized mouse model (1)
- hybrid abutment (1)
- hyperarousal (1)
- hyperexcitability (1)
- hyperglycemia (1)
- hyperhomocysteinemia (1)
- hyperkalemia (1)
- hypertension (1)
- hypoglycaemia (1)
- hypophosphataemia (1)
- iDILI (1)
- iDrug induced liver injury (1)
- image-based risk modelling (1)
- imaging (1)
- immun (1)
- immune checkpoint (1)
- immune checkpoint inhibitors (1)
- immune defense (1)
- immune evasion (1)
- immune response (1)
- immuno-oncotherapy (1)
- immunoprecipitation (1)
- improvement in quality of life (1)
- in vitro (1)
- in vitro in vivo extrapolation (IVIVE) (1)
- in vitro models (1)
- in vivo model of critical size defects (1)
- independent component analysis (ICA) (1)
- indoor air pollution (1)
- induced membrane (1)
- induction chemotherapy (1)
- inertial motion capture (1)
- infant (1)
- infants (1)
- infectious diseases (1)
- inferior frontal gyrus (1)
- inflammatory bowel disease (1)
- inflammatory cytokines (1)
- inflammatory markers (1)
- inhibitors (1)
- injury (1)
- innate and adaptive immune response (1)
- inner ear therapy (1)
- inositol signaling (1)
- insomnia (1)
- instructional interventions (1)
- insulin resistance (1)
- insulitis (1)
- integrated stress response (1)
- inter-individual variability (1)
- interaction partners (1)
- interactome (1)
- interferon type III (1)
- interleukin-6 (1)
- interleukins (1)
- intervertebral disc (IVD) (1)
- intrinsic drug resistance (1)
- invasion (1)
- invasive mold infection (1)
- inverse dynamics (1)
- investigational (1)
- inflammation (1)
- iron deficiency (1)
- iron overload versus deprivation (1)
- iron supplements (1)
- irradiation (1)
- ischaemia (1)
- isolation (1)
- joint bleeding (1)
- joint loading (1)
- joint moments (1)
- juvenile brain lesion (1)
- kaatsu training (1)
- kallikrein inhibitor (1)
- keratinized mucosa (1)
- ketogenic (1)
- ketone body (1)
- kidney formation (1)
- kidney function (1)
- kinase inhibitors (1)
- kinetic fingerprint (1)
- knee adduction moment (1)
- knee joint (1)
- knee noise (1)
- knee sound (1)
- knockout (1)
- kynureninase (1)
- kynurenine (1)
- lacosamide (1)
- lactate (1)
- lamotrigine (1)
- latent class analysis (1)
- left ventricular non-compaction (1)
- left ventricular trabeculation (1)
- leg alignment (1)
- lentiviral vector (1)
- leukocytes (1)
- leukopenia (1)
- levetiracetam (1)
- lichen extracts (1)
- light microscopy (1)
- limb girdle muscular dystrophy type 2B (LGMD2B) (1)
- lipid (1)
- lipid raft (1)
- lipidomic analysis (1)
- lipocalin-2 (1)
- lipoxin A4 (1)
- liquid PRF (1)
- liquid chromatography–mass spectrometry (1)
- liver fibrosis (1)
- liver transplantation (1)
- liver transplantation center (1)
- local inflammation (1)
- local-field potentials (1)
- locus coeruleus (1)
- long reads (1)
- long-term outcome (1)
- long-term potentiation (1)
- long-term prophylaxis (1)
- long-term success (1)
- long-term survival (1)
- longevity (1)
- longitudinal follow-up after epilepsy surgery (1)
- loss (1)
- low doses (1)
- low-density lipoprotein cholesterol (1)
- low-risk (1)
- lower extremity arterial disease (1)
- lumbago (1)
- lumbalgia (1)
- lumbar spinal canal stenosis (1)
- lumican (1)
- lung disease phenotype (1)
- lymphoma (1)
- lysosomes (1)
- mHealth (1)
- mRNA and protein expression (1)
- macrophage polarization (1)
- magentoencephalography (MEG) (1)
- magnetic resonance imaging (1)
- magnetic resonance imaging of the brain (1)
- maintenance (1)
- major adverse cardiovascular events (1)
- major depression (MD) (1)
- major depressive disorder (MDD) (1)
- mammary carcinomas (1)
- management (1)
- mandatory reporting (1)
- maternal tobacco smoke (1)
- mathematical modeling (1)
- matrikine (1)
- matrix metalloproteinases (1)
- mean diffusivity (1)
- measurement properties (1)
- mechanism of action (1)
- mechanistic oral absorption modeling (1)
- medical training (1)
- medication adherence rate (1)
- melanoma (1)
- membrane potential (1)
- membrane repair (1)
- memory (1)
- memory and learning tests (1)
- mental distress (1)
- mesenchymal stem cell (1)
- mesenchymal stromal/stem cells (1)
- meta-analysis (1)
- metabolic reprogramming (1)
- metabolic syndrome (1)
- metabolism (1)
- miR-142-3p (1)
- miR-181 (1)
- miR-6862-5p (1)
- mice (1)
- micro CT (1)
- microdialysis (1)
- microlesions (1)
- microsurgical treatment (1)
- mid-IR spectroscopy (1)
- migration and invasion (1)
- mini gastric bypass (1)
- minimal clinically important difference (1)
- minimal residual disease (1)
- mir-148a (1)
- mitochondrial antiviral signaling protein (MAVS) (1)
- mitochondrial dysfunction (1)
- mitochondrial metabolism (1)
- mitochondrial morphology (1)
- mitochondrial respiration (1)
- mixed lineage kinase domain-like (1)
- model psychosis (1)
- molecular adaptation (1)
- molecular biology (1)
- molecular dynamics (1)
- molecular switch (1)
- molecular tumor board (1)
- molecular typing (1)
- monoamine oxidase A (1)
- monocyte chemotactic protein 1 (MCP-1) (1)
- mononuclear cell (1)
- monotype abutment (1)
- monsoon (1)
- morphogenesis (1)
- morphological filtering (1)
- morphometry (1)
- mortality (1)
- mortality analysis (1)
- mortality risk (1)
- motivation (1)
- motor control exercise (1)
- mouse (1)
- mouse model (1)
- mouse models (1)
- movement pattern (1)
- movement profile (1)
- multi-network (1)
- multi-task learning (1)
- multimodal complex treatment (1)
- multimorbidity (1)
- multiple trauma (1)
- multitarget drugs (1)
- murine model (1)
- muscle (1)
- muscle disease (1)
- muscular dystrophy (1)
- musculoskeletal (1)
- musculoskeletal inflammation (1)
- musculoskeletal pain (1)
- musculoskeletal radiographs (1)
- mutational antigenic profiling (1)
- myocardial perfusion (1)
- myofascial (1)
- myofascial chains (1)
- myofascial force transmission (1)
- myoferlin (1)
- myotonia congenita (1)
- nanobodies (1)
- nanodiscs (1)
- narrative content analysis (1)
- narrative economics (1)
- narrative medicine (1)
- natriuretic peptide (1)
- natural cytotoxicity (1)
- natural killer cell (1)
- naturalistic sample (1)
- necrosis (1)
- neglect (1)
- negligencia (1)
- neonate (1)
- neonates (1)
- neonatology (1)
- neoplasms (1)
- nerve (1)
- nerve injury (1)
- networks (1)
- neurexin (1)
- neurogenesis (1)
- neurological impairment (1)
- neuronal maturation (1)
- neuropathic pain (1)
- neuropathy (1)
- neurophysiology (1)
- neuropsychology (1)
- neuroticism (1)
- neurovascular bundle preservation (1)
- neutralization (1)
- neutralizing antibodies (1)
- newborn (1)
- newborn screening (1)
- next-generation sequencing (1)
- nitroalkylation (1)
- niños (1)
- non-coding RNAs (1)
- non-malignant hematological diseases (1)
- noninterventional (1)
- noninvasive blood glucose analysis (1)
- nonspecific (1)
- non‐selective beta‐blocker (1)
- nuclear receptor (1)
- nucleotide analogue (1)
- nucleotide metabolism (1)
- nutrient endocytosis (1)
- observational study (1)
- occupational health (1)
- off-pump surgery (1)
- oncogenic signaling (1)
- oncological gastrectomy (1)
- oncological outcome (1)
- one anastomosis gastric bypass (1)
- online information processing (1)
- online reasoning patterns (1)
- online survey (1)
- operative (1)
- optical coherence tomography (1)
- orientation (1)
- orthopaedic patients (1)
- oscillations (1)
- osteoarthritis (1)
- osteogenic sarcoma cells (1)
- osteoimmunological changes (1)
- otoferlin (1)
- ouabain (1)
- outcomes (1)
- outside-in signaling (1)
- ovary (1)
- overweight (1)
- own-face perception (1)
- oxidised lipids (1)
- pacemaker implantation (1)
- pain research (1)
- pain screening (1)
- pancreatic ductal adenocarcinoma (1)
- pancreatic surgery (1)
- parkinson’s disease (1)
- passive immunization (1)
- passive smoke (1)
- patient centered care (1)
- patient preferences (1)
- patient questionnaire (1)
- patient triage (1)
- patient-reported outcome measure (1)
- patient’s decree (1)
- patient’s perspective (1)
- paxilline (1)
- peanut allergy (1)
- pediatric (1)
- pediatric epilepsy (1)
- pediatric eye screening (1)
- pediatrics (1)
- pelvic packing (1)
- pelvic ring fracture (1)
- peptide antibiotics (1)
- peptide transport (1)
- perceptual closure (1)
- performance assessment (1)
- performance tests (1)
- peri-implantitis (1)
- pericytes (1)
- periimplantitis (1)
- perineurium (1)
- periodontal disease progression (1)
- periodontal risk assessment (1)
- periodontal risk calculator (1)
- periodontal risk factors (1)
- perioperative outcome (1)
- perioperative period (1)
- peripheral arterial disease (1)
- peri‐implantitis (1)
- peri‐implantitis therapy (1)
- person-oriented approach (1)
- personalised therapy (1)
- pet rabbit (1)
- phage (1)
- phage display (1)
- phage lysis proteins (1)
- phage therapy (1)
- pharmacogenetics (1)
- pharmacokinetics/pharmacodynamics (PK/PD) (1)
- pharmacoresistance (1)
- phenotype/genotype relation (1)
- phenotypic spectrum (1)
- phosphate (1)
- phosphorus (1)
- photothermal detection (1)
- physical activity counseling (1)
- physical training (1)
- physiologically based pharmacokinetic (PBPK) modeling (1)
- pigs (1)
- placenta (1)
- planimetric measurement (1)
- plasma (1)
- plasma-derived factor VIII concentrate, prophylaxis (1)
- plasmid (1)
- plasticity (1)
- pneumocystis (1)
- point of care (1)
- polo-like kinase 1 (1)
- poly(A)-tail (1)
- polylactide (1)
- polyomavirus (1)
- polypharmacology (1)
- polysomnography (1)
- population dynamics (1)
- portosystemic shunt (1)
- positive organizational e-interventions (1)
- post-caesarean uterus (1)
- post-exercise hypotension (1)
- post-liver transplantation management (1)
- post-traumatic (1)
- posterior fossa tumor (1)
- postmonsoon (1)
- postoperative complications (1)
- postoperative delirium (1)
- posttransnational modification (1)
- posttraumatic inflammation (1)
- posttraumatic stress disorder (1)
- ppi1 (1)
- pre-school asthma (1)
- precision weighting (1)
- prediabetes (1)
- predictive coding (1)
- preschool health examination (1)
- primary biliary cirrhosis (1)
- primary sclerosing cholangitis (1)
- proanthocyanidin (1)
- process mining (1)
- prognostic marker (1)
- prognostic value (1)
- proinflammatory microenvironment (1)
- promotion index (1)
- prophylactic vaccine (1)
- prophylaxis (1)
- proprotein convertase subtilisin/kexin type 9 inhibition (1)
- prostate volume (1)
- protease inhibitor (1)
- protein quality control (1)
- protein turnover (1)
- proteoglycan (1)
- proximal tubule (1)
- pseudokinase (1)
- psoriatic arthritis (1)
- psychischer Stress (1)
- psycho-oncology (1)
- psychology (1)
- psychosocial adjustment (1)
- public health department (1)
- public mental health (1)
- pupillometry (1)
- qRT-PCR (1)
- qRT-PCR detection (1)
- quality (1)
- quality of care (1)
- quantitative MRT (1)
