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- nucleic acid (2)
- nucleophilic addition (2)
- nucleosomes (2)
- nucleotide excision-repair (2)
- nucleotide sequence (2)
- nude-mice (2)
- numerical analysis (2)
- numerical hydrodynamics (2)
- nurse bee (2)
- nurses (2)
- o-methoxy-sila-hexocyclium (2)
- object-based classification (2)
- object-based image analysis (2)
- observer (2)
- obstetrics (2)
- occupational medicine/industrial medicine (2)
- oculomotor control (2)
- oestrogen receptor signalling (2)
- office-workers (2)
- oil palm (2)
- older adults (2)
- olfaktorisches Lernen (2)
- oligodendrocyte (2)
- oligorecurrence (2)
- oligothiophenes (2)
- olive (2)
- omega-3 fatty acids (2)
- oncogene-induced senescence (2)
- oncolytic viral therapy (2)
- oncolytic virus therapy (2)
- one-electron oxidation (2)
- online survey (2)
- onset (2)
- open spaces (2)
- opioid peptides (2)
- optic neuritis (2)
- optical (2)
- optical coherence tomography (2)
- optical physics (2)
- optical remote sensing (2)
- optics (2)
- optics and photonics (2)
- optimal control theory (2)
- optimal drug combination (2)
- optogenetic (2)
- oral bioavailability (2)
- oral mucositis (2)
- ordinary culture (2)
- ordinary differential equations (2)
- organ-on-a-chip (2)
- organic electronics (2)
- organic photovoltaic (2)
- organic thin films (2)
- organische Solarzellen (2)
- origin (2)
- orthopedic surgery (2)
- osteoclasts (2)
- osteonecrosis of the jaw (2)
- osteopontin (2)
- osteoradionecrosis (2)
- otitis media (2)
- outer membrane protein (2)
- outer membrane proteins (2)
- outer-membrane proteins (2)
- outpatients (2)
- oxaliplatin (2)
- oxidative addition (2)
- oxygen reduction reaction (2)
- oxygen uptake (2)
- oxytocin (2)
- p-Halbleiter (2)
- p34 (2)
- p38 MAP kinase (2)
- p44 (2)
- p90 ribosomal S6 kinase (2)
- pCa (2)
- pH (2)
- pICln (2)
- paediatric patients (2)
- paediatrics (2)
- pain regulation (2)
- pain sensation (2)
- paleogeography (2)
- palladium (2)
- palliative care (2)
- pandemic (2)
- panel sequencing (2)
- parabiosis (2)
- parallel evolution (2)
- parallel imaging (2)
- parasite biology (2)
- parasitic cell cycles (2)
- parasitoid (2)
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- parkinson's disease (2)
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- parthenogenesis (2)
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- particles (2)
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- pathogen (2)
- pathogenic bacteria (2)
- pathway analysis (2)
- patient education (2)
- patient reported outcome measures (2)
- patient safety (2)
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- patient-reported outcomes (2)
- patient-specific (2)
- pattern (2)
- peak oxygen uptake (2)
- pedagogical content knowledge (2)
- pediatric adrenocortical cancer (2)
- pediatric adrenocortical tumor (2)
- pediatric patients (2)
- peer review (2)
- pelvic examination (2)
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- pembrolizumab (2)
- pemphigus foliaceus (2)
- penicillin allergy (2)
- penicillin hypersensitivity (2)
- pentacoordinate (2)
- people (2)
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- peptide tyrosine tyrosine (PYY) (2)
- peptide vaccination (2)
- peptides (2)
- performance modeling (2)
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- pericyclic reaction (2)
- pericytes (2)
- periodization (2)
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- peripheral nerve (2)
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- peroxisomes (2)
- personalised medicine (2)
- personality traits (2)
- personalized treatment (2)
- perspective taking (2)
- perspectives (2)
- perylene bisimides (2)
- pest control (2)
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- phage (2)
- phagosome maturation (2)
- pharmaceutical analysis (2)
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- pharmacodynamics (2)
- pharmacokinetic (2)
- pharmacology/toxicology (2)
- pharmacovigilance (2)
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- phenprocoumon (2)
- phosphatidylserine (2)
- phosphodiesterase (2)
- phosphoglycolate phosphatase (2)
- phospholipase D (2)
- phosphorus (2)
- photoemission spectroscopy (2)
- photoinduzierter Elektronentransfer (2)
- photolysis (2)
- photon statistics (2)
- photon-counting (2)
- photoreceptor (2)
- photoreceptors (2)
- photoswitchable organic fluorophores (2)
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- physical health (2)
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- physiologically based pharmacokinetic (PBPK) modeling (2)
- phytochemicals (2)
- phytochemistry (2)
- phytohormones (2)
- pi-conjugation (2)
- piRNA (2)
- pig (2)
- pigmentation (2)
- piperacillin/tazobactam (2)
- piperidines (2)
- placebo-controlled trial (2)
- planning (2)
- plant (2)
- plant cuticle (2)
- plant defence (2)
- plant defenses (2)
- plant diversity (2)
- plant immunity (2)
- plant quality (2)
- plant–insect interactions (2)
- plaque (2)
- plasma proteins (2)
- plasminogen (2)
- platelet physiology (2)
- platelet receptors (2)
- platyhelminthes (2)
- plausibility (2)
- pleomorphic adenoma (2)
- pneumolysin (2)
- pneumonia (2)
- point of care testing (2)
- pointing gestures (2)
- polarimetry (2)
- polaritons (2)
- polarized epithelium (2)
- policy (2)
- politics of representation (2)
- pollen analysis (2)
- pollen metabarcoding (2)
- pollen tube (2)
- pollination network (2)
- pollinator decline (2)
- pollinator friendly plants (2)
- pollinators (2)
- poly(2- oxazoline) (2)
- polycationic peptides (2)
- polymavirus (2)
- polymer-peptide-conjugate (2)
- polymorphisms (2)
- polymyalgia rheumatica (2)
- polyploidy (2)
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- population structure (2)
- population-based (2)
