Medizin
Refine
Year of publication
- 2020 (130) (remove)
Document Type
- Article (130)
Language
- English (130)
Has Fulltext
- yes (130)
Is part of the Bibliography
- no (130)
Keywords
- inflammation (6)
- COVID-19 (4)
- cancer (4)
- macrophage (4)
- SARS-CoV-2 (3)
- bladder cancer (3)
- miRNA (3)
- obesity (3)
- prevalence (3)
- quality of life (3)
- stroke (3)
- sulforaphane (3)
- CD44 (2)
- MSD (2)
- Magnetic resonance imaging (2)
- apoptosis (2)
- biomarker (2)
- bipolar disorder (2)
- coagulopathy (2)
- curcumin (2)
- dental education (2)
- dental profession (2)
- drug resistance (2)
- environmental tobacco smoke (2)
- growth (2)
- immunity (2)
- integrins (2)
- iron (2)
- machine learning (2)
- macrophages (2)
- microRNA (2)
- multiple sclerosis (2)
- natural killer cells (2)
- neuroblastoma (2)
- neurodegeneration (2)
- pain (2)
- polytrauma (2)
- proliferation (2)
- prostate cancer (2)
- proteome (2)
- psoriasis (2)
- public health (2)
- renal cell carcinoma (2)
- sphingosine 1-phosphate receptor (2)
- survivin (2)
- thymus (2)
- toxicity (2)
- 16 segment AHA model (1)
- A-FFIP (1)
- ABCB1 (1)
- ABCC1 (1)
- ACLF (1)
- ADGRE1 (1)
- ADHD (1)
- ADHD differential diagnosis (1)
- AML – acute myeloid leukemia (1)
- ASD-specific (1)
- Adverse drug reaction (1)
- Amitriptyline (1)
- Anal cancer (1)
- Anterior cruciate ligament reconstruction (1)
- Anticholinergic (1)
- Ataxia telangiectasia (1)
- Atm (1)
- Autism spectrum disorder (1)
- B cells (1)
- BCL6 (1)
- BIRC5 (1)
- Bee venom allergy (1)
- Body limbs (1)
- Borrelia (1)
- CAD/CAM (1)
- CD19 (1)
- CD41 (1)
- CD62P (1)
- CLP (1)
- COMP (1)
- CPT1A (1)
- Cancer treatment (1)
- Cardiovascular magnetic resonance (1)
- Central nervous system (1)
- Cerebrospinal fluid (1)
- Chemoradiotherapy (1)
- Cognitive impairment (1)
- Cognitive neurology (1)
- Cohort studies (1)
- Cold hardiness (1)
- Cold tolerance (1)
- Computed axial tomography (1)
- Computer hardware (1)
- Computer software (1)
- Computers (1)
- Conservative treatment (1)
- Crohn's disease (1)
- CspA (1)
- CspZ (1)
- Cyp46a1 (1)
- DBS (1)
- DST (1)
- Data processing (1)
- Dental practice (1)
- Diagnostic error (1)
- Disabilities (1)
- Distribution limits (1)
- Double-blind placebo-controlled trial (1)
- Drug susceptibility testing (1)
- EGFR (1)
- EGFRvIII mutation (1)
- EMR1 (1)
- Early intervention (1)
- Elderly (1)
- Emotions (1)
- Epidural abscess (1)
- Evaluation (1)
- Evidence-based dentistry (1)
- Evidence-based medicine (1)
- Exercise challenge (1)
- Exercise-induced asthma (1)
- Exhaled nitric oxide (1)
- F4/80 (1)
- Factor H (1)
- Finevo (1)
- Five-Konzept (1)
- Forced expiratory volume in 1 s (1)
- Functional clustering (1)
- Functional mitral regurgitation (1)
- GABA (1)
- Gait analysis (1)
- Gene expression (1)
- General practice (1)
- Genetics (1)
- HDAC (1)
- HIFT (1)
- HIV (1)
- HbA1c (1)
- Hepatocellular carcinoma (1)
- Hmox1 (1)
- Hymenoptera venom immunotherapy (1)
- IKKε (1)
- IL-1β (1)
- Immune suppression (1)
- Immunology (1)
- Imrt (1)
- Inflammatory bowel disease (1)
- Injury Severity Score (ISS) (1)
- Internet (1)
- Intravenous injections (1)
- Ireb2 (1)
- Joint loading (1)
- K-homology RNA-binding domain (1)
- Knees (1)
- LIR interaction, (1)
- Liver diseases (1)
- Liver transplantation (1)
- Longchain polyunsaturated fatty acids (1)
- Lymphoma (1)
- M. Intracellulare (1)
- M. avium (1)
- M. avium complex (1)
- M. chimaera (1)
- MAGGIC score (1)
- MCAO (1)
- MICA (1)
- MMP14 (1)
- Machine learning algorithms (1)
- Malaria (1)
- Marker genes (1)
- Medical risk factors (1)
- Meta-analysis (1)
- Michael acceptor (1)
- Microglial cells (1)
- MitraClip (1)
- Mouse models (1)
- Mucomaix® matrix (1)
- Multimedication (1)
- Multimorbidity (1)
