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Evaluation of the OPTESK VR training simulator for gastric bleeding treatment. OPTESK VR训练模拟器对胃出血治疗的评价。
IF 6.8
Bioelectronic medicine Pub Date : 2026-10-19 DOI: 10.1186/s42234-026-00216-w
Annika Köhler, Irshath Ali Syed, Jana Sophia Theile, Ioannis Kafetzis, Joel Troya, Jan-Peter Grunz, Ulrike W Denzer, Ivica Grgic, Benjamin M Walter, Rüdiger Pryss, Stavros Dimitriadis, Alexander Hann
{"title":"Evaluation of the OPTESK VR training simulator for gastric bleeding treatment.","authors":"Annika Köhler, Irshath Ali Syed, Jana Sophia Theile, Ioannis Kafetzis, Joel Troya, Jan-Peter Grunz, Ulrike W Denzer, Ivica Grgic, Benjamin M Walter, Rüdiger Pryss, Stavros Dimitriadis, Alexander Hann","doi":"10.1186/s42234-026-00216-w","DOIUrl":"https://doi.org/10.1186/s42234-026-00216-w","url":null,"abstract":"<p><strong>Background: </strong>Bleeding in the upper gastrointestinal tract is a common and potentially life-threatening emergency that requires rapid and highly precise endoscopic intervention. As supervised hands-on training is limited and often restricted to living animal models, an immersive virtual reality (VR) simulation offers a risk-free and accessible alternative.</p><p><strong>Methods: </strong>A novel open-source VR training simulator, OPTESK, was developed for the treatment of upper gastrointestinal (GI) bleeding. The system consists of a combination of conventional endoscopes used in routine clinical practice, which can be operated in conjunction with commercially available head-mounted displays and the in-house developed OPTESK hardware. The simulator covers two scenarios: the treatment of a non-bleeding angiodysplasia with argon plasma coagulation (APC) and the treatment of a bleeding angiodysplasia starting with the injection of adrenaline followed by APC therapy. The simulator was evaluated in a multicenter user study in terms of workload, usability, immersion, cybersickness, and face, content, and construct validity. User performance was assessed via scores on time, amount of treated area, and correctly applied APC intensity.</p><p><strong>Results: </strong>In total, 44 participants from more than 20 centers were included in the study. Successful hemostatic control in the second scenario was achieved by 97.4% of the participants. Regarding the content validity, participants rated the helpfulness of the simulator for training the management of bleeding with a median of 4 on a scale from 1 (strongly disagree) to 5 (strongly agree). Mean perceived workload (NASA-TLX) and usability (SUS) were rated with 34.2/100 and 69.6/100 respectively. Face validity questions regarding the realism of endoscope movement, stomach anatomy, and application of APC were further rated with a median of 4 on the scale from 1 to 5. Regarding construct validity, gastroscopy experience showed significantly faster treatment of bleeding related tasks for both scenario one (p = .008) and two (p = .011) compared to participants with less gastroscopy experience.</p><p><strong>Conclusions: </strong>OPTESK can serve as a valuable training tool for endoscopic treatment of bleeding in the upper GI tract. This approach may help reduce dependence on animal-based training and enable risk-free practice prior to clinical intervention.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stimulation-stability and preclinical bench testing of a new auditory nerve interface. 一种新型听神经界面的刺激稳定性和临床前台架试验。
IF 6.8
Bioelectronic medicine Pub Date : 2026-10-14 DOI: 10.1186/s42234-026-00215-x
Taylor Stump, Stefan Strahl, Joseph Crew, Moritz Leber, Keno Hübner, Sandeep Negi, Justin Vankirk, Meredith E Adams, Thomas Lenarz, Florian Solzbacher, Hubert H Lim, Loren Rieth
