Continuous Electrical Stimulation Research Articles

Repair Engineering of Crystal Structure in van der Waals Materials by Probe Electron Beam.

The advancement of electronic technology has led to increasing research on performance and stability. Continuous electrical pulse stimulation can cause crystal structure changes, affecting performance and accelerating aging. Controlled repair of these defects is crucial. In this study, we investigated crystal structure changes in van der Waals (vdW) InSe crystals under continuous electric pulses by using electron beam lithography (EBL) and spherical aberration corrected transmission electron microscopy (Cs-TEM). Results show that electrical pulses induce amorphous regions in the InSe lattice, increasing the device resistance. We used Cs-STEM probe scanning for precise repair, abbreviated SPRT, to optimize device performance. SPRT is related to electric fields induced by the electron beam and can be applied to other 2D materials like α-In2Se3 and CrSe2, offering a potential approach to extend device lifespan.

Interventional neurorehabilitation for glioma patients: A systematic review

Abstract Harnessing the neuroplastic potential of the human brain is being increasingly recognized as an important neuro-oncological paradigm to facilitate safe resection of brain tumors while preserving neurological function and quality of life. Interventional neurorehabilitation, employing both invasive and noninvasive neuromodulation techniques, represents an important emerging therapeutic strategy to induce or enhance neural plasticity to promote functional recovery in brain tumor patients. This study aimed to conduct a comprehensive review of interventional neurorehabilitation techniques for glioma patients. Methods: In accordance with PRISMA guidelines, searches of Medline, Embase, Web of Science, APA PsycINFO, and Cochrane were undertaken from database inception to November 28, 2023. Studies reporting on neuromodulation applied to glioma patients were included. Results: Seven studies reporting findings from 118 patients met the inclusion criteria. Three neuromodulation techniques were identified and included transcranial magnetic stimulation (TMS) reported in 5 out of 7 (71.4%) studies; transcranial direct current stimulation (tDCS); and continuous cortical electrical stimulation (cCES) using grid electrodes, reported in one study each. All studies applying noninvasive stimulation to ameliorate postoperative deficits demonstrated an improvement on at least one outcome measure. The 2 studies applying tDCS and cCES to induce plasticity reported evidence of functional reorganization. Conclusions: There is emerging evidence of benefits of neuromodulation to improve postoperative outcome in glioma patients. In the current literature, noninvasive stimulation has shown to have a favorable safety profile. Large-scale, double-blind, sham-controlled trials are warranted to further investigate the effectiveness of these interventions for modulating different cognitive networks in patients undergoing glioma surgery.

Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes

Background: Cardiomyocytes (CMs) induced from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and other non-cardiomyocytes. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart. Aim: Create engineered heart tissue (EHT) with left and right ventricular phenotype from hiPSCs by intervening with specific concentrations of RA during hiPSC differentiation towards CM. Methods: hiPSC were derived by reprogramming skin fibroblasts and erythroid progenitors. Different concentrations of RA (Control without RA, LowRA with 0.05 μM and HighRA with 0.1 μM) were administered during third to sixth days of the differentiation process. EHTs were generated by assembling CMs derived from hiPSC (hiPSC-CM) at high cell density in a low collagen hydrogel. EHTs were further matured and grown in a customized biomimetic tissue culture system, that provides continuous electrical stimulation, medium agitation and stretch. Finally, RNA extraction and tissue fixation were performed on CMs and EHTs for RT-qPCR and immunofluorescence staining analysis, while RNA sequencing was conducted on EHTs to examine how RA affects gene expression associated with function and structure of EHTs. Results: HighRA-hiPSC-CMs exhibited highest expression of maturity genes MYH7 and cTnT. The expression of TBX5, NKX2.5 and CORIN, which are transcription factors associated with left ventricular development, was also the highest in the HighRA-hiPSC-CM. The expression of TBX5 and NKX2.5 was also found to be highest in the HighRA-EHTs, while expression of right ventricular transcrition factors TBX20 and ISL1 was highest in control-EHTs. RNAseq of EHTs showed augmented extracellular matrix gene expression in HighRA-EHTs. The HighRA-EHTs were functionally most similar to left ventricle with the highest contraction force, the lowest beating frequency, and the highest sensitivity to hypoxia and isoprenaline. Conclusion: By interfering with the differentiation process of hiPSC with a specific concentration of RA at a specific time, we were able to successfully induce CMs and EHT with a phenotype similar to that of the left ventricle or right ventricle. Our research paves the way for future studies on in vitro left ventricular or right ventricular function, personalized drug screening, and precision medicine. German Center for Cardiovascular Research (DZHK81Z0600207 to D.M. and P.S.) China Scholarship Council (CSC202108410141) and Henan Provincial Medical Science and Technology Research Project. This is the full abstract presented at the American Physiology Summit 2024 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.