- Multiplate (1)
- Multiple-indication review (1)
- Myocardial perfusion (1)
- Myocardial segmentation (1)
- N2 (1)
- NADPH oxidase (1)
- NAFLD (1)
- NASH (1)
- NDBI (1)
- NF-κB pathway (1)
- NF-кB (1)
- NKG2D (1)
- NLRP3 inflammasomes (1)
- NTM (1)
- Nek1 (1)
- Neurons (1)
- Neuropathic pain (1)
- Neuropsychological testing (1)
- Neuropsychology (1)
- Non-tuberculous mycobacteria (1)
- Nordic questionnaire (1)
- Normal distribution (1)
- NoxO1 (1)
- OGTT (1)
- OSA (1)
- Optogenetics (1)
- OspE (1)
- Osteoarthritis (1)
- Overwintering (1)
- PYGL (1)
- Patient safety (1)
- Patterns of care (1)
- Pgrmc1 (1)
- Phenotypic plasticity (1)
- Physicians (1)
- PolySUMOylation (1)
- Polypharmacy (1)
- Primary health care (1)
- Probability density (1)
- Probability distribution (1)
- Prototypes (1)
- Psychological stress (1)
- Psychology (1)
- QbTest® (1)
- Quality of life (1)
- Quantra (1)
- Questionnaire (1)
- RNA chaperone (1)
- RNA therapeutics (1)
- RNF4 (1)
- Radiation exposure (1)
- Randomised trial (1)
- Regret (1)
- Reliability (1)
- Rush protocol (1)
- S1P1–5 (1)
- SCA2 (1)
- SENP6 (1)
- SF-36 (1)
- SNORD95 (1)
- SUMO chains (1)
- Seattle heart failure model (1)
- Serum biomarker (1)
- Side effects (1)
- Slc11a2 (1)
- Slc25a37 (1)
- Software tools (1)
- Spinocerebellar ataxia type 2 (1)
- Sports and exercise medicine (1)
- StUbL (1)
- Statistical data (1)
- Strength training (1)
- Sub-segmentation (1)
- Sub-zero exposure (1)
- Surgery (1)
- Survey (1)
- Surveys (1)
- T cell receptor (1)
- T-cell receptor (1)
- TAPSE (1)
- TBK1 (1)
- TGR(mREN2)27 (1)
- TRIMs (1)
- Tfrc (1)
- Torque (1)
- Total hip arthroplasty (1)
- Transportation (1)
- Treg cell (1)
- Ulcerative colitis (1)
- Ultra-rush protocol (1)
- Uncertainty (1)
- VIM (1)
- Validation (1)
- Vespid venom allergy (1)
- Vmem (1)
- Western diet (1)
- Winter survival (1)
- YM155 (1)
- Yellow fluorescent protein (1)
- acetylation (1)
- acetylcholinesterase (1)
- acquired drug resistance (1)
- actin dynamics (1)
- activities of daily life (1)
- acute lymphoblastic leukemia (1)
- acute respiratory distress syndrome (1)
- acute-on-chronic liver failure (ACLF) (1)
- adhesion (1)
- adipose-derived mesenchymal stem/stromal cells (1)
- adoptive cancer immunotherapy (1)
- affective disorder (1)
- affective disorders (1)
- air flow (1)
- alcoholic hepatitis (1)
- algorithm (1)
- allergy (1)
- alpharetroviral vector (1)
- amlexanox (1)
- amyotrophic lateral sclerosis (ALS) (1)
- anal cancer (1)
- anti-tumor activity (1)
- antireflux surgery (1)
- arachidonate 12/15-lipoxygenase (Alox12/15) (1)
- aspiration (1)
- aspirin (1)
- asthma (1)
- ataxia telangiectasia (1)
- atopy (1)
- augmentation (1)
- autophagy (1)
- bacterial translocation (1)
- bibliometrics (1)
- bio imaging (1)
- bioactive lipids (1)
- bioavailability (1)
- bioluminescence (1)
- biomarkers (1)
- biopsy naïve (1)
- blood (1)
- blood pressure (1)
- blood-brain barrier (1)
- body mass index (1)
- bone healing (1)
- bone marrow mononuclear cells (1)
- brain shift (1)
- brain tumor (1)
- breast cancer (1)
- butyrylcholinesterase (1)
- bypass (1)
- cancer immunobiology (1)
- carcinoma (1)
- cardiac surgery (1)
- cardiothoracic surgery (1)
- cell and focal adhesion (1)
- cell proliferation (1)
- cell survival (1)
- cellular reaction (1)
- ceramides (1)
- cervical cancer (1)
- chaperones (1)
- chelation therapy (1)
- chemoprotection (1)
- chemoresistance (1)
- chemotaxis (1)
- chemotherapy (1)
- chimeric antigen receptor (1)
- chloroplasts (1)
- cholinesterase (1)
- chronic inflammation (1)
- clopidogrel (1)
- coagulation (1)
- cognition (1)
- collagen-based matrix (1)
- colorectal cancer (1)
- colorectal cancer (CRC) (1)
- complement (1)
- complications (1)
- contamination (1)