{"title":"Stimulation-stability and preclinical bench testing of a new auditory nerve interface.","authors":"Taylor Stump, Stefan Strahl, Joseph Crew, Moritz Leber, Keno Hübner, Sandeep Negi, Justin Vankirk, Meredith E Adams, Thomas Lenarz, Florian Solzbacher, Hubert H Lim, Loren Rieth","doi":"10.1186/s42234-026-00215-x","DOIUrl":"10.1186/s42234-026-00215-x","url":null,"abstract":"<p><strong>Objective: </strong>Cochlear implants are the flagship sensory neural prosthetic, enabling improved hearing and speech perception in >1 million patients with hearing loss. Despite over three decades of active work and innovations in cochlear implants, hearing performance for complex tasks such as speech-in-noise and music appreciation are still quite limited, putatively due to the challenge of selectively stimulating the auditory nerve with intracochlear electrodes through the bony cochlear wall. Our approach is to more selectively evoke hearing percepts through the development of an Auditory Nerve Implant (ANI) device that uses penetrating microelectrodes placed directly in the nerve for stimulation, and which will be evaluated through psychophysical testing as part of a first-in-human study. Stability and integrity of ANI electrodes during passive soaking and stimulation are needed to support initiation of the clinical trial, which we evaluated through thermal accelerated saline soak testing and stimulation stability testing.</p><p><strong>Methods: </strong>The ANI electrode stability in saline was assessed by accelerated aging at ≥ 67 [Formula: see text]C with a 1.5-year equivalent endpoint using electrode impedance and microscopy to characterize outcomes. Stimulation stability testing evaluated electrode integrity after 6.3 billion pulses at 100 μA, which is the maximum clinical stimulation intensity, for a one-year equivalent use, and 1200 μA, for a high-dose protocol. Electrode impedance, longitudinal stimulation voltage, and microscopy outcomes were used to the quantify results.</p><p><strong>Results: </strong>All electrodes had stable impedances around 2 kΩ at the end of the accelerated soak test, except for three with higher impedances but still below the 70 kΩ failure criteria. All but one electrode survived stimulation stability testing. Optical and electron microscopy largely showed little to no change during testing, indicating no observable tip degradation, with the exception of one soak-test device.</p><p><strong>Conclusions: </strong>The outcomes from the studies indicate that ANI electrodes exhibit a high degree of integrity and impedance stability. Microscopy characterization proved effective for evaluating electrodes, providing complementary information to standard Backscattered Scanning Electron Microscopy (BSEM). This study suggests the ANI device tolerate a 1.5 year in-dwelling period for a 1 year perceptual study of stimulation evoked percepts, paving the way for clinical translation.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Accelerating the development of bioelectronic medicine: outcomes and innovations from the NIH SPARC initiative. 加速生物电子医学的发展:来自NIH SPARC计划的成果和创新。
IF 6.8
Bioelectronic medicine Pub Date : 2026-09-04 DOI: 10.1186/s42234-026-00213-z
Bhavesh Patel, Victor Pikov, Margot S Damaser, Jyl Boline, Susan J Tappan, David P Nickerson, Matthew P Ward, Pallavi K Gunalan, Esra Neufeld, Kip A Ludwig, Jeffrey S Grethe, Joost B Wagenaar, Maryann E Martone
{"title":"Accelerating the development of bioelectronic medicine: outcomes and innovations from the NIH SPARC initiative.","authors":"Bhavesh Patel, Victor Pikov, Margot S Damaser, Jyl Boline, Susan J Tappan, David P Nickerson, Matthew P Ward, Pallavi K Gunalan, Esra Neufeld, Kip A Ludwig, Jeffrey S Grethe, Joost B Wagenaar, Maryann E Martone","doi":"10.1186/s42234-026-00213-z","DOIUrl":"10.1186/s42234-026-00213-z","url":null,"abstract":"<p><p>The NIH Common Fund's SPARC (Stimulating Peripheral Activity to Relieve Conditions) program was launched in 2015 to catalyze bioelectronic medicine by advancing foundational knowledge of the autonomic nervous system (ANS) and enabling clinical translation of novel bioelectronic medicines. While the program officially ended in 2025, activities related to the program are still ongoing through no-cost extensions, data sharing, and derivative efforts. We provide here an overview of the major outcomes of SPARC under its four focus areas: Anatomical and Functional Mapping, Technology Development, Translational Research, and Data/Modeling Infrastructure. In the Anatomical and Functional Mapping focus areas, teams generated cross-species, cross-organ ANS connectivity datasets, detailed nerve anatomy, along with detailed maps