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- Onkogen (12)
- PCR (12)
- PRRT (12)
- Pharmakologie (12)
- Pilzkörper (12)
- Polytrauma (12)
- Quality of Experience (12)
- Quantenchemie (12)
- Rekonstruktion (12)
- Religion (12)
- Replikation (12)
- Risikofaktor (12)
- Rotatorenmanschette (12)
- Ruthenium (12)
- SMN (12)
- SNP (12)
- Siliciumorganische Verbindungen (12)
- Spracherwerb (12)
- Toll-like-Rezeptoren (12)
- Ultrakurzer Lichtimpuls (12)
- Validierung (12)
- Zelladhäsion (12)
- age (12)
- amygdala (12)
- animal model (12)
- antibody (12)
- biofabrication (12)
- blood–brain barrier (12)
- carbenes (12)
- cartilage (12)
- catalysis (12)
- colorectal carcinoma (12)
- complications (12)
- database (12)
- dementia (12)
- drug delivery (12)
- dynamics (12)
- emotions (12)
- endothelium (12)
- enzyme replacement therapy (12)
- fear conditioning (12)
- genome (12)
- head and neck cancer (12)
- heart rate (12)
- interaction (12)
- lymphocytes (12)
- malignant hyperthermia (12)
- measles (12)
- microarray (12)
- molecular beam epitaxy (12)
- monoclonal antibodies (12)
- neurology (12)
- neuropathy (12)
- optimization (12)
- pollen (12)
- polymers (12)
- proteomics (12)
- rats (12)
- recombination (12)
- screening (12)
- super-resolution microscopy (12)
- synaptic plasticity (12)
- systematic review (12)
- tinnitus (12)
- total knee arthroplasty (12)
- trabeculectomy (12)
- translation (12)
- ubiquitin (12)
- ultrasound (12)
- vitamin D (12)
- vorsprachliche Entwicklung (12)
- zebrafish (12)
- ++ (11)
- 3D (11)
- Alzheimer’s disease (11)
- Anorexia nervosa (11)
- Antigen CD8 (11)
- Arabidopsis (11)
- B-Zelle (11)
- Bioisosterie (11)
- Biosynthese (11)
- Bioverfügbarkeit (11)
- Bruchpilot (11)
- Candida (11)
- Chromatin (11)
- Click-Chemie (11)
- Computertomografie (11)
- Durchflusscytometrie (11)
- Dynamik (11)
- EGFR (11)
- Elektronentransfer (11)
- Enzym (11)
- Epidemiologie (11)
- Epidermaler Wachstumsfaktor-Rezeptor (11)
- Flavonoide (11)
- Fließverhalten (11)
- Fotovoltaik (11)
- Genom (11)
- Geschlecht (11)
- Hypoxie (11)
- Immuncytochemie (11)
- Immunology (11)
- Japankärpfling (11)
- Knochen (11)
- Knochenersatz (11)
- Kolorektales Karzinom (11)
- LPS (11)
- Laser (11)
- Längsschnittuntersuchung (11)
- MS (11)
- Mais (11)
- Mathematik (11)
- Megakaryozyt (11)
- Mensch-Maschine-Kommunikation (11)
- Mesenchymale Stammzellen (11)
- Mesenchymzelle (11)
- Model (11)
- Monitoring (11)
- NIRS (11)
- Nanodiamant (11)
- Neuropathie (11)
- Niereninsuffizienz (11)
- Operation (11)
- Osteoinduktion (11)
- Parathormon (11)
- Perylenbisimid (11)
- Phylogenie (11)
- Proteaseinhibitor (11)
- Proteasen (11)
- Psychiatrie (11)
- Pulmonale Hypertonie (11)
- Quality of life (11)
- Quanten-Hall-Effekt (11)
- Reperfusion (11)
- Risikofaktoren (11)
- Salmonella (11)
- Schizophrenia (11)
- Schlafapnoe (11)
- Schließzelle (11)
- Schule (11)
- Schultergelenk (11)
- Schädel-Hirn-Trauma (11)
- Silicate (11)
- Skala (11)
- Small RNA (11)
- Sphingolipide (11)
- Sprache (11)
- Squark (11)
- Stammzellen (11)
- Sterblichkeit (11)
- Supraleitung (11)
- Symbiose (11)
- T cell (11)
- TWEAK (11)
- Training (11)
- Tuberkelbakterium (11)
- Tumor-Nekrose-Faktor <alpha> (11)
- USA (11)
- Ubiquitin (11)
- Vasodilatator-stimuliertes Phosphoprotein (11)
- Wahrnehmung (11)
- Westafrika (11)
- Zelltod (11)
- adhesion (11)
- allergy (11)
- atrial fibrillation (11)
- biocompatibility (11)
- biofilm (11)
- cancer treatment (11)
- cell adhesion (11)
- cochlear implant (11)
- communication (11)
- coping (11)
- dosimetry (11)
- emotion regulation (11)
- fear (11)
- fluorescence microscopy (11)
- genomics (11)
- glioblastoma multiforme (11)
- hypoxia (11)
- immunology (11)
- kinetics (11)
- lung (11)
- mechanism (11)
- meiosis (11)
- membrane proteins (11)
- microbiome (11)
- microglia (11)
- molecular dynamics (11)
- molecular imaging (11)
- nervous system (11)
- neural networks (11)
- neuroendocrine tumor (11)
- next generation sequencing (11)
- nuclear envelope (11)
- oncolytic virus (11)
- periodontitis (11)
- plasticity (11)
- pollination (11)
- randomized controlled trial (11)
- reactive oxygen species (11)
- relapse (11)
- review (11)
- safety (11)
- signaling (11)
- thrombosis (11)
- tight junctions (11)
- topological insulator (11)
- transport (11)
- tumor microenvironment (11)
- university (11)
- water oxidation (11)
- Alkohol (10)
- Alzheimer's disease (10)
- Antigen CD28 (10)
- Arzneimittelüberwachung (10)
- Atherosclerosis (10)
- BERA (10)
- BMP-2 (10)
- Bacteria (10)
- Bakterielle Infektion (10)
- Beschichtung (10)
- Bildverarbeitung (10)
- Bioinformatics (10)
- Biokompatibilität (10)
- Blazar (10)
- Borole (10)
- CRISPR/Cas-Methode (10)
- CRISPR/Cas9 (10)
- Cadherine (10)
- Calciumphosphate (10)
- Carbene (10)
- Children (10)
- Chronische Niereninsuffizienz (10)
- Churritisch (10)
- Cochlear-Implantat (10)
- Coronaviren (10)
- Covid-19 (10)
- Cyclo-GMP (10)
- Depressivität (10)
- Diamant (10)
- Digital Humanities (10)
- Dimerisierung (10)
- Dotierung (10)
- Echokardiographie (10)
- Eierstockkrebs (10)
- Elektrochemie (10)
- Elektronenkorrelation (10)
- Englisch (10)
- Enzyminhibitor (10)
- Erbkrankheit (10)
- Ereigniskorreliertes Potenzial (10)
- Erwachsener (10)
- Franken (10)
- Frau (10)
- Funktionalisierung <Chemie> (10)
- Funktionelle Kernspintomografie (10)
- Förderung (10)
- Geldpolitik (10)
- Glatter Krallenfrosch (10)
- Grenzfläche (10)
- HSM-Satztest (10)
- Herzmuskelzelle (10)
- Honigbiene (10)
- Hypophosphatasie (10)
- Impfstoff (10)
- Induzierte pluripotente Stammzelle (10)
- Interleukin 4 (10)
- JNK (10)
- Klassifikation (10)
- Kniegelenk (10)
- Kohlenstoff (10)
- Komplikation (10)
- Kooperation (10)
- Kultur (10)
- LASP1 (10)
- LC-MS (10)
- Ladungstransfer (10)
- Ligand (10)
- Lokalisation (10)
- Magnesiumphosphate (10)
- Magnetismus (10)
- Mathematikunterricht (10)
- Mathematisches Modell (10)
- Medulloblastom (10)
- Metakognition (10)
- Metallocene (10)
- Methylphenidat (10)
- Mikrokerne (10)
- Multiple Myeloma (10)
- Musik (10)
- Mutagenität (10)
- Nahrungserwerb (10)
- Nebennierenrindenkarzinom (10)
- Neolithikum (10)
- Neuropathischer Schmerz (10)
- Niger (10)
- Osteosynthese (10)
- Pain (10)
- Panikstörung (10)
- Parasit (10)