- continuous performance test (1)
- contralateral delay activity (1)
- coronavirus (1)
- coronavirus disease 2019 (1)
- cortex, gray matter (1)
- covalent drugs (1)
- critical care (1)
- cyclin Y (1)
- cyclophosphamide (1)
- cystic fibrosis (1)
- cytarabin (1)
- cytokine storm (1)
- cytotoxic lymphocytes (1)
- cytotoxicity (1)
- data science (1)
- debris (1)
- declaration of tobacco ingredients (1)
- decompensated liver cirrhosis (1)
- deep sedation (1)
- deferred treatment (1)
- delayed treatment (1)
- demineralized bone matrix (1)
- dendritic cells (1)
- dental assistants (1)
- dentist (1)
- dentists (1)
- diabetes (1)
- diabetes mellitus (1)
- diabetes therapy (1)
- diffusion tensor imaging (1)
- diuretics (1)
- dog study (1)
- dual antiplatelet therapy (1)
- dysphagia (1)
- early detection (1)
- effort (1)
- electrolytic cleaning (1)
- electrophilic fatty acids (1)
- encoding (1)
- epidemics (1)
- epidemiology (1)
- epithelial-to-mesenchymal transition (EMT) (1)
- essential tremor (1)
- everolimus (1)
- ex-Gaussian analysis (1)
- exercise (1)
- exertion (1)
- experimental pain models (1)
- feeder cells (1)
- fibroblasts (1)
- fibrosis (1)
- fingolimod (1)
- flow cytometry (1)
- fractional anisotropy (1)
- fractionation (1)
- fragile-X-associated tremor-ataxia syndrome (1)
- fronto-temporal lobar dementia (1)
- fronto-temporal-lobar-dementia (1)
- fundoplication (1)
- gastroesophageal reflux (1)
- gene regulation (1)
- gene therapy (1)
- genetic predisposition (1)
- geriatric patients (1)
- glioblastoma (1)
- glucose metabolism (1)
- healthcare workers (1)
- heat stress (1)
- hematopoietic stem and progenitor cells (1)
- hemorrhagic transformation (1)
- hepatic stellate cells (1)
- hepatocellular cancer (1)
- high-throughput nucleotide sequencing (1)
- histological outcomes (1)
- histology (1)
- histomorphometry (1)
- host-pathogen interaction (1)
- human decellularized dermis (1)
- human genomics (1)
- hybrid abutment (1)
- hypoxia (1)
- imaging (1)
- immune checkpoint (1)
- immune defense (1)
- immune response (1)
- immunotherapy (1)
- in vitro models (1)
- indoor air pollution (1)
- induced membrane (1)
- infection (1)
- inflammatory bowel disease (1)
- inhibitors (1)
- inositol signaling (1)
- integrin (1)
- interferon type III (1)
- intrinsic drug resistance (1)
- inflammation (1)
- iron overload versus deprivation (1)
- joint contact forces (1)
- knee adduction moment (1)
- lentiviral vector (1)
- leukopenia (1)
- lichen extracts (1)
- lipocalin-2 (1)
- lipoxin A4 (1)
- liquid PRF (1)
- liver fibrosis (1)
- long-term potentiation (1)
- longevity (1)
- mTOR (1)
- maintenance (1)
- major depression (MD) (1)
- major depressive disorder (MDD) (1)
- maternal tobacco smoke (1)
- matrix metalloproteinases (1)
- mean diffusivity (1)
- mechanism of action (1)
- melanoma (1)
- membrane potential (1)
- mesenchymal stem cell (1)
- mesenchymal stromal cells (1)
- mesenchymal stromal/stem cells (1)
- metabolic syndrome (1)
- miR-142-3p (1)
- miR-181 (1)
- mice (1)
- microlesions (1)
- migration (1)
- migration and invasion (1)
- monocyte chemotactic protein 1 (MCP-1) (1)
- monotype abutment (1)
- monsoon (1)
- mortality analysis (1)
- mouse model (1)
- musculoskeletal (1)
- musculoskeletal disorders (1)
- musculoskeletal inflammation (1)
- musculoskeletal modeling (1)
- musculoskeletal pain (1)
- natural cytotoxicity (1)
- naturalistic sample (1)
- neurexin (1)
- neurocognition (1)
- neurogenesis (1)
- neuronal maturation (1)
- next-generation sequencing (1)
- nitroalkylation (1)
- non-malignant hematological diseases (1)
- nucleotide metabolism (1)
- nutrient endocytosis (1)
- occupational health (1)
- oncogenic signaling (1)
- orientation (1)
- osteoarthritis (1)
