Electrically evoked compound action potentials are associated with the site of intracochlear stimulation.

OBJECTIVES: Objective measurements to predict the position of a cochlear electrode during cochlear implantation surgery may serve to improve the surgical technique and postoperative speech outcome. There is evidence that electrically evoked compound action potentials (ECAP) are a suitable approach to provide information about the site of stimulation. This study aims to contribute to the knowledge about the association between the intraoperative intracochlear ECAP characteristics and the site of stimulation. METHODS: In a retrospective cohort study, patients undergoing cochlear implant surgery with flexible lateral wall electrode arrays (12 stimulating channels) between 2020 and 2022 were analyzed. The CDL was measured using a CT-based clinical planning software. ECAP were measured for all electrode contacts and associated to the CDL as well as to the site of stimulation in degree. RESULTS: Significant differences among the amplitudes and slopes for the individual stimulated electrode contacts at the stimulation sites of 90°, 180°, 270°, 360°, 450° and 540° were found. The values showed a trend for linearity among the single electrodes. CONCLUSIONS: ECAP characteristics correlate with the electrode's position inside the cochlea. In the future, ECAP may be applied to assess the intracochlear position inside the cochlea and support anatomy-based fitting.

Sensing in Sacral Neuromodulation: A Feasibility Study in Subjects With Urinary Incontinence and Retention.

OBJECTIVES: Sacral neuromodulation (SNM) therapy standard of care relies on visual-motor responses and patient-reported sensory responses in deciding optimized lead placement and programming. Automatic detection of stimulation responses could offer a simple, consistent indicator for optimizing SNM. The purpose of this study was to measure and characterize sacral evoked responses (SERs) resulting from sacral nerve stimulation using a commercial, tined SNM lead. MATERIALS AND METHODS: A custom external research system with stimulation and sensing hardware was connected to the percutaneous extension of an implanted lead during a staged (tined lead) evaluation for SNM. The system collected SER recordings across a range of prespecified stimulation settings (electrode configuration combinations for bipolar stimulation and bipolar sensing) during intraoperative and postoperative sessions in 21 subjects with overactive bladder (OAB) and nonobstructive urinary retention (NOUR). Motor and sensory thresholds were collected during the same sessions. RESULTS: SERs were detected in all 21 subjects. SER morphology (number of peaks, magnitude, and timing) varied across electrode configurations within and across subjects. Among subjects and electrode configurations tested, recordings contained SERs at motor threshold and/or sensory threshold in 75% to 80% of subjects. CONCLUSIONS: This study confirmed that implanted SNM leads can be used to directly record SERs elicited by stimulation in subjects with OAB and NOUR. SERs were readily detectable at typical SNM stimulation settings and procedural time points. Using these SERs as possible objective measures of SNM response has the capability to automate patient-specific SNM therapy, potentially providing consistent lead placement, programming, and/or closed-loop therapy.

Effect of congenital inner ear malformations (IEMs) on electrically evoked compound action potential (ECAP) responses in cochlear implant children.

PURPOSE: The study was designed to assess the electrically evoked compound action potential (ECAP) responses in children with inner ear malformations compared to children with normal inner ear anatomy. METHODS: The study included 235 prelingual deaf children who were implanted in cochlear implant unit in King Fahad University hospital-Imam Abdulrahman Bin Faisel University. Subjects were using either Cochlear Nucleus or Medel cochlear implant devices. We had 171 (64.5%) subjects with normal inner ear anatomy and 94 (35.5%) subjects with inner ear malformations (IEMs) and they were classified into 6 groups according to inner ear anatomy. Fourteen subjects (14.9%) subjects had enlarged vestibular aqueduct (EVA), 30 (32%) subjects had Mondini deformity, 25 (26.6%) subjects had incomplete partition type two (IPII), 9 (9.6%) subjects had incomplete partition type one (IPI) and 16 (17%) subjects had hypoplastic cochlea type III or IV. Intraoperative electrically evoked compound action potential (ECAP) responses were analyzed and compared in all subjects. RESULTS AND CONCLUSIONS: Measurable ECAP responses can be elicited in patients with IEMs in most of the channels. Severe malformations can affect the prevalence of measuring ECAP and getting identifiable waveform morphology. Additionally, increased thresholds and lower slope of AGF was observed in IEMs specially in more severe malformations (e.g. IPI). IPI patients with better word recognition scores tended to show more identifiable ECAP measurements. This could suggest the presence of some correlation between ECAP responses and patients' performance after cochlear implantation.

