Stimulation Period Research Articles

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor

BackgroundSymmetric biphasic pulses have been shown to acutely increase the therapeutic window of ventralis intermedius deep brain stimulation (Vim-DBS) for essential tremor (ET) compared to cathodic pulses. Acute supratherapeutic stimulation can induce ataxic side effects in Vim-DBS. ObjectiveTo investigate the effect on tremor, ataxia and dysarthria of 3 h of biphasic stimulation in patients with DBS for ET. MethodsA randomized, doubled-blind, cross-over design was used to compare standard cathodic pulses with symmetric biphasic pulses (anode-first) during a 3-h period per pulse shape. During each 3-h period, all stimulation parameters were identical, except for the pulse shape. Tremor (Fahn-Tolosa-Marin Tremor Rating Scale), ataxia (International Cooperative Ataxia Rating Scale) and speech (acoustic and perceptual measures) were assessed hourly during the 3-h periods. ResultsTwelve ET patients were included. During the 3-h stimulation period, tremor control was equivalent between the two pulse shapes. Biphasic pulses elicited significantly less ataxia than cathodic pulses (p = 0.006). Diadochokinesis rate of speech was better for the biphasic pulse (p = 0.048), but other measures for dysarthria were not significantly different between the pulses. ConclusionSymmetric biphasic pulses induce less ataxia than conventional pulses after 3 h of stimulation DBS in ET patients.

Early or late response in poor responders: does it make a difference in cycle outcome?

Ovarian response to stimulation mainly determines the length of stimulation. However, there is no clarity in the literature regarding the optimal duration required to achieve oocyte maturity in patients with the poor ovarian response (POR) defined by Bologna criteria. Therefore, a total of 267 cycles that fulfilled the inclusion criteria were selected retrospectively. Group A constitute of patients with a stimulation period < 9 d (n = 70); and group B included patients with a stimulation period ≥ 9 d (n = 133). The results showed that antral follicle count (5.72 ± 1.82 vs. 5.10 ± 1.78, p = 0.023), serum oestradiol level on hCG day (1286.88 ± 778.18 pg/mL vs. 820.14 ± 479.04 pg/mL, p = 0.001), and total gonadotropin dose used (2949.53 ± 727.92 IU vs 2020.94 ± 415.17 IU, p = 0.0001) were higher in group B when compared to group A. Although the number of total (5.47 ± 3.32 vs 3.86 ± 2.15, p = 0.0001) and mature oocytes retrieved (4.34 ± 2.88 vs 2.84 ± 1.67, p = 0.0001) were higher in group B, no significant difference was observed in the pregnancy rates between groups (25.6 vs 15.7%, p > 0.05). In conclusion, no deleterious effect of a shorter duration of stimulation on cycle outcome was seen in patients with POR.

PO-04-076 PHRENIC NERVE STIMULATOR LEAD MIGRATION RESULTING IN ATRIAL DYSRHYTHMIA

The phrenic nerve stimulator (PNS) is a novel treatment for central sleep apnea (CSA). The device (Remede, Respicardia Inc) consists of a pulse generator and a lead positioned in the left pericardiophrenic or right brachiocephalic vein. This stimulates the phrenic nerve during sleep resulting in diaphragmatic contraction to restore normal breathing. We report a case of PNS lead migration into the right atrium resulting in atrial dysrhythmias during device stimulation. N/A An 83 year old female with history of ischemic cardiomyopathy status post primary prevention ICD, and severe CSA underwent PNS placement two years ago with the pacing lead in the right brachiocephalic vein. Due to ongoing dyspnea and LBBB she had an upgrade to CRT-D using an epicardial LV lead. Post operatively she developed palpitations with several recorded episodes of wide complex tachycardia (image 1a). Interrogation of her CRT showed nocturnal atrial arrhythmias with aberrancy seemingly triggered by rhythmic electrical interference on her atrial marker channels (image 1b). There were no recorded daytime episodes. When interrogating the CRT-D with the PNS turned on, atrial arrhythmias were reproduced by periods of phrenic nerve stimulation, and ceased with the PNS turned off. A chest X-ray obtained showed migration of the PNS lead below the superior vena cava (SVC)-right atrial junction, possibly stimulating myocardial tissue (image 1c). She was treated by reprogramming the PNS device to pace from the proximal poles of the lead still within the SVC, thereby preventing future atrial arrhythmias. This is the first reported case of PNS lead migration into the right atrium causing atrial dysrhythmias.