- osteogenic sarcoma cells (1)
- ouabain (1)
- outcome (1)
- outside-in signaling (1)
- passive smoke (1)
- patient’s decree (1)
- pediatric (1)
- pediatric epilepsy (1)
- periimplantitis (1)
- perineurium (1)
- phage display (1)
- placenta (1)
- planimetric measurement (1)
- plasma (1)
- point of care (1)
- poly(A)-tail (1)
- portal hypertension (1)
- post-exercise hypotension (1)
- post-translational modifications (1)
- posterior fossa tumor (1)
- postmonsoon (1)
- postoperative delirium (1)
- ppi1 (1)
- prediabetes (1)
- prevention (1)
- prognosis (1)
- prognostic marker (1)
- psoriatic arthritis (1)
- qRT-PCR (1)
- qRT-PCR detection (1)
- quantitative proteomics (1)
- questionnaire (1)
- radical prostatectomy (1)
- radiosensitization (1)
- rat femur critical size defect (1)
- re-osseointegration (1)
- regulatory T cell (1)
- regulatory T helper cells (1)
- renal cell cancer (1)
- renal tubular epithelial cells (1)
- repeat biopsy (1)
- reperfusion injury (1)
- resolution of inflammation (1)
- risk factor (1)
- rotational thromboelastometry (1)
- sarcopenia (1)
- sciatic nerve (1)
- screening (1)
- second-hand smoke (1)
- selection (1)
- selective autophagy receptor (1)
- serum (1)
- severe acute respiratory syndrome coronavirus 2 (1)
- severe congenital neutropenia (1)
- severely injured (1)
- short linear motifs (SLiMs) (1)
- sickle cell anemia (1)
- signaling (1)
- smoking in pregnancy (1)
- soluble MICA (1)
- spatial learning (1)
- specialized pro-resolving lipid mediators (SPMs) (1)
- sphingosine 1-phoshate (1)
- sphingosine 1-phosphate (1)
- sphingosine 1-phosphate antagonistst/inhibitors (1)
- sphingosine 1-phosphate metabolism (1)
- sphingosine 1-phosphate signaling (1)
- sphingosine kinase (1)
- sphingosine-1-phosphate (1)
- spreading (1)
- starvation (1)
- steatosis (1)
- stretching (1)
- swallowing (1)
- synaptic plasticity (1)
- synuclein (1)
- systematic biopsy (1)
- targeted biopsy (1)
- tauopathies (1)
- tauopathy (1)
- test protocol (1)
- thalassemia (1)
- therapy monitoring (1)
- therapy resistance (1)
- thiazolidine and perhydrothiazine derivatives of aldophosphamide and I-aldophosphamide (1)
- thrombopenia (1)
- thrombosis (1)
- tick (1)
- tobacco control (1)
- tobacco products (1)
- toc64 (1)
- total hip replacement (1)
- tracking (1)
- transferrin (1)
- transjugular intrahepatic portosystemic shunt (TIPS) (1)
- translational medical research (1)
- translocon (1)
- transrectal prostate biopsy (1)
- transverse axis (1)
- trauma registry (1)
- traumaticbraininjury(TBI) (1)
- trophoblast (1)
- tumor adhesion (1)
- tumor growth (1)
- tumor migration (1)
- tumor pain (1)
- tumor progression (1)
- tyrosine kinase receptor signaling (1)
- ultrasonic cleaning (1)
- unconventional T cell (1)
- ventralis intermedius nucleus (1)
- vertical transmission (1)
- vitamin D (1)
- vitamin D deficiency (1)
- vitamin D metabolites (1)
- volatile sedation (1)
- waiting time (1)
- walking (1)
- wheezing (1)
- working memory (1)
- workplace health promotion (1)
- xenograft (1)
- fibrogenesis (1)
- fingolimod (1)
Institute
Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study
(2020)
Objectives: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium.
Design: Prospective observational study.
Setting: Single-centre at a European academic hospital.
Primary: and secondary outcome measures In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD.
Results: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD.
Conclusions: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.
Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4–67.3) vs. 18.5 (1.2–51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2–530.6) vs. 330.8 (183.5–560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.
Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli. Cerebellar ataxias and corticospinal motor neuron degeneration are determined by gain/loss in ATXN2 function, so we aimed to identify key molecules in this atrophic process, as potential disease progression markers. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. The earliest changes were detected at three months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found to be affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with the weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, primarily impacting excitability and communication.
Pulmonary failure is the main cause of morbidity and mortality in the human chromosomal instability syndrome Ataxia-telangiectasia (A-T). Major phenotypes include recurrent respiratory tract infections and bronchiectasis, aspiration, respiratory muscle abnormalities, interstitial lung disease, and pulmonary fibrosis. At present, no effective pulmonary therapy for A-T exists. Cell therapy using adipose-derived mesenchymal stromal/stem cells (ASCs) might be a promising approach for tissue regeneration. The aim of the present project was to investigate whether ASCs migrate into the injured lung parenchyma of Atm-deficient mice as an indication of incipient tissue damage during A-T. Therefore, ASCs isolated from luciferase transgenic mice (mASCs) were intravenously transplanted into Atm-deficient and wild-type mice. Retention kinetics of the cells were monitored using in vivo bioluminescence imaging (BLI) and completed by subsequent verification using quantitative real-time polymerase chain reaction (qRT-PCR). The in vivo imaging and the qPCR results demonstrated migration accompanied by a significantly longer retention time of transplanted mASCs in the lung parenchyma of Atm-deficient mice compared to wild type mice. In conclusion, our study suggests incipient damage in the lung parenchyma of Atm-deficient mice. In addition, our data further demonstrate that a combination of luciferase-based PCR together with BLI is a pivotal tool for tracking mASCs after transplantation in models of inflammatory lung diseases such as A-T.
Objective: Spinal epidural abscess (SEA) is a severe and life-threatening disease. Although commonly performed, the effect of timing in surgical treatment on patient outcome is still unclear. With this study, we aim to provide evidence for early surgical treatment in patients with SEA.
Methods: Patients treated for SEA in the authors' department between 2007 and 2016 were included for analysis and retrospectively analyzed for basic clinical parameters and outcome. Pre- and postoperative neurological status were assessed using the American Spinal Injury Association Impairment Scale (AIS). The self-reported quality of life (QOL) based on the Short-Form Health Survey 36 (SF-36) was assessed prospectively. Surgery was defined as "early", when performed within 12 hours after admission and "late" when performed thereafter. Conservative therapy was preferred and recommend in patients without neurological deficits and in patients denying surgical intervention.
Results: One hundred and twenty-three patients were included in this study. Forty-nine patients (39.8%) underwent early, 47 patients (38.2%) delayed surgery and 27 (21.9%) conservative therapy. No significant differences were observed regarding mean age, sex, diabetes, prior history of spinal infection, and bony destruction. Patients undergoing early surgery revealed a significant better clinical outcome before discharge than patients undergoing late surgery (p=0.001) and conservative therapy. QOL based on SF-36 were significantly better in the early surgery cohort in two of four physical items (physical functioning and bodily pain) and in one of four psychological items (role limitation) after a mean follow-up period of 58 months. Readmission to the hospital and failure of conservative therapy were observed more often in patients undergoing conservative therapy.
Conclusion: Our data on both clinical outcome and QOL provide evidence for early surgery within 12 hours after admission in patients with SEA.
Most living organisms possess varying degrees of regenerative capabilities but how these regenerative processes are controlled is still poorly understood. Naturally occurring bioelectric voltages (like Vmem) are thought to be playing instructive role in tissue regeneration, as well as embryonic development. The different distribution of ions on the either side of the cell membrane results in intra- and extra-cellular voltage differences, known as membrane potential or Vmem. The relationship between Vmem and cell physiology is conserved in a wide range of cell types and suggests that Vmem regulation is a fundamental control mechanism for regeneration related processes e.g., proliferation and differentiation. In the present study we measured Vmem in three different cell types (human osteogenic sarcoma cell line (OSC), rat bone marrow derived mesenchymal stem cells (BM-MSC), and rat dermal fibroblasts) and characterized the relationship between their Vmem and proliferation. In order to find out if Vmem controls proliferation, or visa-versa, we blocked and then unblocked Na+/K+-exchanging ATPase using ouabain and measured the proliferation. Our results demonstrate that Vmem can be pharmacologically manipulated to control proliferation in certain cell types like BM-MSC. Taken together, it is clear that control of bioelectrical properties in non-excitable cells could prove to be potentially a useful tool in regenerative medicine efforts.
