Novel surface electrode design for preferential activation of cutaneous nociceptors

2022 ◽  
Author(s):  
Aida Hejlskov Poulsen ◽  
Boudewijn van den Berg ◽  
Federico G Arguissain ◽  
Jenny Tigerholm ◽  
Jan R Buitenweg ◽  
...  
Keyword(s):  
Reaction Times ◽  
Electrode Design ◽  
Perception Threshold ◽  
Pain Mechanisms ◽  
Stimulation Intensity ◽  
Small Fiber ◽  
Array Electrode ◽  
Wide Range ◽  
Numerical Rating ◽  
Preferential Activation

Abstract 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.

scholarly journals Investigating stimulation parameters for preferential small-fiber activation using exponentially rising electrical currents

2019 ◽  
Vol 122 (4) ◽  
pp. 1745-1752
Author(s):  
Rosa Hugosdottir ◽  
Carsten Dahl Mørch ◽  
Ole Kæseler Andersen ◽  
Lars Arendt-Nielsen
Keyword(s):  
Electrical Stimulation ◽  
Small Diameter ◽  
Nerve Fibers ◽  
Perception Threshold ◽  
Pain Mechanisms ◽  
Pulse Trains ◽  
Stimulus Response ◽  
Stimulation Parameters ◽  
Small Fiber ◽  
Large Fiber

Electrical stimulation is widely used in pain research and profiling, but current technologies lack selectivity toward small sensory fibers. Pin electrodes deliver high current density in upper skin layers, and it has been proposed that slowly rising exponential pulses can elevate large-fiber activation threshold and thereby increase preferential small-fiber activation. Optimal stimulation parameters for the combined pin electrode and exponential pulse stimulation have so far not been established, which is the aim of this study. Perception thresholds were compared between pin and patch electrodes using single 1- to 100-ms exponential and rectangular pulses. Stimulus-response functions were evaluated for both pulse shapes delivered as single pulses and pulse trains of 10 Hz using intensities from 0.1 to 20 times perception threshold. Perception thresholds (mA) decreased when duration was increased for both electrodes with rectangular pulses and the pin electrode with exponential pulses. For the patch electrode, perception thresholds for exponential pulses decreased for durations ≤10 ms but increased for durations ≥15 ms, indicating accommodation of large fibers. Stimulus-response curves for single pulses were similar for the two pulse shapes. For pulse trains, the slope of the curve was higher for rectangular pulses. Maximal large-fiber accommodation to exponential pulses was observed for 100-ms pulses, indicating that 100-ms exponential pulses should be applied for preferential small-fiber activation. Intensity of 10 times perception threshold was sufficient to cause maximal pain ratings. The developed methodology may open new opportunities for using electrical stimulation paradigms for small-fiber stimulation and diagnostics. NEW & NOTEWORTHY Selective activation of small cutaneous nerve fibers is pivotal for investigations of the pain system. The present study demonstrated that patch electrode perception thresholds increase with increased duration of exponential currents from 20 to 100 ms. This is likely caused by large-fiber accommodation, which can be utilized to activate small fibers preferentially through small-diameter pin electrodes. This finding may be utilized in studies of fundamental pain mechanisms and, for example, in small-fiber neuropathy.

Advances in Triazole Synthesis from Copper-catalyzed Azide-alkyne Cycloadditions (CuAAC) Based on Eco-friendly Procedures

2019 ◽  
Vol 16 (2) ◽  
pp. 244-257 ◽  
Author(s):  
Marcus Vinicius Nora de Souza ◽  
Cristiane França da Costa ◽  
Victor Facchinetti ◽  
Claudia Regina Brandão Gomes ◽  
Paula Mázala Pacheco
Keyword(s):  
Biological Activities ◽  
Reaction Times ◽  
Water Extract ◽  
Fish Bone ◽  
New Drugs ◽  
Bone Powder ◽  
Wide Range ◽  
Recoverable Catalysts ◽  
Egg Shell ◽  
Work Up