Closed-loop electrical epidural stimulation restores ipsilesional in-phase diaphragm activity in spontaneously breathing rats after acute C2-hemisection

Epidural electrical stimulation has great promise for recovering many functions after spinal cord injury, including breathing. High-frequency stimulation of the thoracic [DiMarco and Kowalski, 2009] and cervical cord [Gonzalez-Rothi et al. 2017] recovers some phrenic and diaphragm activity. However, open-loop stimulation paradigms induce tonic activity and, thus far, have not elicited recovery of breathing function independent of the stimulation period. We have shown in C2-hemisected rats, closed-loop epidural stimulation (CLES; paced from contralateral diaphragm EMG activity) increases excitability in the respiratory motor network [Malone et al. 2022]; still, the ability of CLES to recover respiratory function following spinal cord injury has not been explored. Here, we hypothesized that CLES can elicit phasic ipsilesional diaphragm activity in C2-hemisected rats without tonic output. To test this, 3-5 month female Sprague-Dawley rats were anesthetized via inhaled isoflurane anesthetic, implanted with stimulating wire electrodes on the dorsal dura at C4 and recording electrodes bilaterally on the diaphragm, and C2-hemisected. After injury, a 15-30 minute recovery to ensure abolishment of ipsilateral diaphragm activity was followed by measurement of spinal motor evoked potentials of the diaphragm, and a baseline recording of diaphragm EMG activity. Biphasic CLES (n=3), set to an amplitude of ¼ the motor threshold, or a sham waiting period (n=3) was delivered for 20 minutes. EMG post processing was done in Spike2 using custom scripts. Stimulated animals received on average 101.8 +/- 22.8 Hz of stimulation during breaths. In stimulated animals, phasic ipsilesional diaphragm EMG activity significantly increased during stimulation (23.7 +/- 1.9 spikes per breath vs 4.32 +/- 1.9 at baseline, p &lt; 0.005). Stimulation did not increase tonic activity of the ipsilesional diaphragm, and ipsilesional diaphragm activity stopped with cessation of stim indicating no spontaneous recovery of activity. Additionally, there was no significant recovery of sham animals during the same period (5.2 +/- 1.9 vs 4.5 +/- 1.9 spikes per breath). Peak EMG activity and modulus of the contralesional diaphragm were significantly elevated from baseline during stimulation (peak value 0.19 +/- 0.015 V vs 0.15 +/- 0.005 V baseline p &lt; 0.05, % change modulus 34.9 +/- 5.9%, p &lt; 0.03). This work represents the first report that CLES can increase phasic diaphragm EMG activity both ipsi- and contralaterally after acute C2-hemisection. Further study is necessary to determine if CLES can elicit similar effects in a chronic model of injury. Additionally, work to determine the mechanism underlying these changes is essential to tailor this therapy for improving breathing function in individuals with spinal cord injury. T32HL134621, R01HL153102, SPARC OT2OD023854 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of temperature and water content on wet perception during the static touch of moist paper

[Background] Wet perception plays an essential role in behavioral thermoregulation. It has been suggested that mechanical and thermal stimuli affect wet perception; however, the mechanism remains unclear. This study aimed to clarify the effects of water content and temperature on the wet perception of moist papers. [Methods] Twenty-seven healthy volunteers (14 males and 13 females, age 25 ± 5 years) participated in this study, which comprised two experimental trials. In Experiment 1, participants placed the index finger on 2 x 2 cm filter paper of 6 different water content (0.00, 3.75, 7.50, 11.25, 15.00, or 18.75 μg/cm 2 ) for 15 s, of which temperature was controlled at 30ºC with Peltier apparatus. During the last 5 s of the stimulation period, participants were asked to report if they had wet perception or not. Each water content was presented five times, and the percentage rate of wet perception was calculated. In Experiment 2, participants placed the index finger on 2 x 2 cm filter paper of water content of 18.75 μg/cm 2 for 15 s, of which temperature was controlled at either 20, 25, 30, 35, or 40°C with Peltier apparatus. During the last 5 s of the stimulation period, participants were asked to report the intensity of their thermal and wet sensations with a visual analog scale. Each temperature was presented five times. [Results] Experiment 1: The percentage rates of wet perception of 3.75, 7.50, 11.25, 15.00, and 18.75 μg/cm 2 were significantly higher than that of 0.00 μg/cm 2 ( p &lt; 0.05). The percentage rates of wet perception of 11.25, 15.00, and 18.75 μg/cm 2 were significantly greater than those of 3.75 μg/cm 2 ( p &lt; 0.01) and 7.5 μg/cm 2 ( p &lt; 0.005). Experiment 2: Thermal sensation of the stimuli of 25, 30, 35, and 40ºC was greater than that of the 20ºC stimulus ( p &lt; 0.001). Wet perception of the stimulus of 20ºC was greater than that of 25, 30, 35, and 40ºC. Wet perception of the stimulus of 25ºC was higher than those of 30, 35, and 40ºC ( p &lt; 0.05). [Discussion and Conclusions] The percentage rate of wet perception increased with the water content of the paper. Thus, participants could discriminate such small differences in the water content. The wet perception was augmented by stimulus temperature lower than 30ºC, while stimulus temperature above 30ºC did not show a clear relationship with the intensity of wet perception. The cold sensation may play an important role in modulating wet perception. Research Fellow of Japan Society for the Promotion of Science and Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research A 19H01128. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Electrical auricular tragus stimulation induces release of circulating cardioprotective factors in healthy human volunteers.