- populations (2)
- pore formation (2)
- porphyrins (2)
- pose estimation (2)
- positive selection (2)
- positron emission tomography/computed tomography (2)
- post-processing (2)
- post-transcriptional regulation (2)
- posterior parietal cortex (2)
- postmenopausal women (2)
- postnatal development (2)
- postoperative bleeding (2)
- postoperative care (2)
- postoperative nausea and vomiting (2)
- posttranslational modifications (2)
- postural control (2)
- potassium channel (2)
- power training (2)
- pp Collisions (2)
- pp collisions (2)
- pre-messenger RNA (2)
- precipitation (2)
- precision agriculture (2)
- preconditioning (2)
- predation risk (2)
- predictive factors (2)
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- priming (2)
- printability (2)
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- probability (2)
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- programmed cell death (2)
- projection neurons (2)
- promoter methylation (2)
- propensity score matching (2)
- propulsion (2)
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- prostate-cancer (2)
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- prosthesis (2)
- protease inhibition (2)
- proteasome (2)
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- psychoeducation (2)
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- puberty (2)
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- pyrene dimer (2)
- pyridoxal phosphatase (2)
- qPCR (2)
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- quantitative SPECT/CT (2)
- quantitative analysis (2)
- quantity discrimination (2)
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- real time PCR (2)
- real world evidence (2)
- receptor beta (2)
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- receptor tyrosine kinase (2)
- reconstructed human epidermis (2)
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- reflection (2)
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- revision arthroplasty (2)
- rheology (2)
- rheumatology (2)
- ribonucleases (2)
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- ribozymes (2)
- rice (2)
- ring expansion (2)
- ring-expansion reaction (2)
- risk profiling (2)
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- robotic (2)
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- rodent model (2)
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- rolipram (2)
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- root (2)
- root growth (2)
- roots (2)
- ruthenium bda complexes (2)
- saccharomyces cerevisiae (2)
- safety behavior (2)
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- salicylic acid (2)
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- sar (2)
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- satellite (2)
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- scaffolds (2)
- scalability (2)
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- secondary site infection (2)
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- see (2)
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- semismooth Newton method (2)
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- sentinel-2 (2)
- septic (2)
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- sesame (2)
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- shape fidelity (2)
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- shoulder (2)
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- similarity (2)
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- sirolimus (2)
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- situation awareness (2)
- sizing (2)
- skeletal dysplasia (2)
- skin model (2)
- skinned fiber (2)
- sleep bruxism (2)
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- smart speaker (2)
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- snow cover duration (2)
- social (2)
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- social context (2)
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- social robot (2)
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- sodium channel (2)
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- sofosbuvir (2)
- solar cell (2)
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- solid-state NMR (2)
- solid-state emitters (2)
- solitary bee (2)
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- soluble guanylyl cyclase (2)
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- somatic mosaicism (2)
- somatostatin receptor (SSTR) (2)
- soybean (2)
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- spatial attention (2)
- spatial navigation (2)
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- spatial presence (2)
- spatial scale (2)
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- speckle tracking (2)
- spectral karyotyping (2)
- speech (2)
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- speed (2)
- sperm DNA methylation (2)
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- spermatocytes (2)
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- spheroids (2)
- sphingosine (2)
- sphingosine kinase inhibitor SKI-II (2)
- sphingosine-1-phosphate (2)
- spider (2)
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- spinal cord injury (2)
- spinal-cord (2)
- spinal-cord-injury (2)
- spine (2)
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- spin–orbit coupling (2)
- spiral ganglion neuron (2)
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- splice variant (2)
- split-belt treadmill (2)
- spontaneous blinks (2)
- spontaneous symmetry breaking (2)
- sporidia (2)
- squaraine dyes (2)
- ssVEP (2)
- stability analysis (2)
- stage renal-disease (2)
- startle (2)
- state (2)
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- stereochemistry (2)