Impact of Long-Term Evoked Compound Action Potential Controlled Closed-Loop Spinal Cord Stimulation on Sleep Quality in Patients With Chronic Pain: An EVOKE Randomized Controlled Trial Study Subanalysis.

OBJECTIVE: Spinal cord stimulation (SCS) is considered an effective interventional nonpharmacologic treatment option for several chronic pain conditions. Here we present the effects of the novel evoked compound action potential (ECAP) controlled closed-loop (ECAP-CL) SCS system on long-term sleep quality outcomes from the EVOKE study. MATERIALS AND METHODS: The EVOKE study is a double-blind, randomized, controlled clinical trial conducted at 13 sites in the United States (N = 134 patients). The clinical trial utilized SCS to manage chronic pain and compared novel ECAP-CL technology to open-loop SCS. Additionally, sleep quality data was collected using the Pittsburgh Sleep Quality Index (PSQI) at baseline and all study visits. RESULTS: The mean PSQI global score for ECAP-CL patients at baseline was 14.0 (n = 62; ± 0.5, SD 3.8), indicating poor sleep quality. Clinically meaningful and statistically significant reductions (p < 0.001) in the global PSQI scores were noted at 12 months (n = 55; 5.7 ± 0.6, SD 4.2). A total of 76.4% of ECAP-CL patients met or exceeded Minimal Clinically Important Difference from baseline in PSQI at 12 months. Additionally, 30.9% of ECAP-CL patients achieved "good sleep quality" scores (PSQI ≤ 5), and 29.1% achieved sleep quality remission. "Normative" sleep scores were observed in 29.6% of ECAP-CL patients at 12 months, and these scores were better than the US general population. Additionally, ECAP-CL patients achieved statistically significant changes from baseline (p < 0.01) across all seven subcomponent scores of PSQI at 12 months. CONCLUSIONS: ECAP-CL SCS elicits consistent neural activation of the target leading to less variability in long-term therapy delivery. In the EVOKE study, this resulted in ECAP-CL patients demonstrating clinically superior and sustained pain relief. Results from this study provide new evidence of long-term improvement in sleep quality and quantity in patients with chronic pain resulting from the use of this novel ECAP-CL SCS technology. CLINICAL TRAIL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02924129.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part four. The relationship between the concentration of specific IgE antibodies in serum and types of asthma.

Introduction: Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. Aim: To determine the relationship between the concentration of specific IgE antibodies in serum and types of asthma. Material and methods: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of asthma, skin-prick tests). Results: sIgE antibodies against any allergen were detected in 9.9% (classes 1-6)/7.6% (classes 2-6) of healthy respondents. Comparing sIgE antibodies of respondents with intermittent asthma to sIgE antibodies of respondents with persistent asthma, no statistically significant differences were identified. Relating to allergens of D. pteronyssinus, cat dander, and A. alternata, sIgE antibodies were more frequently detected in respondents with atopic asthma and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.005 to p < 0.001). Relating to allergens of D. pteronyssinus, cat dander, and timothy grass, sIgE antibodies were more frequently detected in respondents with atopic asthma and a weakly positive skin-prick test as compared to healthy respondents with weakly positive skin-prick test (p < 0.05 to p < 0.001). Conclusions: Regarding subjects with a negative or weakly positive skin test, when sIgE antibodies to the same allergen are detected, asthma is much more likely to occur.