- Parodontitis (10)
- Pathogenität (10)
- Platelets (10)
- Plattenepithelkarzinom (10)
- Prevalence (10)
- Prostaglandine (10)
- Präfrontaler Cortex (10)
- Psychotherapie (10)
- Pädagogik (10)
- Qualitätskontrolle (10)
- RNA interference (10)
- RNA-seq (10)
- RNS-Spleißen (10)
- Radiotherapy (10)
- Remote Sensing (10)
- Rhodium (10)
- Rituximab (10)
- SAR (10)
- Schilddrüse (10)
- Silaanaloga (10)
- Silber (10)
- Silicon (10)
- South Africa (10)
- Sprachverstehen (10)
- Starke Kopplung (10)
- Stickstoffmonoxid-Synthase (10)
- Stressreaktion (10)
- Stroke (10)
- Struktur (10)
- T-Lymphozyten (10)
- T-Lymphozyten-Rezeptor (10)
- Tagesrhythmus (10)
- Theologie (10)
- Totalsynthese (10)
- Toxizität (10)
- Transplantat-Wirt-Reaktion (10)
- Transthorakale Echokardiographie (10)
- Treg (10)
- Trypanosomen (10)
- Verwaltungsrecht (10)
- Vitamin D (10)
- Vor- und Frühgeschichte (10)
- Vorschulkind (10)
- Wachstum (10)
- Zebrabärbling (10)
- amino acids (10)
- antimicrobial resistance (10)
- bariatric surgery (10)
- biosynthesis (10)
- boranes (10)
- chemokines (10)
- chronic heart failure (10)
- circadian rhythms (10)
- clinical trial (10)
- comparison (10)
- complex (10)
- coronary artery disease (10)
- decision-making (10)
- density functional calculations (10)
- eNOS (10)
- education (10)
- fatigue (10)
- genome-wide association (10)
- global change (10)
- hydrogels (10)
- immunomodulation (10)
- induced pluripotent stem cells (10)
- injury (10)
- insect (10)
- knockout (10)
- leaf-cutting ants (10)
- leukemia (10)
- lymph nodes (10)
- mapping (10)
- membrane potential (10)
- motivation (10)
- oncology (10)
- oncolytic virotherapy (10)
- oxidativer Stress (10)
- phenotype (10)
- quality assurance (10)
- regulatorische T-Zellen (10)
- remodeling (10)
- senescence (10)
- silicon (10)
- social interaction (10)
- stem cell transplantation (10)
- tDCS (10)
- tumors (10)
- vaccination (10)
- vertigo (10)
- walking (10)
- Östrogene (10)
- 3 (9)
- Adenosin (9)
- Adenosine receptors (9)
- Affekt (9)
- Afrika (9)
- Alps (9)
- Analyse (9)
- Angeregter Zustand (9)
- Anxiety (9)
- Aorta (9)
- Aortenstenose (9)
- Bauchspeicheldrüsenkrebs (9)
- Beyond Standard Model (9)
- Biotransformation (9)
- Bordetella pertussis (9)
- Borylierung (9)
- Boğazkale (9)
- Butyrat (9)
- Carcinogenese (9)
- Catalysis (9)
- Chiralität <Chemie> (9)
- Cloud Computing (9)
- Computational chemistry (9)
- Deep learning (9)
- Dendritic cells (9)
- Diagnose (9)
- Diborane (9)
- Diskursanalyse (9)
- Dünndarm (9)
- Einzelphotonenemission (9)
- Elektroencephalographie (9)
- Elektronenmikroskopie (9)
- Elektronenstruktur (9)
- Elementarteilchenphysik (9)
- Epithel (9)
- Ernährung (9)
- Experimentelle Psychologie (9)
- Extremwertstatistik (9)
- Familie (9)
- Fanconi Anämie (9)
- Fettgewebe (9)
- Fibroblastenwachstumsfaktor (9)
- Fibromyalgie (9)
- Frühgeborene (9)
- GIS (9)
- Geistigbehindertenpädagogik (9)
- Gentherapie (9)
- Geoinformationssystem (9)
- Geruchswahrnehmung (9)
- Glioblastoma (9)
- Google Earth Engine (9)
- Grammatik (9)
- Handlungsorientierung (9)
- Haut (9)
- Herzmuskelkrankheit (9)
- Hethiter (9)
- Hyaluronsäure (9)
- IL-4 (9)
- Immunfluoreszenz (9)
- Immunisierung (9)
- Innovation (9)
- Instrumentelle Analytik (9)
- Integrine (9)
- Interview (9)
- Iran (9)
- Isolierung <Chemie> (9)
- Jugendliche (9)
- Kapillarelektrophorese (9)
- Knorpel (9)
- Kommunikation (9)
- Konflikt (9)
- Koordinationslehre (9)
- Korpus <Linguistik> (9)
- Landsat (9)
- Leber (9)
- Linguistik (9)
- Löslichkeit (9)
- MAPK (9)
- Macrophage (9)
- Magnetische Resonanz (9)
- Mehrfachbindung (9)
- Mehrsprachigkeit (9)
- Messenger-RNS (9)
- Mice (9)
- Molekulare Erkennung (9)
- Monozyt (9)
- Morphologie (9)
- Mukoviszidose (9)
- Myokardprotektion (9)
- NAFLD (9)
- NO (9)
- Nebennierenrindenkrebs (9)
- Neuroinflammation (9)
- Nierentransplantation (9)
- Oberfläche (9)
- Oberflächenphysik (9)
- Optoelektronik (9)
- PD-1 (9)
- PD-L1 (9)
- Pathogenese (9)
- Persönlichkeit (9)
- Pharmakotherapie (9)
- Photolumineszenzspektroskopie (9)
- Physiologie (9)
- Plasmamembran (9)
- Protein (9)
- Pseudomonas syringae (9)
- Psychoonkologie (9)
- Quantenmechanik (9)
- Rechenzentrum (9)
- Rechtsvergleich (9)
- Regeneration (9)
- Regionalentwicklung (9)
- Revision (9)
- Sarkoidose (9)
- Satellit (9)
- Schmalwand <Arabidopsis> (9)
- Schwindel (9)
- Schüttgut (9)
- Sentinel-1 (9)
- Spin-Bahn-Wechselwirkung (9)
- Squaraine (9)
- Staphylococcus (9)
- Stathmin (9)
- Stereoselektive Synthese (9)
- Supply Chain Management (9)
- Syntax (9)
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- Textverstehen (9)
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- Transplantat (9)
- Transport (9)
- Trypanosoma (9)
- Tumorantigen (9)
- Vakuole (9)
- Vergleich (9)
- Visuelle Aufmerksamkeit (9)
- Wurzel (9)
- X-ray crystallography (9)
- Zellkern (9)
- Zentralnervensystem (9)
- Zinkselenid (9)
- adolescence (9)
- aggregation (9)
- agriculture (9)
- aldosterone (9)
- antennal lobe (9)
- anxiety disorders (9)
- aromaticity (9)
- bioinformatics (9)
- biomechanics (9)
- blood brain barrier (9)
- body size (9)
- bone cement (9)
- bone marrow (9)
- cancer therapy (9)
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- cell culture (9)
- cell migration (9)
- cell wall (9)
- central nervous system (9)
- cerebrospinal fluid (9)
- chromatin (9)
- cognitive impairment (9)
- collagen (9)
- coronary heart disease (9)
- cuticular hydrocarbons (9)
- cystic fibrosis (9)
- decision making (9)
- dendritische Zellen (9)
- dialysis (9)
- dispersal (9)
- earth observation (9)
- electron microscopy (9)
- electronic properties and materials (9)
- electrophysiology (9)
- energy (9)
- experimental autoimmune encephalomyelitis (9)
- family (9)
- forest (9)
- gene therapy (9)
- glioma (9)
- glucose (9)
- glycine receptor (9)
- high energy physics (9)
- hip (9)
- hyaluronic acid (9)
- hydrogel (9)
- impact (9)
- incidence (9)
- inhibitor (9)
- interferon (9)
- mechanotransduction (9)
- mesenchymale Stammzellen (9)
- metapopulation (9)
- methylation (9)
- mitosis (9)
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- pathway (9)
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- permeability (9)