Deep brain stimulation: the current and future potential for people with Parkinson's

Parkinson's disease is the fastest growing neurological condition in the world with no cure; therefore, choosing the correct treatment to manage the patient's symptoms and prolonging their quality of life is of the utmost importance. Deep brain stimulation, an established methodology involving continuous electrical stimulation to the brain through surgically implanted electrodes, can present an effective option, but careful patient selection is needed to optimise outcomes. Here, Francesca Ramadan presents an overview of the current impact of deep brain stimulation and the ways in which its potential might be maximised in the future.

Continuous peripheral electrical nerve stimulation improves cardiac function via autonomic nerve regulation in MI rats

BackgroundPeripheral electrical nerve stimulation (PENS) reportedly improves cardiac function after myocardial ischemia (MI) by rebalancing the cardiac autonomic nervous system. The dynamic and continuous influence of PENS on autonomic and cardiac function based on cardiac self-repair is not well understood. ObjectivesThis study aimed to explore the relationship between autonomic nervous balance and functional cardiac repair after MI and to clarify the optimal acupoint selection and time course for PENS. MethodsThe activities of the superior cervical cardiac sympathetic nerve and vagus nerve were recorded to evaluate the autonomic tone directly. The pressure-volume loop system was used for left ventricular diastolic and systolic function. Noninvasive continuous electrocardiography and echocardiography were performed to analyze heart rate, heart rate variability, and left ventricular function. The effect of continuous PENS (cPENS) or instant PENS (iPENS) on autonomic and cardiac indications was tested. ResultsSympathetic nerve activity and vagus nerve activity increased as compensatory self-regulation on days 7 and 14 post-MI, followed by an imbalance of autonomic tone and cardiac dysfunction on day 28. cPENS at acupoint PC6 maintained autonomic hyperexcitability, improved myocardial systolic and diastolic abilities, and reduced myocardial fibrosis on day 28 post-MI, whereas cPENS at acupoint ST36 had a limited effect. Both iPENS at PC6 and ST36 improved the autonomic and cardiac function of rats in the cPENS groups. ConclusionRats showed autonomic fluctuations and cardiac dysfunction 28 days post-MI. cPENS produced sympathomimetic action to sustain cardiac self-compensation, but with acupoint specificity. On the basis of cPENS, iPENS evoked autonomic regulation and cardiac benefits without acupoint differentiation.

Investigation on Synaptic Adaptation and Fatigue in ZnO/HfZrO-Based Memristors under Continuous Electrical Pulse Stimulation

This study investigates the behavior of memristive devices characterized by oxygen-deficient ZnO and HfZrO films under continuous pulse stimulation. This dynamic reflects the adaptability observed in neural synapses when repeatedly subjected to stress, ultimately resulting in a mitigated response to pressure. Observations show that the conductivity of memristors increases with the augmentation of continuous electrical pulses. However, the momentum of this growth trend gradually diminishes, highlighting the devices’ capability to adapt to repetitive pressure. This adjustment correlates with the transition of biological synapses from short-term to persistent memory stages, aligning with the principles of the Ebbinghaus memory model. The architecture of memristors, integrating ZnO and HfZrO in a layered manner, holds promising prospects in replicating the inherent synaptic features found in biological organisms.