and connectivity resources to support query, visualization, and hypothesis-generation. Under the Technology Development focus area, teams developed new tools for recording and stimulating autonomic pathways and built computational pipelines for realistic neuromodulation simulations. Within the Translational Research, teams conducted pre-clinical and clinical proof-of-concept studies and used prize-driven efforts to accelerate clinically ready neuromodulation solutions. Data/Modeling Infrastructure teams built a durable open-science ecosystem enabling FAIR sharing, exploration, and reuse of SPARC datasets, models, and workflows by the broader community. Together, SPARC's integrated approach has lowered barriers to precision neuromodulation research and established reusable resources to sustain the field beyond the program.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Teaching through technology: comparing student experiences of VR and computer simulations in orthoptics education. 科技教学:在正视教育中VR与计算机模拟的学生体验比较。
IF 6.8
Bioelectronic medicine Pub Date : 2026-08-29 DOI: 10.1186/s42234-026-00214-y
Michael Batterley, Georg Meyer, Jignasa Mehta, Simon Campion, Ryan Ward
{"title":"Teaching through technology: comparing student experiences of VR and computer simulations in orthoptics education.","authors":"Michael Batterley, Georg Meyer, Jignasa Mehta, Simon Campion, Ryan Ward","doi":"10.1186/s42234-026-00214-y","DOIUrl":"10.1186/s42234-026-00214-y","url":null,"abstract":"<p><strong>Background: </strong>Virtual Reality (VR) has previously been found to provide both an effective and enjoyable learning environment for users to develop a wide range of skills. However, despite uptake in fields such as medicine and veterinary medicine, there is little research into the use of VR for diagnostics training with Orthoptists.</p><p><strong>Methods: </strong>This study compared students' experiences of a collaborative VR learning environment with the Strabismus desktop computer simulation for practicing the diagnosis of ocular deviations and limitations. The VR system provided stereoscopic depth and natural controller-based interaction, enabling students to practice diagnostic procedures with greater spatial realism than 2D simulators. Thirty one first year and twenty one second year Orthoptics students from the University of Liverpool were tasked with diagnosing simulated patients in both learning environments. After completing their diagnoses, students' user experience, sense of presence, comfort with patient proximity, and their thoughts on the use of VR in higher education (SHEQ) were measured.</p><p><strong>Results: </strong>Students reported higher hedonic user experience scores for VR, whereas pragmatic user experience scores were higher for the desktop simulation. SHEQ responses indicated a general preference for VR as a learning tool. However, there were no significant differences in sense of presence, or comfort with proximity to patient scores.</p><p><strong>Conclusions: </strong>This study shows how commodity VR hardware can be adapted for specialist healthcare training. Although VR did not demonstrate advantages across all measured outcomes, students generally perceived it positively and preferred it over using 2D displays as a learning tool within higher education. These findings suggest that VR may have potential as a supplementary educational resource for Orthoptics training. However, further research is required to determine whether these positive perceptions translate into real world improvements in learning, diagnostic performance, and clinical practice.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Accelerating the development of bioelectronic medicine: overview and impact of the NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiative. 加速生物电子医学的发展:美国国立卫生研究院刺激外周活动缓解条件(SPARC)倡议的概述和影响。
IF 6.8
Bioelectronic medicine Pub Date : 2026-08-19 DOI: 10.1186/s42234-026-00212-0
Katelynn A Milora, Rebecca M Black, Andrew C Weitz, Michael B Wolfson, Jessica Falcone, Eric Hudak, Brooks Gross, Nicholas Langhals, Sahana N Kukke, Daniel Anthony Casco, Kristina Faulk, Julia Berzhanskaya, Wen G Chen, Emrin Horgusluoglu, Felicia Qashu