Background: 1,2,3-triazoles are an important class of organic compounds and because of their aromatic stability, they are not easily reduced, oxidized or hydrolyzed in acidic and basic environments. Moreover, 1,2,3-triazole derivatives are known by their important biological activities and have drawn considerable attention due to their variety of properties. The synthesis of this nucleus, based on the click chemistry concept, through the 1,3-dipolar addition reaction between azides and alkynes is a well-known procedure. This reaction has a wide range of applications, especially on the development of new drugs. Methods: The most prominent eco-friendly methods for the synthesis of triazoles under microwave irradiation published in articles from 2012-2018 were reviewed. Results: In this review, we cover some of the recent eco-friendly CuAAC procedures for the click synthesis of 1,2,3-triazoles with remarks to new and easily recoverable catalysts, such as rhizobial cyclic β-1,2 glucan; WEB (water extract of banana); biosourced cyclosophoraose (CyS); egg shell powder (ESP); cyclodextrin (β- CD); fish bone powder; nanoparticle-based catalyst, among others. Conclusion: These eco-friendly procedures are a useful tool for the synthesis of 1,2,3-triazoles, providing many advantages on the synthesis of this class, such as shorter reaction times, easier work-up and higher yields when compared to classical procedures. Moreover, these methodologies can be applied to the industrial synthesis of drugs and to other areas.

scholarly journals ChCl: Gly (DESs) Promote Environmentally Benign Synthesis of Xanthene Derivatives and Their Antitubercular Activity

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3667
Author(s):  
Mashooq A. Bhat ◽  
Ahmed M. Naglah ◽  
Siddique Akber Ansari ◽  
Hanaa M. Al-Tuwajiria ◽  
Abdullah Al-Dhfyan
Keyword(s):  
Reaction Times ◽  
Antitubercular Activity ◽  
Antimycobacterial Activity ◽  
Environmentally Benign ◽  
Reaction Yield ◽  
Benign Synthesis ◽  
Xanthene Derivatives ◽  
Wide Range ◽  
Major Application

A ChCl: Gly (DESs) promoted environmentally benign method was developed for the first time using the reaction of aryl aldehydes and dimedone to give excellent yields of xanthene analogues. The major application of this present protocol is the use of green solvent, a wide range of substrate, short reaction times, ease of recovery, the recyclability of the catalyst, high reaction yield, and ChCl: Gly as an alternative catalyst and solvent. In addition to this, all the synthesized compounds were evaluated for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 3d, 3e, 3f, and 3j showed significant antitubercular activity against MTB and M. bovis strains with minimum inhibitory concentration (MIC) values of 2.5−15.10 µg/mL and 0.26–14.92 µg/mL, respectively. The compounds 3e, 3f, and 3j were found to be nontoxic against MCF-7, A549, HCT 116, and THP-1 cell lines. All the prepared compounds were confirmed by 1H NMR and 13C NMR analysis.

scholarly journals Ureido Functionalization through Amine-Urea Transamidation under Mild Reaction Conditions

Polymers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1583
Author(s):  
Natalia Guerrero-Alburquerque ◽  
Shanyu Zhao ◽  
Daniel Rentsch ◽  
Matthias M. Koebel ◽  
Marco Lattuada ◽  
...  
Keyword(s):  
Aqueous Media ◽  
Reaction Times ◽  
Reaction Rates ◽  
Secondary Amines ◽  
Isocyanic Acid ◽  
Advantages And Disadvantages ◽  
Major Disadvantage ◽  
Wide Range ◽  
Potential Alternative ◽  
Full Conversion

Ureido-functionalized compounds play an indispensable role in important biochemical processes, as well as chemical synthesis and production. Isocyanates, and KOCN in particular, are the preferred reagents for the ureido functionalization of amine-bearing compounds. In this study, we evaluate the potential of urea as a reagent to graft ureido groups onto amines at relatively low temperatures (<100 °C) in aqueous media. Urea is an inexpensive, non-toxic and biocompatible potential alternative to KOCN for ureido functionalization. From as early as 1864, urea was the go-to reagent for polyurea polycondensation, before falling into disuse after the advent of isocyanate chemistry. We systematically re-investigate the advantages and disadvantages of urea for amine transamidation. High ureido-functionalization conversion was obtained for a wide range of substrates, including primary and secondary amines and amino acids. Reaction times are nearly independent of substrate and pH, but excess urea is required for practically feasible reaction rates. Near full conversion of amines into ureido can be achieved within 10 h at 90 °C and within 24 h at 80 °C, and much slower reaction rates were determined at lower temperatures. The importance of the urea/amine ratio and the temperature dependence of the reaction rates indicate that urea decomposition into an isocyanic acid or a carbamate intermediate is the rate-limiting step. The presence of water leads to a modest increase in reaction rates, but the full conversion of amino groups into ureido groups is also possible in the absence of water in neat alcohol, consistent with a reaction mechanism mediated by an isocyanic acid intermediate (where the water assists in the proton transfer). Hence, the reaction with urea avoids the use of toxic isocyanate reagents by in situ generation of the reactive isocyanate intermediate, but the requirement to separate the excess urea from the reaction product remains a major disadvantage.