Accelerating wound healing with flexible zinc ion microbatteries coupled with endogenous electrical fields

Wound healing is an important physiological process in living organisms, involving the migration and proliferation of cells in the endogenous electric field (EEF). Continuous and stable electrical stimulation by an external power supply can effectively mimic the EEF, accelerating the biological processes involved in wound healing. However, the clumsiness of conventional external power supplies and the unstable voltage output of novel power supplies greatly limit the application of electric fields for wound healing. Here we demonstrate the use of a flexible and wearable microbattery for wound healing. The annular electrode is designed to generate an annular electric field in the same direction as the EEF of the wound, allowing for faster, more uniform fibroblast migration, proliferation, and transdifferentiation processes, thus accelerating wound healing. Studies on rats show that skin wounds given a stable electric field using aqueous Zn-MnO2 microbatteries with an operating voltage of 1.5 V healed completely within 6 days, while the blank control group took 10 days or longer. Further, the series connection of microbatteries can match wounds of different areas, enabling rapid healing. These advantages make flexible microbatteries highly promising for practical applications in the biomedical field.

Combined repetitive facilitative exercise under continuous neuromuscular electrical stimulation and task-oriented training for hemiplegic upper extremity during convalescent phase after stroke: before-and-after feasibility trial.

Whereas repetitive facilitative exercise (RFE) affects primarily recovery of motor impairment after stroke, task-oriented training (TOT) focuses on facilitating daily use of the affected upper extremity. However, feasibility of combined RFE and TOT has not been reported. We originated "task-oriented RFE," as a new combination therapy for patients with hemiplegic upper extremity after subacute stroke, to examine its feasibility in convalescent rehabilitation wards. This is a before-and-after pilot study. Eight patients with hemiplegic upper extremity after subacute stroke received the task-oriented RFE program for 6 weeks at 80 min per day (20-60 min of TOT applied after 60-20 min of RFE under continuous neuromuscular electrical stimulation) in a convalescent rehabilitation ward. In the current program, we introduced the Aid for Decision-making in Occupation Choice (ADOC) iPad application as a goal-setting method for determining tasks. Feasibility was assessed with adherence to the protocol, adverse events in response to the intervention, and preliminary efficacy. Motor functions, amount of use and quality of movement in the hemiparetic upper extremity, and satisfaction of the patients were evaluated with Fugl-Meyer Assessment (FMA), the Action Research Arm Test (ARAT), the motor activity log (MAL) for the amount of use (AOU) and quality of movement (QOM) of the paralyzed hand, and ADOC. All participants accomplished the program, which was implemented as originally planned; neither nonattendance nor an adverse event occurred during the study. Favorable outcomes were obtained with all measures; mean changes in FMA, ARAT in the dominant hand, MAL-AOU, and MAL-QOM were greater than minimal clinically important differences. Mean changes in ADOC were greater than the minimal detectable change. The task-oriented RFE program was safe, well-tolerated, beneficial, and feasible within 80 min a day of occupational therapy, which means also within the procedural constraints of the Japanese health insurance system during the convalescent phase. Future studies are warranted to examine whether combined RFE and TOT enhances the efficacies of each program alone.

Enhancing regeneration and repair of long-distance peripheral nerve defect injuries with continuous microcurrent electrical nerve stimulation.

Peripheral nerve injuries, especially those involving long-distance deficits, pose significant challenges in clinical repair. This study explores the potential of continuous microcurrent electrical nerve stimulation (cMENS) as an adjunctive strategy to promote regeneration and repair in such cases. The study initially optimized cMENS parameters and assessed its impact on Schwann cell activity, neurotrophic factor secretion, and the nerve regeneration microenvironment. Subsequently, a rat sciatic nerve defect-bridge repair model was employed to evaluate the reparative effects of cMENS as an adjuvant treatment. Functional recovery was assessed through gait analysis, motor function tests, and nerve conduction assessments. Additionally, nerve regeneration and denervated muscle atrophy were observed through histological examination. The study identified a 10-day regimen of 100uA microcurrent stimulation as optimal. Evaluation focused on Schwann cell activity and the microenvironment, revealing the positive impact of cMENS on maintaining denervated Schwann cell proliferation and enhancing neurotrophic factor secretion. In the rat model of sciatic nerve defect-bridge repair, cMENS demonstrated superior effects compared to control groups, promoting motor function recovery, nerve conduction, and sensory and motor neuron regeneration. Histological examinations revealed enhanced maturation of regenerated nerve fibers and reduced denervated muscle atrophy. While cMENS shows promise as an adjuvant treatment for long-distance nerve defects, future research should explore extended stimulation durations and potential synergies with tissue engineering grafts to improve outcomes. This study contributes comprehensive evidence supporting the efficacy of cMENS in enhancing peripheral nerve regeneration.