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- platelet activation (9)
- platelet aggregation (9)
- prognostic factors (9)
- quantification (9)
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- reveals (9)
- selection (9)
- serum (9)
- spinal muscular atrophy (9)
- subthalamic nucleus (9)
- synapse (9)
- systematic uncertainty (9)
- temperature (9)
- tolerance (9)
- transcription factor (9)
- transient absorption (9)
- transmission (9)
- type 2 diabetes (9)
- vaccine (9)
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- Übersetzung (9)
- ATLAS (8)
- Adhärenz (8)
- Aggregat <Chemie> (8)
- Akt (8)
- Aktiver galaktischer Kern (8)
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- Ancistrocladaceae (8)
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- Antigen (8)
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- Aortenklappenersatz (8)
- Arthrose (8)
- Arthroskopie (8)
- Arzneimittelforschung (8)
- Asymmetrie (8)
- Asymmetrische Synthese (8)
- Auge (8)
- Autoaggressionskrankheit (8)
- Autonomer Roboter (8)
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- Bauchspeicheldrüse (8)
- Biradikal (8)
- Blimp-1 (8)
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- Botanik (8)
- Brain (8)
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- CD28 (8)
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- CD95 (8)
- COMT (8)
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- Caenorhabditis elegans (8)
- Camponotus floridanus (8)
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- Cross-Section (8)
- Cysteinproteasen (8)
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- DLBCL (8)
- Darm (8)
- Data Mining (8)
- Datenbank (8)
- Degradation (8)
- Demenz (8)
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- Diborene (8)
- ERK (8)
- Elektronenspin (8)
- Elektronenspinresonanz (8)
- Emotionsregulation (8)
- Endothelzellen (8)
- Engagement (8)
- Erbrechen (8)
- Europa (8)
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- Femtosekundenbereich (8)
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- Finite-Elemente-Methode (8)
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- Fluoreszenzspektroskopie (8)
- Forschung (8)
- Fußball (8)
- GABA (8)
- Gammastrahlung (8)
- Gedächtnisleistung (8)
- Geschlechtsunterschied (8)
- Gewebe (8)
- Gliom (8)
- Graphen (8)
- HPLC-MS (8)
- Habichtskraut (8)
- Haemophilus influenzae (8)
- Harnwegsinfektion (8)
- Hernie (8)
- Hochbegabung (8)
- Hubbard-Modell (8)
- Humangenetik (8)
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- Hüftgelenk (8)
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- In vivo (8)
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- Inklusion (8)
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- Kleinsatellit (8)
- Knockout (8)
- Komposit <Zahnmedizin> (8)
- Kondo-Effekt (8)
- Korrelation (8)
- Kreuzband (8)
- Kristallstruktur (8)
- LC-MS/MS (8)
- Landwirtschaft (8)
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- Multiple myeloma (8)
- N-heterocyclic carbenes (8)
- NSCLC (8)
- Nachsorge (8)
- Naturstoff (8)
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- Optogenetik (8)
- Organisches Molekül (8)
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- PONV (8)
- Pankreaskarzinom (8)
- Parton distributions (8)
- Pemphigus (8)
- Peptide (8)
- Periphere arterielle Verschlusskrankheit (8)
- Permeabilität (8)
- Pharmakodynamik (8)
- Photodissoziation (8)
- Photovoltaik (8)
- Platin (8)
- Pollen (8)
- Polycyclische Aromaten (8)
- Protein p53 (8)
- Protein-Tyrosin-Kinasen (8)
- Proteinbindung (8)
- Protonen-NMR-Spektroskopie (8)
- Präkonditionierung (8)
- Psychische Störung (8)
- Pump-Probe-Technik (8)
- Quantendynamik (8)
- Quelle (8)
- Quran (8)
- Radikal <Chemie> (8)
- Raf <Biochemie> (8)
- Raf-Kinasen (8)
- Raman spectroscopy (8)
- Rastertunnelmikroskop (8)
- Rechenzentrum Universität Würzburg (8)
- Regenerative Medizin (8)
- Rekombination (8)
- Retroviren (8)
- Ringöffnungspolymerisation (8)
- Roman (8)
- Röntgen-Photoelektronenspektroskopie (8)
- Salmonella typhimurium (8)
- Schmerzforschung (8)
- Schwämme (8)
- Semimagnetischer Halbleiter (8)
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- Statistik (8)
- Stent (8)
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- Survival (8)
- Synthesis (8)
- T cell activation (8)
- T lymphocytes (8)
- T-Zelle (8)
- TDM (8)
- Tabak (8)
- Tagung (8)
- Text Mining (8)
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- Thrombosis (8)
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- Thymus (8)
- Tight junction (8)
- Titan (8)
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- Trauma (8)
- Trypanosomiase (8)
- Tumorimmunologie (8)
- UAV (8)
- Ultraschalldiagnostik (8)
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- Vulnerabilität (8)
- Wirkstofffreisetzung (8)
- Zahnmedizin (8)
- Zeitreihenanalyse (8)
- absorption (8)
- actin cytoskeleton (8)
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- - (6)
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- Nebenwirkungen (4)
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- Nervennetz (4)
- Nestbau (4)
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- Numerisches Modell (4)
- Oberflächenzustand (4)
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- Omarthrose (4)
- Online-Handel (4)
- Onlinehandel (4)
- OpenSpaceAlps (4)
- Operationstechnik (4)
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- Overlay-Netz (4)
- Oxidative Stress (4)
- Oxidative stress (4)
- PAK (4)
- PBMC (4)
- PEG (4)
- PER (4)
- PI3K (4)
- PSA (4)
- PSMA-RADS (4)
- PTCA (4)
- PTCDA (4)
- PTEN (4)
- PTH (4)
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- Pe (4)
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- Phobie (4)
- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (4)
- Phosphoglykolatphosphatase (4)
- Phospholipide (4)
- Phosphor (4)
- Photorezeptor (4)
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Schriftenreihe
- Cultural Animal Studies, Band 3 (24)
- Spezielle Didaktik der Sportarten (2)
- Aesthetische Eigenzeiten, 17 (1)
- Akten des ... Symposiums des Mediävistenverbandes; 13,2 (1)
- Alter Orient und Altes Testament : Sonderreihe Veröffentlichungen zur Kultur und Geschichte des Alten Orients ; 3 (1)
