Electrical Pulse Stimulation Research Articles

GDF15 Mediates the Effect of Skeletal Muscle Contraction on Glucose-Stimulated Insulin Secretion.

Exercise improves glucose-stimulated insulin secretion through direct interorgan communication. Contracting skeletal muscle releases growth differentiation factor 15 (GDF15), which is required to synergistically enhance glucose-stimulated insulin secretion. GDF15 enhances glucose-stimulated insulin secretion by activating the canonical insulin release pathway. Increased levels of circulating GDF15 after exercise training are related to improvements in β-cell function in patients with type 2 diabetes.

Ion Transporters Involved in Dissipation of Transmembrane Na+ and K+ Gradients in C2C12 Myotubes Triggered by Electrical Pulse Stimulation

Background/Aims: Cultured skeletal muscle cells subjected to electrical pulse stimulation (EPS) are widely employed as an in vitro model of exercising skeletal muscle. Numerous studies demonstrated that sustained excitation of skeletal muscle results in the dissipation of the transmembrane gradient of monovalent cations. During exercises the impending loss of excitability has to be counterbalanced by rapid restoration of the Na+i/K+i ratio. To understand mechanisms of the maintenance of muscle contractility, it is necessary to know which transporters are participated in the dissipation of Na+i and K+i gradients and how to activate Na,K-ATPase for its regeneration. This study was aimed at the identification of ion transporters involved in the dissipation of the transmembrane gradients of Na+ and K+induced by EPS, and Na,K-ATPase isoforms involved in its restoration. Methods: The differentiated C2C12 myotubes were subjected to electrical pulse stimulation in the presence or absence of different ion transport systems inhibitors followed by measurement of intracellular monovalent cations by flame atomic absorption spectrometry. Results: Electrical pulse stimulation of C2C12 myotubes results in the dissipation of Na+i/K+i gradient, which is maintained by α2-Na,K-ATPase. Na-K-2Cl cotransporter (NKCC), voltage-gated Na+ (Nav), and large conductance Ca2+-activated K+ channels (BKCa), and Na/H exchanger (NHE) are involved in the dissipation of this gradient. Suppression of calmodulin-dependent protein kinase II (CaMKII) increases Na+ efflux in EPS-treated C2C12 myotubes. Conclusion: NKCC, Nav, BKCa, and NHE are involved in the dissipation of Na+i/K+i gradient in EPS-treated C2C12 myotubes.

Filamin-A-interacting protein 1 (FILIP1) is a dual compartment protein linking myofibrils and microtubules during myogenic differentiation and upon mechanical stress

Variations in the gene encoding filamin-A-interacting protein 1 (FILIP1) were identified to be associated with a combination of neurological and muscular symptoms. While FILIP1 was shown to regulate motility of brain ventricular zone cells, a process important for corticogenesis, the function of the protein in muscle cells has been less well characterized. The expression of FILIP1 in regenerating muscle fibres predicted a role in early muscle differentiation. Here we analysed expression and localization of FILIP1 and its binding partners filamin-C (FLNc) and microtubule plus-end-binding protein EB3 in differentiating cultured myotubes and adult skeletal muscle. Prior to the development of cross-striated myofibrils, FILIP1 is associated with microtubules and colocalizes with EB3. During further myofibril maturation its localization changes, and FILIP1 localizes to myofibrillar Z-discs together with the actin-binding protein FLNc. Forced contractions of myotubes by electrical pulse stimulation (EPS) induce focal disruptions in myofibrils and translocation of both proteins from Z-discs to these lesions, suggesting a role in induction and/or repair of these structures. The immediate proximity of tyrosylated, dynamic microtubules and EB3 to lesions implies that also these play a role in these processes. This implication is supported by the fact that in nocodazole-treated myotubes that lack functional microtubules, the number of lesions induced by EPS is significantly reduced. In summary, we here show that FILIP1 is a cytolinker protein that is associated with both microtubules and actin filaments, and might play a role in the assembly of myofibrils and their stabilization upon mechanical stress to protect them from damage.

Multisite thalamic recordings to characterize seizure propagation in the human brain.

Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.