Background: Vagal activation during remote ischemic conditioning (RIC) with subsequent release of cardioprotective factors from the spleen into the circulation reduces infarct size. These humoral cardioprotective factors can be transferred with plasma-dialysate from donors undergoing RIC to isolated recipient hearts where they reduce infarct size. Electrical auricular tragus stimulation (ATS) has been demonstrated to reduce the cardiac injury biomarker release and the frequency of ventricular arrhythmias and to improve contractile function in patients with acute myocardial infarction. Aim: To determine whether ATS, as RIC, induces release of cardioprotective factors into the circulation. Methods: Healthy volunteers (3 females, 7 males, 26±5 years) were randomized to receive ATS or RIC, respectively, with an interval of at least two weeks between protocols. ATS was induced by bipolar electrical rectangular pulses of 200μs width at a frequency of 30 Hz (Curamed TEN630, CURAmed, Shenzen Dongdixin Technology, Shenzhen, China). The amplitude (5.5 ± 0.81 mA) was set for each volunteer to not be perceived as uncomfortable over the total stimulation period. A microprocessor-controlled circuit periodically interrupted the stimulation signal after 5 s of stimulation for 5 s. ATS was continued over 30 min. RIC served as a reference to induce the release of cardioprotective factors by 3 x 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/ 5 min deflation. Venous blood samples were taken before and 60 min after ATS or RIC, respectively, and used to prepare plasma-dialysates (1:10 dialysis against buffer for 24 h, cut-off 12-14 kDa). Male Lewis rats were sacrificed and their hearts isolated and perfused at constant pressure with buffer. Plasma-dialysates from samples taken before and 60 min after ATS or RIC, respectively, were infused for 8 min followed by 2 min washout into rat hearts before global 30 min ischemia/ 120 min reperfusion. Infarct size was demarcated by triphenyl tetrazolium chloride staining and calculated as percent of ventricular mass. Results: With infusion of plasma-dialysate before ATS infarct size was 30.9±4.5% of ventricular mass and not different from that with infusion of plasma-dialysate before RIC (35.8±5.8%). Infusion of plasma-dialysate after ATS reduced infarct size to 18.3±3.9%. This cardioprotective effect was similar to that seen with infusion of plasma-dialysate after RIC (20.1±3.5%). Conclusion: ATS induces release of cardioprotective factors into the circulation of healthy volunteers. Plasma-dialysates after ATS or RIC, respectively, reduce myocardial infarct size by the same magnitude in ex vivo isolated perfused rat hearts with global ischemia/ reperfusion. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interferential therapy for chronic constipation in adults: The CON-COUR randomizedcontrolled trial.

Chronic constipation (CC) is a frequent condition, and the first-line treatment includes dietary rules, the use of laxatives, and biofeedback for evacuation disorders. However, almost half of the patients are dissatisfied with their current treatment. We report the first double-blind randomized multicenter trial assessing the effectiveness of transabdominal electrical stimulation by interferential therapy (IFT) in the treatment of CC in adults. A prospective, multicenter, randomized, double-blind, sham-controlled, parallel-group, phase 3 trial was conducted at 7 centers in France. The primary endpoint was 8-week efficacy as defined by the number of complete spontaneous bowel movements during the last 4weeks of the 8-week stimulation period. Secondary endpoints included the evaluation of the effects of IFT on symptoms (Patient Assessment of Constipation Symptoms questionnair (PAC-SYM)), quality of life (QOL) (Patient Assessment of Constipation Quality of Life), Colonic transit time (CTT), anorectal manometry, and patient satisfaction. The proportion of 8-week responders was not significantly different between the two groups (73.2% in the IFT group vs. 67.1% in the sham group). After 8weeks of stimulation, the mean overall PAC-SYM score and the mean reduction in the overall PAC-SYM score were significantly greater in the IFT group than in the sham group. No differences were observed concerning CTT, anorectal manometry, or patient satisfaction. Although the primary endpoint was not reached, IFT can significantly alleviate the symptoms and improve the QOL of CC patients. It can be assumed that new treatments require different modes of evaluation and that the assessment of patient-reported outcomes may become a priority among therapeutic targets of CC. Trial registration number NCT02381665.