- quantitative proteomics (1)
- quantitative sensory testing (1)
- quantum cascade laser (QCL) (1)
- questionnaire (1)
- radiation oncology (1)
- radical prostatectomy (1)
- radioimmunotherapy (1)
- radiomic (1)
- radiosensitization (1)
- radiotherapy (1)
- radon therapy (1)
- range of motion (1)
- rare disease (1)
- rare diseases (1)
- rare variants (1)
- rat femur critical size defect (1)
- rct (1)
- re-osseointegration (1)
- re-transplantation (1)
- reaction (1)
- reaction time (1)
- readmission rates (1)
- receptor for advanced glycation end product (RAGE) (1)
- recombinant vesicular stomatitis virus‐Zaire ebolavirus (1)
- regioisomers (1)
- regulatory T cell (1)
- regulatory T cells (1)
- regulatory T helper cells (1)
- rehabilitation (1)
- relapsing fever (1)
- relaxometry (1)
- reliable change index (1)
- remodelling (1)
- renal cell cancer (1)
- renal transplantation (1)
- renal tubular cells (1)
- renal tubular epithelial cells (1)
- repeat biopsy (1)
- repeated (1)
- reperfusion injury (1)
- repetition suppression (RS) (1)
- repetitive firing (1)
- replicative fitness (1)
- repsonse process patterns (1)
- requirements analysis (1)
- resective surgery (1)
- resistance (1)
- resistance mutation (1)
- resolution (1)
- resolution of inflammation (1)
- resonance (1)
- resting EEG (1)
- reticulocyte haemoglobin (1)
- retinal (1)
- retinoid X receptor (1)
- rhabdomyosarcoma (1)
- rheumatoid arthritis (1)
- rhodopsin (1)
- ridge preservation (1)
- right heart catheter (1)
- risk factor (1)
- risk score (1)
- rotational thromboelastometry (1)
- sCD163 (1)
- sCD206 (1)
- safety (1)
- sarcoma (1)
- sarcopenia (1)
- scanner noise (1)
- scavenger receptor (1)
- sciatic nerve (1)
- second-hand smoke (1)
- seizures (1)
- selection (1)
- selective autophagy receptor (1)
- self‐expanding (1)
- sensorimotor (1)
- sensory coding (1)
- sensory neuropathy (1)
- serine protease (NS3-4A) (1)
- serology (1)
- serum (1)
- severe acute respiratory syndrome coronavirus (1)
- severe asthma (1)
- severe congenital neutropenia (1)
- severely injured (1)
- sex (1)
- shock filter (1)
- short linear motifs (SLiMs) (1)
- shrinkage (1)
- shunt (1)
- sialitis (1)
- sickle cell anemia (1)
- signaling (1)
- skeletal muscle (1)
- sleepiness (1)
- small molecule inhibitor (1)
- smoking in pregnancy (1)
- social determinants (1)
- social isolation (1)
- socioeconomic status (1)
- soft drinks (1)
- soluble MICA (1)
- sonography (1)
- sparse imaging (1)
- spatial learning (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- specific learning disorder (1)
- sphingosine 1-phoshate (1)
- sphingosine 1-phosphate antagonistst/inhibitors (1)
- sphingosine 1-phosphate metabolism (1)
- sphingosine 1-phosphate signaling (1)
- sphingosine kinase (1)
- sphingosine-1-phosphate (1)
- spiral ganglion cells (1)
- spirochetes (1)
- spirometry (1)
- spontaneous portosystemic shunt (1)
- sports (1)
- sports performance (1)
- spreading (1)
- squamous cell carcinoma (1)
- stabilization (1)
- standardization (1)
- standardized regression-based change norms (1)
- starvation (1)
- steady-state condition (1)
- stearic acid (1)
- steatosis (1)
- stem cell transplantation (1)
- stem cells (1)
- steroid control of aging (1)
- stiripentol (1)
- strength training (1)
- streptozotocin (1)
- stress response (1)
- stretching (1)
- stromal-derived factor 1 (1)
- structural biology (1)
- structure constraints (1)
- structure–activity relationships (1)
- substance abuse disorder (1)
- suicidality (1)
- suicide (1)
- supervision (1)
- supervisión (1)
- supplementary motor area (1)
- supportive periodontal therapy (1)
- suprapubic catheter (1)
- surfactant (1)
- surgical margin (1)
- surgical procedures (1)
- swallowing (1)
- sympathicus (1)
- symptoms (1)
- synaesthesia (1)
- synaptic plasticity (1)
- synaptic scaling (1)
- synergistic interaction (1)
- synovium (1)
- synuclein (1)
- systematic biopsy (1)
- systematic scoping review (1)
- tailored treatment schedule (1)
- talent development (1)
- talent identification (1)
- targeted biopsy (1)
- targeted therapy (1)
- targeting (1)
- tauopathies (1)
- tauopathy (1)
- tea (1)
- telemedicine (1)
- tension type headache (1)
- terapia cognitivo conductual enfocada en trauma (1)
- test protocol (1)
- testis (1)
- tetrahydrocannabinol (1)
- thalassemia (1)
- therapy monitoring (1)
- therapy resistance (1)
- thiazolidine and perhydrothiazine derivatives of aldophosphamide and I-aldophosphamide (1)
- third (1)
- three-dimensional analysis (1)
- three‐dimensional analysis (1)
- thrombopenia (1)
- thrombotic microangiopathy (1)
- thrombotic thrombocytopenic purpura (1)
- tick (1)
- time-lapse imaging (1)
- tissue slice co-cultures (1)
- tobacco control (1)
- tobacco products (1)
- toc64 (1)
- tooth (1)
- tooth autotransplantation (1)
- tooth loss (1)
- tooth transplantation (1)
- total hip replacement (1)
- tracking (1)
- traditional Chinese medicine (1)
- traffic accident (1)
- trafficking (1)
- training effects (1)
- transcatheter aortic valve replacement (TAVR) (1)
- transcatheter aortic valve replacement (TAVR), aortic valve stenosis (AS) (1)
- transcriptomics (1)
- transferrin (1)
- transforming growth factor-β (1)
- transfusion (1)
- transgenically augmented CAR NK cell (1)
- transjugular intrahepatic portosystemic shunt (TIPS) (1)
- transjugular portosystemic intrahepatic (1)
- translational medical research (1)
- translational medicine (1)
- translational reseach (1)
- translatome (1)
- translocon (1)
- transmission routes (1)
- transportation (1)
- transrectal prostate biopsy (1)
- transurethral catheter (1)
- transverse axis (1)
- trauma (1)
- trauma registry (1)
- traumafocused cognitive behavioural therapy (1)
- traumatic brain injury (1)
- traumatic brain injury (TBI) (1)
- traumaticbraininjury(TBI) (1)
- treatment-related changes (1)
- trigeminal pain (1)
- trophoblast (1)
- tryptophan (1)
- tumor adhesion (1)
- tumor angiogenesis (1)
- tumor hypoxia (1)
- tumor infiltrating lymphocytes (1)
- tumor invasion (1)
- tumor migration (1)
- tumor pain (1)
- tumor perfusion (1)
- tumor stroma (1)
- tumor xenograft (1)
- tumor-associated macrophages (1)
- type 1 diabetes (1)
- type 2 diabetes (1)
- type-1-diabetes (1)
- tyrosinase inhibitor (1)
- tyrosine kinase inhibitor (1)
- tyrosine kinase inhibitors (1)
- tyrosine kinase inhibitors. (1)
- tyrosine kinase receptor signaling (1)
- ubiquitin (1)
- ubiquitin hydrolase (1)
- ubiquitin receptor (1)
- ultrasonic cleaning (1)
- ultrasound (1)
- unanticipated (1)
- unconventional T cell (1)
- unilateral hip osteoarthritis (1)
- unspecific low back pain (1)
- urethral stricture (1)
- urethroplasty (1)
- urinary tract development (1)
- uterine wall (1)
- vaccination (1)
- vacuuming (1)
- valproic acid (1)
- value frameworks (1)
- variability (1)
- variable silent delay (1)
- vascular endothelial growth factor receptor (1)
- vascular surgery (1)
- vector (1)
- venous occlusion (1)
- ventralis intermedius nucleus (1)
- venturesomeness (1)
- vertical transmission (1)
- vestibular schwannoma (1)
- vibroarthrographic (1)
- vigilance (1)
- vincristine (1)
- viral infection (1)
- viruses (1)
- vision (1)
- visual attention (1)
- visual priming (1)
- vitamin B deficiency (1)
- vitamin B12 (1)
- vitamin D (1)
- vitamin D deficiency (1)
- vitamin D metabolites (1)
- vitamin k antagonists (1)
- volatile sedation (1)
- von Willebrand diseases (1)
- waiting time (1)
- walking (1)
- weakly supervised learning (1)
- weight loss (1)
- wheezing (1)
- white matter hyperintensity (1)
- whole abdominal radiotherapy (1)
- whole genome sequencing (1)
- whole slide image (1)
- working memory (1)
- workplace health promotion (1)
- xenograft (1)
- yellow flags (1)
- youth football (1)
- zebrafish development (1)
- Öffentlichkeit (1)
- Übertragungswege (1)
- ΔNp63 (1)
- α-amylase inhibitor (1)
- α-particles (1)
- γ‐H2AX (1)
- fibrogenesis (1)
- fingolimod (1)
Institute
- Medizin (732)
- Biochemie, Chemie und Pharmazie (41)
- Biowissenschaften (22)
- Frankfurt Institute for Advanced Studies (FIAS) (21)
- Sportwissenschaften (21)
- MPI für Hirnforschung (14)
- Präsidium (14)
- Biochemie und Chemie (11)
- Psychologie und Sportwissenschaften (11)
- Ernst Strüngmann Institut (9)
Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.
Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
Einleitung: Die Obduktion nimmt einen wichtigen Stellenwert in der Medizin ein, da sie nicht nur der Klärung der Todesart und -ursache eines Verstorbenen dient, sondern auch zum Verständnis der Pathophysiologie von Erkrankungen beiträgt. In diesem zweiten Teil der Studie wurden aktuelle Normwerte für das Gewicht für die folgenden adulten Organe entwickelt: Leber, Lunge, Milz, Nieren. Zudem wurden Zusammenhänge zwischen Organgewichten und der Todesart untersucht. Material und Methoden: Die im Dreijahreszeitraum von 2011 bis 2013 im Institut für Rechtsmedizin in Frankfurt am Main durchgeführten Obduktionen wurden retrospektiv ausgewertet. Die statistischen Berechnungen erfolgten mithilfe des Programmes „BiAS. für Windows“ (epsilon-Verlag GbR, Hochheim-Darmstadt, Deutschland). Ergebnisse: Folgende Normwerte bzw. -bereiche wurden an der Studienpopulation erhoben: Leber 1047,0–2740,0 g (♂, n = 191) bzw. 749,0–2182,0 g (♀, n = 115), linke Lunge 230,0–840,0 g (♂, n = 119) bzw. 186,8–891,3 g (♀, n = 97), rechte Lunge 249,3–1005,8 g (♂, n = 116) bzw. 215,3–907,5 g (♀, n = 100), Milz 55,0–373,2 g (♂, n = 306) bzw. 50,0–355,0 g (♀, n = 204), linke Niere 110,0–255,0 g (♂, n = 258) bzw. 71,8–215,0 g (♀, n = 137), rechte Niere 100,0–270,0 g (♂, n = 266) bzw. 75,0–212,1 g (♀, n = 140). Für die am stärksten mit Organgewichten korrelierenden Körpermaße, nämlich Body-Mass-Index (BMI), Körperoberfläche („body surface area“, BSA) und Körpergewicht, wurden nach Subgruppen getrennte Normwerte ermittelt. Ein signifikanter Unterschied des Organgewichtes je nach Todesart lag bei Männern bei der Milz und bei den Nieren vor. Bei Frauen war bei keinem der Organe ein von der Todesart abhängiger signifikanter Gewichtsunterschied feststellbar. Außerdem wurden Organindizes entwickelt, mittels derer der Anwender berechnen kann, ob ein Organgewicht, Körpermaßen bzw. Alter entsprechend, im Normbereich liegt. Diskussion: Organgewichte unterliegen wie Körpermaße einem säkularen Trend, welcher jedoch nicht linear und für jedes Organ individuell verläuft. Für die Auswertung von Organgewichten im Rahmen der Obduktion werden deshalb aktuelle, an einer vergleichbaren Population erhobene Normtabellen benötigt. Bei deren Erstellung können sowohl Fälle mit natürlichem als auch mit nichtnatürlichem Tod unter weitestgehendem Ausschluss pathologisch veränderter Organe herangezogen werden.