The importance of specific IgE antibodies in the epidemiology of allergic rhinitis and asthma (ECAP survey): part five. The relationship between the concentration of specific IgE antibodies in serum and types of rhinitis.

Introduction: Specific immunoglobulins E (sIgE) are important parameters for the estimation of severity of allergic diseases. Aim: To determine the relationship between the concentration of specific IgE antibodies in serum and types of rhinitis. Material and methods: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, and Alternaria alternata were determined in the serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml or ≥ 0.7 IU/ml) were correlated to clinical diagnosis (types of rhinitis, skin-prick tests). Results: sIgE antibodies are more frequently detected in respondents with intermittent/seasonal allergic rhinitis and a negative skin-prick test as compared to healthy respondents with a negative skin-prick test (p < 0.05 to p < 0.001). Relating to allergens of D. pteronyssinus and cat dander, sIgE antibodies are more frequently detected in respondents with persistent/perennial allergic rhinitis and a negative or weakly positive skin-prick test as compared to healthy respondents with a negative or weakly positive skin-prick test (p < 0.05 to p < 0.001). Conclusions: The occurrence of intermittent/seasonal allergic rhinitis is much more probable in respondents with a negative skin-prick test, when IgE antibodies against the same allergen are detected. And the occurrence of persistent/perennial allergic rhinitis is much more probable in respondents with a negative or weakly positive skin-prick test with allergens of D. pteronyssinus or cat dander, when IgE antibodies against the same allergen are detected.

ECAP is a key negative regulator mediating different pathways to modulate salt stress-induced anthocyanin biosynthesis in Arabidopsis.

Anthocyanins are a subgroup of plant flavonoids with antioxidant activities and are often induced by various biotic and abiotic stresses in plants, probably to efficiently scavenge free radicals and reactive oxygen species. However, the regulatory mechanisms of salt stress-induced anthocyanin biosynthesis remain unclear. Using molecular and genetic techniques we demonstrated key roles of ECAP in differential salt-responsive anthocyanin biosynthesis pathways in Arabidopsis thaliana. ECAP, JAZ6/8 and TPR2 are known to form a transcriptional repressor complex, and negatively regulate jasmonate (JA)-responsive anthocyanin accumulation. In this study, we demonstrated that under moderate salt stress, the accumulation of anthocyanins is partially dependent on JA signaling, which degrades JAZ proteins but not ECAP. More interestingly, we found that high salinity rather than moderate salinity induces the degradation of ECAP through the 26S proteasome pathway, and this process is independent of JA signaling. Further analysis revealed that ECAP interacts with MYB75 (a transcription factor activating anthocyanin biosynthetic genes) and represses its transcriptional activity in the absence of high salinity. Our results indicated that plants adopt different strategies for fine-tuning anthocyanin accumulation under different levels of salt stress, and further elucidated the complex regulation of anthocyanin biosynthesis during plant development and responses to environmental stresses.

Comparison of automated and traditional ECAP recording approaches in clinical practice.

OBJECTIVE: The traditional method of recording electrically evoked compound action potentials (ECAPs), as implemented in the MAESTRO clinical software (standard ART), requires manual adjustments during threshold determination through a specialist. The "FineGrain" research tool (FineGrain RT) uses a continuous stimulation paradigm combined with automatic ECAP threshold determination. The aim of this study was to compare the FineGrain RT with standard ART. DESIGN: ECAPs were recorded with standard ART and the FineGrain RT in paediatric cochlear implant recipients. Different stimulation rates were used for FineGrain ECAP recordings (40, 60, and 76 Hz). STUDY SAMPLE: Thirteen children (6 - 19 years) participated in this study - nine were bilaterally and four unilaterally implanted, resulting in a total of twenty-two implanted ears. RESULTS: ECAP threshold determination success rates were similar between the two approaches (92% and 89%) and ECAP thresholds correlated well (r: 0.94, p < 2.2e-16) with average ART thresholds being lower than FineGrain RT thresholds. FineGrain stimulation with different stimulation rates did not have a significant effect on ECAP thresholds but ECAP thresholds at medial and apical contacts were lower compared to basal contacts. CONCLUSIONS: TheFineGrain research approach is a reliable replacement for standard ART in clinical practice.