- Aventiuren; 13 (1)
- Berichte aus der Informatik (1)
- Deuterocanonical and Cognate Literature Studies (1)
- Deuterocanonical and Cognate Literature Yearbook (1)
- Epistemata. Reihe Literaturwissenschaft ; 483 (1)
Sonstige beteiligte Institutionen
- VolkswagenStiftung (24)
- Johns Hopkins School of Medicine (18)
- Fraunhofer-Institut für Silicatforschung ISC (8)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
- Akademie der Wissenschaften und der Literatur, Mainz (6)
- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (6)
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ResearcherID
- B-1911-2015 (1)
- B-4606-2017 (1)
- C-2593-2016 (1)
- D-1221-2009 (1)
- D-1250-2010 (1)
- D-3057-2014 (1)
- I-5818-2014 (1)
- J-8841-2015 (1)
- M-1240-2017 (1)
- N-2030-2015 (1)
Background: Aging increases individual susceptibility to falls and injuries, suggesting poorer adaptation of balance responses to perturbation during locomotion, which can be measured with the locomotor adaptation task (LAT). However, it is unclear how aging and lifestyle factors affect these responses during walking. Hence, the present study investigates the relationship between balance and lifestyle factors during the LAT in healthy individuals across the adult lifespan using a correlational design. Methods: Thirty participants aged 20–78 years performed an LAT on a split-belt treadmill (SBT). We evaluated the magnitude and rate of adaptation and deadaptation during the LAT. Participants reported their lifelong physical and cognitive activity. Results: Age positively correlated with gait-line length asymmetry at the late post-adaptation phase (p = 0.007). These age-related effects were mediated by recent physical activity levels (p = 0.040). Conclusion: Our results confirm that locomotor adaptive responses are preserved in aging, but the ability to deadapt newly learnt balance responses is compromised with age. Physical activity mediates these age-related effects. Therefore, gait symmetry post-adaptation could effectively measure the risk of falling, and maintaining physical activity could protect against declines in balance.
Background: Monitoring the vital signs of delirious patients in an intensive care unit (ICU) is challenging, as they might (un-)intentionally remove devices attached to their bodies. In mock-up scenarios, we systematically assessed whether a motion detector (MD) attached to the bed may help in identifying emergencies. Methods: We recruited 15 employees of the ICU and equipped an ICU bed with an MD (IRON Software GmbH, Grünwald, Germany). Participants were asked to replay 22 mock-up scenes of one-minute duration each: 12 scenes with movements and 10 without movements, of which 5 were emergency scenes (“lying dead-still, with no or very shallow breathing”). Blinded recordings were presented to an evaluation panel consisting of an experienced ICU nurse and a physician, who was asked to assess and rate the presence of motions. Results: Fifteen participants (nine women; 173 ± 7.0 cm; 78 ± 19 kg) joined the study. In total, 286 out of 330 scenes (86.7%) were rated correctly. Ratings were false negative (FN: “no movements detected, but recorded”) in 7 out of 180 motion scenes (3.9%). Ratings were false positive (FP: “movements detected, but not recorded”) in 37 out of 150 scenes (24.7%), more often in men than women (26 out of 60 vs. 11 out of 90, respectively; p < 0.001). Of note, in 16 of these 37 FP-rated scenes, a vibrating mobile phone was identified as a potential confounder. The emergency scenes were correctly rated in 64 of the 75 runs (85.3%); 10 of the 11 FP-rated scenes occurred in male subjects. Conclusions: The MD allowed for identifying motions of test subjects with high sensitivity (96%) and acceptable specificity (75%). Accuracy might increase further if activities are recorded continuously under real-world conditions.
In this thesis, a model system of a magnetic topological heterostructure is studied, namely a heterosystem consisting of a single ferromagnetic septuple-layer (SL) of \(MnBi_2Te_4\) on the surface of the three-dimensional topological insulator \(Bi_2Te_3\).
Using MBE and developing a specialized experimental setup, the first part of this thesis deals with the growth of \(Bi_2Te_3\) and thin films of \(MnBi_2Te_4\) on \(BaF_2\)-substrates by the co-evaporation of its binary constituents. The structural analysis is conducted along several suitable probes such as X-ray diffraction (XRD, XRR), AFM and scanning tunnelling electron microscopy (STEM). It is furthermore found that the growth of a single septuple-layer of \(MnBi_2Te_4\) on the surface of \(Bi_2Te_3\) can be facilitated.
By using X-ray absorption and circular magnetic dichroism (XAS, XMCD), the magnetic properties of \(MnBi_2Te_4\) are explored down to the monolayer limit. The layered nature of the vdW crystal and a strong uniaxial magnetocrystalline anisotropy establish stable out-of plane magnetic order at the surface of \(MnBi_2Te_4\), which is stable even down to the 2D limit. Pushing the material system to there, i.e. a single SL \(MnBi_2Te_4\) further allows to study the phase transition of this 2D ferromagnet and extract its critical behaviour with \(T_c \, = \, 14.89~k\) and \(\beta \, = \, 0.484\).
Utilizing bulk crystals of the ferromagnetic \(Fe_3GeTe_2\) as substrate allows to influence, enhance and bias the magnetism in the single SL of \(MnBi_2Te_4\). By growing heterostructures of the type \(MnBi_2Te_4\) -- n layer \(Bi_2Te_3\) -- \(Fe_3GeTe_2\)for n between 0 and 2, it is shown, that a considerable magnetic coupling can be introduced between the \(MnBi_2Te_4\) top-layer and the substrate.
Finally the interplay between topology and magnetism in the ferromagnetic extension is studied directly by angle-resolved photoemission spectroscopy. The heterostructure is found to host a linearly dispersing TSS at the centre of the Brillouin zone. Using low temperature and high-resolution ARPES a large magnetic gap opening of \(\sim\) 35 meV is found at the Dirac point of the TSS. By following its temperature evolution, it is apparent that the scaling behaviour coincides with the magnetic order parameter of the modified surface.