In Deutschland erkranken pro Jahr bis zu 12.000 Menschen neu an Leukämie. Leukämie ist eine schwere onkologische Erkrankung, bei der reifes Knochenmarkgewebe in Folge von Mutationen unreifer und defekter Vorläuferzellen (leukämischen Blasten) verdrängt wird. Dies führt zu einer zunehmend eingeschränkten Blutbildung. Akute Leukämieformen können unbehandelt innerhalb von wenigen Wochen zum Tode führen und erfordern deshalb eine umgehende Diagnostik sowie einen raschen Therapiebeginn. Heilungschancen bestehen dann, wenn durch die Transplantation von gesunden hämatopoetischen Stammzellen (HSZT) das erkrankte Knochenmark ausreichend ersetzt wird. Leider sind Abstoßungsreaktionen des Spendermaterials (engl.: Graft-versus-Host-Disease, GvHD) keine Seltenheit.
Natürliche Killerzellen (NK-Zellen) stellen die kleinste Lymphozytenpopulation im menschlichen Blut dar und werden dem angeborenen Immunsystem zugerechnet. Sie wurden erstmals 1975 durch die Forscher Kiessling, Klein et al. entdeckt.17 Aufgrund ihrer Fähigkeit bestimmte Tumorzellen in vitro zu töten, wächst das Interesse an der Erforschung ihrer aktivierenden und inhibierenden Oberflächenrezeptoren. Die Killer-Zell-Immunoglobulin-ähnlichen Rezeptoren (KIRs) bilden dabei eine besonders diverse NKZell-Rezeptorfamilie. Lokalisiert auf Chromosom 19 liegen bis zu 17 hochpolymorphe KIRGene. Die genetische Ausstattung und Oberflächenexpression variiert von Individuum zu Individuum und bildet die Voraussetzung für die vorhandene Diversität KIR-exprimierender NK-Zellen. NK-Zellen besitzen die Fähigkeit, Gewebezellen in „körpereigen“ oder „fremd“ zu kategorisieren. Inhibitorische Killer-Immunoglobulin-ähnliche Rezeptoren (iKIR) nutzen dazu HLA-Klasse-I-Proteine (MHC-I) auf der Oberfläche gesunder Zellen. Diese schützen sie vor einem zytotoxischen NK-Zell-Angriff. NK-Zellen durchlaufen im Vorfeld einen komplexen Ausbildungssprozess48, an dessen Ende lizensierte Effektorzellen stehen. Diese können mittels gezielter Zytolyse krebstransformierte, zellulär-gestresste, sowie viralinfizierte Zellen im intakten Organismus erkennen und abtöten.
Die Spenderauswahl ist ein wichtiger Faktor für den Erfolg einer Stammzelltransplantation. Infundierte Spender NK-Zellen schützen das Transplantat, indem sie als wirksame Effektorzellen verbleibende Leukämiezellen aktiv eliminieren. Diese wünschenswerte Nebenwirkung wird als Graft-versus-Leukämie (GvL)-Effekt bezeichnet. Ruggeri et al. konnte zeigen, dass insbesondere Transplantationsstrategien, die auf KIR-Ligand-Fehlpaarungen (engl.: KIR-HLA-mismatch) basieren, zu weniger Rückfällen, weniger GvHD und einem besseren Gesamtüberleben bei Patienten mit akuter myeloischer Leukämie (AML) nach HSZT führt. Der KIR-HLA-mismatch wird mittlerweile aufgrund ausreichender Datenlage bei der Auswahl passender NK-Zell-Spender berücksichtigt und die Untersuchung auf die An- bzw. Abwesenheit bestimmter KIR-Gene (Haplotypisierung)
mittlerweile neben der HLA-Typisierung standardisiert in vielen Instituten durchgeführt. Daneben finden sich immer mehr Hinweise dafür, dass bereits einzelne allelische Polymorphismen innerhalb der KIR-Gene einzelner Spender großen Einfluss auf die Funktionalität ihrer NK-Zellen nehmen. Die allelische Subtypisierung von KIRs stellt aufgrund stetig steigender Zahlen neu entdeckter Allele eine Herausforderung dar. Im Januar 2019 sind für KIR2DL1 bereits 66 Allele beschrieben und für KIR3DL1 sogar 150 Allele in der Immuno Polymorphism Database (IPD) hinterlegt.
Die vorliegende Arbeit präsentiert ein praktikables Subtypisierungsverfahren, um allelische Unterschiede innerhalb der Genloci der NK-Zell-Rezeptoren KIR2DL1 und KIR3DL1 zu untersuchen. Für die Experimente wurden NK-Zellen von 20 gesunden Spendern funktionell untersucht und KIR-genetisch analysiert. Ziel war es innerhalb dieser Individuen besonders potente NK-Zellspender zu identifizieren und diese anhand bestimmter Polymorphismen und/ oder der Expression von KIR-Rezeptoren zu charakterisieren. Bei der Subtypisierung der KIR2DL1-Gene konnten 12 verschiedene, bereits bekannte KIR2DL1-Allele bestimmt werden. Die häufigsten Allele waren dabei 2DL1*001, *00201, *00302, *00401 und *00403. 5 der 20 Spender konnten der funktionell hochpotenten R245–Allelgruppe (AS Arginin an Pos. 245) zugeordnet werden. Spender 13 zeigte bei negativer KIR2DL1-SSP eine vermeintlich neue Nullallelvariante, Spender 20 eine neue heterozygote Variante, resultierend in der Kombination eines Arginin mit Alanin (R/A). Bei der allelischer Subtypisierung von KIR3DL1 wurden 25 verschiedene, bereits bekannte KIR3DL1-Allele bei den 20 Spendern bestimmt. Spender 2 zeigt zahlreiche, vorwiegend homozygote Abweichungen von der Referenzfrequenz, insbesondere im Exon 5, und wurde als neue Allelvariante gewertet. Die häufigsten KIR3DL1-Allele waren 3DL1*00101, *002 und *087. Mittels durchflusszytometrischer Messung konnte gezeigt werden, dass das bekannte Nullallel 3DL1*0040101 bei Spender 14 zu keiner Oberflächenexpression des Rezeptors führt215, während Spendern 11 und 16 als Träger des 3DL1*00402 Allels eine Oberflächenexpression von rund 10% präsentierten. Um die Spender NK-Zellen der gebildeten Gruppen funktionell zu testen, wurden die NK-Zellen experimentell mit vier unterschiedlichen transgenen L721.221-Zelllinien stimuliert. Die funktionelle Potenz der
gespendeten NK-Zellen wurde mittels eines CD107-Degranulationsassays gemessen. Nach aktuellem Stand sind nur für 53 der 150 KIR3DL1-Allele die allelischen Expressionsmuster untersucht worden. Dies bedeutet im Umkehrschluss, dass für rund 65% der bekannten KIR3DL1-Allele Daten zur Funktionalität fehlen, und damit der größte Anteil der ermittelten Allele von 6 Spendern der unknown-Expression (KIR3DL1u/u) Gruppe zugeordnet wurde. Die Spender 4 und 19 der high-Expressiongruppe (KIR3DL1h/h), sowie Spender 5 und 10 der KIR3DL1u/u-Gruppe mit den Allelen 3DL1*053, *087, *109 und Spender 2 als Träger zweier neuer KIR3DL1-Allele, zeigten in toto die besten funktionellen Ergebnisse in den Experimenten gegen die verwendete B-lymphoblastoide L721.221-Zellinien. Die Ergebnisse der vorliegenden Arbeit zeigen, dass bei der Spenderauswahl für NK-Zellbasierten Immuntherapie neben der Genotypisierung die allelische KIR-Subtypisierung als wertvolles Werkzeug entschiedener berücksichtigt werden sollte. Dafür ist es jedoch notwendig weiter an KIR-Subtypisierung und -Gruppierung Strategien zu arbeiten, um Natürlichen Killerzellen Wege in die klinische Standardpraxis zu bahnen.
Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promising pre-clinical results in the therapy of several inflammatory diseases. Since inflammation is a main driver of disease progression in alcoholic hepatitis, we investigated the impact of endogenous ALOX15-dependent lipid mediators and exogenously applied LXA4 on AH development. A mouse model for alcoholic steatohepatitis (NIAAA model) was tested in Alox12/15+/+ and Alox12/15−/− mice, with or without supplementation of LXA4. Absence of Alox12/15 aggravated parameters of liver disease, increased hepatic immune cell infiltration in AH, and elevated systemic neutrophils as a marker for systemic inflammation. Interestingly, i.p. injections of LXA4 significantly lowered transaminase levels only in Alox12/15−/− mice and reduced hepatic immune cell infiltration as well as systemic inflammatory cytokine expression in both genotypes, even though steatosis progressed. Thus, while LXA4 injection attenuated selected parameters of disease progression in Alox12/15−/− mice, its beneficial impact on immunity was also apparent in Alox12/15+/+ mice. In conclusion, pro-resolving lipid mediators may be beneficial to reduce inflammation in alcoholic hepatitis.
Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia and immunodeficiency. The neurological decline may be caused by multiple factors of which ongoing inflammation and oxidative stress may play a dominant role. The objective of the present investigation was to determine cerebrospinal fluid (CSF) proteins and possible low-grade inflammation and its relation to age and neurological deterioration. In the present study, we investigated 15 patients with A-T from 2 to 16 years. Our investigation included blood and CSF tests, clinical neurological examination, A-T score, and MRI findings. The albumin ratio (AR) was analyzed to determine the blood–brain-barrier function. In addition, inflammatory cytokines (IL-1α, IL-6, IL-8, IL-12 p40, IL-17A, IFN-γ, TNF-α) were measured by the multiplex cytometric bead array. We compared the results with those from an age-matched control group. Three of the A-T patients were analyzed separately (one after resection of a cerebral meningioma, one after radiation and chemotherapy due to leukemia, one after stem cell transplantation). Patient had significantly more moderate and severe side effects due to CSF puncture (vomiting, headache, need for anti-emetic drugs) compared with healthy controls. Total protein, albumin, and the AR increased with age indicating a disturbed blood barrier function in older children. There were no differences for cytokines in serum and CSF with the exception of IL-2, which was significantly higher in controls in serum. The AR is significantly altered in A-T patients, but low-grade inflammation is not detectable in serum and CSF.
The aging process is characterized by a chronic, low‐grade inflammatory state, termed “inflammaging.” It has been suggested that macrophage activation plays a key role in the induction and maintenance of this state. In the present study, we aimed to elucidate the mechanisms responsible for aging‐associated changes in the myeloid compartment of mice. The aging phenotype, characterized by elevated cytokine production, was associated with a dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and diminished serum corticosteroid levels. In particular, the concentration of corticosterone, the major active glucocorticoid in rodents, was decreased. This could be explained by an impaired expression and activity of 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), an enzyme that determines the extent of cellular glucocorticoid responses by reducing the corticosteroids cortisone/11‐dehydrocorticosterone to their active forms cortisol/corticosterone, in aged macrophages and peripheral leukocytes. These changes were accompanied by a downregulation of the glucocorticoid receptor target gene glucocorticoid‐induced leucine zipper (GILZ) in vitro and in vivo. Since GILZ plays a central role in macrophage activation, we hypothesized that the loss of GILZ contributed to the process of macroph‐aging. The phenotype of macrophages from aged mice was indeed mimicked in young GILZ knockout mice. In summary, the current study provides insight into the role of glucocorticoid metabolism and GILZ regulation during aging.
Three AKT serine/threonine kinase isoforms (AKT1/AKT2/AKT3) mediate proliferation, metabolism, differentiation and anti-apoptotic signals. AKT isoforms are activated down- stream of PI3-kinase and also by PI3-kinase independent mechanisms. Mutations in the lipid phosphatase PTEN and PI3-kinase that increase PIP3 levels increase AKT signaling in a large proportion of human cancers. AKT and other AGC kinases possess a regulatory mechanism that relies on a conserved hydrophobic motif (HM) C-terminal to the catalytic core. In AKT, the HM is contiguous to the serine 473 and two other newly discovered (serine 477 and tyrosine 479) regulatory phosphorylation sites. In AKT genes, this regulatory HM region is encoded in the final exon. We identified a splice variant of AKT2 (AKT2-13a), which contains an alternative final exon and lacks the HM regulatory site. We validated the presence of mRNA for this AKT2-13a splice variant in different tissues, and the presence of AKT2-13a protein in extracts from HEK293 cells. When overexpressed in HEK293 cells, AKT2-13a is phosphorylated at the activation loop and at the zipper/turn motif phosphoryla- tion sites but has reduced specific activity. Analysis of the human transcriptome correspond- ing to other AGC kinases revealed that all three AKT isoforms express alternative transcripts lacking the HM regulatory motif, which was not the case for SGK1-3, S6K1-2, and classical, novel and atypical PKC isoforms. The transcripts of splice variants of Akt1-3 excluding the HM regulatory region could lead to expression of deregulated forms of AKT.