Unilateral neurostimulation-assisted cervical epidural anesthesia for upper limb surgeries—a case series

BackgroundThe role of neurostimulation-aided cervical epidural anesthesia (CEA) in shoulder surgery has been described in the literature. The use of nerve stimulators and the infusion of local anesthetic (LA) in the cervical epidural space has also been mentioned. Epidural needle rotation prior to insertion of the catheter is not described, and it is not clear if general anesthesia was administered in these cases.Case presentationIn this case series, we performed CEA at the level of C7-T1 in 12 patients undergoing various surgeries on the proximal open shoulder and mid humerus after informed consent. Ipsilateral motor responses elicited by continuous electrical stimulation were used to identify lateralization of the epidural catheter tip. The placement of catheters was confirmed under an intraoperative image intensifier. Using the median approach at the level of C7-T1, an ipsilateral twitch was noted in all patients. Neurostimulation persisted with an advancement of stimulating catheter 3–4 cm in the cervical epidural space in all patients. A cervical radiograph confirmed the placement of an ipsilateral catheter and contrast injection there upon revealing the spread of the LA agent. All patients had successful awake shoulder and mid-humerus surgeries under sole cervical epidural anesthesia as evidenced by the absence of pain response at the surgical incision.ConclusionsIpsilateral CEA can be offered for unilateral upper limb surgeries. Low volumes of LA can be injected after precise placement of the tip of the catheter corresponding to the level of surgical incision.

Wirelessly powered deformable electronic stent for noninvasive electrical stimulation of lower esophageal sphincter

Electrical stimulation is a promising method to modulate gastrointestinal disorders. However, conventional stimulators need invasive implantation and removal surgeries associated with risks of infection and secondary injuries. Here, we report a battery-free and deformable electronic esophageal stent for wireless stimulation of the lower esophageal sphincter in a noninvasive fashion. The stent consists of an elastic receiver antenna infilled with liquid metal (eutectic gallium-indium), a superelastic nitinol stent skeleton, and a stretchable pulse generator that jointly enables 150% axial elongation and 50% radial compression for transoral delivery through the narrow esophagus. The compliant stent adaptive to the dynamic environment of the esophagus can wirelessly harvest energy through deep tissue. Continuous electrical stimulations delivered by the stent in vivo using pig models significantly increase the pressure of the lower esophageal sphincter. The electronic stent provides a noninvasive platform for bioelectronic therapies in the gastrointestinal tract without the need for open surgery.

Biomimetic cultivation of atrial tissue slices as novel platform for in-vitro atrial arrhythmia studies

Living myocardial slices (LMS) are beating sections of intact human myocardium that maintain 3D microarchitecture and multicellularity, thereby overcoming most limitations of conventional myocardial cell cultures. We introduce a novel method to produce LMS from human atria and apply pacing modalities to bridge the gap between in-vitro and in-vivo atrial arrhythmia studies. Human atrial biopsies from 15 patients undergoing cardiac surgery were dissected to tissue blocks of ~ 1 cm2 and cut to 300 µm thin LMS with a precision-cutting vibratome. LMS were placed in a biomimetic cultivation chamber, filled with standard cell culture medium, under diastolic preload (1 mN) and continuous electrical stimulation (1000 ms cycle length (CL)), resulting in 68 beating LMS. Atrial LMS refractory period was determined at 192 ± 26 ms. Fixed rate pacing with a CL of 333 ms was applied as atrial tachyarrhythmia (AT) model. This novel state-of-the-art platform for AT research can be used to investigate arrhythmia mechanisms and test novel therapies.