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- structure-activity (2)
- structure-function relationships (2)
- structured illumination (2)
- structured illumination microscopy (2)
- student training (2)
- study design (2)
- sturgeon (2)
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- sub-Saharan Africa (2)
- subcutaneous animal model (2)
- substantia nigra pars compacta (2)
- succession (2)
- suffering (2)
- suicidality (2)
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- sulfates (2)
- sun exposure (2)
- super-resolution fluorescence microscopy (2)
- superparamagnetism (2)
- supervisors (2)
- support vector machines (2)
- supraglacial lakes (2)
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- supramolekulare Chemie (2)
- supraparticles (2)
- surface states (2)
- surfaces, interfaces and thin films (2)
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- survival analysis (2)
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- swimming (2)
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- synapse formation (2)
- synapsin (2)
- synapsis (2)
- synaptische Proteine (2)
- synaptonemal complex (2)
- syndrome (2)
- synergistic effect (2)
- synovial fluid (2)
- synthetic aperture RADAR (2)
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- synthetic mesh (2)
- systematics (2)
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- time (2)
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- tissue model (2)
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- tobacco (2)
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- tolerability (2)
- toll-like receptors (2)
- tool use (2)
- tooth extraction (2)
- top quark decay (2)
- topic modeling (2)
- topologische Isolatoren (2)
- total joint arthroplasty (2)
- toxicology (2)
- toxin (2)
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- tracer (2)
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- tracking (2)
- training intensity distribution (2)
- trait emotional intelligence (2)
- trans-Golgi network (2)
- trans-formanilide (2)
- transcranial magnetic stimulation (2)
- transcription factor MIZ-1 (2)
- transcriptional profiling (2)
- transcriptomic analysis (2)
- transcutaneous vagus nerve stimulation (2)
- transfer learning (2)
- transformation (2)
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- transforming growth factor-beta 1 (2)
- transient dynamics (2)
- transient middle cerebral artery occlusion (2)
- transiente Absorption (2)
- transiente Absorptionsspektroskopie (2)
- transition (2)
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- translation initiation (2)
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- triplet (2)
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- two-dimensional topological insulator (2)
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- two-stage exchange (2)
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- type VII secretion system (2)
- tyramine (2)
- tyrosine (2)
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- ultrafast spectroscopy (2)
- ultrafiltration (2)
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- umbilical hernia (2)
- unconventional superconductivity (2)
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- unfolded protein response (2)
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- unmanned aerial vehicles (2)
- unpleasant pictures (2)
- up-regulation (2)
- update (2)
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- usability (2)
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- vacancy (2)
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- vacuole (2)
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- variant surface glycoprotein (2)
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- vasculature (2)
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- vasopressin (2)
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- velocity-dependent collision frequency (2)
- vemurafenib (2)
- venous system (2)
- ventral hernia (2)
- verdünnt magnetische Halbleiter (2)
- vertebral metastases (2)
- vertebrate (2)
- vertigo (2)
- very-long-baseline interferometry (2)
- vesicle trafficking (2)
- vibration (2)
- vicinal surfaces (2)
- video analysis (2)
- virology (2)
- virtual agent (2)
- virtual body ownership (2)
- virtuelle Realität (2)
- virus reactivation (2)
- viscosity (2)
- visible cross section (2)
- visual (2)
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- vitamin D deficiency (2)
- vitamins (2)
- vocabulary (2)
- volatile anesthetics (2)
- volatiles (2)
- voltage clamp (2)
- volume regulation (2)
- voluntary movement (2)
- voxel-based morphometry (2)
- vulnerability (2)
- wR factor = 0.068 (2)
- wasps (2)
- water balance (2)
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Proximitized materials
(2019)
Advances in scaling down heterostructures and having an improved interface quality together with atomically thin two-dimensional materials suggest a novel approach to systematically design materials. A given material can be transformed through proximity effects whereby it acquires properties of its neighbors, for example, becoming superconducting, magnetic, topologically nontrivial, or with an enhanced spin–orbit coupling. Such proximity effects not only complement the conventional methods of designing materials by doping or functionalization but also can overcome their various limitations. In proximitized materials, it is possible to realize properties that are not present in any constituent region of the considered heterostructure. While the focus is on magnetic and spin–orbit proximity effects with their applications in spintronics, the outlined principles also provide a broader framework for employing other proximity effects to tailor materials and realize novel phenomena.