Onkologische Erkrankungen im Kindesalter und jungen Erwachsenenalter haben nicht selten eine gute Prognose. Entsprechend wird für Betroffene früher oder später die Frage relevant, inwieweit nach einer onkologischen Behandlung die Fertilität beeinträchtigt ist. Nicht nur der Zeitraum der Fertilität, sondern auch die Wahrscheinlichkeit eines vorzeitigen Ovarialversagens mit allen Risiken eines längerfristigen Östrogenmangels ist für die Lebensplanung der Frauen wichtig. Mittlerweile können vor Behandlung fertilitätserhaltende Maßnahmen angeboten werden. Sie bieten manchmal die einzige Chance, auf ovarielle Reserven nach Behandlung zurückgreifen zu können, sind aber nicht immer nötig und von späterem Nutzen. Das Anti-Müller-Hormon (AMH) hat sich als validester Marker für die Beurteilung der ovariellen Reserve herausgestellt. Mithilfe dessen sind Prognosen über die Ovarreserve vor und nach der onkologischen Therapie möglich. Dies erleichtert die Entscheidung für die Indikation für fertilitätserhaltende Maßnahmen und kann wegweisend in der Lebensplanung der Frauen und Familien sein.
Working memory (WM) performance varies substantially among individuals but the precise contribution of different WM component processes to these functional limits remains unclear. By analyzing different types of responses in a spatial WM task, we recently demonstrated a functional dissociation between confident and not-confident errors reflecting failures of WM encoding and maintenance, respectively. Here, we use event-related brain potentials to further explore this dissociation. Healthy participants performed a delayed orientation-discrimination task and rated their response confidence for each trial. The encoding-related N2pc component was significantly reduced for confident errors compared to confident correct responses, which is indicative of an encoding failure. In contrast, the maintenance-related contra-lateral delay activity was similar for these response types indicating that in confident error trials, WM representations – potentially the wrong ones – were maintained accurately and with stability throughout the delay interval. However, contra-lateral delay activity measured during the early part of the delay period was decreased for not-confident errors, potentially reflecting compromised maintenance processes. These electrophysiological findings contribute to a refined understanding of the encoding and maintenance processes that contribute to limitations in WM performance and capacity.
ABC transporters fulfill diverse physiological functions in different cellularlocalizations ranging from the plasma membrane to intracellular membranouscompartments. Several ABC transporters have been spotted in the endolyso-somal system, which consists of endosomes, autophagosomes, lysosomes, andlysosome-related organelles. In this review, we present an overview of lysoso-mal ABC transporters including ABCA2, ABCA3, ABCA5, ABCB6,ABCB9, and ABCD4, discussing their trafficking routes, putative substrates,potential physiological functions, and associated diseases. In addition, weoffer a critical evaluation of the literature linking ABC transporters to lyso-somal drug sequestration, examining pitfalls associated with in vitro modelsof drug resistance.
Analyse der Genauigkeit des neurochirurgischen Operationsroboters Robotic Surgery Assistant (ROSA)
(2020)
In der vorliegenden Arbeit sollte untersucht werden, ob der Roboter ROSA bei der Durchführung von intrakraniellen Biopsien oder Elektrodenimplantationen eine Alternative zur klassischen, rahmenbasierten Stereotaxie darstellt. Dazu sollte die mechanische und die Anwendungsgenauigkeit des Systems ermittelt werden. Zur Bestimmung der mechanischen Genauigkeit wurde eine experimentelle Phantomstudie durchgeführt. Hier wurden durch den Roboter wiederholt zehn Trajektorien an einem Stereotaxiephantom angefahren. Der Abstand der robotischen Nadel zum Zielpunkt im Phantom wurde anhand von Röntgenbildern bestimmt. Die Wiederholung des Versuchsaufbaus unter Variation der Planungsbildgebung erlaubte den Vergleich verschiedener Schichtdicken sowie zwischen low-dose und normal-dose Verfahren. Die Anwendungsgenauigkeit sollte durch die Analyse operativer Ergebnisse der ROSA erfasst werden. Dazu wurde anhand von postoperativen Bildern die Genauigkeit anhand des Abstands zwischen geplanter und tatsächlicher Lage von Stereoelektroenzephalographie-Elektroden ermittelt. Es wurden verschiedene Referenzierungstechniken, die der Orientierung des Roboters dienen und bei denen eine präoperative Planungsbildgebung (CT oder MRT) mit einem Abbild des OP-Gebietes (durch Oberflächenerkennung oder durch einen Stereotaxierahmen) referenziert wird, verglichen, nämlich CT-Laser; CT-Leksell-Rahmen und MRT-Laser. Die Ergebnisse wurden einer statistischen Analyse unterzogen. Dabei zeigte sich, dass der ROSA-Roboter eine sehr hohe mechanische Genauigkeit im Submillimeterbereich erreicht. Genauigkeitseinbußen bei einer größeren Schichtdicke der zur Planung verwendeten Computertomographie sind messbar, aber gering. Ein signifikanter Einfluss bei der Verwendung eines low-dose-Protokolls konnte nicht festgestellt werden. Dennoch zeigte sich, dass der entscheidende Teil der Ungenauigkeiten in der klinischen Anwendung entsteht und dabei insbesondere durch die Referenzierungstechnik bestimmt wird. Referenzierungen, die auf einer Computertomographie basierten, erwiesen sich als zufriedenstellend genau und als konkurrenzfähig zur konventionellen Methode. Der Unterschied zwischen dem rahmenbasierten und dem auf Oberflächenerkennung basierenden Verfahren war dabei so gering, dass letzteres sich angesichts seiner Vorteile in der Anwendung als besonders günstiges Verfahren hervortut. Im Gegensatz dazu stand das MRT-Laser-Verfahren, welches bei relativ hohen Abweichungen nur eingeschränkt anwendbar scheint und sich damit eher für Anwendungsbereiche mit geringeren Genauigkeitsanforderungen eignet, wie bspw. Biopsien. Weiterhin kann der Verlauf der Trajektorie an den höheren Sicherheitsabstand angepassten werden. Bei der Einordnung der ermittelten Genauigkeiten ist zu beachten, dass es viele weitere, von der Referenzierungs- und Bildgebungsmethode unabhängige Einflussfaktoren gibt. In dieser Arbeit war der Einfluss der erfassten externen Paramter zwar limitiert, bei anderen Autoren zeigte sich jedoch ein signifikanter Effekt. Dennoch deckt sich die Gesamtgenauigkeit mit den Ergebnissen anderer Arbeiten.
In Zusammenschau der Ergebnisse weist die vom ROSA-Assistenzsystem assistierte Stereotaxie eine verbesserte Prozessqualität auf, unter anderem durch die erhebliche Zeitersparnis, ggf. der Wegfall des Transports des narkotisierten Patienten, die Adaptionsmöglichkeiten der Prozessteilschritte an den Patienten, sowie eine hohe Nutzerfreundlichkeit. Entscheidend ist jedoch, dass es sich um ein sehr sicheres Verfahren handelt: Durch die hohe Genauigkeit wird das Operationsrisiko minimiert, gleichzeitig erlauben Laser-gestützte Registrierungsverfahren eine Reduktion der Strahlenexposition. Zur Konsolidierung der in dieser Arbeit gewonnenen Erkenntnisse sind weitere klinische Daten notwendig.
Ziel dieser klinischen Studie war es, die Ergebnisse der operativen Behandlung eines idiopathischen Makulaforamens durch Vitrektomie, ggf. in Kombination mit einer Phakoemulsifikation, ILM-Peeling und einer Tamponade entweder mit Luft oder mit 20%-igem SF6-Gas zu vergleichen. Primärer Endpunkt war die Verschlussrate nach einer Vitrektomie und die Reoperationsrate bei primär nicht geschlossenen Makulaforamina. Sekundärer Endpunkt war die Visusentwicklung in der ersten postoperativen Woche und nach 3 Monaten.
In der vorliegenden Arbeit wurden hierzu retrospektiv 117 Augen von 117 konsekutiven Patienten analysiert. Es wurden die Ergebnisse von 2 Patientengruppen verglichen. In der ersten Gruppe wurden 66 Augen (m=27, w=39, Altersmedian 70 Jahre), bei denen am Ende der Vitrektomie eine Tamponade mit Luft erfolgte, untersucht. In der zweiten Gruppe wurden die Ergebnisse von 51 Augen (m=20, w=31, Altersmedian 71 Jahre), bei denen 20%-SF6-Gas als Tamponade verwendet wurde, ausgewertet. Bei etwa 70 % der Augen beider Gruppen erfolgte eine simultane Phakoemulsifikation. Der Verschluss des Makulaforamens wurde bereits in den ersten postoperativen Tagen mit einem modifizierten Fourier Domain-OCT untersucht. Sobald der Verschluss des Makulaforamens im OCT gesichert werden konnte, wurde die postoperative „Gesicht nach unten“-Lagerung („Bauchlage“) beendet. Die mediane Lagerungszeit betrug 1 Tag (Spanne 1-6 Tage). Der Zeitraum der Nachbeobachtung betrug 3 Monate (Median).
Die Verschlussrate nach einer Vitrektomie aller Makulaforamina betrug 87,2% (102/117 Augen). Die primäre Verschlussrate der Luft-Gruppe und der SF6-Gas-Gruppe betrug 83,3% (55/66 Augen) bzw. 92,2% (47/51 Augen). Bei Augen mit einem persistierenden Foramen erfolgte eine frühe Reoperation. Die Verschlussrate nach 3 Monaten lag insgesamt bei 99,1% (116/117 Augen), in der Luft-Gruppe bei 98,5% (65/66 Augen) und in der SF6-Gas-Gruppe bei 100% (51/51 Augen). Es zeigte sich kein statistisch signifikanter Unterschied der Verschlussrate bzw. der anatomischen Ergebnisse zwischen den beiden Endotamponade-Gruppen.
Es konnte jedoch ein statistisch signifikanter Unterschied des Fernvisus bei der Entlassung zwischen beiden Endotamponadegruppen nachgewiesen werden. Der logMAR-Visus bei Entlassung lag in der Luft-Gruppe mit 1,3 (Median) deutlich unter dem Visus der SF6-Gas-Gruppe mit 1,9 (Median). Die Anwendung von Luft führte somit im Vergleich zu SF6 zu einem schnelleren postoperativen Visusanstieg. In beiden Gruppen zeigte sich nach 3 Monaten eine signifikante Visusbesserung. Es ließ sich kein signifikanter Unterschied des Fernvisus zwischen den beiden Gruppen mehr nachweisen.
Die Makulaforamenchirurgie mit pars plana Vitrektomie und Peeling der ILM erzielte sowohl mit einer Luft- als auch mit einer 20%-SF6-Gas-Tamponade guten anatomischen und funktionellen Ergebnissen. Mit einer kurz wirksamen Endotamponade erscheint eine postoperative Lagerung essenziell, dürfte aber in den meisten Fällen nur wenige Tage erforderlich sein, um den Verschluss eines durchgreifenden Makulaforamens zu erreichen. Die Reoperations-Rate nach einer Lufttamponade war bei sehr großen Foramina (> 600 µm) signifikant höher als bei Foramina mit einem Durchmesser kleiner 600 µm. Daher scheint die Anwendung von Gasen, die länger als Luft wirken, nur bei sehr großen Foramina erforderlich zu sein. Vorteil einer kurz wirkenden Lufttamponade ist die postoperativ um einige Tage schneller einsetzende visuelle Rehabilitation, so dass die Patienten früher in ihren Alltag zurückkehren können. Eine frühe postoperative Untersuchung der Makula unter Einsatz der optischen Kohärenztomographie ist Voraussetzung für eine individualisierte Steuerung der Lagerung und für eine möglichst frühe Erkennung und Reoperation von nicht geschlossenen Makulalöchern.
Cerumen was found to be a promising alternative specimen for the detection of drugs. In a pilot study, drugs of abuse were identified at a higher detection rate and a longer detection window in cerumen than in urine. In this study, cerumen from subjects was analyzed after they ingested the designer stimulant 4-fluoroamphetamine (4-FA) in a controlled manner. Methods: Twelve subjects ingested placebo and 100 mg of 4-FA. Five of them were also given 150 mg of 4-FA in 150 mL Royal Club bitter lemon drink at least after 7 days. Cerumen was sampled using cotton swabs at baseline, 1 h after the ingestion of the drug and at the end of the study day (12 h). After extraction with ethyl acetate followed by solid-phase extraction, the extracts were analyzed using liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Results and discussion: In the cerumen of all 12 subjects, 4-FA was detected 12 h after its ingestion; in most subjects, cerumen was detected after 1 h of ingestion, ranging from 0.06 to 13.90 (median 1.52) ng per swab. The detection of 4-FA in cerumen sampled 7 days or more after the first dose suggested a long detection window of cerumen. Conclusions: Cerumen can be successfully used to detect a single drug ingestion even immediately after the ingestion when a sufficient amount of cerumen is used.