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway

BackgroundVagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. ObjectiveTo investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. MethodsRats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. ResultsIntact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. ConclusionContinuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

Combining Electrostimulation with Impedance Sensing to Promote and Track Osteogenesis within a Titanium Implant

(1) Background: Electrical stimulation is a promising alternative to promote bone fracture healing but with the limitation of tracking the osteogenesis progress in vivo. To overcome this issue, we present an opportunity to combine the electrical stimulation of a commercial titanium implant, which promotes osteogenesis within the fracture, with a real-time readout of the osteogenic progress by impedance sensing. This makes it possible to adjust the electrical stimulation modalities to the individual patient's fracture healing process. (2) Methods: In detail, osteogenic differentiation of several cell types was monitored under continuous or pulsatile electrical stimulation at 0.7 V AC/20 Hz for at least seven days on a titanium implant by electric cell-substrate impedance sensing (ECIS). For control, chemical induction of osteogenic differentiation was induced. (3) Results: The most significant challenge was to discriminate impedance changes caused by proliferation events from those initiated by osteogenic differentiation. This discrimination was achieved by remodeling the impedance parameter Alpha (α), which increases over time for pulsatile electrically stimulated stem cells. Boosted α-values were accompanied by an increased formation of actin stress fibers and a reduced expression of the focal adhesion kinase in the cell periphery; morphological alterations known to occur during osteogenesis. (4) Conclusions: This work provided the basis for developing an effective fracture therapy device, which can induce osteogenesis on the one hand, and would allow us to monitor the induction process on the other hand.

The effects of acute normobaric hypoxia on vestibular-evoked balance responses in humans.

Hypoxia influences standing balance and vestibular function. The purpose here was to investigate the effect of hypoxia on the vestibular control of balance. Twenty participants (10 males; 10 females) were tested over two days (normobaric hypoxia and normoxia). Participants stood on a force plate (head rotated leftward) and experienced random, continuous electrical vestibular stimulation (EVS) during trials of eyes open (EO) and closed (EC) at baseline (BL), after 5 (H1), 30 (H2) and 55-min (H3) of hypoxia, and 10-min into normoxic recovery (NR). Vestibular-evoked balance responses were quantified using cumulant density, coherence, and gain functions between EVS and anteroposterior forces. Oxyhemoglobin saturation, end-tidal oxygen and carbon dioxide decreased for H1-3 compared to BL; however, end-tidal carbon dioxide remained reduced at NR with EC (p≤0.003). EVS-AP force peak-to-peak amplitude was lower at H3 and NR than at BL (p≤0.01). At multiple frequencies, EVS-AP force coherence and gain estimates were lower at H3 and NR than BL for females; however, this was only observed for coherence for males. Overall, vestibular-evoked balance responses are blunted following normobaric hypoxia >30 min, which persists into NR and may contribute to the reported increases in postural sway.

Pulse Capacitive Coupling Electric Field Regulates Cell Migration, Proliferation, Polarization, and Vascularization to Accelerate Wound Healing.

Objectives: Accelerating wound healing using continuous exogenous electrical stimulation is limited due to some serious side effects, including thermal damage. Many previous studies based on direct current contact stimulation may cause chemical burns or blisters, thereby increasing patients suffering. The aim of this study was to develop a safer and more convenient pulse capacitive coupling electrical field (PCCEF) stimulation to accelerate wound healing. Approach: A PCCEF-generating platform was self-designed to facilitate wound healing. The promoting effects and appropriate pulse width were explored by applying PCCEFs (54 mV/mm, 60 Hz) of different pulse widths to various cells involved in wound healing and mouse models for 2 h daily. Results: PCCEFs of ≥10 μs pulse width showed marked promotion of the migration and proliferation of human dermal fibroblasts and HaCaT cells, enhanced the M2-type polarization and YPA/TAZ expression of macrophages, and facilitated the wound healing of mouse models. Comprehensive histological results suggested that PCCEF of 100 μs pulse width exerted the most positive effects. Innovation: A safe and effective PCCEF was developed to promote wound healing, which prevented prolonged stimulation and averted direct contact. Conclusion: PCCEF accelerated wound healing, especially at the optimal 100 μs pulse width, and was expected to be translated to clinical application, helping alleviate patient suffering, while reducing side effects.