Optogenetic activation of septal inhibitory cells abates focal seizures.

Emerging evidence suggests that the medial septum can control seizures occurring in focal epileptic disorders, thus representing a therapeutic target. Therefore, we investigated whether continuous optogenetic activation of inhibitory parvalbumin (PV)-positive interneurons in the medial septum can reduce the occurrence of spontaneous seizures in the pilocarpine model of mesial temporal lobe epilepsy (MTLE). Light pulses (450 nm, 25 mW, 20-ms pulse duration) were delivered at 0.5 Hz (5 min ON, 10 min OFF) with a laser diode fiber light source between day 8 and day 12 after status epilepticus (SE) in PV-ChR2 mice (n = 8). Seizure rates were significantly lower during time periods of optogenetic stimulation (days 8-12) compared with before implementation of optogenetics (days 4-7) (P < 0.05). Moreover, between day 13 and day 21 after SE seizure rates were still significantly lower compared with before optogenetic stimulation (i.e., between day 4 and day 7) (P < 0.05). No seizures were recorded between day 10 and day 12 in all animals, and no seizures occurred up to 3 days after the end of optogenetic stimulation (days 13-15). Our findings indicate that activation of PV interneurons in the medial septum abates seizures in the pilocarpine model of MTLE. Moreover, the persisting anti-ictogenic effects suggest that stimulation of the medial septum could alter the progression of MTLE.NEW & NOTEWORTHY The medial septum could represent a therapeutic target to treat patients with focal epilepsy. In this study, we show that optogenetic activation of inhibitory parvalbumin-positive interneurons in the medial septum can block spontaneous seizures and prevents their reoccurrence for ∼5 days after the end of stimulation. Our findings suggest that the anti-ictogenic effects induced by stimulation of the medial septum could also alter the progression of mesial temporal lobe epilepsy.

PD26-11 ERECTILE DYSFUNCTION IN PEYRONIE’S DISEASE: PREVALENCE AND ETIOLOGY AS DEMONSTRATED BY COLOR DUPLEX DOPPLER ULTRASOUND