Background: While systemic inflammation is recognized as playing a central role in the pathogenesis of organ failures in patients with liver cirrhosis, less is known about its relevance in the development of classical hepatic decompensation. Aim: To characterize the relationship between systemic inflammation, hemodynamics, and anemia with decompensation of liver cirrhosis. Methods: This is a post-hoc analysis of a cohort study of outpatients with advanced liver fibrosis or cirrhosis. Results: Analysis included 338 patients of whom 51 patients (15%) were hospitalized due to decompensation of liver cirrhosis during a median follow-up time of six months. In univariate analysis, active alcoholism (p = 0.002), model of end-stage liver disease (MELD) score (p = 0.00002), serum IL-6 concentration (p = 0.006), heart rate (p = 0.03), low arterial blood pressure (p < 0.05), maximal portal venous flow (p = 0.008), and low hemoglobin concentration (p < 0.00001) were associated with hospitalization during follow-up. Multivariate analysis revealed an independent association of low hemoglobin (OR = 0.62, 95% CI = 0.51–0.78, p = 0.001) and serum IL-6 concentration (OR = 1.02, 95% CI = 1.01–1.04, p = 0.03)—but not of hemodynamic parameters—with hepatic decompensation. An inverse correlation between hemoglobin concentration and portal venous flow (R = −0.362, p < 0.0001) was detected for the non-hospitalized patients. Accuracy of baseline hemoglobin levels for predicting hospitalization (AUC = 0.84, p < 0.000001) was high. Conclusion: Anemia and systemic inflammation, rather than arterial circulatory dysfunction, are strong and independent predictors of hepatic decompensation in outpatients with liver cirrhosis.
Die Bestimmung von ACE im Serum oder Heparinplasma stellt einen wesentlichen Bestandteil der Diagnostik, Verlaufskontrolle und Therapieüberwachung von benignen Lungenerkrankungen dar. ACE ist ein Marker, der bei Sarkoidose wertvolle Aussagen zur Diagnosefindung ermöglicht. Hier zeichnet er sich durch hohe Sensitivität und Spezifität aus.
Experiments in cadavers have demonstrated significant mechanical interactions between constituents of myofascial chains. However, evidence for such force transmission effects is scarce under in vivo conditions. The purpose of this trial was to examine the impact of ankle motion on soft tissue displacement of the dorsal thigh. Eleven healthy active individuals (26.8 ± 4.3 years, six males), in prone position and with the knee extended, underwent passive calf stretches (ankle dorsal extension) imposed by an isokinetic dynamometer. High-resolution ultrasound was used to simultaneously capture the displacement of the semimembranosus muscle, which was quantified by means of cross-correlation analysis. Inactivity of the leg muscles was controlled using surface electromyography (EMG). One participant had to be excluded due to major EMG activity during the experiment. According to a one-sample t test testing the difference to the neutral zero position, ankle dorsal extension induced substantial caudal muscle displacements (5.76 ± 2.67 mm, p < 0.0001). Correlation analysis (Spearman), furthermore, revealed a strong association between maximal dorsal extension and semimembranosus motion (rho = 0.76, p = 0.02). In conclusion, the present trial provides initial in vivo evidence for a mechanical force transmission between serially connected skeletal muscles. This means that local alterations of the mechanical tissue properties may modify flexibility in neighboring (superior or inferior) joints.
Mobile genetic elements (MGEs), especially multidrug-resistance plasmids, are major vehicles for the dissemination of antimicrobial resistance determinants. Herein, we analyse the MGEs in three extensively drug-resistant (XDR) Klebsiella pneumoniae isolates from Germany. Whole genome sequencing (WGS) is performed using Illumina and MinION platforms followed by core-genome multi-locus sequence typing (MLST). The plasmid content is analysed by conjugation, S1-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot experiments. The K. pneumoniae isolates belong to the international high-risk clone ST147 and form a cluster of closely related isolates. They harbour the blaOXA-181 carbapenemase on a ColKP3 plasmid, and 12 antibiotic resistance determinants on an multidrug-resistant (MDR) IncR plasmid with a recombinogenic nature and encoding a large number of insertion elements. The IncR plasmids within the three isolates share a high degree of homology, but present also genetic variations, such as inversion or deletion of genetic regions in close proximity to MGEs. In addition, six plasmids not harbouring any antibiotic resistance determinants are present in each isolate. Our study indicates that genetic variations can be observed within a cluster of closely related isolates, due to the dynamic nature of MGEs. The mobilome of the K. pneumoniae isolates combined with the emergence of the XDR ST147 high-risk clone have the potential to become a major challenge for global healthcare.
Andropogon virginicus is an invasive weed that seriously threatens agricultural production and economics worldwide. In this research, dried aerial parts of A. virginicus were extracted, applying Soxhlet and liquid-liquid phase methods to acquire the total crude (T-Anvi), hexane (H-Anvi), ethyl acetate (E-Anvi), butanol (B-Anvi), and water (W-Anvi) extracts, respectively. In which, T-Anvi contains the highest total phenolic and flavonoid contents (24.80 mg gallic acid and 37.40 mg rutin equivalents per g dry weight, respectively). Via anti-radical (ABTS and DPPH), and reducing power assays, E-Anvi exhibits the most potent activities (IC50 = 13.96, 43.59 and 124.11 µg/mL, respectively), stronger than butylated hydroxytoluene (BHT), a standard antioxidant, while the lipid peroxidation inhibitory effect of E-Anvi (LPI = 90.85% at the concentration of 500 µg/mL) is close to BHT. E-Anvi shows the most substantial inhibition (IC50 = 2.58 mg/mL) on tyrosinase. Notably, α-amylase is significantly suppressed by H-Anvi (IC50 = 0.72 mg/mL), over twice stronger than the positive control, palmitic acid. In the cytotoxic assay, E-Anvi is the strongest extract inhibiting K562 cells (IC50 = 112.01 µg/mL). Meanwhile, T-Anvi shows the highest prevention on Meg-01 expansion (IC50 = 91.40 µg/mL). Dominant compounds detected in E-Anvi by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) are identified as flavonoids. However, among four major compounds identified in H-Anvi by gas chromatography-mass spectrometry (GC-MS), palmitic acid and phytol are the most abundant compounds with peak areas of 27.97% and 16.42%, respectively. In essence, this is the first report describing that A. virginicus is a potential natural source of antioxidants, tyrosinase and α-amylase inhibitors, and anti-chronic myeloid leukemia (CML) agents which may be useful in future therapeutics as promising alternative medicines.
Aims: Acetylsalicylic acid (ASA) is widely used for the prevention of atherothrombotic events in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), but the risk of vascular events remains high. We aimed at identifying randomised controlled trials (RCTs) on antithrombotic treatments in patients with chronic CAD or PAD.
Methods: Searches were conducted on MEDLINE, EMBASE, and CENTRAL on March 1st, 2018. This systematic review (SR) uses a narrative synthesis to summarize the evidence for the efficacy and safety of antiplatelet and anticoagulant therapies in the population of both chronic CAD or PAD patients.
Results: Four RCTs from 27 publications were included. Study groups included 15,603 to 27,395 patients. ASA alone was the most extensively studied (n = 3); other studies included rivaroxaban with or without ASA (n = 1), vorapaxar alone (n = 1), and clopidogrel with (n = 1) or without ASA (n = 1). Clopidogrel alone and clopidogrel plus ASA compared to ASA presented similar efficacy with comparable safety profile. Rivaroxaban plus ASA significantly reduced the risk of the composite of cardiovascular death, myocardial infarction, and stroke compared to ASA alone, although major bleeding with rivaroxaban plus ASA increased.
Conclusion: There is limited and heterogeneous evidence on the prevention of atherothrombotic events in patients with chronic CAD or PAD. Clopidogrel alone and clopidogrel plus ASA did not demonstrate superiority over ASA alone. A combination of rivaroxaban plus ASA may offer significant additional benefit in reducing cardiovascular outcomes, yet it may increase the risk of bleeding, compared to ASA alone.
Background and Objective: Macrophages’ cytokine expression and polarization play a substantial role in the host's “destructive” inflammatory response to periodontal and peri‐implant pathogens. This study aimed to evaluate cell viability, anti‐inflammatory activity, and macrophage polarization properties of different cranberry concentrates.
Methods: THP‐1 cells (monocytic line) were treated with phorbol myristic acid to induce macrophage differentiation. Human gingival fibroblasts (HFIB‐G cell line), osteosarcoma‐derived osteoblasts (SAOS‐2 cell line), and induced macrophages were treated with cranberry concentrates at 25, 50, and 100 µg/mL for 120 seconds, 1 hour and 24 hours. Untreated cells at the same time points served as controls. For anti‐inflammatory analysis, induced macrophages exposed to cranberry concentrates (A‐type PACs) were stimulated with lipopolysaccharides (LPS) derived from E coli for 24 hours. Cell viability, interleukin (IL)‐8, IL‐1 ß, IL‐6, and IL‐10 expression of LPS‐stimulated macrophages, and macrophage polarization markers were evaluated through determination of live‐cell protease activity, enzyme‐linked immunosorbent assay, and immunofluorescence staining semi‐quantification.
Results: Cranberry concentrates (A‐type PACs) did not reduce HGF, SAOS‐2, and macrophage viability after 24 hours of exposure. Pro‐inflammatory cytokine expression (ie IL‐8 and IL‐6) was downregulated in LPS‐stimulated macrophages by cranberry concentrates at 50 and 100 µg/mL. Anti‐inflammatory IL‐10 expression was significantly upregulated in LPS‐stimulated macrophages by cranberry concentrates at 100 µg/mL after 24 hours of exposure. M1 polarization significantly decreased when LPS‐stimulated macrophages were exposed to cranberry concentrates. High levels of positive M1 macrophages were present in all untreated control groups. M2 polarization significantly increased at all LPS‐stimulated macrophages exposed to cranberry concentrates for 1 and 24 hours.
Conclusion: Cranberry‐derived proanthocyanidins may have the potential to act as an anti‐inflammatory component in the therapy of periodontal and peri‐implant diseases.
APPEAL‐1: A pan‐European survey of patient/caregiver perceptions of peanut allergy management
(2020)
Background: Peanut allergy (PA) is associated with marked quality‐of‐life (QoL) impairment. However, data are lacking on the experience and impact of living with PA from the perspectives of persons with PA (PwPA) and their caregivers. Allergy to Peanuts imPacting Emotions And Life study 1 (APPEAL‐1) was a pan‐European survey investigating these perspectives. This first of two articles reports clinical characteristics of PwPA and PA management practices.
Methods: APPEAL‐1 was a quantitative, online survey conducted in eight European countries, developed by eight representatives of patient advocacy groups and five healthcare professionals and researchers. Eligible participants included adults with PA and parents/caregivers of PwPA who responded by self‐report and provided proxy‐report for the PwPA under their care. Data were summarized using nonweighted descriptive statistics.
Results: Of 1846 completed/analysed questionnaires, 528 were from adults with PA (self‐report); 437 by proxy for children with PA (34 aged 0‐3 years, 287 aged 4‐12 years, 116 aged 13‐17 years) and 881 from parents/caregivers (self‐report). Of PwPA (N = 965), 95% reported diagnosis by healthcare professionals, mostly by clinical history and peanut‐specific allergy testing. Rates of allergic rhinitis, asthma and other food allergies in PwPA were 50%, 42% and 79%, respectively. Only 31% of PwPA received HCP advice/support following their worst allergic reaction, and 28% had not been prescribed an adrenaline auto‐injector. Results were similar by country but varied by age group.
Conclusions: The APPEAL‐1 findings contribute to greater understanding of PA impact on PwPA, caregivers and family members and the need for improved PA management across Europe.