The expression of the MYC proto-oncogene is elevated in a large proportion of patients with pancreatic ductal adenocarcinoma (PDAC). Previous findings in PDAC have shown that this increased MYC expression mediates immune evasion and promotes S-phase progression. How these functions are mediated and whether a downstream factor of MYC mediates these functions has remained elusive. Recent studies identifying the MYC interactome revealed a complex network of interaction partners, highlighting the need to identify the oncogenic pathway of MYC in an unbiased manner.
In this work, we have shown that MYC ensures genomic stability during S-phase and prevents transcription-replication conflicts. Depletion of MYC and inhibition of ATR kinase showed a synergistic effect to induce DNA damage. A targeted siRNA screen targeting downstream factors of MYC revealed that PAF1c is required for DNA repair and S-phase progression. Recruitment of PAF1c to RNAPII was shown to be MYC dependent. PAF1c was shown to be largely dispensable for cell proliferation and regulation of MYC target genes.
Depletion of CTR9, a subunit of PAF1c, caused strong tumor regression in a pancreatic ductal adenocarcinoma model, with long-term survival in a subset of mice. This effect was not due to induction of DNA damage, but to restoration of tumor immune surveillance.
Depletion of PAF1c resulted in the release of RNAPII with transcription elongation factors, including SPT6, from the bodies of long genes, promoting full-length transcription of short genes. This resulted in the downregulation of long DNA repair genes and the concomitant upregulation of short genes, including MHC class I genes. These data demonstrate that a balance between long and short gene transcription is essential for tumor progression and that interference with PAF1c levels shifts this balance toward a tumor-suppressive transcriptional program. It also directly links MYC-mediated S-phase progression to immune evasion. Unlike MYC, PAF1c has a stable, known folded structure; therefore, the development of a small molecule targeting PAF1c may disrupt the immune evasive function of MYC while sparing its physiological functions in cellular growth.
(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.
Ag- but not ZnO-nanoparticles disturb the airway epithelial barrier at subtoxic concentrations
(2023)
Inhalation is considered to be the most relevant source of human exposure to nanoparticles (NPs); however, only a few investigations have addressed the influence of exposing the respiratory mucosal barrier to subcytotoxic doses. In the nasal respiratory epithelium, cells of the mucosa represent one of the first contact points of the human organism with airborne NPs. Disruption of the epithelial barrier by harmful materials can lead to inflammation in addition to potential intrinsic toxicity of the particles. The aim of this study was to investigate whether subtoxic concentrations of zinc oxide (ZnO)- and silver (Ag)-NPs have an influence on upper airway barrier integrity. Nasal epithelial cells from 17 donors were cultured at the air–liquid interface and exposed to ZnO- and Ag-NPs. Barrier function, quantified by transepithelial electrical resistance (TEER), decreased after treatment with 10 µg/mL Ag-NPs, but FITC-dextran permeability remained stable and no change in mRNA levels of tight junction proteins and E-cadherin was detected by real-time quantitative PCR (RT-qPCR). The results indicate that subtoxic concentrations of Ag-NPs may already induce damage of the upper airway epithelial barrier in vitro. The lack of similar disruption by ZnO-NPs of similar size suggests a specific effect by Ag-NPs.
Kisspeptins (KPs, KISS1) and their receptor (KISS1R) play a pivotal role as metastasis suppressor for many cancers. Low or lost KP expression is associated with higher tumor grade, increased metastatic potential, and poor prognosis. Therefore, KP expression has prognostic relevance and correlates with invasiveness in cancers. Furthermore, KISS1R represents a very promising target for molecular imaging and therapy for KISS1R-expressing tumors. The goal of this study was to evaluate the developed KISS1-54 derivative, [\(^{68}\)Ga]KISS1-54, as a PET-imaging probe for KISS1R-expressing tumors. The NODAGA-KISS1-54 peptide was labeled by Gallium-68, and the stability of the resulting [\(^{68}\)Ga]KISS1-54 evaluated in injection solution and human serum, followed by an examination in different KISS1R-expressing tumor cell lines, including HepG2, HeLa, MDA-MB-231, MCF7, LNCap, SK-BR-3, and HCT116. Finally, [\(^{68}\)Ga]KISS1-54 was tested in LNCap- and MDA-MB-231-bearing mice, using µ-PET, assessing its potential as an imaging probe for PET. [\(^{68}\)Ga]KISS1-54 was obtained in a 77 ± 7% radiochemical yield and at a >99% purity. The [\(^{68}\)Ga]KISS1-54 cell uptake amounted to 0.6–4.4% per 100,000 cells. Moreover, the accumulation of [\(^{68}\)Ga]KISS1-54 was effectively inhibited by nonradioactive KISS1-54. In [\(^{68}\)Ga]KISS1-54-PET, KISS1R-positive LNCap-tumors were clearly visualized as compared to MDA-MB-231-tumor implant with predominantly intracellular KISS1R expression. Our first results suggest that [\(^{68}\)Ga]KISS1-54 is a promising candidate for a radiotracer for targeting KISS1R-expressing tumors via PET.
Ziel der vorliegenden Studie war es zu untersuchen, ob anhand geometrischer Merkmale der HWK im Kindesalter eine sichere individuelle Vorhersage der Morphologie der HWK zum Ende der Entwicklung möglich ist. Hierdurch könnte eine Individualisierung der CVM-Methode und somit eine Einschätzung des bereits verstrichenen Wachstums erfolgen.
Zu diesem Zweck wurden insgesamt 1377 FRS-Aufnahmen von 267 Patienten – 110 weibliche und 157 männliche – aus dem Archiv der Poliklinik für Kieferorthopädie des Universitätsklinikums Würzburg digitalisiert und untersucht. Die HWK wurden im Programm OnyxCeph (Herst.: Image Instruments GmbH) quantifiziert und die berechneten Werte mit der Software SPSS statistisch ausgewertet. Mittels linearer Regressionen wurde versucht, anhand der Morphologie der Wirbelkörper vor dem puberalen Wachstumsschub auf die Geometrie der HWK im Erwachsenenalter zu schließen. Zur Illustrierung wurden Streudiagramm und die dazugehörigen Abfolgen von Röntgenbildern dargestellt.
Eine Schätzung der Geometrie der HWK im Erwachsenenalter würde bei den separat betrachteten Parametern und bei einer gemeinsamen Betrachtung der Parameter kaum zu korrekten Einschätzungen führen.
Die Streudiagramme mit den Bilderabfolgen stützen diese These ebenfalls und illustrieren die mögliche Fehleinschätzung der Geometrie.
Die Ergebnisse der Studie zeigen erneut, dass die Geometrie der HWK im Erwachsenenalter sehr variabel ist, wie komplex die Entwicklung der HWK ist und dass anhand ihrer Geometrie im Kindesalter keine sichere Einschätzung der skelettalen Reife möglich ist.
Eine Individualisierung der CVM-Methode ist anhand der in dieser Studie untersuchten Parameter nicht möglich. Somit lässt sich schlussfolgern, dass die CVM-Methode nicht als alleinige Methode zur präzisen skelettalen Alterseinschätzung verlässlich genutzt werden kann, sondern für eine sichere Beurteilung weitere Reifeindikatoren hinzugezogen werden sollten. Allerdings sollten hierzu zusätzliche radiologische Untersuchungen, wie beispielsweise die Handröntgenaufnahme, nur dann durchgeführt werden, wenn diese dem ALARA-Prinzip entsprechen.
