Nocebo Effects on Muscular Performance – An Experimental Study About Clinical Situations

Introduction: Nocebo effects are not only seen in studies of pharmacology and placebo/nocebo research but also in clinical everyday situations. For generation of objective and quantitative data on the impact of negative communication we have evaluated the immediate effects of common sentences, non-verbal signals and situations in the medical context on muscular performance.Methods: In an experimental study, 46 volunteers were tested by dynamometry of the deltoid muscle group to evaluate the maximal muscular strength during arm abduction. Baseline values were compared to performance after exposure to 18 verbal and non-verbal suggestions. Suggestions suspected to be negative were alternated with and compared to positively formulated alternatives.Results: Verbal and non-verbal communication produced significant effects on muscular performance, resulting mainly in weakening. The decrease in muscle strength after risk information for informed consent (91.4% of baseline) was absent, when benefits of the treatment were named coincidently. The weakening effect of asking about “pain” and “nausea” (89.4%), and of the announcement of medical interventions (91.7%) could be avoided with alternative wording. Impairment of muscular performance was also observed with the nocebo-inducers negative memory (89.5%) or uncertain future (93.3%), in contrast to a positive memory or the orientation into the presence. Non-verbal suggestions like overhead anesthesia induction (89.9%), a transport in strict flat supine position (89.1%), or a view from the window to a parking lot (94.1%) significantly reduced maximal muscle strength, whereas face-to face induction, half-sitting position and a view into the landscape did not. 8 out of 9 tested clinical situations reduced maximal arm muscle strength significantly, whereas alternative formulations did not.Conclusion: This study describes a quick, simple and uniform test using objective measurement of maximal muscle strength to allow for identification, quantification, and comparison of negative suggestions, regardless of their specific content and effect. Muscle strength is a clinically relevant parameter with regard to early mobilization, risk of falling and sufficient breathing. Furthermore, the observed impairment of muscular performance could reflect a general “weakening effect” of negative suggestions. In addition, the test facilitates development and verification of appropriate alternatives to prevent nocebo effects in patients, thereby improving patient communication

E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up

The molybdenum isotopic composition of the modern ocean

Natural variations in the isotopic composition of molybdenum (Mo) are showing increasing potential as a tool in geochemistry. Although the ocean is an important reservoir of Mo, data on the isotopic composition of Mo in seawater are scarce. We have recently developed a new method for the precise determination of Mo isotope ratios on the basis of preconcentration using a chelating resin and measurement by multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), which allows us to measure every stable Mo isotope. In this study, 172 seawater samples obtained from 9 stations in the Pacific, Atlantic, and Southern Oceans were analyzed, giving global coverage and the first full depth-profiles. The average isotope composition in δA/95Mo (relative to a Johnson Matthey Mo standard solution) was as follows: δ92/95Mo = –2.54 ± 0.16‰ (2SD), δ94/95Mo = –0.73 ± 0.19‰, δ96/95Mo = 0.85 ± 0.07‰, δ97/95Mo = 1.68 ± 0.08‰, δ98/95Mo = 2.48 ± 0.10‰, and δ100/95Mo = 4.07 ± 0.18‰. The δ values showed an excellent linear correlation with atomic mass of AMo (R2 = 0.999). Three-isotope plots for the Mo isotopes were fitted with straight lines whose slopes agreed with theoretical values for mass-dependent isotope fractionation. These results demonstrate that Mo isotopes are both uniformly distributed and follow a mass-dependent fractionation law in the modern oxic ocean. A common Mo standard is urgently required for the precise comparison of Mo isotopic compositions measured in different laboratories. On the other hand, our results strongly support the possibility of seawater as an international reference material for Mo isotopic composition

Renin inhibition by substituted piperidines: A novel paradigm for the inhibition of monomeric aspartic proteinases?

BackgroundThe aspartic proteinase renin catalyses the first and rate-limiting step in the conversion of angiotensinogen to the hormone angiotensin II, and therefore plays an important physiological role in the regulation of blood pressure. Numerous potent peptidomimetic inhibitors of this important drug target have been developed, but none of these compounds have progressed past clinical phase II trials. Limited oral bioavailability or excessive production costs have prevented these inhibitors from becoming new antihypertensive drugs. We were interested in developing new nonpeptidomimetic renin inhibitors.ResultsHigh-throughput screening of the Roche compound library identified a simple 3,4-disubstituted piperidine lead compound. We determined the crystal structures of recombinant human renin complexed with two representatives of this new class. Binding of these substituted piperidine derivatives is accompanied by major induced-fit adaptations around the enzyme's active site.ConclusionsThe efficient optimisation of the piperidine inhibitors was facilitated by structural analysis of the renin active site in two renin-inhibitor complexes (some of the piperidine derivatives have picomolar affinities for renin). These structural changes provide the basis for a novel paradigm for inhibition of monomeric aspartic proteinases

RNA-Seq Mapping and Detection of Gene Fusions with a Suffix Array Algorithm

High-throughput RNA sequencing enables quantification of transcripts (both known and novel), exon/exon junctions and fusions of exons from different genes. Discovery of gene fusions–particularly those expressed with low abundance– is a challenge with short- and medium-length sequencing reads. To address this challenge, we implemented an RNA-Seq mapping pipeline within the LifeScope software. We introduced new features including filter and junction mapping, annotation-aided pairing rescue and accurate mapping quality values. We combined this pipeline with a Suffix Array Spliced Read (SASR) aligner to detect chimeric transcripts. Performing paired-end RNA-Seq of the breast cancer cell line MCF-7 using the SOLiD system, we called 40 gene fusions among over 120,000 splicing junctions. We validated 36 of these 40 fusions with TaqMan assays, of which 25 were expressed in MCF-7 but not the Human Brain Reference. An intra-chromosomal gene fusion involving the estrogen receptor alpha gene ESR1, and another involving the RPS6KB1 (Ribosomal protein S6 kinase beta-1) were recurrently expressed in a number of breast tumor cell lines and a clinical tumor sample

Constrained 2-D/3-D Registration for Motion Compensation in AFib Ablation Procedures

Abstract. Fluoroscopic overlay images rendered from pre-operative vol-umetric data can provide additional guidance for physicians during catheter ablation procedures for treatment of atrial fibrillation (AFib). As these overlay images are compromised by cardiac and respiratory motion, mo-tion compensation methods have been proposed. The approaches so far either require simultaneous biplane imaging for 3-D motion compensa-tion or, in case of mono-plane X-ray imaging, provide only a limited 2-D functionality. To overcome the downsides of the previously suggested methods, we propose a new approach that facilitates full 3-D motion compensation even if only mono-plane X-ray views are available. To this end, we use constrained model-based 2-D/3-D registration to track a circumferential mapping catheter which is commonly used during AFib catheter ablation procedures. Our approach yields an average 2-D track-ing error of 0.6 mm and an average 3-D tracking error of 2.1 mm.

E.U. paediatric MOG consortium consensus: Part 5 – Treatment of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

In recent years, the understanding about the different clinical phenotypes, diagnostic and prognostic factors of myelin oligodendrocyte glycoprotein-antibody-associated disorders (MOGAD) has significantly increased. However, there is still lack of evidence-based treatment protocols for acute attacks and children with a relapsing course of the disease. Currently used acute and maintenance treatment regimens are derived from other demyelinating central nervous system diseases and are mostly centrespecific. Therefore, this part of the Paediatric European Collaborative Consensus attempts to provide recommendations for acute and maintenance therapy based on clinical experience and evidence available from mainly retrospective studies. In the acute attack, intravenous methy