Biomechanical factors may explain why grasping violates Weber's law

Copyright © 2015. Published by Elsevier Ltd. Acknowledgments The experiment was part of N. Aschenneller’s MD thesis. The study was funded by the Staedtler Stiftung (Nuremberg, Germany).Peer reviewedPostprin

Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies

Objectives: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year. Methods: Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change. Results: Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability. Conclusions: Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable

Now You Feel both: Galvanic Vestibular Stimulation Induces Lasting Improvements in the Rehabilitation of Chronic Tactile Extinction

Tactile extinction is frequent, debilitating, and often persistent after brain damage. Currently, there is no treatment available for this disorder. In two previous case studies we showed an influence of galvanic vestibular stimulation (GVS) on tactile extinction. Here, we evaluated in further patients the immediate and lasting effects of GVS on tactile extinction. GVS is known to induce polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas. Tactile extinction was examined with the Quality Extinction Test (QET) where subjects have to discriminate six different tactile fabrics in bilateral, double simultaneous stimulations on their dorsum of hands with identical or different tactile fabrics. Twelve patients with stable left-sided tactile extinction after unilateral right-hemisphere lesions were divided into two groups. The GVS group (N = 6) performed the QET under six different experimental conditions (two Baselines, Sham-GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, and a Follow-up test). The second group of patients with left-sided extinction (N = 6) performed the QET six times repetitively, but without receiving GVS (control group). Both right-cathodal/left-anodal as well as left-cathodal/right-anodal GVS (mean: 0.7 mA) improved tactile identification of identical and different stimuli in the experimental group. These results show a generic effect of GVS on tactile extinction, but not in a polarity-specific way. These observed effects persisted at follow-up. Sham-GVS had no significant effect on extinction. In the control group, no significant improvements were seen in the QET after the six measurements of the QET, thus ruling out test repetition effects. In conclusion, GVS improved bodily awareness permanently for the contralesional body side in patients with tactile extinction and thus offers a novel treatment option for these patients

Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis

Objectives: With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients’ implicit preferences for oral versus parenteral DMTs and identified factors influencing patients’ treatment preference. Methods: Patients with relapsing–remitting MS (n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios. Based on this questionnaire a choice-based conjoint analysis was conducted. Results: Treatment frequency and route of administration showed a stronger influence on patient preference compared with frequency of mild side effects. The latter attribute was more important for treatment-naïve patients compared with DMT-experienced patients. The higher the Extended Disability Status Scale score, the more likely pills, and the less likely fewer side effects were preferred. Pills were preferred over injections by 93% of patients, when treatment frequency and frequency of side effects were held constant. However, preference switched to injections when pills had to be taken three times daily and injections only once per week. Injections were also preferred when pills were associated with frequent side effects. Conclusions: Our results suggest that route of administration and treatment frequency play an important role in the patients’ preference for a given DMT

Visual feedback explains why propointing is better than antipointing in spatial neglect

Kathrin S. Utz held a post-doctoral research fellowship of the Friedrich-AlexanderUniversity Erlangen-Nuremberg (program for the promotion of equal opportunities of women in science) at the time of data collection. Thomas Schenk was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, grant no’s: DFG-SCHE 735/2-1 and DFG-SCHE 735/3-1).Peer reviewedPostprin

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Now you feel both: Galvanic vestibular stimulation induces lasting improvements in the rehabilitation of chronic tactile extinction

Tactile extinction is frequent, debilitating and often persistent after brain damage. Currently, there is no treatment available for this disorder. In two previous case studies we showed an influence of galvanic vestibular stimulation (GVS) on tactile extinction. Here, we evaluated in further patients the immediate and lasting effects of GVS on tactile extinction. GVS is known to induce polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas. Tactile extinction was examined with the Quality Extinction Test (QET) where subjects have to discriminate six different tactile fabrics in bilateral, double simultaneous stimulations (DSS) on their dorsum of hands with identical or different tactile fabrics. Twelve patients with stable left-sided tactile extinction after unilateral right-hemisphere lesions were divided into two groups. The GVS group (N=6) performed the QET under six different experimental conditions (two Baselines, Sham-GVS, left-cathodal/right-anodal GVS, right-cathodal/left-anodal GVS, and a follow-up test). The second group of patients with left-sided extinction (N=6) performed the QET six times repetitively, but without receiving GVS (control group). Both right-cathodal/left-anodal as well as left-cathodal/right-anodal GVS (mean: 0.67 mA) improved tactile identification of identical and different stimuli in the experimental group. These results show a generic effect of GVS on tactile extinction, but not in a polarity-specific way. These observed effects persisted at Follow-up. Sham-GVS had no significant effect on extinction. In the control group, no significant improvements were seen in the QET after the six measurements of the QET, thus ruling out test repetition effects. In conclusion, GVS improved bodily awareness permanently for the contralesional body side in patients with tactile extinction and thus offers a novel treatment option for these patients