You have accessJournal of UrologyCME1 Apr 2023PD26-11 ERECTILE DYSFUNCTION IN PEYRONIE’S DISEASE: PREVALENCE AND ETIOLOGY AS DEMONSTRATED BY COLOR DUPLEX DOPPLER ULTRASOUND Laura Geldmaker, Daniela Haehn, Sarah Hampton, Christopher Walker, Colleen Ball, and Gregory Broderick Laura GeldmakerLaura Geldmaker More articles by this author , Daniela HaehnDaniela Haehn More articles by this author , Sarah HamptonSarah Hampton More articles by this author , Christopher WalkerChristopher Walker More articles by this author , Colleen BallColleen Ball More articles by this author , and Gregory BroderickGregory Broderick More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003304.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Peyronie’s Disease (PD) can coexist with erectile dysfunction (ED). International guidelines recommend that PD management includes an assessment of each patient’s ability to initiate and sustain erection, by intracavernosal injection (ICI) test with or without duplex Doppler ultrasound. Distress caused by PD may limit a patient’s ability to assess adequacy of penile rigidity. Our objective was to assess vascular erectile integrity non-invasively in the setting of PD. METHODS: Consecutive patients who underwent ICI followed by Color Doppler Duplex Ultrasound (CDDU) at our institution were retrospectively reviewed. CDDU findings were recorded following injection of alprostadil and again after a period of privacy and visual sexual stimulation (VSS). Erectile re-observations were made with patient standing after VSS. Erectile rigidity was assessed by one physician and all patients were asked to compare to their best quality home erection. CDDU findings including peak systolic velocities, end diastolic velocities, and resistive indices were recorded. Among patients diagnosed with PD, comparisons of patient characteristics between those with and without a diagnosis of ED were made using a Wilcoxon rank sum test (continuous characteristics) or Fisher’s exact test (categorical characteristics). RESULTS: Our assessment of 1853 men using CDDU found 1239 were diagnosed with PD by CDDU. Among those with PD, 353 (28.5%) were diagnosed with PD only (vascular normal) and 886 (71.5%) were diagnosed with PD+ED. Patients with a CDDU diagnosis of PD only were younger [median: 57 (49, 62) vs. 61 (55, 67) years, p<0.001], less likely to have hypertension [119/349 (34.1%) vs. 424/885 (47.9%), p<0.001], less likely to have used PDE-5 inhibitor [243/348 (69.8%) vs. 692/882 (78.5%), p=0.002], and less likely to have failed to a PDE-5 inhibitor [150/243 (61.7%) vs. 531/691 (76.8%), p<0.001] compared to men with PD+ED. Mean SHIM scores were not normal in either group. SHIM scores were higher among those with PD only [median (interquartile range): 14 (8–20) vs. 10 (6–18), p<0.001]. CDDU diagnoses for men with PD+ED were AI 284/886 (32.1%), CVOD 371/886 (41.9%), mixed vascular ED 231/886 (26.1%). CONCLUSIONS: In our practice more than 90% of men undergo history and physical examination with same day CDDU for the evaluation of PD. In this series, Doppler analysis found that 71.5% of PD patients have some form of vascular ED. We recommend an evidence-based assessment of vascular erectile integrity before any patient is triaged to medical or surgical intervention. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e739 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Laura Geldmaker More articles by this author Daniela Haehn More articles by this author Sarah Hampton More articles by this author Christopher Walker More articles by this author Colleen Ball More articles by this author Gregory Broderick More articles by this author Expand All Advertisement PDF downloadLoading ...

MP03-12 FUNCTIONAL MRI EXPLORATION OF THE SACRAL SPINAL CORD: A BULBOCAVERNOSUS REFLEX TASK-BASED STIMULATION

You have accessJournal of UrologyCME1 Apr 2023MP03-12 FUNCTIONAL MRI EXPLORATION OF THE SACRAL SPINAL CORD: A BULBOCAVERNOSUS REFLEX TASK-BASED STIMULATION Charles Mazeaud, Betsy Salazar, Kris Hoffman, Christof Karmonik, and Rose Khavari Charles MazeaudCharles Mazeaud More articles by this author , Betsy SalazarBetsy Salazar More articles by this author , Kris HoffmanKris Hoffman More articles by this author , Christof KarmonikChristof Karmonik More articles by this author , and Rose KhavariRose Khavari More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lower urinary tract (LUT) is under the control of the central nervous system. Functional MRI (fMRI) is designed to explore neuronal activity, however, its application at the level of the spinal cord has been challenging and not explored. The bulbocavernosus reflex (BCR) is a reliable means of assessing the integrity of the spinal cord, particularly at the sacral level of the LUT control. The BCR is usually triggered by a gentle squeezing of the penis glans or the clitoris, especially with a full bladder. A similar and more convenient method is to tap on the midline of the suprapubic region when the bladder is full. The objectives of this project are twofold: (1) to establish a feasible and MRI compatible BCR assessment within the MRI scanner, (2) to assess the feasibility of spinal cord fMRI during a full bladder BCR in regard to LUT control in healthy individuals. METHODS: An MRI compatible hammer was designed and generated to deliver the stimulation within the MRI tunnel to elicit BCR. Two healthy males with no previous history of LUT symptoms or spinal cord injury were recruited for this trial. The participants were instructed to consume 500 ml of water and empty their bladder immediately before entering the MRI. When they reported a full bladder, they underwent a task-based fMRI of four blocks of 40 seconds of tapping (BCR) and 40 seconds of control (rest). The regions of interest (ROIs) involved in the BCR, were defined as the area of the terminal cone (S1-S4 roots) known to be involved in LUT control. The blood level oxygen-dependent (BOLD) signal within ROIs was analyzed with the FSL software. RESULTS: The ROIs identified in the sacral spinal cord showed a significant increase in signal upon BCR stimulation. BOLD activations were present and time-related to the stimulation period (Figure 1). CONCLUSIONS: This is the first study to demonstrate that: There is a feasible and modest approach to elicit BCR within the MRI to assess spinal cord integrity in regard to LUT control. The activity of the sacral spinal cord during the BCR stimulation can be revealed in fMRI. These preliminary results pave the way for further study of the functional role of the spinal cord in larger cohorts of healthy individuals and in individuals with spinal cord injury. Source of Funding: Funding provided by the National Institute of Health, NIDDK R03DK126994-01 award and the CAIRIBU Core collaboration award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e26 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charles Mazeaud More articles by this author Betsy Salazar More articles by this author Kris Hoffman More articles by this author Christof Karmonik More articles by this author Rose Khavari More articles by this author Expand All Advertisement PDF downloadLoading ...