Maladaptive avoidance behaviors can contribute to the maintenance of fear, anxiety, and anxiety disorders. It has been proposed that, throughout anxiety disorder progression, extensively repeated avoidance may become a habit (i.e., habitual avoidance) instead of being controlled by internal threat-related goals (i.e., goal-directed avoidance). However, the process of the acquisition of habitual avoidance in anxiety disorders is not yet well understood. Accordingly, the current thesis aimed to investigate experimentally whether trait anxiety and anxiety disorders are associated with an increased shift from goal-directed to habitual avoidance.
The aim of Study 1 was to develop an experimental operationalization of maladaptive habitual avoidance. To this end, we adapted a commonly used action control task, the outcome devaluation paradigm. In this task, habitual avoidance was operationalized as persistent responses after extensive training to avoid an unpleasant stimulus when the aversive outcome was devalued, i.e., when individuals knew the aversive outcome could not occur anymore. We included indicators for costly and low-cost habitual avoidance, whereby habitual avoidance was associated with a monetary cost, while low-cost habitual avoidance was not associated with monetary costs. In Experiment 1 of Study 1, a pronounced costly and non-costly outcome devaluation effect was observed. However, this result may have partly resulted from trial-and-error learning or a better-safe-than-sorry strategy since not instructions about the stimulus-response-outcome contingencies after the outcome devaluation procedure had been provided to the participants. In Experiment 2 of Study 1, instructions on these stimulus-response-outcome contingencies were included to prevent the potential confounders. As a result, we observed no indicators for costly habitual avoidance, but evidence for low-cost habitual avoidance, potentially because competing goal-directed responses could easily be implemented and inhibited costly habitual avoidance tendencies.
In Study 2, the strength of habitual avoidance acquisition was compared between participants with and without anxiety disorders, using the experimental task of Experiment 1 in Study 1. The results indicated that costly and low-cost habitual avoidance was not more pronounced in participants with anxiety disorders than in the healthy control group. However, in an exploratory subgroup comparison, panic disorder predicted more substantial habitual avoidance acquisition than social anxiety disorder.
In Study 3, we investigated whether trait anxiety as a risk factor for anxiety disorders is associated with a specific increased shift from goal-directed to habitual avoidance and approach. The task from the Experiment 1 of Study 1 was adapted to include parallel versions for operationalizing habitual avoidance and habitual approach responses. Using a within-subjects design, the individuals – pre-screened for high and low trait anxiety – took part in the approach and the avoidance outcome devaluation task version. The results suggested stronger non-costly habitual responses in more highly trait-anxious individuals independent of the task version, and suggested a tendency towards an impact of trait anxiety on costly habitual approach rather than on costly habitual avoidance.
In summary, individuals with high trait anxiety or anxiety disorders did not develop habitual avoidance more readily than individuals with low trait anxiety or without anxiety disorders. Therefore, this thesis does not support the assumption that an increased tendency to acquire habitual avoidance contributes to persistent maladaptive avoidance in anxiety disorders. The thesis also contributes to the discourse on the validity of outcome devaluation studies in general by highlighting the impact of task features, such as the instructions after the outcome devaluation procedure or the task difficulty in the test phase, on the experimental results. Such validity issues may partly explain the heterogeneity of findings in research with the outcome devaluation paradigm. We suggest ways towards more valid operationalizations of habitual avoidance in future studies.
Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [\(^{123/131}\)I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted.
Die vorliegende Studie untersuchte den Effekt von Levosimendan auf die mitochondriale Funktionen im Herzmuskel, insbesondere im Zusammenhang mit dem Ischämie/Reperfusions-Schaden. Methoden: In der Studie wurde ein retrogrades Langendorff-Modell verwendet, um die Auswirkungen von Levosimendan, dem Ischämie/Reperfusions-Schaden sowie deren Kombination auf die mitochondrialen Funktionen im Herzmuskel zu untersuchen. Dazu wurden vier verschiedene Gruppen von Rattenherzen entsprechend den experimentellen Bedingungen perfundiert, und ihre Funktionen wurden analysiert. Ergebnisse: Der Ischämie/Reperfusions-Schaden beeinträchtigte die myokardiale Ventrikelfunktion. Zusätzlich wurde eine Hypopolarisation des mithochondrialen Membranpotentials in den mit Levosimendan oder Ischämie behandelten Gruppen festgestellt. Die ATP-Synthese in den Gruppen mit Levosimendan und Ischämie war reduziert. Schlussfolgerung: Levosimendan zeigt signifikante Einflüsse auf die Atmungsfunktion der mitochondrialen Komplexe IV und V sowie auf das Membranpotential. Diese Phänomene könnten einem mito-K+ ATP-abhängigen Mechanismus zugrunde liegen. Obwohl Levosimendan während des Ischämie/Reperfusionsschadens eine protektive Wirkung hinsichtlich einer Ca2+- Überlastung aufweist, bleibt der kumulative Einfluss der beeinträchtigten ATP-Generierung auf die gesamte Myokardfunktion zu klären.
Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce. Patients were included in this retrospective study if pre-therapeutic hormone values, regular tumour evaluation by imaging, steroid measurements by LC–MS/MS, and details on therapies were available. The utility of steroid profiles in detecting recurrence or disease progression was assessed, whereby “endocrine progress” was defined by an elevation of at least 3 of 13 analysed hormones. Cohort A included 47 patients after R0 resection, of whom 15 experienced recurrence and 32 did not. In cohort B, 52 patients with advanced disease (including 7 patients of cohort A with recurrence) could be evaluated on 74 visits when progressive disease was documented. In 20 of 89 cases with documented disease progression, “endocrine progress” was detectable prior to radiological progress. In these cases, recurrence/progression was detected at a median of 32 days earlier by steroid measurement than by imaging, with 11-deoxycortisol and testosterone being the most sensitive markers. Notably, these patients had significantly larger tumour burden. In conclusion, steroid profiling by LC–MS/MS is of value in detecting recurrent/progressive disease in ACC.
To grow larger, insects must shed their old rigid exoskeleton and replace it with a new one. This process is called molting and the motor behavior that sheds the old cuticle is called ecdysis. Holometabolic insects have pupal stages in between their larval and adult forms, during which they perform metamorphosis. The pupal stage ends with eclosion, i.e., the emergence of the adult from the pupal shell. Insects typically eclose at a specific time during the day, likely when abiotic conditions are at their optimum. A newly eclosed insect is fragile and needs time to harden its exoskeleton. Hence, eclosion is regulated by sophisticated developmental and circadian timing mechanisms.
In Drosophila melanogaster, eclosion is limited to a daily time window in the morning, regarded as the “eclosion gate”. In a population of laboratory flies entrained by light/dark cycles, most of the flies eclose around lights on. This rhythmic eclosion pattern is controlled by the circadian clock and persists even under constant conditions.