scholarly journals Severe violations of independence in response inhibition tasks

2021 ◽  
Vol 7 (12) ◽  
pp. eabf4355
Author(s):  
Patrick G. Bissett ◽  
Henry M. Jones ◽  
Russell A. Poldrack ◽  
Gordon D. Logan
Keyword(s):  
Response Inhibition ◽  
Theoretical Foundation ◽  
Reaction Times ◽  
Stop Signal ◽  
Experimental Paradigm ◽  
Signal Delay ◽  
Independence Assumption ◽  
Analysis Techniques ◽  
Wide Range ◽  
Saccadic Responses

The stop-signal paradigm, a primary experimental paradigm for understanding cognitive control and response inhibition, rests upon the theoretical foundation of race models, which assume that a go process races independently against a stop process that occurs after a stop-signal delay (SSD). We show that severe violations of this independence assumption at short SSDs occur systematically across a wide range of conditions, including fast and slow reaction times, auditory and visual stop signals, manual and saccadic responses, and especially in selective stopping. We also reanalyze existing data and show that conclusions can change when short SSDs are excluded. Last, we suggest experimental and analysis techniques to address this violation, and propose adjustments to extant models to accommodate this finding.

Recent advance in ester synthesis by Multi Component Reactions (MCRs): A Review

2021 ◽  
Vol 25 ◽  
Author(s):  
Dhaval B. Patel ◽  
Jagruti A. Parmar ◽  
Siddharth S. Patel ◽  
Unnati J. Naik ◽  
Hitesh D. Patel
Keyword(s):  
Multicomponent Reactions ◽  
Medicinal Chemistry ◽  
Reaction Times ◽  
Synthetic Methods ◽  
Ester Synthesis ◽  
One Pot ◽  
Wide Range ◽  
Recent Developments ◽  
Ester Linkage ◽  
The One

: The synthesis of ester containing heterocyclic compounds via multicomponent reaction is one of the most preferable process in the synthetic organic chemistry and medicinal chemistry. Compounds containing ester linkage have a wide range of biological application in the pharmaceutical field. Therefore, many method have been developed for the synthesis of these type of derivatives. However, some of them are carried out in the presence of toxic solvents and catalysts, with lower yields, longer reaction times, low selectivities and by-products. Thus, the development of new synthetic methods for the ester synthesis is required in the medicinal chemistry. As we know, multicomponent reactions (MCRs) are a powerful tool towards the one-pot ester synthesis, so in this article we have reviewed the recent developments in ester synthesis. This work covers selected explanation of methods via multicomponent reactions to explore the methodological development in ester synthesis.

scholarly journals Functional connectivity of fMRI using differential covariance predicts structural connectivity and behavioral reaction times

2021 ◽  
Author(s):  
Yusi Chen ◽  
Qasim Bukhari ◽  
Tiger Wutu Lin ◽  
Terrence J Sejnowski
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Functional Connectivity ◽  
Resting State ◽  
Structural Connectivity ◽  
Reaction Times ◽  
Resonance Imaging ◽  
Brain Areas ◽  
Human Connectome Project ◽  
Wide Range

Recordings from resting state functional magnetic resonance imaging (rs-fMRI) reflect the influence of pathways between brain areas. A wide range of methods have been proposed to measure this functional connectivity (FC), but the lack of ''ground truth'' has made it difficult to systematically validate them. Most measures of FC produce connectivity estimates that are symmetrical between brain areas. Differential covariance (dCov) is an algorithm for analyzing FC with directed graph edges. Applied to synthetic datasets, dCov-FC was more effective than covariance and partial correlation in reducing false positive connections and more accurately matching the underlying structural connectivity. When we applied dCov-FC to resting state fMRI recordings from the human connectome project (HCP) and anesthetized mice, dCov-FC accurately identified strong cortical connections from diffusion Magnetic Resonance Imaging (dMRI) in individual humans and viral tract tracing in mice. In addition, those HCP subjects whose rs-fMRI were more integrated, as assessed by a graph-theoretic measure, tended to have shorter reaction times in several behavioral tests. Thus, dCov-FC was able to identify anatomically verified connectivity that yielded measures of brain integration causally related to behavior.