Brief periods of transcutaneous auricular vagus nerve stimulation improve autonomic balance and alter circulating monocytes and endothelial cells in patients with metabolic syndrome: a pilot study

BackgroundThere is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS.MethodsWe conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up.ResultsAn improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile.ConclusionThese results are of interest for further study of TAVNS as treatment of MetS.

Bullwhip effect: Modelling and simulation of a sinusoidal stimulus considering food waste

Background: The current coronavirus disease 2019 (COVID-19) pandemic has stressed why a change towards resilient, robust and sustainable supply chains is more imperative than ever. This is especially true for supply chains of perishable foods, where issues such as the bullwhip effect cause not only economic but also environmental damage.Objectives: The key objectives of this study are to gain a deeper insight into correlations regarding the causes of the bullwhip effect and to see how a sinusoidal stimulus is affecting the generation of food waste.Method: A simplified beef food chain was modelled in Tecnomatix Plant Simulation®. As the bullwhip effect consists of a simplified parameterisation of an excitation duration (period length) and its height (amplitude), these two variables were used to generate a sinusoidal stimulus. The simulation results were statistically verified and checked for commonalities and differences with the already established scientific knowledge.Results: While the expected higher sensitivity of the front links of the supply chain to waste generation can be confirmed, the results of a long stimulation period suggest that the negative effects of the bullwhip effect do not increase indefinitely.Conclusion: The analysis of the results has shown that previous theories can be transferred, but that the variation of the variables entails new insights for the interdependencies of the amplitude and period length and their influence on the output variable waste.Contribution: The study contributes to a more holistic understanding of the bullwhip effect and, in particular, its implications within a perishable food supply chain.

Deep brain stimulation normalizes amygdala responsivity in treatment-resistant depression.

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.

Functional OCT angiography reveals early retinal neurovascular dysfunction in diabetes with capillary resolution.

Altered retinal neurovascular coupling may contribute to the development and progression of diabetic retinopathy (DR) but remains highly challenging to measure due to limited resolution and field of view of the existing functional hyperemia imaging. Here, we present a novel modality of functional OCT angiography (fOCTA) that allows a 3D imaging of retinal functional hyperemia across the entire vascular tree with single-capillary resolution. In fOCTA, functional hyperemia was evoked by a flicker light stimulation, recorded by a synchronized time-lapse OCTA (i.e., 4D), and extracted precisely from each capillary segment (space) and stimulation period (time) in the OCTA time series. The high-resolution fOCTA revealed that the retinal capillaries, particularly the intermediate capillary plexus, exhibited apparent hyperemic response in normal mice, and significant functional hyperemia loss (P < 0.001) at an early stage of DR with few overt signs of retinopathy and visible restoration after aminoguanidine treatment (P < 0.05). Retinal capillary functional hyperemia has strong potential to provide sensitive biomarkers of early DR, and retinal fOCTA would provide new insights into the pathophysiology, screening and treatment of early DR.

Effects of trunk neuromuscular electrical stimulation on the motor circuits of able-bodied individuals

Upper- and lower-limb neuromuscular electrical stimulation (NMES) is known to modulate the excitability of the neural motor circuits. However, it remains unclear whether short-duration trunk muscle NMES could achieve similar neuromodulation effects. We assessed motor evoked potentials (MEPs) elicited through transcranial magnetic stimulation of the primary motor cortex representation of the trunk extensor muscles to evaluate corticospinal excitability. Moreover, cervicomedullary motor evoked potentials (CMEPs) were assessed through cervicomedullary junction magnetic stimulation to evaluate subcortical excitability. Twelve able-bodied individuals participated in the MEP study, and another twelve in the CMEP study. During the interventions, NMES was applied bilaterally to activate the erector spinae muscle and produce intermittent contractions (20 s ON/20 s OFF) for a total of 20 min while participants remained seated. Assessments were performed: (i) before; (ii) during (in brief periods when NMES was OFF); and (iii) immediately after the interventions to compare MEP or CMEP excitability. Our results showed that MEP responses were not affected by trunk NMES, while CMEP responses were facilitated for approximately 8 min during the intervention, and returned to baseline before the end of the 20 min stimulating period. Our findings therefore suggest that short-duration NMES of the trunk extensor muscles likely does not affect the corticospinal excitability, but it has a potential to facilitate subcortical neural circuits immediately after starting the intervention. These findings indicate that short-duration application of NEMS may be helpful in rehabilitation to enhance neuromodulation of the trunk subcortical neural motor circuits.

