Gadolinium contrast agents: dermal deposits and potential effects on epidermal small nerve fibers

Small fiber neuropathy (SFN) affects unmyelinated and thinly myelinated nerve fibers causing neuropathic pain with distal distribution and autonomic symptoms. In idiopathic SFN (iSFN), 30% of the cases, the underlying aetiology remains unknown. Gadolinium (Gd)-based contrast agents (GBCA) are widely used in magnetic resonance imaging (MRI). However, side-effects including musculoskeletal disorders and burning skin sensations were reported. We investigated if dermal Gd deposits are more prevalent in iSFN patients exposed to GBCAs, and if dermal nerve fiber density and clinical parameters are likewise affected. 28 patients (19 females) with confirmed or no GBCA exposure were recruited in three German neuromuscular centers. ISFN was confirmed by clinical, neurophysiological, laboratory and genetic investigations. Six volunteers (two females) served as controls. Distal leg skin biopsies were obtained according to European recommendations. In these samples Gd was quantified by elemental bioimaging and intraepidermal nerve fibers (IENF) density via immunofluorescence analysis. Pain phenotyping was performed in all patients, quantitative sensory testing (QST) only in a subset (15 patients; 54%). All patients reported neuropathic pain, described as burning (n = 17), jabbing (n = 16) and hot (n = 11) and five QST scores were significantly altered. Compared to an equal distribution significantly more patients reported GBCA exposures (82%), while 18% confirmed no exposures. Compared to unexposed patients/controls significantly increased Gd deposits and lower z-scores of the IENF density were confirmed in exposed patients. QST scores and pain characteristics were not affected. This study suggests that GBCA exposure might alter IENF density in iSFN patients. Our results pave the road for further studies investigating the possible role of GBCA in small fiber damage, but more investigations and larger samples are needed to draw firm conclusions

Patients’ perspectives on prescription cannabinoid therapies: a cross-sectional, exploratory, anonymous, one-time web-based survey among German patients

Introduction: Since cannabinoids were partially legalized as prescription medicines in Germany in 2017, they are mostly used when conventional therapies do not suffice. Ambiguities remain regarding use, benefits and risks. This web-based survey explored the perspectives of patients whose experiences are not well enough known to date. Methods: In an anonymous, exploratory, cross-sectional, one-time web-based observational study, participants receiving cannabinoid therapy on prescription documented aspects of their medical history, diagnoses, attitudes toward cannabinoids, physical symptoms, and emotional states. Participants completed the questionnaires twice here: first regarding the time of the survey and then, retrospectively, for the time before their cannabinoid therapy. Participants were recruited in a stratified manner in three German federal states. Results: N = 216 participants (48.1% female, aged 51.8 +/- 14.0) completed the survey, most of which (72%, n = 155) reported pain as their main reason for cannabinoid therapy. When comparing the current state with the retrospectively assessed state, participants reported greater satisfaction with their overall medical therapy (TSQM II: +47.9 +/- 36.5, p < 0.001); improved well-being (WHO-5: +7.8 +/- 5.9, p < 0.001) and fewer problems in PROMIS subscales (all p < 0.001). Patients suffering primarily from pain (72%, n = 155) reported a reduction of daily pain (NRS: -3.2 +/- 2.0, p < 0.001), while participants suffering mainly from spasticity (8%, n = 17) stated decreased muscle spasticity (MSSS: -1.5 +/- 0.6, p < 0.001) and better physical mobility (-0.8 +/- 0.8, p < 0.001). Data suggests clinically relevant effects for most scores. Participants' attitudes toward cannabinoids (on a 5-point scale) improved (+1.1 +/- 1.1, p < 0.001). Most patients (n = 146, 69%) did not report major difficulties with the cannabinoid prescription process, while (n = 27; 19%) had their cannabinoid therapy changed due to side effects. Discussion: Most participants experienced their therapy with cannabinoids as more effective than their previous therapy. There are extensive limitations to this cross-sectional study: the originally intended representativeness of the dataset was not reached, partly due to the SARS-CoV-2 pandemic; the sample has a larger proportion of privately insured and self-paying patients. Results does not suggest that cannabinoid patients belong to a particular clientele. Effect sizes observed for pain reduction, quality of life, social participation, and other outcomes suggest a therapeutic potential, particularly in the treatment of chronic pain

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (PPeer reviewe

Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer

Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10−5). For three cis-eQTL associations (P<1.4 × 10−3, FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10−10 for risk variants (P<10−4) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC

Ein Leben für das Hören. Karl Karst, Auditorix-Erfinder und langjähriger Programmchef des Kulturradios WDR 3, im Gespräch mit Matthias Preis

Preis M, Karst K. Ein Leben für das Hören. Karl Karst, Auditorix-Erfinder und langjähriger Programmchef des Kulturradios WDR 3, im Gespräch mit Matthias Preis. In: Josting P, Preis M, eds. Klangwelten für Kinder und Jugendliche. Hörmedien in ästhetischer, didaktischer und historischer Perspektive. kjl&amp;m 21.extra. München: kopaed; 2021: 81-87

Alteration in forward model prediction of sensory outcome of motor action in focal hand dystonia

Focal hand dystonia in musicians is a movement disorder affecting highly trained movements. Rather than being a pure motor disorder related to movement execution only, movement planning, error prediction and sensorimotor integration are also impaired. Internal models, of which two types, forward and inverse models have been described and most likely processed in the cerebellum, are known to be involved in these tasks. Recent results indicate that the cerebellum may be involved in the pathophysiology of focal dystonia. Thus the aim of our study was to investigate whether an internal model deficit plays a role in focal dystonia. We focused on the forward model, which predicts sensory consequences of motor commands and allows the discrimination between external sensory input and input deriving from motor action. We investigated 19 patients, aged 19-59 and 19 healthy musicians aged 19-36 as controls. Tactile stimuli were applied to fingers II–V of both hands by the experimenter or the patient. After each stimulus the participant rated the stimulus-intensity on a scale between 0 (no sensation) and 1 (maximal intensity). The difference of perceived intensity between self- &amp; externally applied stimuli was then calculated for each finger. For assessing differences between patients and controls we performed a cluster analysis of the affected hand and the corresponding hand of the controls using the fingers II–V as variables in a 4-dimensional hyperspace (chance level=0.5). Using a cluster analysis, we found a correct classification of the affected finger in 78,9%-94.7%. There was no difference between patients and healthy controls of the absolute value of the perceived stimulus intensity. Our results suggest an altered forward model function in focal hand dystonia. It has the potential of suggesting a neural correlate within the cerebellum and of helping integrate findings with regard to altered sensorimotor processing and altered prediction in FD in a single framework

Percutaneous Bioelectric Current Stimulation in the Treatment of Chronic Achilles Tendinopathy: Protocol for a Double-Blind, Placebo-Controlled Randomized Multicenter Trial

BackgroundThe consensus for the optimal treatment strategy for chronic Achilles tendinopathy (AT) is still debated and treatment options are limited. This results in a significant medical need for more effective treatment options. ObjectiveThe aim of this study is to investigate the therapeutic effects of percutaneous bioelectric current stimulation (PBCS) on AT. MethodsA multicenter, randomized, double-blind, placebo-controlled clinical trial will be conducted. A total of 72 participants with chronic (ie, >3 months) midpoint AT will be randomized and receive four PBCS sessions—either verum or placebo—over 3 weeks. Both groups will complete daily Achilles tendon loading exercises in addition to the intervention. Evaluation sessions will be completed at baseline and during the intervention (weeks 0-3). Self-reported outcome measures will be completed at follow-up at weeks 4, 12, 26, and 52. The primary outcomes are the Victorian Institute of Sports Assessment–Achilles questionnaire scores and statistical evaluation of intraindividual differences between baseline and 12-week evaluations after initial treatment of verum therapy compared to control. Secondary outcomes will assess Pain Disability Index scores; average pain, using the 11-point Numeric Rating Scale; return to sports; and use of emergency medication. ResultsThe study began in May 2021. As of October 2022, we randomized 66 out of 72 participants. We anticipate completing recruitment by the end of 2022 and completing primary data analysis by March 2023. ConclusionsThe study will evaluate the effects of PBCS on pain, physical function, and clinical outcomes. Trial RegistrationGerman Clinical Trials Register DRKS00017293; https://tinyurl.com/mvz7s98k International Registered Report Identifier (IRRID)DERR1-10.2196/4089

In vivo myograph measurement of muscle contraction at optimal length

We have introduced a new technical solution for valid, reproducible in vivo force measurements on every possible point of the stretching curve. Thus it should be possible to study the muscle contraction in vivo to the same level of accuracy as is achieved in tests with in vitro organ preparations