The Value of off-Road Tests in the Assessment of Driving Potential of Unlicensed Disabled People

1987 ◽  
Vol 50 (10) ◽  
pp. 357-361 ◽  
Author(s):  
Dinah Croft ◽  
Richard D Jones
Keyword(s):  
Retrospective Study ◽  
Brain Damage ◽  
Damage Assessment ◽  
Reaction Times ◽  
Occupational Therapist ◽  
Disabled People ◽  
Road Test ◽  
Wide Range ◽  
The Mean ◽  
Driving Potential

A retrospective study was undertaken to determine the effectiveness of off-road tests in assessing the driving potential of 151 unlicensed disabled people. Assessment was carried out by an occupational therapist and consisted of several off-road tests (vision, reaction timing, computerized preview tracking task and general medical/psychological appraisal) and an on-road test. The mean age of this group was 22.9 years (15–76 years) and the group comprised 84 females and 67 males. Diagnoses covered a wide range but 67% of the group had some form of brain damage. Assessment recommendations were: 57% pass, 37% fail and 5% not assessed. Of the 57 fail recommendations, 7 were unable to meet the legal acuity requirements, 20 had unacceptable reaction times and/or tracking scores, 25 were failed on a combination of marginal and/or subjective off-road criteria and 5 were failed on-road. Quantitative off-road tests have been successful at helping to determine driving potential by means which are objective, systematic and safe.

scholarly journals PAIN CARE ESSENTIALS

2021 ◽  
Vol 25 (2) ◽  
Author(s):  
Professor Liaquat Ali
Keyword(s):  
Pain Management ◽  
Care Management ◽  
Treatment Modalities ◽  
Integrative Care ◽  
Therapeutic Approaches ◽  
Management Options ◽  
Nerve Blocks ◽  
Pain Mechanisms ◽  
Wide Range ◽  
Pain Care

The best kept secret in pain management is in your own hands. Pain Care Essentials offers the readers a fingertip access to numerous topics in still emerging   field of pain medicine, including physical rehabilitation in pain management, peripheral nerve blocks, neuropathic pain, pediatric and elderly pain. This book provides an overview of pain mechanisms as currently understood, and details a variety of approaches to pain management used across a wide range of complementary disciplines. Divided into four convenient sections; the book addresses Fundamentals and Evaluation, Treatment Modalities (including opioids, interventions and alternative medicine), common Chronic Pain and Urgent Pain Problems. Integrative care concepts are presented, emphasizing multi-disciplinary approaches to address the pain. Expert contributors describe therapeutic approaches of various pain conditions and implementing self-care management options.

Sonocatalyzed Total Synthesis of N,N-diaryl-formamides Through Oxidation and Hydrolysis Reaction of gem-dichloroaziridines using DMSO/H2O

2018 ◽  
Vol 15 (7) ◽  
pp. 1014-1019
Author(s):  
Khadijeh Rabiei ◽  
Hossein Naeimi
Keyword(s):  
Total Synthesis ◽  
Schiff Bases ◽  
Ultrasonic Irradiation ◽  
Reaction Times ◽  
Organic Reactions ◽  
Hydrolysis Reaction ◽  
Neutral Medium ◽  
Ultrasound Technique ◽  
Complex Molecules ◽  
Wide Range

Background:.Aziridine compounds are among the most fascinating intermediates in organic synthesis, acting as precursors of many complex molecules due to the strain incorporated in their skeletons and can be opened in a stereo controlled manner with various nucleophiles, providing access to a wide range of important nitrogen-containing products. Sonochemistry involves the use of ultrasound technique to promote organic reactions. In recent years sonochemistry has been widely used in organic syntheses as it offers a versatile and facile pathway for a bewildering range of organic reactions. Materials and Method: The synthesis of some Schiff bases was done in according the previously reported procedure in literature. The synthesized Schiff bases in the presence of magnesium powder and CCl4 in anhydrous tetrahydrofuran was converted to gem-dichloroaziridines at ultrasonic irradiation. Finally, the synthesized 2,2- dichloro-1,3-bis(4-chlorophenyl) aziridine was treated with DMSO and H2O with ultrasonic irradiation to produce the N-(4-chlorophenyl)-N-[4-(chlorophenyl)hydroxy-methyl] formamides. Results: Here, total synthesis of N-(α-hydroxybenzyl)-formamides through ultrasonic promoted oxidation and hydrolysis reaction of gem-dichloroaziridine derivatives in the presence of dimethyl sulfoxide and water has been investigated. Conclusion: In this study, ultrasonic promoted oxidation and hydrolysis of gem-dichloroaziridines toward N- (α-hydroxybenzyl)-formamides in the presence of DMSO and H2O under neutral medium reaction conditions has been reported. Excellent yields of products were obtained through this method. Other advantages of this reaction are short reaction times, simplicity of the method and high purity of products.

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