Lighting Up a 1 km Fault near a Hydraulic Fracturing Well Using a Machine Learning-Based Picker

Abstract The development of portable nodal array in the recent years greatly improved the seismic monitoring ability across multiple scales. The dense arrays also directly benefit microseismic monitoring by providing relatively low-cost surface recordings. However, the rapid growth of seismic data is accompanied by the increased demand for efficient seismic phase picking. On the other hand, machine learning-based phase picking techniques achieved high stability and accuracy, showing promising potential to replace human labors and traditional automatic pickers. In this study, we applied a state-of-the-art package on newly collected nodal array data around a hydraulic fracturing well in southwestern China. The array consists of up to 85 nodes with an average station spacing of less than a kilometer. Within the hydraulic fracturing stimulation periods, we detected ∼3000 seismic events with magnitude down to ∼−2. After waveform cross-correlation-based relocation, the 1979 relocated events clearly light up a 1 km long fault structure and several fractures. Furthermore, the frequency–magnitude distribution of the catalog exhibits weak bilinear features with relatively low b-value (0.88) and a moderate coefficient of variation (Cv ∼2). The nature and origin of the observed earthquake cluster are then discussed and defined based on the industrial information, high-resolution earthquake catalog, and basic statistics. Finally, we summarized our experience and provided recommendations for applying similar approaches to other local scale, surface microseismic monitoring scenarios.

How to entrain a selected neuronal rhythm but not others: open-loop dithered brain stimulation for selective entrainment

Objective. While brain stimulation therapies such as deep brain stimulation for Parkinson’s disease (PD) can be effective, they have yet to reach their full potential across neurological disorders. Entraining neuronal rhythms using rhythmic brain stimulation has been suggested as a new therapeutic mechanism to restore neurotypical behaviour in conditions such as chronic pain, depression, and Alzheimer’s disease. However, theoretical and experimental evidence indicate that brain stimulation can also entrain neuronal rhythms at sub- and super-harmonics, far from the stimulation frequency. Crucially, these counterintuitive effects could be harmful to patients, for example by triggering debilitating involuntary movements in PD. We therefore seek a principled approach to selectively promote rhythms close to the stimulation frequency, while avoiding potential harmful effects by preventing entrainment at sub- and super-harmonics. Approach. Our open-loop approach to selective entrainment, dithered stimulation, consists in adding white noise to the stimulation period. Main results. We theoretically establish the ability of dithered stimulation to selectively entrain a given brain rhythm, and verify its efficacy in simulations of uncoupled neural oscillators, and networks of coupled neural oscillators. Furthermore, we show that dithered stimulation can be implemented in neurostimulators with limited capabilities by toggling within a finite set of stimulation frequencies. Significance. Likely implementable across a variety of existing brain stimulation devices, dithering-based selective entrainment has potential to enable new brain stimulation therapies, as well as new neuroscientific research exploiting its ability to modulate higher-order entrainment.

Methods and system for recording human physiological signals from implantable leads during spinal cord stimulation.

This article presents a method-including hardware configuration, sampling rate, filtering settings, and other data analysis techniques-to measure evoked compound action potentials (ECAPs) during spinal cord stimulation (SCS) in humans with externalized percutaneous electrodes. The goal is to provide a robust and standardized protocol for measuring ECAPs on the non-stimulation contacts and to demonstrate how measured signals depend on hardware and processing decisions. Two participants were implanted with percutaneous leads for the treatment of chronic pain with externalized leads during a trial period for stimulation and recording. The leads were connected to a Neuralynx ATLAS system allowing us to simultaneously stimulate and record through selected electrodes. We examined different hardware settings, such as online filters and sampling rate, as well as processing techniques, such as stimulation artifact removal and offline filters, and measured the effects on the ECAPs metrics: the first negative peak (N1) time and peak-valley amplitude. For accurate measurements of ECAPs, the hardware sampling rate should be least at 8 kHz and should use a high pass filter with a low cutoff frequency, such as 0.1 Hz, to eliminate baseline drift and saturation (railing). Stimulation artifact removal can use a double exponential or a second-order polynomial. The polynomial fit is 6.4 times faster on average in computation time than the double exponential, while the resulting ECAPs' N1 time and peak-valley amplitude are similar between the two. If the baseline raw measurement drifts with stimulation, a median filter with a 100-ms window or a high pass filter with an 80-Hz cutoff frequency preserves the ECAPs. This work is the first comprehensive analysis of hardware and processing variations on the observed ECAPs from SCS leads. It sets recommendations to properly record and process ECAPs from the non-stimulation contacts on the implantable leads.