{"title":"Accelerating the development of bioelectronic medicine: overview and impact of the NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiative.","authors":"Katelynn A Milora, Rebecca M Black, Andrew C Weitz, Michael B Wolfson, Jessica Falcone, Eric Hudak, Brooks Gross, Nicholas Langhals, Sahana N Kukke, Daniel Anthony Casco, Kristina Faulk, Julia Berzhanskaya, Wen G Chen, Emrin Horgusluoglu, Felicia Qashu","doi":"10.1186/s42234-026-00212-0","DOIUrl":"https://doi.org/10.1186/s42234-026-00212-0","url":null,"abstract":"<p><p>The National Institutes of Health (NIH) Common Fund supports bold scientific programs that catalyze discovery across all biomedical and behavioral research to address high priority challenges for the NIH as a whole and make a broader impact in the scientific community. In 2015, the NIH Common Fund established the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program. This program's overall goal was to accelerate the development of neuromodulation, a field of study that uses bioelectronic devices to deliver electrical current to nervous system tissues to produce therapeutic effects in patients. Because the nervous system impacts all bodily functions, neuromodulation therapies have the potential to treat a variety of health conditions by regulating nerves that innervate affected bodily tissues and organs, with high specificity and few side effects. The SPARC program aimed to capitalize on recent advances in technology to deliver detailed, integrated functional and anatomical neural circuit maps for organs and to provide the necessary scientific foundation for clinical translation of more effective and advanced neuromodulation devices and stimulation protocols. Here we outline the SPARC program's contribution to the field of neuromodulation over the past ten years, laying a comprehensive foundation of knowledge to inspire future research and accelerate translation. We discuss the reasoning behind the formation of the program, its structure, and outcomes.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Continuous vs. intermittent chronic vagus nerve stimulation: effects on T-cell dependent antibody response, heart rate variability and body weight in immunized mice. 连续与间歇性慢性迷走神经刺激:对免疫小鼠t细胞依赖性抗体反应、心率变异性和体重的影响
IF 6.8
Bioelectronic medicine Pub Date : 2026-07-22 DOI: 10.1186/s42234-026-00211-1
Michael Gerber, Ibrahim Mughrabi, Izumi Kurata-Sato, Ethan Paliwoda, The Anh Vu, Betty Diamond, Stavros Zanos
{"title":"Continuous vs. intermittent chronic vagus nerve stimulation: effects on T-cell dependent antibody response, heart rate variability and body weight in immunized mice.","authors":"Michael Gerber, Ibrahim Mughrabi, Izumi Kurata-Sato, Ethan Paliwoda, The Anh Vu, Betty Diamond, Stavros Zanos","doi":"10.1186/s42234-026-00211-1","DOIUrl":"10.1186/s42234-026-00211-1","url":null,"abstract":"<p><p>Vagal-immune interactions are increasingly recognized to play a role in the pathogenesis of diseases associated with immune dysfunction. To study the direct effects of altered vagal activity on adaptive immune function and antibody production, we modeled a state of elevated vagal activation by delivering chronic vagus nerve stimulation (VNS) in immunized mice. We delivered VNS for 14 days before and 14 days after immunization with an antigen, using 2 schedules: Twice Daily VNS, to model intermittently elevated vagal activity, and Continuous Burst VNS, to model chronically elevated vagal activity. We found that Continuous Burst VNS is associated with increased heart rate variability (HRV) on the first week of treatment, remodeling of cellular splenic compartments, as well as weight loss. Such changes are not seen with Twice Daily VNS. High-affinity antibody production is reduced with both Continuous Burst and Twice Daily VNS, compared to no VNS. Total IgG antibody titers are reduced in Continuous Burst VNS, even prior to immunization, likely an effect of weight loss. In conclusion, both continuously and intermittently elevated vagal tone limits the antibody response. Nonselective, whole nerve VNS produces multiple effects that may confound interpretation of specific immune effects at higher stimulation doses.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Autonomic and neural responses to varying transcutaneous cervical electrical stimulation parameters. 自主神经系统对不同经皮颈部电刺激参数的反应。