Objectives. In diabetes accumulated advanced glycation end products (AGEs) are involved in the striking cardiovascular morbidity/mortality. We asked whether a hypovitaminosis D associates with an increased formation and toxicity of AGEs in diabetes.
Methods. In 276 diabetics (160M/116 F, age: 65.0 ± 13.4; 43 type 1,T1DM, and 233 type 2 patients, T2DM) and 121 nondiabetic controls (60 M/61 F; age: 58.6 ± 15.5 years) routine biochemistry, levels of 25-hydroxyvitamin D\(_{3}\) (25-(OH)D), skin autofluorescence (SAF), plasma AGE-associated fluorescence (AGE-FL), N\(^{ε}\) -(carboxymethyl) lysine (CML), soluble receptor for AGEs (sRAGE), soluble vascular adhesion protein-1 (sVAP-1), high sensitive C-reactive protein (hs-CRP), and renal function (eGFR) were determined.
Results. In the diabetics SAF and AGE-Fl were higher than those of the controls and correlated with age, duration of diabetes, and degree of renal impairment. In T2DM patients but not in T1DM the age-dependent rise of SAF directly correlated with hs-CRP and sVAP-1. 25-(OH)D levels in diabetics and nondiabetics were lowered to a similar degree averaging 22.5 ng/mL. No relationship between 25-(OH)D and studied markers except for sVAP-1 was observed in the diabetics. Conclusion. In diabetics hypovitaminosis D does not augment accumulation of AGEs and studied markers of microinflammation and oxidative stress except for sVAP-1.
Background and Objective
The aim of this single‐centre, two‐arm, parallel‐group, double‐blinded, randomised controlled trial was to investigate the disputed specific effectiveness of acupuncture by comparing acupuncture on specific and non‐specific points among patients with non‐chronic, painful TMDs.
Methods
Following predefined eligibility criteria, 49 consecutive patients of both sexes were recruited to the study. All subjects were diagnosed with a non‐chronic (Graded Chronic Pain Scale grade <3) painful TMD, as assessed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD). Patients were randomly assigned to group A (acupuncture on specific points) or group B (acupuncture on non‐specific points) after the initial examination (T0). Both acupuncture treatment sessions were conducted by a trained dentist once a week for four weeks. The examination was repeated five weeks (T5) after T0 by one calibrated examiner who was unaware of the study groups. Characteristic pain intensity (CPI) was evaluated as the main outcome criterion and compared between times and treatment groups by means of non‐parametric tests (significance level set at P = .05). Secondary outcomes comprised the maximum corrected active mouth‐opening without pain (MAO); patients’ expectations regarding acupuncture treatment and pain development; depressivity; and oral health‐related quality of life (OHRQoL).
Results
A total of 41 patients (38 female) successfully completed the study (mean age: 40.17 ± 16.61). The two groups did not differ significantly at any time in terms of age and CPI. However, CPI was significantly (P < .05) lower at T5 than at T0 for both groups (29.66 and 30.35% lower in group A and group B, respectively). An increase in MAO was observed at T5 for both groups but was significant for group B only (P = .016). All patients had positive expectations of acupuncture therapy, and the two groups did not differ significantly at T5 with regard to the extent to which their expectations had been fulfilled by the treatment (P = .717). Comparison of T0 and T5 showed a statistically significant reduction of depressivity for group A (P = .0205), but no significant change for group B (P = .329). At T5, OHRQoL had improved significantly for both groups (group A, P = .018; group B, P < .001) compared with at T0.
Conclusions
Acupuncture on both specific and non‐specific points reduces the non‐dysfunctional pain of TMD patients. The effect of acupuncture on painful TMD cannot be attributed to the specific point selection.
Background
Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters.
Results
A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 % of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file.
Conclusions
The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.
Background
Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN.
Methods
Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1β, IL-2, and IL-8).
Results
IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar.
Conclusion
While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.