Evoked potentials in the amplitude-time spectrum of the electroencephalogram are commonly used to assess the extent of brain responses to stimulation with noxious contact heat. The magnitude of the N- and P-waves are used as a semi-objective measure of the response to the painful stimulus: the higher the magnitude, the more painful the stimulus has been perceived. The strength of the N-P-wave response is also largely dependent on the chosen reference electrode site. The goal of this study was to examine which reference technique excels both in practical and theoretical terms when analyzing noxious contact heat evoked potentials (CHEPS) in the amplitude-time spectrum. We recruited 21 subjects (10 male, 11 female, mean age of 55.79 years). We applied seven noxious contact heat stimuli using two temperatures, 51°C, and 54°C, to each subject. During EEG analysis, we aimed to identify the referencing technique which produces the highest N-wave and P-wave amplitudes with as little artifactual influence as possible. For this purpose, we applied the following six referencing techniques: mathematically linked A1/A2 (earlobes), average reference, REST, AFz, Pz, and mathematically linked PO7/PO8. We evaluated how these techniques impact the N-P amplitudes of CHEPS based on our data from healthy subjects. Considering all factors, we found that mathematically linked earlobes to be the ideal referencing site to use when displaying and evaluating CHEPS in the amplitude-time spectrum.
Background: WATSU (portmanteau word: water and shiatsu) is a form of passive hydrotherapy in chest-deep thermoneutral water (35°C = 95°F = 308.15 K). It combines elements of myofascial stretching, joint mobilization, massage, and shiatsu and is reported to be used to address physical and mental issues. The objective of this systematic review (PROSPERO Registration No. CRD42016029347) and the meta-analyses was to assess the applications, indications, and the effects of WATSU to form a basis for further studies.
Methods: A search for "WATSU OR watershiatsu OR (water AND shiatsu)" was conducted without any restrictions in 32 databases. Peer reviewed original articles addressing WATSU as a stand-alone hydrotherapy were assessed for risk of bias. Quantitative data of effects on pain, physical function, and mental issues were processed in random model meta-analyses with subgroup analyses by study design. Effect sizes were expressed as Hedges's g (± 95% confidence intervals).
Results: Of 1,906 unique citations, 27 articles regardless of study design were assessed for risk of bias. WATSU has been applied to individuals of all ages. Indications covered acute (e.g. pregnancy related low back pain) and chronic conditions (e.g. cerebral palsy) with beneficial effects of WATSU regarding e.g. relaxation or sleep quality. Meta-analyses suggest beneficial effect sizes of WATSU on pain (overall Hedges’s g = -0.71, 95% CI = -0.91 to -0.51), physical function (overall Hedges’s g = -0.76, 95% CI = -1.08 to -0.44), and mental issues (overall Hedges’s g = -0.68, 95% CI = -1.02 to -0.35).
Conclusion: Various applications, indications and beneficial effects of WATSU were identified. The grade of this evidence is estimated to be low to moderate at the best. To strengthen the findings of this study, high-quality RCTs are needed.
Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is the cause of the current coronavirus disease 19 (COVID-19) pandemic. Protease inhibitors are under consideration as virus entry inhibitors that prevent the cleavage of the coronavirus spike (S) protein by cellular proteases. Herein, we showed that the protease inhibitor aprotinin (but not the protease inhibitor SERPINA1/alpha-1 antitrypsin) inhibited SARS-CoV-2 replication in therapeutically achievable concentrations. An analysis of proteomics and translatome data indicated that SARS-CoV-2 replication is associated with a downregulation of host cell protease inhibitors. Hence, aprotinin may compensate for downregulated host cell proteases during later virus replication cycles. Aprotinin displayed anti-SARS-CoV-2 activity in different cell types (Caco2, Calu-3, and primary bronchial epithelial cell air–liquid interface cultures) and against four virus isolates. In conclusion, therapeutic aprotinin concentrations exert anti-SARS-CoV-2 activity. An approved aprotinin aerosol may have potential for the early local control of SARS-CoV-2 replication and the prevention of COVID-19 progression to a severe, systemic disease.
Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
Background: Bone age (BA) assessment performed by artificial intelligence (AI) is of growing interest due to improved accuracy, precision and time efficiency in daily routine. The aim of this study was to investigate the accuracy and efficiency of a novel AI software version for automated BA assessment in comparison to the Greulich-Pyle method.
Methods: Radiographs of 514 patients were analysed in this retrospective study. Total BA was assessed independently by three blinded radiologists applying the GP method and by the AI software. Overall and gender-specific BA assessment results, as well as reading times of both approaches, were compared, while the reference BA was defined by two blinded experienced paediatric radiologists in consensus by application of the Greulich-Pyle method.
Results: Mean absolute deviation (MAD) and root mean square deviation (RSMD) were significantly lower between AI-derived BA and reference BA (MAD 0.34 years, RSMD 0.38 years) than between reader-calculated BA and reference BA (MAD 0.79 years, RSMD 0.89 years; p < 0.001). The correlation between AI-derived BA and reference BA (r = 0.99) was significantly higher than between reader-calculated BA and reference BA (r = 0.90; p < 0.001). No statistical difference was found in reader agreement and correlation analyses regarding gender (p = 0.241). Mean reading times were reduced by 87% using the AI system.
Conclusions: A novel AI software enabled highly accurate automated BA assessment. It may improve efficiency in clinical routine by reducing reading times without compromising the accuracy compared with the Greulich-Pyle method.
Objective: The establishment of patient-centered measures capable of empirically determining meaningful cognitive change after surgery can significantly improve the medical care of epilepsy patients. Thus, this study aimed to develop reliable change indices (RCIs) and standardized regression-based (SRB) change norms for a comprehensive neuropsychological test battery in the German language.
Methods: Forty-seven consecutive patients with temporal lobe epilepsy underwent neuropsychological assessments, both before and 12 months after surgery. Practice-effect-adjusted RCIs and SRB change norms for each test score were computed. To assess their usefulness, the presented methods were applied to a clinical sample, and binary logistic regression analyses were conducted to model the odds of achieving improvement in quality of life (QOL) after surgery.
Results: The determined RCIs at 90% confidence intervals and the SRB equations for each test score included in the test battery are provided. Cohen’s kappa analyses revealed a moderate mean agreement between the two measures, varying from slight to almost perfect agreement across test scores. Using these measures, a negative association between improvement in QOL and decline in verbal memory functions after surgery was detected (adjusted odds ratio = 0.09, p = 0.006).
Significance: To the best of our knowledge, this study is the first to develop RCIs and SRB change norms necessary for the objective determination of neuropsychological change in a comprehensive test battery in the German language, facilitating the individual monitoring of improvement and decline in each patients’ cognitive functioning and psychosocial situations after epilepsy surgery. The application of the described measures revealed a strong negative association between improvement in QOL and decline in verbal memory functions after surgery.
The aim of the study was to obtain volumetric data of the components of the inner ear using three-dimensional reconstruction of high-resolution cone-beam computed tomography (CBCT) images. Two hundred three CBCT image series of the temporal bone from 118 anatomically normal patients (55 women and 63 men; mean age: 49.4 ± 20.4 years) with different suspected disorders were included in this study. Normative volumetric measurements of the inner ear, the cochlea, the semicircular canals (SSC), and the vestibule were determined using a semi-automated reconstruction method of the Workstation. Volumetric measurements were successfully completed in all 118 patients. Mean inner ear, cochlear, and vestibule volumes were statistically significantly larger in males than in females on both sides (p < 0.001). Regarding the semicircular canals, no statistically significant (p = 0.053) volume difference was found. The difference between the volumes on both sides was not significant. No correlation between the patient’s age and the volume of the compartments was seen (p > 0.05). There was no significant difference between mean bony inner ear volumes when the clinical diagnoses were compared (p > 0.05 for all clinical diagnoses and volumes). Our study concluded that three-dimensional reconstruction and assessment of the volumetric measurements of the inner ear can be obtained using high-resolution CBCT imaging.
This case series assessed a commercial airline flight from Tel Aviv, Israel, to Frankfurt, Germany, that occurred on March 9th, 2020. Among 102 passengers on a Boeing 737-900 aircraft were 24 members of a tourist group. Starting 7 days earlier, the group had contact with a hotel manager who later received a diagnosis of coronavirus disease 2019 (COVID-19). No member of the group had received a diagnosis of COVID-19 before the flight, and no measures to prevent transmission (eg, wearing of masks) had been applied. The flight duration was 4 hours 40 minutes.
Objectives: The aim of this study was to investigate the relationship between anamnestic, axiographic and occlusal parameters and postural control in healthy women aged between 41 and 50 years. Materials and methods: A total of 100 female participants aged between 41 and 50 (45.12 ± 2.96) years participated in the study. In addition to completing a general anamnesis questionnaire, lower jaw movements were measured axiographically, dental occlusion parameters were determined using a model analysis and postural parameters were recorded using a pressure measurement platform. The significance level was 5%. Results: An increasing weight and a rising BMI lead to a weight shifted from the rearfoot (p ≤ 0.01/0.04) to the forefoot (p ≤ 0.01/0.02). A limited laterotrusion on the right resulted in a lower forefoot load and an increased rearfoot load (p ≤ 0.01). Laterotrusion to the left (extended above the standard) showed a lower frontal sway (p ≤ 0.02) and a reduced elliptical area, height and width (p ≤ 0.01, 0.02, 0.03). Thus, the extent of deviation correlated with reduced right forefoot loading (p ≤ 0.03) and the extent of deflection correlated with increased left foot loading (p ≤ 0.01). The higher the extent of angle class II malocclusion, the larger the ellipse area (p ≤ 0.04) and the ellipse height (p ≤ 0.02) resulted. Conclusions: There is a connection between weight, BMI and laterotrusion, as well as between angle class II malocclusion and postural control in women aged between 41 and 50 years. Interdisciplinary functional examinations of mandibular movements treating possible limitations can be conducive for an improvement of postural control. Clinical relevance: Angle class II malocclusion has a negative influence on postural control.
Background: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms). Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed. Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters. Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.
Suicide represents a major challenge to public mental health. In order to provide empirical evidence for prevention strategies, we hypothesized current levels of low socioeconomic status (SES) and high social isolation (SI) to be linked to increased suicide rates in N = 390 administrative districts since SES and SI are associated with mental illness. Effects of SES on suicide rates were further expected to be especially pronounced in districts with individuals showing high SI levels as SI reduces the reception of social support and moderates the impact of low SES on poor mental health. We linked German Microcensus data to register data on all 149,033 German suicides between 1997 and 2010 and estimated Prentice and Sheppard’s model for aggregate data to test the hypotheses, accounting for spatial effect correlations. The findings reveal increases in district suicide rates by 1.20% (p < 0.035) for 1% increases of district unemployment, suicide rate decreases of −0.39% (p < 0.028) for 1% increases in incomes, increases of 1.65% (p < 0.033) in suicides for 1% increases in one-person-households and increases in suicide rates of 0.54% (p < 0.036) for 1% decreases in single persons’ incomes as well as suicide rate increases of 3.52% (p < 0.000) for 1% increases in CASMIN scores of individuals who moved throughout the year preceding suicide. The results represent appropriate starting points for the development of suicide prevention strategies. For the definition of more precise measures, future work should focus on the causal mechanisms resulting in suicidality incorporating individual level data.
Speech perception is mediated by both left and right auditory cortices but with differential sensitivity to specific acoustic information contained in the speech signal. A detailed description of this functional asymmetry is missing, and the underlying models are widely debated. We analyzed cortical responses from 96 epilepsy patients with electrode implantation in left or right primary, secondary, and/or association auditory cortex (AAC). We presented short acoustic transients to noninvasively estimate the dynamical properties of multiple functional regions along the auditory cortical hierarchy. We show remarkably similar bimodal spectral response profiles in left and right primary and secondary regions, with evoked activity composed of dynamics in the theta (around 4–8 Hz) and beta–gamma (around 15–40 Hz) ranges. Beyond these first cortical levels of auditory processing, a hemispheric asymmetry emerged, with delta and beta band (3/15 Hz) responsivity prevailing in the right hemisphere and theta and gamma band (6/40 Hz) activity prevailing in the left. This asymmetry is also present during syllables presentation, but the evoked responses in AAC are more heterogeneous, with the co-occurrence of alpha (around 10 Hz) and gamma (>25 Hz) activity bilaterally. These intracranial data provide a more fine-grained and nuanced characterization of cortical auditory processing in the 2 hemispheres, shedding light on the neural dynamics that potentially shape auditory and speech processing at different levels of the cortical hierarchy.