IF 6.8
Bioelectronic medicine Pub Date : 2026-07-06 DOI: 10.1186/s42234-026-00210-2
Shubham Debnath, Fylaktis Fylaktou, Blake T Gurfein, Theodoros P Zanos
{"title":"Autonomic and neural responses to varying transcutaneous cervical electrical stimulation parameters.","authors":"Shubham Debnath, Fylaktis Fylaktou, Blake T Gurfein, Theodoros P Zanos","doi":"10.1186/s42234-026-00210-2","DOIUrl":"10.1186/s42234-026-00210-2","url":null,"abstract":"<p><strong>Background: </strong>Transcutaneous cervical electrical stimulation (TCES) offers a noninvasive approach to modulate the autonomic nervous system (ANS), but optimal stimulation parameters remain undefined. This pilot study aimed to identify optimal TCES parameters by evaluating autonomic and neural responses across varying frequencies, current intensities, electrode montages, and durations, using heart rate variability (HRV) and electroencephalography (EEG) alpha-band power as biomarkers of parasympathetic activity.</p><p><strong>Methods: </strong>Twenty healthy adults completed four testing sessions, each examining one stimulation parameter. Autonomic data were collected including electrocardiography, non-invasive blood pressure, pupillometry, photoplethysmography, and dry-electrode EEG. Four frequencies (10, 25, 40, 150 Hz), three current intensities (sub-sensation threshold, sensation threshold, supra-sensation threshold), three electrode montages (bilateral, left-only, right-only), and two durations (4, 20 min) were tested. Root mean square of successive differences (RMSSD) and global EEG alpha-band power were primary outcomes. Parameters were sequentially optimized across visits based on individual RMSSD responses.</p><p><strong>Results: </strong>No single frequency produced a significantly higher RMSSD or alpha-band power response. However, each participant exhibited a personalized preferred frequency yielding a mean 41% RMSSD increase in visit 1. This individualized frequency was selected for further visits varying current intensity and electrode montage. Supra-sensation threshold intensity was most effective, with 60% of participants responding strongest at this level. Left-sided stimulation resulted in a decrease in both RMSSD and alpha-band power, while right-sided and bilateral montages resulted in similar increases for these biomarkers. Due to decreasing cardiac vagal response in successive sessions, the preferred frequency was reevaluated before testing duration. The mean RMSSD response increased 54% upon recalibration in visit 4, though the preferred frequency shifted in 75% of participants. Autonomic vitals did not significantly modulate more with longer stimulation duration; pulse rate variability during 20-min stimulation revealed oscillatory autonomic dynamics with peak parasympathetic responses emerging around 4 min.</p><p><strong>Conclusions: </strong>TCES can modulate cardiac vagal and cortical responses as measured by RMSSD and EEG alpha-band power, respectively, and a personalized, biomarker-guided approach to TCES parameter optimization is essential for future clinical applications targeting autonomic dysfunction.</p><p><strong>Trial registration: </strong>This study was registered with Clinicaltrials.gov, identifier NCT04100486, on September 16, 2019.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148392636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vagus nerve control of HMGB1 accessibility: a bioelectronic strategy for inflammation and pain. 迷走神经控制HMGB1可及性:炎症和疼痛的生物电子策略。
IF 6.8
Bioelectronic medicine Pub Date : 2026-06-24 DOI: 10.1186/s42234-026-00209-9
Huan Yang, Michael Brines, Ulf Andersson