Effect of the ratios of estradiol increase on the outcome of in vitro fertilization-embryo transfer with antagonist regimens: a single center retrospective cohort study

BackgroundThe outcome of in vitro fertilization-embryo transfer (IVF) is often determined according to follicle and estradiol levels following gonadotropin stimulation. In previous studies, although most of them analyzed the estrogen level from ovaries or the average estrogen level of a single follicle, there was no study on the ratio of estrogen increase, which was also correlated with pregnancy outcomes in the clinic. This study aimed to make timely adjustments to follow-up medication to improve clinical outcomes based on the potential value of estradiol growth rate.MethodsWe comprehensively analyzed estrogen growth during the entire ovarian stimulation period. Serum estradiol levels were measured on the day of gonadotropin treatment (Gn1), five days later (Gn5), eight days later (Gn8), and on the trigger day (HCG). This ratio was used to determine the increase in estradiol levels. According to the ratio of estradiol increase, the patients were divided into four groups: A1 (Gn5/Gn1 ≤ 6.44), A2 (6.44 < Gn5/Gn1 ≤ 10.62), A3 (10.62 < Gn5/Gn1 ≤ 21.33), and A4 (Gn5/Gn1 > 21.33); B1 (Gn8/Gn5 ≤ 2.39), B2 (2.39 < Gn8/Gn5 ≤ 3.03), B3 (3.03 < Gn8/Gn5 ≤ 3.84), and B4 (Gn8/Gn5 > 3.84). We analyzed and compared the relationship between data in each group and pregnancy outcomes.ResultsIn the statistical analysis, the estradiol levels of Gn5 (P = 0.029, P = 0.042), Gn8 (P < 0.001, P = 0.001), and HCG (P < 0.001, P = 0.002), as well as Gn5/Gn1 (P = 0.004, P = 0.006), Gn8/Gn5 (P = 0.001, P = 0.002), and HCG/Gn1 (P < 0.001, P < 0.001) both had clinical guiding significance, and lower one significantly reduced the pregnancy rate. The outcomes were positively linked to groups A (P = 0.036, P = 0.043) and B (P = 0.014, P = 0.013), respectively. The logistical regression analysis revealed that group A1 (OR = 0.376 [0.182–0.779]; P = 0.008*, OR = 0.401 [0.188–0.857]; P = 0.018*) and B1 (OR = 0.363 [0.179–0.735]; P = 0.005*, OR = 0.389 [0.187–0.808]; P = 0.011*) had opposite influence on outcomes.ConclusionMaintaining a serum estradiol increase ratio of at least 6.44 on Gn5/Gn1 and 2.39 on Gn8/Gn5 may result in a higher pregnancy rate, especially in young people.

Short periods of perinatal acoustic experience alter the developmental trajectory of auditory cortex

Compared to hearing subjects, psychophysical studies have revealed specific superior visual abilities following hearing loss early in development. The neural substrate for these superior abilities resides in auditory cortex that have been reorganized through crossmodal plasticity. Furthermore, the cartography of auditory cortex is altered following the loss of auditory input early in life. This study examined how perinatal exposure to brief periods of acoustic stimulation alters the developmental trajectory of auditory cortex. Movement detection, localization in the visual periphery, and face discrimination learning are superior in congenitally deaf cats. To examine the role of acoustic experience in mediating these enhanced functions, hearing animals were chemically deafened at increasing ages postnatal. Animals had 1–16 weeks of acoustic exposure prior to deafness onset. Overall, &amp;gt;9 weeks of acoustic experience resulted in no enhanced visual abilities. With &amp;gt;4 weeks of acoustic exposure, enhanced motion detection was not evident. As acoustic experience increased during development, the overall size of auditory cortex, and the size of individual auditory areas also expanded. These results demonstrate that increasingly longer periods of perinatal acoustic experience result in reduced enhanced visual abilities and an increased size of auditory cortex.