BAG3, a multifunctional HSP70 co-chaperone and anti-apoptotic protein that interacts with the ATPase domain of HSP70 through its C-terminal BAG domain plays a key physiological role in cellular proteostasis. The HSP70/BAG3 complex determines the levels of a large number of selective client proteins by regulating their turnover via the two major protein degradation pathways, i.e. proteasomal degradation and macroautophagy. On the one hand, BAG3 competes with BAG1 for binding to HSP70, thereby preventing the proteasomal degradation of its client proteins. By functionally interacting with HSP70 and LC3, BAG3 also delivers polyubiquitinated proteins to the autophagy pathway. BAG3 exerts a number of key physiological functions, including an involvement in cellular stress responses, proteostasis, cell death regulation, development, and cytoskeletal dynamics. Conversely, aberrant BAG3 function/expression has pathophysiological relevance correlated to cardiomyopathies, neurodegeneration, and cancer. Evidence obtained in recent years underscores the fact that BAG3 drives several key hallmarks of cancer, including cell adhesion, metastasis, angiogenesis, enhanced autophagic activity, and apoptosis inhibition. This review provides a state-of-the-art overview on the role of BAG3 in stress and therapy resistance of cancer, with a particular focus on BAG3-dependent modulation of apoptotic signaling and autophagic/lysosomal activity.
Ataxia-Telangiectasia (A-T), a pleiotropic chromosomal breakage syndrome, is caused by the loss of the kinase Ataxia-telangiectasia mutated (ATM). ATM is not only involved in the response to DNA damage, but also in sensing and counteracting oxidative stress. Since a disturbed redox balance has been implicated in the pathophysiology of A-T lung disease, we aimed to further explore the interplay between ATM and oxidative stress in lung cells. Using a kinetic trapping approach, we could demonstrate an interaction between the trapping mutant TRX1-CS and ATM upon oxidative stress. We could further show that combined inhibition of thioredoxin reductase (TrxR) and ATM kinase activity, using Auranofin and KU55933 respectively, induced an increase in cellular reactive oxygen species (ROS) levels and protein oxidation in lung cells. Furthermore, ATM inhibition sensitized lung cells to Auranofin-induced cell death that could be rescued by ROS scavengers. As a consequence, targeted reduction of ATM by TRX1 could serve as a regulator of oxidative ATM activation and contribute to the maintenance of the cellular redox homeostasis. These results highlight the importance of the redox-active function of ATM in preventing ROS accumulation and cell death in lung cells.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Background: Children who are frequently aggressive or lack empathy show various deficits in their social information processing. Several findings suggest that children with conduct problems (CP) show a tendency to interpret ambiguous situations as hostile (hostile attribution bias) and have difficulties to disengage from negative stimuli (attentional bias). The role that additional callous-unemotional traits (CU-traits) play in these biases is yet unclear. Investigating both attentional and attributional aspects of social information processing in children can help us to understand where anomalies in the processing pathway occur and whether the biases are associated with CP and CU-traits separately or in an interactive manner.
Methods: We compared three groups of children: (a) 25 children with CP and low levels of CU-traits (b) 25 children with CP and elevated levels of CU-traits (c) 50 gender (68% male), age (8–17 years) and intelligence score-matched typically developing children, on a pictorial emotional stroop task and a hostile attribution bias task.
Results: In contrast to our predictions, there were no significant group differences regarding attentional biases or hostile attribution biases. Boys with CP and high levels of CU-traits showed a significantly higher hostile attribution bias compared to girls with CP and high levels of CU-traits. The attention bias to angry stimuli significantly correlated with the hostile attribution bias. Compared to the control group the CP group with low levels of CU-traits showed a significantly stronger association between the attention bias to angry stimuli and the hostile attribution bias.
Conclusions: The current study provides evidence that boys with CP and high levels of CU-traits interpret ambiguous situations as more hostile than girls do. Our results further provide indications that the interaction of attentional and attributional biases in children with CP might contribute to their increased aggressive behavior.
Background: Autism spectrum disorder (“autism”) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions—A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. Results: Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. Conclusions: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.
Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.
Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.
Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Hintergrund: Die stationäre Aufnahme von Patienten mit Prellungen wird in Kliniken der Akutversorgung regelhaft praktiziert. Dabei stehen die pathophysiologischen Unfallfolgen oft im Hintergrund. Ziel dieser retrospektiven monozentrischen Untersuchung war die Untersuchung der Ätiologie sowie der kostenverursachenden Faktoren und Refinanzierung bei Aufnahmen durch Prellungen.
Methodik: Es erfolgte die Abfrage der Patienten entsprechend den Entlassdiagnosen aus dem krankenhausinternen Informationssystem (KIS). Eingeschlossen wurden 117 Patienten in einem Zeitraum von 2 Jahren. Es erfolgten hier die Klassifizierung nach Unfallmechanismus sowie die Einteilung in Altersgruppen. Des Weiteren erfolgte die Kostenkalkulation anhand von abteilungs- und klinikspezifischen Tagessätzen.
Ergebnisse: Bezüglich der Ätiologie war der häusliche Sturz die häufigste Ursache (48,7 %), gefolgt von dem Hochrasanztrauma (22,8 %). Innerhalb der Gruppe des häuslichen Sturzes lag das Durchschnittsalter im Mittel bei 77,8 Jahre. Diese Gruppe zeigte die längste Verweildauer (VWD) mit 5,2 Tagen. Im Rahmen der kalkulierten Kosten zeigte die Gruppe nach häuslichem Sturz die höchsten Kosten mit 2596,24 € bei einem mittleren DRG-Erlös von 1464,51 €.
Diskussion: Die Auswertung der klinikinternen Daten bestätigte die subjektive Wahrnehmung, dass ein Großteil der nach Prellung aufgenommenen Patienten aus der Altersgruppe >65 Jahre stammt. Die Aufnahme erfolgt hier vor dem Hintergrund der in dieser Altersgruppe zunehmenden Komorbiditäten sowie zur Abwendung von Folgeerkrankungen und Folgen der Immobilisierung. Ebenfalls konnte gezeigt werden, dass die Versorgungskosten gesundheitsökomisch relevant sind und die Behandlung in diesen Fällen nicht kostendeckend ist.
Hintergrund: Den derzeitigen Therapiestandard in der Behandlung des lokal begrenzten Prostatakarzinoms stellen die radikale Prostatektomie und perkutane Radiotherapie dar. Aufgrund der besonderen Strahlenbiologie des PCa (α-/β-Wert 1,5 Gy) ist von einer höheren Sensitivität gegenüber einer Hypofraktionierung auszugehen. Die aktuellen Literaturdaten zeigen eine Nichtunterlegenheit der moderaten Hypofraktionierung gegenüber dem konventionellen Regime, jedoch sind Langzeitergebnisse hinsichtlich der Spättoxizität noch spärlich. In dieser Arbeit werden onkologische Ergebnisse sowie GI-/ und GU-Toxizität nach moderat hypofraktionierter, intensitätsmodulierter (IMRT/VMAT) und bildgeführter (IGRT) Radiotherapie mit simultan integriertem Boost (SIB) in einem universitären Tumorzentrum untersucht.
Patienten und Methoden: In den Jahren 2010 bis 2016 wurden an der Uniklinik Frankfurt 170 Patienten mit histologisch gesichertem lokal begrenzten bis fortgeschrittenen PCa (T1-4, N0-1, M0) mittels moderat hypofraktionierter EBRT in IG-IMRT- bzw. IG-VMAT- und SIB-Technik behandelt. Alle Patienten wurden nach D’Amico-Klassifikation stratifiziert und risikoadaptiert therapiert. Die GI- und GU-Toxizität wurde gemäß CTC v4.0 wöchentlich unter der Therapie und während der Nachbeobachtungszeit erfasst. Ein biochemisches Rezidiv wurde definiert als PSA-Nadir + 2 ng/ml. Die Nachbeobachtung erfolgte 6-8 Wochen, 2-3 Monate und 6 Monate nach Radiotherapie sowie anschließend mindestens einmal jährlich. Die Datenauswertung erfolgte retrospektiv. Für die statistischen Analysen wurden die Software-Programme Excel und SPSS verwendet. Die Kaplan-Meier-Überlebensanalysen wurden mittels Log-Rank-Test verglichen und bei signifikanten Unterschieden in eine Cox-Regression-Analyse aufgenommen. Ein möglicher Zusammenhang zwischen dosimetrischen/klinischen Parametern und GI-/GU-Toxizität wurde mittels Chi-Quadrat-Test nach Pearson geprüft. Für alle durchgeführten Analysen galt ein p-Wert von <0,05 als statistisch signifikant. Ergebnisse: Patienten der low-risk- (n = 15) sowie intermediate- und high-risk-Gruppe mit Z.n. TURP (n= 14) erhielten eine GRD von 73,6 Gy für das PTV1 bzw. 58,24 Gy (PTV2) mit einer Einzeldosis von 2,3 Gy (SIB) bzw. 1,82 Gy in 32 Fraktionen. Patienten der intermediate- (n = 70) und high-risk- (n = 71) Gruppe erhielten eine GRD von 75,9 Gy (PTV1) bzw. 60,06 Gy (PTV2) mit einer Einzeldosis von 2,3 Gy (SIB) bzw. 1,82 Gy in 33 Fraktionen. Eine zusätzliche Bestrahlung des LAG (PTV3) mit einer GRD von 46,0 Gy und 1,84 Gy Einzeldosis in 25 Fraktionen erhielten alle Patienten mit radiologischer cN1-Situation bzw. im Falle eines LK-Befallsrisikos von >20% nach Roach-Formel (n = 86). Eine (neo-) adjuvante AHT erhielten insg. 98 Patienten. Die mediane Nachbeobachtungszeit betrug 36 Monate (Range: 5-84 Monate). Die 24-, 36-, und 60-Monate-ÜLR lagen in der IR-Gruppe bei 98,4%, 96,1% bzw. 89,7% (OS), 98,6% bzw. 94,9% (BC), 97% bzw. 84,5% (DFS) und 98,6% (FFM), in der HR-Gruppe bei 93,1% bzw. 88,8% (OS), 89%, 84,7% bzw. 75,3% (BC), 82,5%, 74,2% bzw. 65,9% (DFS) und 98%, 95,7% bzw. 84,8% (FFM). Weder für die AHT noch die RT des LAG konnte eine Verbesserung des OS, DFS, FFM sowie der BC gezeigt werden. Eine Akuttoxizität Grad 2 trat bei 6,5% (GI) bzw. 16,5% (GU) und Grad 3 bei 0,6% (GI) bzw. 0% (GU) auf. Eine Spättoxizität Grad 2 trat bei 2,9% (GI) bzw. 12,4% (GU) und Grad 3 bei 0,6% (GI) bzw. 1,2% (GU) auf.
Schlussfolgerung: Mit Implementierung der moderat hypofraktionierten EBRT nach o.g. Schema (73,6 Gy (79,9 Gy nach EQD2 (αβ 1,5)) bzw. 75,9 Gy (82,4 Gy nach EQD2 (αβ 1,5)) konnten im Rahmen dieser retrospektiven Kohortenstudie sehr gute Ergebnisse für intermediate- und high risk-Patienten des lokal begrenzten bis fortgeschrittenen PCa hinsichtlich der onkologischen Endpunkte sowie der GI-/GU-Toxizität, vergleichbar mit den besten Ergebnissen aktueller Publikationen, erzielt werden. Diese Ergebnisse bekräftigen die zunehmende Anwendung dieser Bestrahlungstechnik. Die Kohorte sollte zur Validierung der Ergebnisse weiter expandiert und mit einer längeren Nachbeobachtungszeit erneut ausgewertet werden.
Non-random connectivity can emerge without structured external input driven by activity-dependent mechanisms of synaptic plasticity based on precise spiking patterns. Here we analyze the emergence of global structures in recurrent networks based on a triplet model of spike timing dependent plasticity (STDP) which depends on the interactions of three precisely-timed spikes and can describe plasticity experiments with varying spike frequency better than the classical pair-based STDP rule. We derive synaptic changes arising from correlations up to third-order and describe them as the sum of structural motifs which determine how any spike in the network influences a given synaptic connection through possible connectivity paths. This motif expansion framework reveals novel structural motifs under the triplet STDP rule, which support the formation of bidirectional connections and ultimately the spontaneous emergence of global network structure in the form of self-connected groups of neurons, or assemblies. We propose that under triplet STDP assembly structure can emerge without the need for externally patterned inputs or assuming a symmetric pair-based STDP rule common in previous studies. The emergence of non-random network structure under triplet STDP occurs through internally-generated higher-order correlations, which are ubiquitous in natural stimuli and neuronal spiking activity, and important for coding. We further demonstrate how neuromodulatory mechanisms that modulate the shape of the triplet STDP rule or the synaptic transmission function differentially promote structural motifs underlying the emergence of assemblies, and quantify the differences using graph theoretic measures.