{"title":"Vagus nerve control of HMGB1 accessibility: a bioelectronic strategy for inflammation and pain.","authors":"Huan Yang, Michael Brines, Ulf Andersson","doi":"10.1186/s42234-026-00209-9","DOIUrl":"10.1186/s42234-026-00209-9","url":null,"abstract":"<p><p>High mobility group box 1 protein (HMGB1) is a central mediator of inflammation and pain, but efforts to neutralize it therapeutically have had limited clinical success. This gap suggests that the essential problem is not simply the abundance of extracellular HMGB1, but its accessibility: its availability to assemble into pathogenic complexes, engage receptors such as the receptor for advanced glycation end products (RAGE), enter cells, and deliver inflammatory cargo to the cytosol. Here, a perspective is advanced that integrates HMGB1 biology with the inflammatory reflex and the cholinergic anti-inflammatory pathway. In this framework, HMGB1 promotes inflammatory entry and amplification, whereas acetylcholine, acting through the vagus nerve and alpha7 nicotinic acetylcholine receptors, limits HMGB1 release and uptake of HMGB1-containing complexes. Vagus nerve stimulation therefore emerges as a bioelectronic strategy to restrict upstream access of danger signals to intracellular inflammatory pathways, in addition to suppressing downstream cytokine signaling. This formulation does not alter the established biology of HMGB1; rather, it places existing observations into a unifying model with direct relevance to inflammation and pain.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13292432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148310546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of transcutaneous auricular vagus nerve stimulation or combined vagal and trigeminal nerve stimulation on platelet function and laboratory hemostasis parameters in healthy human subjects. 经皮耳迷走神经刺激或迷走三叉神经联合刺激对健康人血小板功能和实验室止血参数的影响。
IF 6.8
Bioelectronic medicine Pub Date : 2026-06-05 DOI: 10.1186/s42234-026-00208-w
Jared M Huston, Carlos E Bravo-Iñiguez, Julien Papoin, Maaryj Ahmad, Brooke Le, Isabella Mirro, Melanie McWade, Caroline Benner, Alejandro Covalin, Christopher J Czura, Navid Khodaparast, Lionel Blanc
{"title":"Effects of transcutaneous auricular vagus nerve stimulation or combined vagal and trigeminal nerve stimulation on platelet function and laboratory hemostasis parameters in healthy human subjects.","authors":"Jared M Huston, Carlos E Bravo-Iñiguez, Julien Papoin, Maaryj Ahmad, Brooke Le, Isabella Mirro, Melanie McWade, Caroline Benner, Alejandro Covalin, Christopher J Czura, Navid Khodaparast, Lionel Blanc","doi":"10.1186/s42234-026-00208-w","DOIUrl":"10.1186/s42234-026-00208-w","url":null,"abstract":"<p><strong>Background: </strong>Traumatic or surgical hemorrhage causes substantial morbidity and mortality. Electrical vagus nerve stimulation (VNS) reduces traumatic hemorrhage in animal models. VNS targets acetylcholine-producing T lymphocytes in the spleen to increase intracellular calcium within circulating platelets via α7 nicotinic acetylcholine receptors. Elevated calcium levels facilitate platelet activation (priming) after tissue injury to accelerate and increase clot formation that improves hemostasis. Trigeminal nerve stimulation (TNS) also decreases traumatic hemorrhage in mice, but the mechanism remains unknown. Recently, we showed that transcutaneous auricular neurostimulation (tAN; combined auricular VNS and TNS) reduces blood loss and days of menstruation in women with idiopathic or von Willebrand disease related heavy menstrual bleeding. The ability of tAN or transcutaneous auricular VNS (taVNS) to improve platelet function or laboratory hemostasis remains unknown.</p><p><strong>Methods: </strong>Here we performed a prospective, randomized, double-blind, sham-controlled, single-center, first-in-human exploratory trial to determine the safety and efficacy of taVNS or tAN to prime platelets and augment clot formation. Healthy adult subjects received sham stimulation before taVNS or tAN, followed by serial measurements of platelet and hemostasis markers, including platelet functional analysis, thrombin generation, blood counts, coagulation assays, and thromboelastography. Repeated measures one-way ANOVA followed by Bonferroni's test was used for comparisons between three or more time points. Two-tailed paired T-test was used for comparisons between two time points.