Development of Custom Sound® Pro software utilising big data and its clinical evaluation.

OBJECTIVES: To inform and optimise a cochlear implant (CI) fitting software design through an analysis of big data to define array-specific comfort (C) level profiles, frequently-used MAP parameters, and the minimum number of Neural Response Telemetry thresholds (tNRT) needed to create an accurate profile. To evaluate the software's ease of use and completion time for AutoNRT®s. DESIGN: MAPs analysis. Clinical study evaluating software use in creating MAPs, addressing sound-quality issues and setting patient goals. STUDY SAMPLE: MAPs (N = 39,885); CI recipients (N = 47) and clinicians (N = 19). RESULTS: Distinct C-level profiles were observed for lateral-wall, contour, and slim-modiolar electrode arrays. Default settings were used for most MAP parameters (13/16) except for Pulse Width, Rate, and Maxima. Nine tNRT measurements were required for an accurate C-level profile. Measurement-time of nine tNRTs via the new algorithm was comparable to five tNRTs using the previous algorithm. Nearly all (99%) clinical tasks were completed by clinicians with the first use of the software. Most CI recipients (79.5%) rated goal-setting as valuable. CONCLUSION: Custom Sound Pro fitting software developed based on big data analysis incorporates a guided fitting workflow and expected fitting ranges. It helps to improve clinical efficiency, is easy to use and supports patient-centred care.

Place of residence, gender, month of birth and age influence on the concentration of specific IgE antibodies in serum. The Epidemiology of Allergic Diseases in Poland (ECAP survey): part three.

Introduction: Specific immunoglobulins E (sIgE) are important parameters to estimate the severity of allergic diseases. Aim: To determine the influence of gender, age and place of residence on the concentration of specific IgE antibodies in serum. Material and methods: The concentration of sIgE antibodies against allergens of Dermatophagoides pteronyssinus, cat dander, timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated with answers to ECAP questionnaires. Results: IgE antibodies are less frequently detected in respondents living in the country (p < 0.05 to p < 0.005); and they are less frequently detected in respondents living in cities of hardly industrialised regions than in respondents living in cities of industrialised regions (D. pteronyssinus p < 0.05, cat dander p < 0.01). IgE antibodies are more frequently detected in men (p < 0.005 to p < 0.001). IgE antibodies are more frequently detected in respondents born in May-July (timothy grass p < 0.005, Alternaria alternata p < 0.005) and less frequently detected in respondents born in August-October (timothy grass p < 0.005, Alternaria alternata p < 0.05). Conclusions: Characteristics of the urban environment, non-specific factors and gender affect the concentration of specific IgE antibodies in serum. Influence of seasonal allergens within the first months of life and/or in the course of the foetal period alters the production of specific IgE antibodies.

Is There Any Correlation between Spread of Excitation Width and the Refractory Properties of the Auditory Nerve in Cochlear Implant Users?