Fabry disease (FD) is an X-linked lysosomal storage disorder associated with pain triggered by heat or febrile infections. We modelled this condition by measuring the cytokine expression of peripheral blood mononuclear cells (PBMC) from FD patients in vitro upon stimulation with heat and lipopolysaccharide (LPS). We enrolled 67 FD patients and 37 healthy controls. We isolated PBMC, assessed their gene expression of selected pro- and anti-inflammatory cytokines, incubated them with heat, LPS, globotriaosylceramide (Gb3), and tumor necrosis factor-α (TNF), and measured TNF secretion in the supernatant and intracellular Gb3 accumulation, respectively. We found increased TNF, interleukin (IL-)1β, and toll-like receptor 4 (TLR4) gene expression in FD men (p < .05 to p < .01). TNF and IL-10 were higher, and IL-4 was lower in the subgroup of FD men with pain compared to controls (p < .05 to p < .01). Hereby, TNF was only increased in FD men with pain and classical mutations (p < .05) compared to those without pain. PBMC from FD patients secreted more TNF upon stimulation with LPS (p < .01) than control PBMC. Incubation with Gb3 and an additional α-galactosidase A inhibitor did not further increase TNF secretion, but incubation with TNF greatly increased the Gb3 load in FD PBMC compared to controls (p < .01). Also, LPS incubation and heat challenge (40 °C) increased Gb3 accumulation in PBMC of patients compared to baseline (p < .05 each), while no alterations were observed in control PBMC. Our data show that TNF holds a crucial role in the pathophysiology of FD associated pain, which may open a novel perspective for analgesic treatment in FD pain.
Interleukin-4 (IL-4) is an anti-inflammatory and analgesic cytokine that induces opioid receptor transcription. We investigated IL-4 knockout (ko) mice to characterize their pain behavior before and after chronic constriction injury (CCI) of the sciatic nerve as a model for neuropathic pain. We investigated opioid responsivity and measured cytokine and opioid receptor gene expression in the peripheral and central nervous system (PNS, CNS) of IL-4 ko mice in comparison with wildtype (wt) mice. Naïve IL-4 ko mice displayed tactile allodynia (wt: 0.45 g; ko: 0.18 g; p<0.001), while responses to heat and cold stimuli and to muscle pressure were not different. No compensatory changes in the gene expression of tumor necrosis factor-alpha (TNF), IL-1β, IL-10, and IL-13 were found in the PNS and CNS of naïve IL-4 ko mice. However, IL-1β gene expression was stronger in the sciatic nerve of IL-4 ko mice (p<0.001) 28 days after CCI and only IL-4 ko mice had elevated IL-10 gene expression (p = 0.014). Remarkably, CCI induced TNF (p<0.01), IL-1β (p<0.05), IL-10 (p<0.05), and IL-13 (p<0.001) gene expression exclusively in the ipsilateral spinal cord of IL-4 ko mice. The compensatory overexpression of the anti-inflammatory and analgesic cytokines IL-10 and IL-13 in the spinal cord of IL-4 ko mice may explain the lack of genotype differences for pain behavior after CCI. Additionally, CCI induced gene expression of μ, κ, and δ opioid receptors in the contralateral cortex and thalamus of IL-4 ko mice, paralleled by fast onset of morphine analgesia, but not in wt mice. We conclude that a lack of IL-4 leads to mechanical sensitivity; the compensatory hyperexpression of analgesic cytokines and opioid receptors after CCI, in turn, protects IL-4 ko mice from enhanced pain behavior after nerve lesion.
High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know
(2014)
Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza ; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs.
High-resolution ultrasonography (HRUS) is an emerging new tool in the investigation of peripheral nerves. We set out to assess the utility of HRUS performed at lower extremity nerves in peripheral neuropathies. Nerves of 26 patients with polyneuropathies of different etiologies and 26 controls were investigated using HRUS. Patients underwent clinical, laboratory, electrophysiological assessment, and a diagnostic sural nerve biopsy as part of the routine work-up. HRUS was performed at the sural, tibial, and the common, superficial, and deep peroneal nerves. The superficial peroneal nerve longitudinal diameter (LD) distinguished best between the groups: patients with immune-mediated neuropathies (n = 13, including six with histology-proven vasculitic neuropathy) had larger LD compared to patients with non-immune-mediated neuropathies (p < 0.05) and to controls (p < 0.001). Among all subgroups, patients with vasculitic neuropathy showed the largest superficial peroneal nerve LD (p < 0.001) and had a larger sural nerve cross-sectional area when compared with disease controls (p < 0.001). Enlargement of the superficial peroneal and sural nerves as detected by HRUS may be a useful additional finding in the differential diagnosis of vasculitic and other immune-mediated neuropathies.
Background
The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity.
Methods
At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data.
Results
We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy.
Conclusions
Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.