</p><p><strong>Results: </strong>Administration of taVNS or tAN was well tolerated without observable adverse events during the study period. taVNS or tAN primed platelets via collagen- or ADP-mediated signaling pathways, respectively. taVNS accelerated clot initiation, propagation, and stabilization as measured by thromboelastography. There were no differences in systemic or local thrombin generation, circulating white or red blood cell counts, platelet counts, prothrombin time, partial thromboplastin time, or INR assays after administration of taVNS or tAN.</p><p><strong>Conclusions: </strong>These results provide evidence that taVNS or tAN primes human platelets and taVNS accelerates clotting kinetics as quantified by thromboelastography. taVNS and tAN warrant additional clinical study as therapies for traumatic or surgical hemorrhage and congenital or acquired coagulopathies.</p><p><strong>Trial registration: </strong>This study is registered with the ClinicalTrials.gov database ( http://clinicaltrials.gov ). The registration number is NCT05977946. The study start is 10-31-2023.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148165823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel, wearable, in-ear EEG technology to assess sleep and daytime sleepiness. 一种新颖的、可穿戴的、入耳式脑电图技术,用于评估睡眠和白天困倦。
IF 6.8
Bioelectronic medicine Pub Date : 2026-05-22 DOI: 10.1186/s42234-026-00207-x
Jonathan Berent, Prabhjyot Saini, Andrew X Stewart, Devansh Bheda, Konstantin Borodin, Akshay Paul, Brian Tracey, Caroline Dong, Dmitri Volfson, Derek L Buhl, David B Rye
{"title":"A novel, wearable, in-ear EEG technology to assess sleep and daytime sleepiness.","authors":"Jonathan Berent, Prabhjyot Saini, Andrew X Stewart, Devansh Bheda, Konstantin Borodin, Akshay Paul, Brian Tracey, Caroline Dong, Dmitri Volfson, Derek L Buhl, David B Rye","doi":"10.1186/s42234-026-00207-x","DOIUrl":"10.1186/s42234-026-00207-x","url":null,"abstract":"<p><p>In-ear electroencephalography (EEG) has emerged as a promising alternative to traditional in-laboratory sleep studies, offering greater comfort and practicality. Here we present a novel in-ear EEG system, comparing in-ear recordings against scalp EEG channels acquired concurrently as part of polysomnography (PSG). The study enrolled 16 healthy control participants in a single-visit overnight-plus-daytime design, and 8 participants with central disorders of hypersomnolence (CDH) in a randomized crossover daytime design (medication vs. medication-holiday). For overnight sleep recordings, ear-EEG and scalp EEG sleep staging showed substantial agreement (Cohen's [Formula: see text]). For daytime MWT trials, agreement was moderate (Cohen's [Formula: see text]), reflecting the predominance of wake epochs in this paradigm. For the primary Maintenance of Wakefulness Test (MWT) endpoint of sleep onset latency (SOL), at the per-subject level ([Formula: see text])-averaging across trials as in standard clinical practice-agreement was good (ICC = 0.71, [Formula: see text], MAD = 5.1 min). Among the 37 of 126 trials where both devices detected sleep (approximately 30% of trials), agreement was strong (ICC = 0.82, MAD = 1.9 min), with excellent agreement in healthy controls (ICC = 0.95, MAD = 1.2 min). Overall trial-level agreement across all 126 trials was moderate (ICC = 0.55), reflecting 22 discordant trials in which scalp EEG detected sleep but in-ear EEG did not-predominantly brief, subtle N1 transitions, concentrated in a subset of CDH participants. For overnight sleep architecture ([Formula: see text] healthy controls), total sleep time ([Formula: see text], ICC = 0.85), sleep efficiency ([Formula: see text]), and wake after sleep onset ([Formula: see text]) showed strong agreement, with small systematic biases consistent with reduced N1 detection sensitivity. These findings support the feasibility of in-ear EEG for sleep staging and daytime sleepiness assessment in laboratory settings, and motivate larger confirmatory studies-including home-based longitudinal monitoring-to establish clinical utility, particularly in populations with altered sleep architecture.</p>","PeriodicalId":72363,"journal":{"name":"Bioelectronic medicine","volume":"12 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13195905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147990216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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