Novel surface electrode design for preferential activation of cutaneous nociceptors

Objective Small area electrodes enable preferential activation of nociceptive fibers. It is debated, however, whether co-activation of large fibers still occurs for the existing electrode designs. Moreover, existing electrodes are limited to low stimulation intensities, for which behavioral and physiological responses may be considered less reliable. A recent optimization study showed that there is a potential for improving electrode performance and increase the range of possible stimulation intensities. Based on those results, the present study introduces and tests a novel planar concentric array electrode design for small fiber activation in healthy volunteers. Approach Volunteers received electrical stimulation with the planar concentric array electrode and a regular patch electrode. Perception thresholds were estimated at the beginning and the end of the experiment. Evoked cortical potentials were recorded in blocks of 30 stimuli. For the patch, stimulation intensity was set to two times perception threshold (PT), while three intensities, 2, 5, and 10 times PT, were applied with the planar concentric array electrode. Sensation quality, numerical-rating scores, and reaction times were obtained for each PT estimation and during each block of evoked potential recordings. Main results Stimulation with the patch electrode was characterized as dull, while stimulation with the planar concentric array electrode was characterized as sharp, with increased sharpness for increasing stimulus intensity. Likewise, NRS scores were higher for the planar concentric array electrode compared to the patch and increased with increasing stimulation intensity. Reaction times and ERP latencies were longer for the planar concentric array electrode compared to the patch. Significance The presented novel planar concentric array electrode is a small, non-invasive, and single-use electrode that has the potential to investigate small fiber neuropathy and pain mechanisms, as it is small fiber preferential for a wide range of stimulation intensities.

Time-Averaged Wavefront Analysis Demonstrates Preferential Pathways of Atrial Fibrillation, Predicting Pulmonary Vein Isolation Acute Response

Electrical activation during atrial fibrillation (AF) appears chaotic and disorganised, which impedes characterisation of the underlying substrate and treatment planning. While globally chaotic, there may be local preferential activation pathways that represent potential ablation targets. This study aimed to identify preferential activation pathways during AF and predict the acute ablation response when these are targeted by pulmonary vein isolation (PVI). In patients with persistent AF (n = 14), simultaneous biatrial contact mapping with basket catheters was performed pre-ablation and following each ablation strategy (PVI, roof, and mitral lines). Unipolar wavefront activation directions were averaged over 10 s to identify preferential activation pathways. Clinical cases were classified as responders or non-responders to PVI during the procedure. Clinical data were augmented with a virtual cohort of 100 models. In AF pre-ablation, pathways originated from the pulmonary vein (PV) antra in PVI responders (7/7) but not in PVI non-responders (6/6). We proposed a novel index that measured activation waves from the PV antra into the atrial body. This index was significantly higher in PVI responders than non-responders (clinical: 16.3 vs. 3.7%, p = 0.04; simulated: 21.1 vs. 14.1%, p = 0.02). Overall, this novel technique and proof of concept study demonstrated that preferential activation pathways exist during AF. Targeting patient-specific activation pathways that flowed from the PV antra to the left atrial body using PVI resulted in AF termination during the procedure. These PV activation flow pathways may correspond to the presence of drivers in the PV regions.

Aberrant Activation of the Mentalizing Brain System During Eye Gaze Discrimination in Bipolar Disorder

Bipolar disorder (BD) is associated with a range of social cognitive deficits. This study investigated the functioning of the mentalizing brain system in BD probed by an eye gaze perception task during fMRI. Compared with healthy controls (n = 21), BD participants (n = 14) showed reduced preferential activation for self-directed gaze discrimination in the medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ), which was associated with poorer cognitive and social functioning. Aberrant functions of the mentalizing system should be further investigated as marker of social dysfunction and treatment targets.

Reproducibility and Concurrent Validity of Manual Palpation with Rehabilitative Ultrasound Imaging for Assessing Deep Abdominal Muscle Activity: Analysis with Preferential Ratios

The abdominal drawing-in maneuver (ADIM) is a clinical tool used for identifying preferential activity of deep abdominal muscles. However, concurrent validity and reproducibility of palpation during the ADIM has not been formally investigated. The aims of this study were (1) to assess intra- and interrater reliability of manual palpation during the ADIM, and (2) to determine the concurrent validity of manual palpation during the ADIM by calculating preferential activation ratio cut-off as assessed with ultrasound imaging (RUSI). Thirty-two subjects (n = 16 patients with nonspecific low back pain and 16 comparable healthy individuals) performed the ADIM in a supine hook-lying position. Two experienced assessors evaluated the presence or absence of preferential contraction of the deep abdominal muscles by palpation during the ADIM on 2 different days. Intrarater (test-retest) and interrater reliability of palpation were calculated using Cohen’s kappa coefficients. Muscle thickness of the transverse abdominis (TrA), internal oblique (IO), and external oblique (EO) muscles at rest and during the ADIM were also measured. TrA-Contraction Ratio (TrA-CR), TrA-Preferential Activation Ratio (TrA-PAR), and Modified-TrA-PR (M-TrA-PAR) were calculated. The concurrent validity of manual palpation was determined using the correlation between manual palpation and imaging and by calculating ROC curve (operating characteristics curve), Youden index, and sensitivity and specificity. Intra- and interrater reliability of manual palpation during the ADIM was excellent (k: 0.82–1.00) and good to excellent (k: 0.71–1.00), respectively. Interrater reliability for muscle thickness ranged from good to excellent (ICC3,1 0.79–0.91). Manual palpation and TrA ratio showed low to moderate correlations (r: 0.36–0.60). When evaluating the diagnostic accuracy of manual palpation, the best predictive model (ROC value: 0.89; p < 0.001) for correct a preferential contraction of TrA was obtained when the M-TrA-PAR was ≥0.08 (sensitivity: 0.95–1.00; specificity: 0.62). Good to excellent intra- and interrater reliability of manual palpation was found during the ADIM in both patients and healthy groups. Manual palpation showed concurrent validity for identifying the preferential activity of the TrA muscle supporting its use in clinical practice.