Although the big tobacco companies offer the same cigarette brands across countries, little is known about the potential regional differences of the particulate matter (PM) emissions of apparently equal brands. PM emissions of three cigarette brands (Marlboro Gold, Winston Red resp. Classic, Parliament Platinum resp. Night Blue) from the United Arab Emirates (UAE) and Germany were analysed. Second-hand smoke was produced in a 2.88 m3 measuring cabin by an automatic environmental tobacco smoke emitter. PM size fractions PM10, PM2.5, and PM1 were detected in real-time using laser aerosol spectrometry. Depending on the PM fraction Marlboro cigarettes from UAE showed 33%–35% higher PM amounts. Moreover, Winston cigarettes from UAE showed distinctly higher PM values (28–31%) than the German counterparts. The “lighter” Parliament from UAE emitted 3%–9% more PM than the German one. The measured mean PM10 values laid between 778 and 1163 µg/m3 (mean PM2.5: 777–1161 µg/m3; mean PM1: 724–1074 µg/m3). That means smoking in enclosed rooms causes massive PM burden. The PM emission of equal or similar tobacco products from different countries can differ distinctly. Hence, the declaration of PM emission values, besides nicotine, tar, and carbon monoxide amounts, should be obligatory worldwide. Furthermore, complete information about the ingredients and production processes of tobacco products should be provided to health officials and the public. This can help to minimise or ban substances or product designs that make smoking even more harmful, and to enhance the awareness of the risks of smoking.
Children are commonly exposed to second-hand smoke (SHS) in the domestic environment or inside vehicles of smokers. Unfortunately, prenatal tobacco smoke (PTS) exposure is still common, too. SHS is hazardous to the health of smokers and non-smokers, but especially to that of children. SHS and PTS increase the risk for children to develop cancers and can trigger or worsen asthma and allergies, modulate the immune status, and is harmful to lung, heart and blood vessels. Smoking during pregnancy can cause pregnancy complications and poor birth outcomes as well as changes in the development of the foetus. Lately, some of the molecular and genetic mechanisms that cause adverse health effects in children have been identified. In this review, some of the current insights are discussed. In this regard, it has been found in children that SHS and PTS exposure is associated with changes in levels of enzymes, hormones, and expression of genes, micro RNAs, and proteins. PTS and SHS exposure are major elicitors of mechanisms of oxidative stress. Genetic predisposition can compound the health effects of PTS and SHS exposure. Epigenetic effects might influence in utero gene expression and disease susceptibility. Hence, the limitation of domestic and public exposure to SHS as well as PTS exposure has to be in the focus of policymakers and the public in order to save the health of children at an early age. Global substantial smoke-free policies, health communication campaigns, and behavioural interventions are useful and should be mandatory.
The quantified behavioral test - a confirmatory test in the diagnostic process of adult ADHD?
(2020)
The differential diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood is complicated by comorbid disorders, but also by the overlapping of main symptoms such as inattentiveness, impulsivity, and hyperactivity with other disorders. Neuropsychological tests like continuous performance tests (CPT) try to solve this dilemma by objectively measurable parameters. We investigated in a cohort of n=114 patients presenting to an ADHD outpatient clinic how well a commercially available CPT test (QbTest®) can differentiate between patients with ADHD (n=94) and patients with a disconfirmed ADHD diagnosis (n=20). Both groups showed numerous comorbidities, predominantly depression (27.2% in the ADHD group vs. 45% in the non-ADHD group) and substance-use disorders (18.1% vs. 10%, respectively). Patients with ADHD showed significant higher activity (2.07 ± 1.23) than patients without ADHD (1.34 ± 1.27, dF=112; p=0.019), whereas for the other core parameters, inattention and impulsivity no differences could be found. Reaction time variability has been discussed as a typical marker for inattention in ADHD. Therefore, we investigated how well ex-Gaussian analysis of response time can differentiate between ADHD and other patients, showing, that it does not help to identify patients with ADHD. Even though patients with ADHD showed significantly higher activity, this parameter differed only poorly between patients (accuracy AUC 65% of an ROC-Curve). We conclude that CPTs do not help to identify patients with ADHD in a specialized outpatient clinic. The usability of this test for differentiating between ADHD and other psychiatric disorders is poor and a sophisticated analysis of reaction time did not decisively increase the test accuracy.
Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.
Background: This study investigated whether work ability is associated with the duration of unemployment, heart rate variability (HRV), and the level of physical activity. Methods: Thirty-four unemployed persons (mean 55.7 ± standard deviation 33.3 years, 22 female, 12 male, unemployed: range 1–22.5 years) participated in the cross-sectional study. The Work Ability Index (WAI) and International Physical Activity Questionnaire (IPAQ) were applied. Short-term (five minutes) resting HRV (Low Frequency (LF), High Frequency (HF), Total Power (TP)) was collected. Results: Work ability was positively associated with the HRV: LF (r = 0.383; p = 0.025), HF (r = 0.412; p = 0.015) and TP (r = 0.361; p = 0.036). The WAI showed a positive linear correlation with the amount of total physical activity (r = 0.461; p = 0.006) as well as with the amount of moderate to vigorous physical activity (r = 0.413; p = 0.015). No association between the WAI and the duration of unemployment occurred. Conclusions: the relation between self-perceived work ability, health-associated parameters, the HRV and the level of physical activity points out the relevance of health-care exercise and the need of stress-reducing interventions to improve perceived work ability. Our results point out the need for the further and more holistic development of healthcare for the unemployed.
Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.
Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially,thedevelopmentoffibrosisandportalhypertensioninNAFLDpatientsrequirestreatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. Asexpected,WDinducedobesityandliverfibrosisasconfirmedbySiriusRedandOilRed O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increasedduringfeedingofWD,indicatinginfiltrationofmacrophagesintotheliver,eventhoughthis increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin–angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity.
Objectives: To review systematically the past 10 years of research activity into the healthcare experiences (HCX) of patients with chronic heart failure (CHF) in Germany, in order to identify research foci and gaps and make recommendations for future research. Design: In this scoping review, six databases and grey literature sources were systematically searched for articles reporting HCX of patients with CHF in Germany that were published between 2008 and 2018. Extracted results were summarised using quantitative and qualitative descriptive analysis. Results: Of the 18 studies (100%) that met the inclusion criteria, most were observational studies (60%) that evaluated findings quantitatively (60%). HCX were often concerned with patient information, global satisfaction as well as relationships and communication between patients and providers and generally covered ambulatory care, hospital care and rehabilitation services. Overall, the considerable heterogeneity of the included studies’ outcomes only permitted relatively trivial levels of synthesis. Conclusion: In Germany, research on HCX of patients with CHF is characterised by missing, inadequate and insufficient information. Future research would benefit from qualitative analyses, evidence syntheses, longitudinal analyses that investigate HCX throughout the disease trajectory, and better reporting of sociodemographic data. Furthermore, research should include studies that are based on digital data, reports of experiences gained in under-investigated yet patient-relevant healthcare settings and include more female subjects.
Background: Ataxia telangiectasia (A-T) is a rare autosomal-recessive multisystem disorder characterized by pronounced cerebellar ataxia, telangiectasia, cancer predisposition and altered body composition. In addition, evidence is rising for endocrine dysfunction.
Objectives: To determine the evolution of diabetes and its prevalence in a larger A-T cohort.
Methods: A retrospective analysis of the patient charts of 39 subjects from the Frankfurt A-T cohort was performed between August 2002 and 2018 concerning HbA1c and oral glucose tolerance (OGTT). The median follow-up period was 4 years (1–16 years). In addition, in 31 A-T patients aged 1 to 38 years HbA1c and fasting glucose were studied prospectively from 2018 to 2019.
Results: In the retrospective analysis, we could demonstrate a longitudinal increase of HbA1c. The prospective analysis showed a significant increase of HbA1c and fasting glucose with age (r = 0.79, p ≤ 0.0001). OGTT has a good sensitivity for insulin resistance screening, whereas HbA1c can be used to evaluate individual courses and therapy response. Seven out of 39 (17.9%) patients suffered from diabetes. Metformin did not always lead to sufficient diabetes control; one patient was treated successfully with repaglinide.
Conclusion: Diabetes is a common finding in older A-T patients and often starts in puberty. Our data clearly demonstrate the need for an annual diabetes screening in patients > 12 years.
Background: Many patients suffering from exercise-induced asthma (EIA) have normal lung function at rest and show symptoms and a decline in FEV1 when they do sports or during exercise-challenge. It has been described that long-chain polyunsaturated fatty acids (LCPUFA) could exert a protective effect on EIA.
Methods: In this study the protective effect of supplementation with a special combination of n-3 and n-6 LCPUFA (sc-LCPUFA) (total 1.19 g/ day) were investigated in an EIA cold air provocation model. Primary outcome measure: Decrease in FEV1 after exercise challenge and secondary outcome measure: anti-inflammatory effects monitored by exhaled NO (eNO) before and after sc-LCPUFA supplementation versus placebo.
Results: Ninety-nine patients with exercise-induced symptoms aged 10 to 45 were screened by a standardized exercise challenge in a cold air chamber at 4 °C. Seventy-three patients fulfilled the inclusion criteria of a FEV1 decrease > 15% and were treated double-blind placebo-controlled for 4 weeks either with sc-LCPUFA or placebo. Thirty-two patients in each group completed the study. Mean FEV1 decrease after cold air exercise challenge and eNO were unchanged after 4 weeks sc-LCPUFA supplementation.
Conclusion: Supplementation with sc-LCPUFA at a dose of 1.19 g/d did not have any broncho-protective and anti-inflammatory effects on EIA.