Developmental timing is under the control of complex hormonal signaling, including the steroid ecdysone, insulin-like peptides, and prothoracicotropic hormone (PTTH). The interactions of the central circadian clock in the brain and a peripheral clock in the prothoracic gland (PG) that produces ecdysone are important for the circadian timing of eclosion. These two clocks are connected by a bilateral pair of peptidergic PTTH neurons (PTTHn) that project to the PG. Before each molt, the ecdysone level rises and then falls shortly before ecdysis. The falling ecdysone level must fall below a certain threshold value for the eclosion gate to open. The activity of PTTHn is inhibited by short neuropeptide F (sNPF) from the small ventrolateral neurons (sLNvs) and inhibition is thought to lead to a decrease in ecdysone production.
The general aim of this thesis is to further the understanding of how the circadian clock and neuroendocrinal pathways are coordinated to drive eclosion rhythmicity and to identify when these endocrinal signaling pathways are active. In Chapter I, a series of conditional PTTHn silencing-based behavioral assays, combined with neuronal activity imaging techniques such as non-invasive ARG-Luc show that PTTH signaling is active and required shortly before eclosion and may serve to phase-adjust the activity of the PG at the end of pupal development. Trans-synaptic anatomical stainings identified the sLNvs, dorsal neurons 1 (DN1), dorsal neurons 2 (DN2), and lateral posterior neurons (LPNs) clock neurons as directly upstream of the PTTHn.
Eclosion motor behavior is initiated by Ecdysis triggering hormone (ETH) which activates a pair of ventromedial (Vm) neurons to release eclosion hormone (EH) which positively feeds back to the source of ETH, the endocrine Inka cells. In Chapter II trans-synaptic tracing showed that most clock neurons provide input to the Vm and non-canonical EH neurons. Hence, clock can potentially influence the ETH/EH feedback loop. The activity profile of the Inka cells and Vm neurons before eclosion is described. Vm and Inka cells are active around seven hours before eclosion. Interestingly, all EH neurons appear to be exclusively peptidergic.
In Chapter III, using chemoconnectomics, PTTHns were found to express receptors for sNPF, allatostatin A (AstA), allatostatin C (AstC), and myosuppressin (Ms), while EH neurons expressed only Ms and AstA receptors. Eclosion assays of flies with impaired AstA, AstC, or Ms signaling do not show arrhythmicity under constant conditions. However, optogenetic activation of the AstA neurons strongly suppresses eclosion.
Chapter IV focuses on peripheral ventral’ Tracheal dendrite (v’Td) and class IV dendritic arborization (C4da) neurons. The C4da neurons mediate larval light avoidance through endocrine PTTH signaling. The v’Td neurons mainly receive O2/CO2 input from the trachea and are upstream of Vm neurons but are not required for eclosion rhythmicity. Conditional ablation of the C4da neurons or torso (receptor of PTTH) knock-out in the C4da neurons impaired eclosion rhythmicity. Six to seven hours before eclosion, PTTHn, C4da, and Vm neurons are active based on ARG-Luc imaging. Thus, C4da neurons may indirectly connect the PTTHn to the Vm neurons.
In summary, this thesis advances our knowledge of the temporal activity and role of PTTH signaling during pupal development and rhythmic eclosion. It further provides a comprehensive characterization of the synaptic and peptidergic inputs from clock neurons to PTTHn and EH neurons. AstA, AstC, and Ms are identified as potential modulators of eclosion circuits and suggest an indirect effect of PTTH signaling on EH signaling via the peripheral sensory C4da neurons.
Neural stem cells (NSCs) have previously been described up to the adult stage in the rat cochlear nucleus (CN). A decreasing neurogenic potential was observed with critical changes around hearing onset. A better understanding of molecular factors affecting NSCs and neurogenesis is of interest as they represent potential targets to treat the cause of neurologically based hearing disorders. The role of genes affecting NSC development and neurogenesis in CN over time on hearing capacity has remained unclear. This study investigated the mRNA abundance of genes influencing NSCs and neurogenesis in rats’ CN over time. The CN of rats on postnatal days 6, 12, and 24 were examined. Real-time quantitative polymerase chain reaction arrays were used to compare mRNA levels of 84 genes relevant to NSCs and neurogenesis. Age- and hearing-specific patterns of changes in mRNA abundance of neurogenically relevant genes were detected in the rat CN. Additionally, crucial neurogenic factors with significant and relevant influence on neurogenesis were identified. The results of this work should contribute to a better understanding of the molecular mechanisms underlying the neurogenesis of the auditory pathway.
Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study
(2024)
Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.
The immune system is responsible for the preservation of homeostasis whenever a given organism is exposed to distinct kinds of perturbations. Given the complexity of certain organisms like mammals, and the diverse types of challenges that they encounter (e.g. infection or disease), the immune system evolved to harbor a great variety of distinct immune cell populations with specialized functions. For instance, the family of T cells is sub-divided into conventional (Tconv) and unconventional T cells (UTCs). Tconv form part of the adaptive arm of the immune system and are comprised of αβ CD4+ or CD8+ cells that differentiate from naïve to effector and memory populations upon activation and are essential during infection and cancer. Furthermore, UTCs, which include γδ T cells, NKT and MAIT, are involved in innate and adaptive immune responses, due to their dual mode of activation, through cytokines (innate-like) or TCR (adaptive), and function. Despite our understanding of the basic functions of T cells in several contexts, a great number of open questions related to their basic biology remain. For instance, the mechanism behind the differentiation of naïve CD4+ and CD8+ T cells into effector and memory populations is not fully understood. Moreover, the exact function and relevance of distinct UTC subpopulations in a physiological context have not been fully clarified. Here, we investigated the factors mediating naïve CD8+ T cell differentiation into effector and memory cells. By using flow cytometry, mass spectrometry, enzymatic assays, and transgenic mouse models, we found that the membrane bound enzyme sphingomyelin-phosphodiesterase acid-like 3b (Smpdl3b) is crucial for the maintenance of memory CD8+ T cells. Our data show that the absence of Smpdl3b leads to diminished CD8+ T cell memory, and a loss of stem-like memory populations due to an aggravated contraction. Our scRNA-seq data suggest that Smpdl3b could be involved in clathrinmediated endocytosis through modulation of Huntingtin interacting protein 1 (Hip1) levels, likely regulating TCR-independent signaling events. Furthermore, in this study we explored the role of UTCs in lymph node-specific immune responses. By using transgenic mouse models for photolabeling, lymph node transplantation models, infection models and flow cytometry, we demonstrate that S1P regulates the migration of tissue-derived UTC from tissues to draining lymph nodes, resulting in heterogeneous immune responses mounted by lymph nodes draining different tissues. Moreover, our unbiased scRNAseq and single lineage-deficient mouse models analysis revealed that all UTC lineages (γδ T cells, NKT and MAIT) are organized in functional units, based on transcriptional homogeneity, shared microanatomical location and migratory behavior, and numerical and functional redundancy. Taken together, our studies describe additional cell intrinsic (Smpdl3b) and extrinsic (S1Pmediated migration) functions of sphingolipid metabolism modulating T cell biology. We propose the S1P/S1PR1/5 signaling axis as the potential survival pathway for Smpdl3b+ memory CD8+ T cells and UTCs, mainly in lymph nodes. Possibly, Smpdl3b regulates S1P/S1PR signaling by balancing ligandreceptor endocytosis, while UTCs migrate to lymph nodes during homeostasis to be exposed to specific levels of S1P that assure their maintenance. Our results are clinically relevant, since several drugs modulating the S1P/S1PR signaling axis or the levels of Smpdl3b are currently used to treat human diseases, such as multiple sclerosis and B cell-mediated diseases. We hope that our discoveries will inspire future studies focusing on sphingolipid metabolism in immune cell biology.