BACKGROUND: The spread of excitation (SOE) and auditory nerve recovery function (REC) are objective measures recorded by neural response telemetry and may interfere in cochlear implant (CI) stimulation. OBJECTIVE: To analyze and correlate SOE with the refractory periods in subjects with pre- and postlingual deafness implanted with different electrode arrays. METHODS: This was a retrospective study of 323 ears separated by perimodiolar or straight arrays and by pre- or postlingually deaf recipients. Measures were collected intraoperatively on electrode 11. The SOE width was measured in millimeters at the 0.75 point of the curve, and the relative (tau) and absolute (t0) refractory periods were measured in microseconds. RESULTS: There was a statistical correlation between the SOE and the t0 in the patients with postlingual deafness implanted with the perimodiolar array. The SOE width was statistically different between the straight and perimodiolar arrays and between the pre- and postlingual groups in the perimodiolar array. Tau was statistically different between the pre- and postlingual groups with the straight array and the t0, between the pre- and postlingual groups with the perimodiolar array. Neural response threshold and amplitude of the neural response were not statistically different among groups. CONCLUSION: There was a correlation between SOE width and t0 only in patients with acquired deafness. The findings suggest that different factors influence SOE and REC, considering SOE is different according to the electrode array and REC being different according the onset of deafness.

Stress Corrosion Cracking Behavior of Fine-Grained Al5083 Alloys Processed by Equal-Channel Angular Pressing (ECAP).

In the present study, the stress corrosion cracking (SCC) behavior of ECAP Al5083 alloy was investigated in air as well as in 3.5 % NaCl solution using the slow strain rate tensile test (SSRT). The characteristics of grain boundary precipitates (GBPs), specifically the microchemistry of the SCC behavior of Al5083 alloys, both in "as-received" condition and when deformed by the ECAP process, were examined. The correlations between the SCC resistance and GBP microchemistry were examined. A microstructural evaluation was performed using an optical microscope. SCC tests were carried out using a universal tensile testing machine and the fracture surfaces were studied using scanning electron microscopy (SEM). A strain rate of 1×10-6 s-1 was applied for the SSRT. As the passes increased, the SCC susceptibility of the fine-grained ECAP Al5083 alloy also increased. Moreover, higher ultimate tensile strength and greater elongation were observed. This was due to grain refinement, high-density separations, and the expanded extent of high-density dislocations instigated by severe plastic deformation. Due to the high strength and elongation, the failure analysis showed a ductile mode of fracture. Electron backscattering diffraction (EBSD) analysis was performed to determine more clearly the nature of cracking. EBSD analysis showed that the crack propagation occurred in both transgranular and intergranular modes.

Stimulation of an immune system by different types of allergens causes seasonal (late spring and summer) factors to increase probability of allergic rhinitis symptoms. The Epidemiology of Allergic Diseases in Poland (ECAP) survey: part two.

INTRODUCTION: Specific immunoglobulins E (sIgE) are important parameters to estimate severity of allergic diseases. AIM: To determine the relationship between the concentration of sIgE antibodies in serum and clinical outcome of allergic diseases. MATERIAL AND METHODS: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, Timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 9 regions (ECAP study). Positive results of sIgE (≥ 0.35 IU/ml) were correlated with answers in ECRHSII and ISAAC questionnaires. RESULTS: IgE antibodies are more frequently detected in respondents aged over 4 years when they had their first attack of asthma (cat dander p < 0.05, Timothy grass p < 0.05). IgE antibodies are less frequently detected in respondents aged over 29 years when they had the first allergic rhinitis symptoms as compared to respondents aged 0-19 years when they had the first allergic rhinitis symptoms (p < 0.05 to p < 0.001). Among respondents showing allergic rhinitis symptoms, IgE antibodies are more frequently detected in respondents showing those symptoms from May to August (p < 0.05 to p < 0.005). CONCLUSIONS: The first attack of asthma appears later mainly in patients whose immune systems are more strongly stimulated by allergens. Development of allergic rhinitis in patients aged over 29 years presumably needs weaker stimulation of their immune systems by allergens than in patients aged 0-19 years. Stimulation of an immune system by different types of allergens modifies its response in such a way that seasonal (late spring and summer) factors increase probability of allergic rhinitis symptoms.

Effects of a sequential cochlear implant of minimum comfort, impedance and electrically evoked compound action potential values of the initial cochlear implant.