Die vorliegende Arbeit beschäftigt sich mit der außerhäuslichen Alltagsmobilität älterer Menschen, die eine zentrale Schlüsselfunktion in der Erhaltung von Lebensqualität und Gesundheit besonders im höheren Lebensalter einnimmt. Außerhäusliche Alltagsmobilität vollzieht sich stets in einem räumlichen Umweltausschnitt und kann aus ökogerontologischer Perspektive als Ergebnis eines gelungenen Person-Umwelt-Austauschs verstanden werden. Inwiefern psychologische Ressourcen im Sinne mobilitätsspezifischer Einstellungen zum Verständnis von zielgerichteter und habitualisierter Alltagsmobilität älterer Menschen beitragen können, ist Gegenstand der vorliegenden Arbeit. Altersspezifische, mobilitätsrelevante Einstellungen im außerhäuslichen Kontext werden sowohl in der sozialwissenschaftlichen Mobilitäts- und Alternsforschung als auch in der Praxis, etwa im Rahmen einer altersgerechten Stadtgestaltung, bislang noch zu wenig berücksichtigt. Die vorliegende Arbeit reagiert auf dieses Forschungsdesiderat, indem sie mobilitätsspezifische Einstellungen im höheren Lebensalter konzeptuell beschreibt, in den Kontext ökogerontologischer Theorien einbettet und ihre Bedeutung für den Erhalt eines aktiven und gelingenden Alterns untersucht. Im Rahmen der Dissertation wurde zunächst auf der Basis klassischer und neuer ökogerontologischer Modelle das Konstrukt der mobilitätsbezogenen Handlungsflexibilität und Routinen (MBFR) konzeptuell entwickelt. MBFR umfasst einerseits die individuelle Überzeugung, das eigene Mobilitätsverhalten an Herausforderungen außer Haus anpassen zu können (FLEX) und andererseits die Präferenz für mobilitätsbezogene Alltagsroutinen (ROU). Daraufhin wurde ein standardisiertes Messinstrument zur Erfassung des MBFR-Konzepts entwickelt, optimiert und hinsichtlich seiner psychometrischen Qualität untersucht. Die Formulierung der Testitems erfolgte in Anlehnung an bereits existierende Fragebögen zu verwandten Konstrukten. In der vorwiegend online durchgeführten Pilotstudie (Penger & Oswald, 2017) wurden die Items mittels explorativer Faktorenanalysen hinsichtlich ihrer dimensionalen Struktur untersucht. Die Stichprobe umfasste 265 Personen im Alter von 65 Jahren oder älter. Die Analysen des MBFR-Instruments ergaben nach Ausschluss von Items mit niedrigen und nicht eindeutigen Ladungen drei substanzielle Faktoren. Die Items der ersten Dimension bildeten die Überzeugung ab, flexibel mit personenbezogenen, altersassoziierten Herausforderungen (z. B. Schwierigkeiten im Gehen oder auf eine Gehhilfe angewiesen sein) umgehen zu können, um außerhäuslich mobil zu sein. Die Items der zweiten Dimension erfassten die Überzeugung, flexibel mit herausfordernden außerhäuslichen Umweltbedingungen (z. B. eine verlegte Haltestelle oder ein schlechter Zustand der Gehwege) umgehen zu können. Items, die auf den dritten Faktor luden, bildeten die Neigung zu Routinen im Mobilitätsalltag ab, z. B. bekannte Wege beizubehalten oder bei der Ausübung von außerhäuslichen Aktivitäten vertraute Orte aufzusuchen. Während die ersten beiden Faktoren mobilitätsbezogene Handlungsflexibilität (FLEX) messen, werden im dritten Faktor habitualisierte Verhaltensweisen (ROU) erfasst. Alle drei Faktoren wiesen eine akzeptable Reliabilität auf. Auf Basis von Rückmeldungen der Studienteilnehmer:innen wurde das MBFR-Instrument anschließend sprachlich angepasst und gekürzt. Der modifizierte Fragebogen wurde daraufhin in der empirischen Studie „MOBIL bleiben in Stuttgart“ (MBIS) eingesetzt. Dabei sollte die Frage beantwortet werden, ob das finale MBFR-Instrument die zugrundeliegenden Konstrukte valide und reliabel erfasst und die Testwerte somit ausreichende Gültigkeit hinsichtlich faktorieller, Konstrukt- und Kriteriumsvalidität bei älteren Menschen im urbanen Raum aufweisen (Penger & Conrad, eingereicht). Es wurden insgesamt 211 privatwohnende Stuttgarter:innen ab 65 Jahren in persönlichen Interviews und mithilfe eines 7-tägigen Wegetagebuchs zu verschiedenen Aspekten ihrer Mobilität im Wohnumfeld befragt. Statistische Analysen auf latenter Ebene erfolgten mittels Strukturgleichungsmodellen. Bivariate Zusammenhänge und Subgruppenanalysen wurden mittels Korrelations- und Regressionsanalysen berechnet. Die dreifaktorielle Struktur des MBFR-Fragebogens konnte im konfirmatorischen Modell empirisch bestätigt werden. Zudem fiel die interne Konsistenz aller drei Faktoren gut aus. Zusammenhänge zu konstruktverwandten Merkmalen – wie allgemeine und mobilitätsspezifische Einstellungen – deuten darauf hin, dass das MBFR-Instrument ausreichend konvergente Validität aufweist. Analysen auf latenter Ebene ergaben, dass Befragte durchschnittlich mehr außerhäusliche Wege zurückzulegten, wenn sie in stärkerem Maße überzeugt waren, flexibel auf mobilitätsbezogene Herausforderungen reagieren zu können (FLEX). Weiterhin ließen sich positive Zusammenhänge zwischen FLEX und der erlebten Selbstständigkeit sowie dem subjektiven Wohlbefinden aufzeigen. Die Befunde belegen somit hinreichende Übereinstimmungsvalidität der Testwerte. Differenzierte Analysen machten darüber hinaus deutlich, dass FLEX vor allem bei Befragten mit Mobilitätseinschränkungen bedeutsam zur Vorhersage des außerhäuslichen Mobilitätsverhaltens beitrug. ...
The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated selective macroautophagy. To adapt cellular homeostasis to stress, BAG3 modulates and functions in various cellular processes and signaling pathways. Noteworthy, dysfunction and deregulation of BAG3 and its pathway are pathophysiologically linked to myopathies, cancer, and neurodegenerative disorders. Here, we report a BAG3 proteomic signature under proteostasis stress. To elucidate the dynamic and multifunctional action of BAG3 in response to stress, we established BAG3 interactomes under basal and proteostasis stress conditions by employing affinity purification combined with quantitative mass spectrometry. In addition to the identification of novel potential BAG3 interactors, we defined proteins whose interaction with BAG3 was altered upon stress. By functional annotation and protein-protein interaction enrichment analysis of the identified potential BAG3 interactors, we confirmed the multifunctionality of BAG3 and highlighted its crucial role in diverse cellular signaling pathways and processes, ensuring cellular proteostasis and cell viability. These include protein folding and degradation, gene expression, cytoskeleton dynamics (including cell cycle and transport), as well as granulostasis, in particular.
Baseline presence of NAFLD predicts weight loss after gastric bypass surgery for morbid obesity
(2020)
Background. Bariatric surgery is a widely used treatment for morbid obesity. Prediction of postoperative weight loss currently relies on prediction models, which mostly overestimate patients’ weight loss. Data about the influence of Non-alcoholic fatty liver disease (NAFLD) on early postoperative weight loss are scarce. Methods. This prospective, single-center cohort study included 143 patients receiving laparoscopic gastric bypass surgery (One Anastomosis-Mini Gastric Bypass (OAGB-MGB) or Roux-en-Y Gastric Bypass (RYGB)). Liver biopsies were acquired at surgery. NAFLD activity score (NAS) assigned patients to “No NAFLD”, “NAFL” or “NASH”. Follow up data were collected at 3, 6 and 12 months. Results. In total, 49.7% of patients had NASH, while 41.3% had NAFL. Compared with the No NAFLD group, NAFL and NASH showed higher body-mass-index (BMI) at follow-up (6 months: 31.0 kg/m2 vs. 36.8 kg/m2 and 36.1 kg/m2, 12 months: 27.0 kg/m2 vs. 34.4 and 32.8 kg/m2) and lower percentage of total body weight loss (%TBWL): (6 months: 27.1% vs. 23.3% and 24.4%; 12 months: 38.5% vs. 30.1 and 32.6%). Linear regression of NAS points significantly predicts percentage of excessive weight loss (%EWL) after 6 months (Cologne-weight-loss-prediction-score). Conclusions. Histopathological presence of NAFLD might lead to inferior postoperative weight reduction after gastric bypass surgery. The mechanisms underlying this observation should be further studied.
Hintergrund: Mit dem Masterplan 2020 und den an mehreren Universitäten eingeführten Modellstudiengängen befindet sich das Medizinstudium aktuell im Umbruch. Sowohl im Regel- als auch im Modellstudiengang werden medizinrechtliche Aspekte überwiegend im Rahmen rechtsmedizinischer Ausbildungsabschnitte unterrichtet. Allerdings werden Studierende bereits während Famulaturen oder im praktischen Jahr mit juristischen Fragen konfrontiert.
Ziel der Studie war es herauszufinden, ob und in welchem Umfang Studierende der Humanmedizin insbesondere zur ärztlichen Aufklärung und zu den ärztlichen Informationspflichten bis zum Beginn des 4. bzw. 5. klinischen Semesters auf medizinrechtliche Aspekte vorbereitet wurden, und ob Verbesserungen bei der medizinrechtlichen Lehre gewünscht werden.
Material und Methoden: Zwischen den Sommersemestern 2017 und 2019 wurde zu Beginn des Kurses für Rechtsmedizin eine quantitative, standardisierte Umfrage mit insgesamt 373 Studierenden durchgeführt.
Ergebnisse: Wenngleich 98,8 % der Studierenden angaben, Aufklärungsgespräche bereits (mehrfach) praktisch ausgeübt zu haben, bestanden deutliche Defizite in Bezug auf die juristischen Anforderungen an das ärztliche Aufklärungsgespräch und dessen Delegation. So gaben lediglich 5,1 % der Studierenden an, die rechtlichen Grundlagen der ärztlichen Aufklärung sowie die entsprechende Norm aus dem Zivilrecht zu kennen. Über 80 % der Befragten fühlten sich unzureichend auf die rechtlichen Aspekte des praktischen Jahres vorbereitet. Über 90 % der Studierenden wünschten sich eine bessere medizinrechtliche Ausbildung.
Diskussion: Eine fächerübergreifende Etablierung sowie eine über das gesamte Studium verteilte Lehre von Medizinrecht könnte die Vorbereitung auf das praktische Jahr verbessern und das Verständnis für die rechtlichen Anforderungen an die ärztliche Berufstätigkeit fördern. Nach dem derzeitigen Stand der Umsetzung des Masterplans 2020 soll das Medizinrecht in der Learning Opportunities, Objectives and Outcomes Platform (LOOOP) als verbindlicher Ausbildungs- und Lehrinhalt etabliert werden.
With obesity having doubled in the last decade, hypertension is on the rise. In one-third of hypertensive patients the metabolic syndrome is present. This might be one factor for the increasing number of prescriptions for angiotensin receptor blockers and calcium-channel blockers besides a more favorable risk-to-benefit ratio. The aim of the present study was to evaluate a therapeutic drug monitoring (TDM) method for assessment of adherence based on cut-offs in inpatients and to compare it to an established urine drug screening in outpatients. A method for quantification of calcium-channel blockers and angiotensin receptor blockers using high-performance liquid chromatography-tandem mass spectrometric analysis (LC-MS/MS) was developed and validated. The method was applied to serum samples of 32 patients under supervised medication to establish cut-off values for adherence assessment based on dose-related concentrations (DRC, calculated from pharmacokinetic data). Furthermore, corresponding urine and blood samples of 42 outpatients without supervised medication were analysed and the results compared with regard to adherence assessment. All serum concentrations measured for amlodipine (n = 40), lercanidipine (n = 14), candesartan (n = 10), telmisartan (n = 4) and valsartan (n = 10) in inpatients were above the patient specific lower DRC confirming adherence. Of 42 outpatients the identification of analytes in urine as well as the quantification in serum exhibited differing results. According to urinalysis, adherence was demonstrated in only 87.0% of prescriptions, compared to 91.3% for serum analyses. Differences were observed for amlodipine, lercanidipine and candesartan which can be explained by a higher specificity of the serum analysis approach due to pharmacokinetics. The present study confirms that assessing adherence based on serum drug concentrations with individually calculated lower DRCs is more accurate than using qualitative urine analysis. In particular, drugs with low bioavailability, low renal excretion or high metabolism rate such as lercanidipine and candesartan may lead to underestimation of adherence via urine analysis.