Abstract 12829: Biomimetic Cardiac Tissue Culture Model to Emulate Cardiac Physiology and Pathophysiology Ex Vivo

Introduction: There is an urgent need for a reliable in vitro system to accurately replicate the cardiac physiological and pathological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Our group developed a culture system for pig/human heart slices that enables functional and structural viability for 6 days using continuous electrical stimulation and enriched media. This culture system can more reliably detect cardiotoxic effects compared to hiPSC-CMs. However, by day 10, the slices undergo cardiomyocyte dedifferentiation and fibrotic remodeling making them inadequate for long-term drug testing. Hypothesis: To determine whether incorporating physiological mechanical, and humoral cues within the culture system can fully emulate cardiac physiology and pathophysiology in culture. Methods and results: We have developed a novel c ardiac t issue c ulture m odel (CTCM) that can electro-mechanically stimulate heart slices with physiological (0 to 80 mmHg) preload and afterload during each cardiac cycle. After 12 days in culture, this approach alone partially improved the viability of heart slices but did not maintain the structural integrity. Therefore, following a small molecule screening, we found that incorporating 100 nM tri-iodothyronine (T3) and 1 μM dexamethasone (Dex) into our culture media preserved the structural integrity of the slices for 12 days. When combined with T3/Dex, the CTCM system fully maintained the transcriptional profile, viability, metabolic activity, and structural integrity for 12 days at the same levels as fresh heart tissue. Furthermore, to test the ability of the CTCM to emulate cardiac hypertrophy, increasing the peak pressure to 140 mmHg resulted in induced cardiac hypertrophy within 6 days in culture as indicated by a 3-fold increase in NT-ProBNP release, increased NFATC4 and P-ERK expression, and increased cardiomyocyte cross-sectional area. Conclusions: This new CTCM heart slice culture system incorporating physiological electromechanical and humoral cues can emulate cardiac physiology and pathophysiology in culture, which could be used for drug screening for new therapeutics and cardiotoxins.

The influence of reduced foot dorsum cutaneous sensitivity on the vestibular control of balance.

Foot sole cooling increases vestibular-evoked balance responses, but less is known about foot dorsum temperature alterations. The purpose was to determine whether decreasing cutaneous receptor sensitivity via foot dorsum cooling modulates the vestibular control of balance. Eighteen participants (9 males; 9 females) stood quietly on a force plate with feet together, eyes closed, and head rotated leftward during 4, 90-s trials (2 control; 2 cooled) of continuous electrical vestibular stimulation (EVS). Icepacks placed on the dorsum of both feet for 15min induced cooling and remained throughout the EVS trials. Monofilament testing was performed at multiple locations before and after cooling to determine tactile detection thresholds. T-type thermocouples monitored skin temperature over the tibialis anterior, soleus, foot dorsum and arch of the right leg. Vestibular-evoked balance responses were characterized using time (cumulant density) and frequency (coherence and gain) domain analyses to determine the relationship between the EVS input and motor output (anteroposterior force-AP force; right medial gastrocnemius electromyography-MG EMG). Skin temperature of the foot dorsum and arch decreased ~ 70 and 15%, respectively during cooling (p < 0.05), but was unaltered at other locations (p ≥ 0.10). Detection thresholds for the foot dorsum increased following cooling (p < 0.05). Surprisingly, cooling reduced EVS-AP force and EVS-MG EMG coherence and gain at multiple frequencies, and peak-to-peak amplitude compared to control (p < 0.05). Our results indicate that vestibular-driven balance responses are reduced following foot dorsum cooling, likely owing to alterations in cutaneous mechanoreceptor sensitivity and subsequent alterations in the transformation of vestibular cues for balance control.

Randomised, controlled crossover trial of intermittent and continuous transcutaneous electrical stimulation of the genioglossus muscle for obstructive sleep apnoea

PurposeContinuous transcutaneous electrical stimulation (CTES) of the genioglossus muscle may benefit patients with obstructive sleep apnoea (OSA). However, the therapeutic value of intermittent transcutaneous electrical stimulation (ITES) for OSA is...