PURPOSE: To evaluate the impact of sequential second CI on the electrophysiological parameters of the initial CI. METHODS: Totally, 30 children who received sequential CIs between January and July 2018 were included in the study. All patients received the same brand of CI (Advanced Bionics, HIRES 90K Advantage 1J). Of 16 CI electrodes, 3rd (E3), 7th (E7) and 11th (E11), and 15th (E15) electrodes which were corresponding to the apical, middle, and basal cochlea were used in the measurements. The tNRI, electrode impedance and M levels were recorded as the contralateral CI was switched off and on, respectively. RESULTS: As the second CI was switched off, the impedance, tNRI and M values of initial CI 1st, 3rd and 6th months were not significantly different (p > 0.05). There was a significant difference between the impedance, tNRI and M values of initial CI as the second CI was switched on (p < 0.05). CONCLUSION: Activation of the sequential second CI leads to a decrease in the tNRI and M levels of the initial CI. This condition can increase the efficiency obtained by CIs. However, these changes should be remembered during CI programming.

Evoked Compound Action Potentials Reveal Spinal Cord Dorsal Column Neuroanatomy.

INTRODUCTION: The electrically evoked compound action potential (ECAP) is a measure of the response from a population of fibers to an electrical stimulus. ECAPs can be assessed during spinal cord stimulation (SCS) to elucidate the relationship between stimulation, electrophysiological response, and neuromodulation. This has consequences for the design and programming of SCS devices. METHODS: Sheep were implanted with linear epidural SCS leads. After a stimulating pulse, electrodes recorded ECAPs sequentially as they propagated orthodromically or antidromically. After filtering, amplification, and signal processing, ECAP amplitude and dispersion (width) was measured, and conduction velocity was calculated. Similar clinical data was also collected. A single-neuron computer model that simulated large-diameter sensory axons was used to explore and explain the observations. RESULTS: ECAPs, both animal and human, have a triphasic structure, with P1, N1, and P2 peaks. Conduction velocity in sheep was 109 ms-1 , which indicates that the underlying neural population includes fibers of up to 20 µm in diameter. For travel in both directions, propagation distance was associated with decrease in amplitude and increase in dispersion. Importantly, characteristics of these changes shifted abruptly at various positions along the cord. DISCUSSION: ECAP dispersion increases with propagation distance due to the contribution of slow-conducting small-diameter fibers as the signal propagates away from the source. An analysis of the discontinuities in ECAP dispersion changes with propagation revealed that these are due to the termination of smaller-diameter, slower-conducting fibers at corresponding segmental levels. The implications regarding SCS lead placement, toward the goal of maximizing clinical benefit while minimizing side-effects, are discussed. CONFLICT OF INTEREST: John Parker is the founder and CEO of Saluda Medical and holds stock options. Milan Obradovic, Nastaran Hesam Shariati, Dean M. Karantonis, Peter Single, James Laird-Wah, Robert Gorman and Mark Bickerstaff are employees of Saluda Medical with stock options. At the time the data was collected for the study, Prof. Cousins was a paid consultant for Saluda Medical. John Parker, Milan Obradovic, Dean Karantonis, James Laird-Wah, Robert Gorman and Peter Single are co-inventors in one or more patents related to the topics discussed in this work.

Fine-grain recordings of the electrically evoked compound action potential amplitude growth function in cochlear implant recipients.

BACKGROUND: In cochlear implants (CI) measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the electrode-nerve interface as well as establishing a basis for a map to program the speech processor. In a standard clinical setup recordings are averaged over 25-100 repetitions to allow for the detection of ECAPs within the noise floor. To obtain an amplitude growth function, these measurements are normally performed for 5-10 different stimulation levels. We evaluate a recording paradigm where the stimulation intensity is increased in quasi-continuous steps and instead of averaging repeated recordings with identical stimulation parameters, running averages over small intervals of stimulation levels are computed. The first visible nerve response was manually identified by two experts. RESULTS: Both recording paradigms were evaluated in 39 cochlear implants, showing an on average lower threshold of the first nerve response for the quasi-continuous measurement paradigm (Wilcoxon signed-rank test, p = 6.2e-08) compared to the clinical standard paradigm. The mean maximal loudness over all implants and stimulation electrodes was 13% lower at the 80 pulses/s quasi-continuous paradigm compared to the 44 pulses/s clinical standard paradigm. CONCLUSIONS: Beside a more robust determination of the ECAP threshold, the proposed quasi-continuous stimulation paradigm results in a more robust behavioral feedback of the CI user upon the maximal acceptable loudness percept. Furthermore this paradigm can also reveal the fine-structure in the amplitude growth function.