The Western Honeybee (Apis mellifera) is among the most versatile species in the world. Its adaptability is rooted in thousands of the differently specialized individuals acting jointly together. Thus, bees that are able to handle a certain task or condition well can back up other individuals less capable to do so on the colony level. Vice versa, the latter individuals might perform better in other situations. This evolutionary recipe for success ensures the survival of colonies despite challenging habitat conditions. In this context, the ectoparasitic mite Varroa destructor reflects the most pronounced biotic challenge to honeybees worldwide. Without proper treatment, infested colonies rapidly dwindle and ultimately die. Nevertheless, resistance behaviours against this parasite have evolved in some populations through natural selection, enabling colonies to survive untreated. In this, different behaviours appear to be adapted to the respective habitat conditions and may complement each other. Yet, the why and how of this behavioural response to the mite remains largely unknown. My thesis focuses on the biological background of Varroa-resistance traits in honeybees and presents important findings for the comprehension of this complex host-parasite interaction. Based on this, I draw implications for both, applied bee breeding and scientific investigations in the field of Varroa-resistance. Specifically, I focus on two traits commonly found in resistant and, to a lower degree, also mite-susceptible colonies: decreased mite reproduction and the uncapping and subsequent recapping of sealed brood cells. Examining failures in the reproductive success of mites as a primary mechanism of Varroa-resistance, I was able to link them to specific bee behaviours and external factors. Since mite reproduction and the brood rearing of bees are inevitably connected, I first investigated the effects of brood interruption on the reproductive success of mites. Brood interruption decreased the reproductive success of mites both immediately and in the long term. By examining the causes of reproductive failure, I could show that this was mainly due to an increased share of infertile mites. Furthermore, I proved that interruption in brood rearing significantly increased the expression of recapping behaviour. These findings consequently showed a dynamic modulation of mite reproduction and recapping, as well as a direct effect of brood interruption on both traits. To further elucidate the plasticity in the expression of both traits, I studied mite reproduction, recapping behaviour and infestation levels over the course of three years. The resulting extensive dataset unveiled a significant seasonal variation in mite reproduction and recapping. In addition, I show that recapping decreases the reproductive success of mites by increasing delayed developing female offspring and cells lacking male offspring. By establishing a novel picture-based brood investigation method, I could furthermore show that both the removal of brood cells and recapping activity specifically target brood ages in which mite offspring would be expected. Recapping, however, did not cause infertility of mites. Considering the findings of my first study, this points towards complementary mechanisms.
This underlines the importance of increased recapping behaviour and decreased mite reproduction as resistance traits, while at the same time emphasising the challenges of reliable data acquisition. To pave the way for a practical application of these findings in breeding, we then investigated the heritability (i.e., the share of genotypic variation on the observed phenotypic variation) of the accounted traits. By elaborating comparable test protocols and compiling data from over 4,000 colonies, we could, for the first time, demonstrate that recapping of infested cells and decreased reproductive success of mites are heritable (and thus selectable) traits in managed honeybee populations.
My thesis proves the importance of recapping and decreased mite reproduction as resistance traits and therefore valuable goals for breeding efforts. In this regard, I shed light on the underlying mechanisms of both traits, and present clear evidence for their interaction and heritability.
The present review examines retrospective analyses of training intensity distribution (TID), i.e., the proportion of training at moderate (Zone 1, Z1), heavy (Z2) and severe (Z3) intensity by elite-to-world-class endurance athletes during different phases of the season. In addition, we discuss potential implications of our findings for research in this field, as well as for training by these athletes. Altogether, we included 175 TIDs, of which 120 quantified exercise intensity on the basis of heart rate and measured time-in-zone or employed variations of the session goal approach, with demarcation of zones of exercise intensity based on physiological parameters. Notably, 49% of the TIDs were single-case studies, predominantly concerning cross-country skiing and/or the biathlon. Eighty-nine TIDs were pyramidal (Z1 > Z2 > Z3), 65 polarized (Z1 > Z3 > Z2) and 8 “threshold” (Z2 > Z1 = Z3). However, these relative numbers varied between sports and the particular phases of the season. In 91% (n = 160) of the TIDs >60% of the endurance exercise was of low intensity. Regardless of the approach to quantification or phase of the season, cyclists and swimmers were found to perform a lower proportion of exercise in Z1 (<72%) and higher proportion in Z2 (>16%) than athletes involved in the triathlon, speed skating, rowing, running, cross-country skiing or biathlon (>80% in Z1 and <12% in Z2 in all these cases). For most of the athletes their proportion of heavy-to-severe exercise was higher during the period of competition than during the preparatory phase, although with considerable variability between sports. In conclusion, the existing literature in this area does not allow general conclusions to be drawn. The methods utilized for quantification vary widely and, moreover, contextual information concerning the mode of exercise, environmental conditions, and biomechanical aspects of the exercise is often lacking. Therefore, we recommend a more comprehensive approach in connection with future investigations on the TIDs of athletes involved in different endurance sports.
Here, we performed a non-systematic analysis of the strength, weaknesses, opportunities, and threats (SWOT) associated with the application of artificial intelligence to sports research, coaching and optimization of athletic performance. The strength of AI with regards to applied sports research, coaching and athletic performance involve the automation of time-consuming tasks, processing and analysis of large amounts of data, and recognition of complex patterns and relationships. However, it is also essential to be aware of the weaknesses associated with the integration of AI into this field. For instance, it is imperative that the data employed to train the AI system be both diverse and complete, in addition to as unbiased as possible with respect to factors such as the gender, level of performance, and experience of an athlete. Other challenges include e.g., limited adaptability to novel situations and the cost and other resources required. Opportunities include the possibility to monitor athletes both long-term and in real-time, the potential discovery of novel indicators of performance, and prediction of risk for future injury. Leveraging these opportunities can transform athletic development and the practice of sports science in general. Threats include over-dependence on technology, less involvement of human expertise, risks with respect to data privacy, breaching of the integrity and manipulation of data, and resistance to adopting such new technology. Understanding and addressing these SWOT factors is essential for maximizing the benefits of AI while mitigating its risks, thereby paving the way for its successful integration into sport science research, coaching, and optimization of athletic performance.
Universal prevention for non-suicidal self-injury in adolescents is scarce - A systematic review
(2023)
Non-suicidal self-injury (NSSI) during adolescence is a high-risk marker for the development and persistence of mental health problems and has been recognized as a significant public health problem. Whereas targeted prevention has indeed shown to be effective in reducing NSSI and improve mental health problems, access to such programs is limited. By face validity, universal prevention of NSSI seems an ideal starting point for a stepped-care model to circumvent a lack of resources in the medical care system. However, it is yet unclear how effective such approaches are. Here, we provide a summary of existing work on universal prevention of NSSI in adolescents younger than 21 years based on a systematic literature search. We found that only seven studies are available. None of the programs evaluated was found to be effective in reducing the incidence or frequency of NSSI. After providing a comprehensive summary of the existing work, we evaluate the fact that existing work primarily focusses on selected/targeted prevention and on psychoeducational methods. We derive implications for future directions in the field of universal prevention of NSSI.