Quantification of Cytokines in Lip Tissue from Infants Affected by Congenital Cleft Lip and Palate

Cleft lip and palate are amongst the most common congenital malformations worldwide presenting with variable manifestations. Previous research has been primarily focused on the genetical aspects of its complex and multifactorial etiology. In the present study, we investigated the role of cytokines as mediators of epithelial–mesenchymal crosstalk and local site inflammation in cleft affected infants. Lip material was obtained from 12 children aged before primary dentition who suffered from orofacial clefting. The quantification of 12 cytokines (Interleukin-2,4,5,6,10,12,13,17A, Tumor Necrosis Factor-α, Interferon-γ, Transforming Growth Factor beta-1 and Granulocyte-Colony Stimulating Factor) was done using ELISA. Nonparametric Spearman Rho was used to ascertain the correlation between the expression levels of different cytokines. A significantly strong positive correlation was found between IL-2 and IFN-γ coupled with an IL4/IFN-γ ratio favoring IFN-γ. These findings indicate a shift towards the preferential activation of the Th1 differentiation pathway. Further, a pathological reduction in TGFβ-1 levels was noted, which may contribute to mucosal damage. IL-6 was more highly correlated to IFN-γ and IL-12 indicating its potential proinflammatory role in cleft affected tissues. This preferential activation of Th1 cell differentiation and consistent expression of IL-2,6,13 and TNF-α in cleft patients may indicate certain underlying mechanisms for inflammation mediation at the site of clefting.

Preferential activation of the posterior Default-Mode Network with sequentially predictable task switches

The default-mode network (DMN) has been primarily associated with internally-directed and self-relevant cognition. This perspective is expanding to recognise its importance in executive behaviours like switching. We investigated the effect different task-switching manipulations have on DMN activation in two studies with novel fMRI paradigms. In the first study, the paradigm manipulated visual discriminability, visuo-perceptual distance and sequential predictability during switching. Increased posterior cingulate/precuneus (PCC/PrCC) activity was evident during switching; critically, this was strongest when the occurrence of the switch was predictable. In the second study, we sought to replicate and further investigate this switch-related effect with a fully factorial design manipulating sequential, spatial and visual-feature predictability. Whole-brain analysis again identified a PCC/PrCC-centred cluster that was more active for sequentially predictable versus unpredictable switches, but not for the other predictability dimensions. We propose PCC/PrCC DMN subregions may play a prominent executive role in mapping the sequential structure of complex tasks.

Effectiveness of netakimab in real clinical practice in patients with severe forms of psoriasis

Psoriasis refers to genetically deterministic chronic inflammatory dermatoses, which are characterized by systemic immuno-mediated inflammatory response with preferential activation of the IL -23/-17 axis, growth deviation and keratinocyte differentiation.Material and methods. There were 21 patients under supervision with moderate to severe plaque psoriasis. Nine (42.8 %) patients did not receive previous systemic therapy; 3 (14.2 %) patients received apremilast at a dose of 30 mg twice a day during a year, 4 (19.0 %) patients were prescribed methotrexate at a dose of 15 mg subcutaneously weekly, for at least a year; 5 (23.8 %) patients received secukinumab at 300 mg subcutaneously once every 4 weeks for a year. All patients had a lost of effect or had developed side effects, which determined a change in therapeutic tactics.Results. Among the patients who were earlier not receiving treatment treatment after therapy with netakimab was started, the PASI index made 3.5 ± 1.1 (decrease by 94.4 %), the PASI index at the patients who were earlier receiving sekukinumab was 4.5 ± 1.1 (decrease by 81.9 %), among the patients who were earlier receiving the methotrexate the PASI index was 8.5 ± 1.3 (decrease by 89.9 %), at the patients who were earlier receiving apremilast the PASI index was 9.5 ± 2.1 (decrease by 86.3 %).Conclusions. Improvement in skin symptoms was accompanied by improvement of patients’ quality of life. Thus, the DLQI decreased by 77.9 % in the group of patients who had not previously received systemic therapy, by 77.4 % and 76.4 % in patients who had previously received sekukinumab and methotrexate therapy, respectively, and by 85.2 % in the group of patients who had previously received apremilast.