Effective Relief of Pain and Associated Symptoms With Closed-Loop Spinal Cord Stimulation System: Preliminary Results of the Avalon Study.

OBJECTIVES: Conventional spinal cord stimulation (SCS) delivers a fixed-input of energy into the dorsal column. Physiologic effects such as heartbeat, respiration, spinal cord movement, and history of stimulation can cause both the perceived intensity and recruitment of stimulation to increase or decrease, with clinical consequences. A new SCS system controls stimulation dose by measuring the recruitment of fibers in the dorsal column and by using the amplitude of the evoked compound action potentials (ECAPs) to maintain stimulation within an individualized therapeutic range. Safety and efficacy of this closed-loop system was evaluated through six-month postimplantation. MATERIALS AND METHODS: Chronic pain subjects with back and/or leg pain who were successfully trialed received a permanent system (Evoke; Saluda Medical, Sydney, Australia). Ratings of pain (100-mm visual analogue scale [VAS] and Brief Pain Instrument [BPI]), quality of life (EuroQol instrument [EQ-5D-5L]), function (Oswestry Disability Index [ODI]), and sleep (Pittsburgh Sleep Quality Index [PSQI]) were collected at baseline and repeated three and six months after implantation. RESULTS: Fifty-one subjects underwent a trial procedure; permanent implants were placed in 36 subjects. The proportion of subjects with ≥50% relief was 92.6% (back) and 91.3% (leg) at three months, and 85.7% (back) and 82.6% (leg) at six months. The proportion with ≥80% pain relief was 70.4% (back) and 56.5% (leg) at three months, and 64.3% (back) and 60.9% (leg) at six months. Statistically significant improvements in mean BPI, EQ-5D-5L, ODI, and PSQI were also observed at both time points. CONCLUSIONS: The majority of subjects experienced profound pain relief at three and six months, providing preliminary evidence for the effectiveness of the closed-loop SCS system. The exact mechanism of action for these outcomes is still being explored, although one likely hypothesis holds that ECAP feedback control may minimize recruitment of Aß nociceptors and Aδ fibers during daily use of SCS.

Microstructure Optimization of Mg-Alloys by the ECAP Process Including Numerical Simulation, SPD Treatments, Characterization, and Hydrogen Sorption Properties.

Both numerical simulation and hardness measurements were used to determine the mechanical and microstructural behavior of AZ31 bulk samples when submitted to the Equal Channel Angular Pressing (ECAP) technique. Billets of this representative of Mg-rich alloys were submitted to different numbers of passes for various ECAP modes (anisotropic A, isotropic BC). The strain distribution, the grain size refinement, and the micro-hardness were used as indicators to quantify the effectiveness of the different processing routes. Structural characterizations at different scales were achieved using Scanning Electron Microscopy (SEM), micro-analysis, metallography, Small Angle Neutron Scattering SANS, X-Ray Diffraction (XRD), and texture determination. The grain and crystallite size distribution and orientation as well as defect impacts were determined. Anelastic Spectroscopy (AS) on mechanically deformed samples have shown that the temperature of ECAP differentiate the fragile to ductile regime. MgH2 consolidated powders were checked for using AS to detect potential hydrogen motions and interaction with host metal atoms. After further optimization, the different mechanically-treated samples were submitted to hydrogenation/dehydrogenation (H/D) cycles, which shows that, for a few passes, the BC mode is better than the A one, as supported by theoretical and experimental microstructure analyses. Accordingly, the hydrogen uptake and (H/D) reactions were correlated with the optimized microstructure peculiarities and interpreted in terms of Johnson-Avrami- Mehl-Kolmogorov (JAMK) and Jander models, successively.