Trial registration: Clinical trial registration number: NCT02410096. Registered 7 February 2015 at Clinicaltrial.gov
Reduced external knee adduction moments in the second half of stance after total hip replacement have been reported in hip osteoarthritis patients. This reduction is thought to shift the load from the medial to the lateral knee compartment and as such increase the risk for knee osteoarthritis. The knee adduction moment is a surrogate for the load distribution between the medial and lateral compartments of the knee and not a valid measure for the tibiofemoral contact forces which are the result of externally applied forces and muscle forces. The purpose of this study was to investigate whether the distribution of the tibiofemoral contact forces over the knee compartments in unilateral hip osteoarthritis patients 1 year after receiving a primary total hip replacement differs from healthy controls. Musculoskeletal modeling on gait was performed in OpenSim using the detailed knee model of Lerner et al. (2015) for 19 patients as well as for 15 healthy controls of similar age. Knee adduction moments were calculated by the inverse dynamics analysis, medial and lateral tibiofemoral contact forces with the joint reaction force analysis. Moments and contact forces of patients and controls were compared using Statistical Parametric Mapping two-sample t-tests. Knee adduction moments and medial tibiofemoral contact forces of both the ipsi- and contralateral leg were not significantly different compared to healthy controls. The contralateral leg showed 14% higher medial tibiofemoral contact forces compared to the ipsilateral (operated) leg during the second half of stance. During the first half of stance, the lateral tibiofemoral contact force of the contralateral leg was 39% lower and the ratio 32% lower compared to healthy controls. In contrast, during the second half of stance the forces were significantly higher (39 and 26%, respectively) compared to healthy controls. The higher ratio indicates a changed distribution whereas the increased lateral tibiofemoral contact forces indicate a higher lateral knee joint loading in the contralateral leg in OA patients after total hip replacement (THR). Musculoskeletal modeling using a detailed knee model can be useful to detect differences in the load distribution between the medial and lateral knee compartment which cannot be verified with the knee adduction moment.
Colorectal cancer (CRC) is one of the most frequently diagnosed tumor in humans and one of the most common causes of cancer-related death worldwide. The pathogenesis of CRC follows a multistage process which together with somatic gene mutations is mainly attributed to the dysregulation of signaling pathways critically involved in the maintenance of homeostasis of epithelial integrity in the intestine. A growing number of studies has highlighted the critical impact of members of the tripartite motif (TRIM) protein family on most types of human malignancies including CRC. In accordance, abundant expression of many TRIM proteins has been observed in CRC tissues and is frequently correlating with poor survival of patients. Notably, some TRIM members can act as tumor suppressors depending on the context and the type of cancer which has been assessed. Mechanistically, most cancer-related TRIMs have a critical impact on cell cycle control, apoptosis, epithelial–mesenchymal transition (EMT), metastasis, and inflammation mainly through directly interfering with diverse oncogenic signaling pathways. In addition, some recent publications have emphasized the emerging role of some TRIM members to act as transcription factors and RNA-stabilizing factors thus adding a further level of complexity to the pleiotropic biological activities of TRIM proteins. The current review focuses on oncogenic signaling processes targeted by different TRIMs and their particular role in the development of CRC. A better understanding of the crosstalk of TRIMs with these signaling pathways relevant for CRC development is an important prerequisite for the validation of TRIM proteins as novel biomarkers and as potential targets of future therapies for CRC.
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.
Objective: To study the effect of total hip replacement (THR) on serum cartilage oligomeric matrix protein concentration (sCOMP) and its correlation with joint loading during gait in patients with unilateral hip osteoarthritis.
Design: In this prospective multimodal (clinical, biomechanical, biochemical) study blood samples from 15 patients were taken before and up to three times after THR (7 days, 3 months and 1 year), each after a resting period of at least 30 min, for analysis of sCOMP. Gait analysis was performed before and 1 year after THR to determine hip and knee joint moments.
Results: Seven days after THR, sCOMP decreased significantly compared to the preoperative measurement (p < 0.001). Three months and 1 year postoperatively, sCOMP reverted to concentrations in the range of the preoperative value. One year postoperatively, a linear correlation between sCOMP and the maximum hip flexion moment was indicated in the first half of the stance phase on the unaffected side (r = −0.736, p = 0.024). No further correlations could be determined.
Conclusions: Surprisingly, the removal of a joint affected by osteoarthritis did not have a sustained effect on sCOMP. Both before and after THR there was no scientifically substantiated correlation between sCOMP and joint moments from gait analysis. Consequently, the examination of sCOMP is not useful to detect altered joint loads that may influence degenerative changes of adjacent joints after THR.
The registration number in the German Registry of Clinical Trials is DRKS00015053.