The importance of specific IgE antibodies in epidemiology of allergic rhinitis and asthma - the Epidemiology of Allergic Diseases in Poland (ECAP) survey: part one. Influence of allergy risk factors on concentration of specific IgE antibodies in serum.

INTRODUCTION: Specific immunoglobulins E (sIgE) are important parameters to estimate severity of allergic diseases. AIM: To determine the influence of allergy risk factors on the concentration of specific IgE antibodies in serum. MATERIAL AND METHODS: The concentration of sIgE antibodies against allergens Dermatophagoides pteronyssinus, cat dander, timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 9 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated to answers in questionnaires ECRHSII and ISAAC. RESULTS: sIgE are more frequently detected in respondents declaring an allergic disease of a father than of a mother (D. pteronyssinus p < 0.05, A. alternata p < 0.01). An early beginning to attend school, kindergarten or nursery increases the frequency of sIgE detection (p < 0.05). If the number of children who slept in the same room as a respondent before the respondent was five years old, was lower, sIgE antibodies are more frequently detected (p < 0.05). Relating to: 1) all 4 allergens, sIgE are the most frequently detected in respondents declaring absence of a carpet/rug at home (p < 0.05), 2) cat dander - less frequently detected in respondents who have a cat at home at the age of 1-4 years (p < 0.005). CONCLUSIONS: Carpets/rugs capture a portion of mite, epidermal, mould allergens located at home, wherefore absence of a carpet or rug causes greater stimulation of an immune system by these allergens; as a consequence, IgE antibodies are the most frequently detected in respondents. Household contacts of the respondents, at the age of 1-4 years, with cats induced partial immune tolerance to cat dander.

(-)-Epicatechin 3-O-ß-D-allopyranoside prevent ovariectomy-induced bone loss in mice by suppressing RANKL-induced NF-κB and NFATc-1 signaling pathways.

BACKGROUND: Davallia formosana Hayata is a herb that has been used in Chinese medicine to treat bone diseases, including arthritis, bone fractures and osteoporosis. The rhizome of D. formosana H. has been found to be rich in (-)-Epicatechin 3-O-ß-D-allopyranoside (ECAP), which is considered to be the active component of the plant in terms of its antiosteoporotic effect. This study investigated the molecular mechanism of the antiosteoporotic property of ECAP isolated from the roots of D. formosana H. using both in vitro and in vivo models. METHODS: We studied the effects of ECAP on the signaling pathways of the receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis and ovariectomy-induced osteoporosis. In the in vitro study, the inhibitory action of ECAP on RANKL-induced osteoclastogenesis and the expression of osteoclast-related marker genes were investigated, and in the in vivo study, the effects of ECAP on bone were evaluated using ovariectomized (OVX) mice orally-administered ECAP for 4 weeks. RESULTS: We demonstrated that ECAP dose-dependently inhibited RANKL- and nuclear factor of activated T-cells, and cytoplasmic 1 (NFATc-1)-induced osteoclastogenesis by RAW 264.7 cells, and reduced the extent of bone resorption. Furthermore, µCT images and TRAP staining showed that oral administration of ECAP to OVX mice prevented bone loss. ECAP administration also exerted recovery effects on serum C-terminal telopeptide of type I collagen and osteocalcin levels in OVX mice. In addition, we also found that MMP-9 expression was decreased in vivo and in vitro. CONCLUSIONS: Overall, our findings suggested that ECAP suppresses RANKL-induced osteoclastogenesis through NF-κB and NFATc-1 signaling pathways, and has the potential for use in osteoporosis treatment.