Towards optimizing single pulse electrical stimulation: High current intensity, short pulse width stimulation most effectively elicits evoked potentials

BackgroundWhile single pulse electrical stimulation (SPES) is increasingly used to study effective connectivity, the effects of varying stimulation parameters on the resulting cortico-cortical evoked potentials (CCEPs) have not been systematically explored. ObjectiveWe sought to understand the interacting effects of stimulation pulse width, current intensity, and charge on CCEPs through an extensive testing of this parameter space and analysis of several response metrics. MethodsWe conducted SPES in 11 patients undergoing intracranial EEG monitoring using five combinations of current intensity (1.5, 2.0, 3.0, 5.0, and 7.5 mA) and pulse width at each of three charges (0.750, 1.125, and 1.500 μC/phase) to study how CCEP amplitude, distribution, latency, morphology, and stimulus artifact amplitude vary with each parameter. ResultsStimulations with a greater charge or a greater current intensity and shorter pulse width at a given charge generally resulted in greater CCEP amplitudes and spatial distributions, shorter latencies, and increased waveform correlation. These effects interacted such that stimulations with the lowest charge and highest current intensities resulted in greater response amplitudes and spatial distributions than stimulations with the highest charge and lowest current intensities. Stimulus artifact amplitude increased with charge, but this could be mitigated by using shorter pulse widths. ConclusionsOur results indicate that individual combinations of current intensity and pulse width, in addition to charge, are important determinants of CCEP magnitude, morphology, and spatial extent. Together, these findings suggest that high current intensity, short pulse width stimulations are optimal SPES settings for eliciting strong and consistent responses while minimizing charge.

Electrical pulse stimulation-induced muscle contraction alters the microRNA and mRNA profiles of circulating extracellular vesicles in mice.

Extracellular vesicles, such as exosomes, are secreted by skeletal muscle tissues and may play a role in physiological adaptations induced by exercise. Endurance exercise changes the microRNA (miRNA) profile of circulating extracellular vesicles; however, the effects of resistance exercise are unknown. In this study, we examined the effect of resistance exercise as electrical pulse stimulation (EPS)-induced muscle contraction on the miRNA and mRNA profiles of circulating extracellular vesicles in mice using a comprehensive RNA sequencing-based approach. EPS-induced muscle contraction resulted in changes in the miRNA profile of circulating extracellular vesicles. In particular, 90 min after EPS-induced muscle contraction, a considerable increase in expression of muscle-specific microRNAs, such as miR-1, miR-133, and miR-206, was observed. Furthermore, we found that the expression of 208 mRNAs was considerably altered immediately after EPS-induced muscle contraction and that of 267 mRNAs changed considerably after 90 min. Gene ontology enrichment analysis showed that mRNA expression changes in circulating extracellular vesicles after EPS-induced muscle contraction promoted angiogenesis and regulated the immune response. Changes in the properties of circulating extracellular vesicles owing to muscle contraction may play an important role in resistance exercise-induced physiological adaptations.

Effect of electrical stimulation on the content of pAkt in myocyte cell culture under hyperglycemia

Introduction. The problems of studying the molecular mechanisms of pathogenesis, insulin resistance and finding new ways to correct them are still relevant.Aim: To study the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions.Material and Methods. We studied the effect of electrical stimulation on the amount of pAkt in a cell culture of C2C12 mouse myoblasts cultivated under hyperglycemic conditions. Cells were cultured in a medium containing 25 mM glucose and subjected to electrical impulse stimulation for 2, 6, and 24 hours.Results. It has been shown that the cultivation of C2C12 myoblasts in a medium with excess glucose is accompanied by a decrease in the amount of pAkt in cells, while pulsed electrical stimulation from 2 to 6 hours increases the concentration of this enzyme and restores the sensitivity of its phosphorylation pathways to insulin.Conclusions. The results obtained suggest that the contractile activity of muscle cells contributes to the restoration of cell sensitivity to insulin and the ability to absorb glucose, using the same regulatory and transport pathways that are affected i the development of type 2 diabetes.

Quantum Dot Light‐Emitting Synaptic Transistor for Parallel Data Transmission of Diverse Artificial Neural Network

AbstractArtificial synaptic devices serve as the cornerstone of artificial neural networks, much research is devoted to the development of artificial synaptic devices with multiple functions for the future construction of large‐scale artificial neural networks. By adding optical signal output to traditional synaptic devices, the strategy of transforming the devices from a single electrical interconnection to an optoelectronic interconnection is considered to be an effective way to solve the problem of wire cross‐talk in large‐scale artificial neural networks. Herein, a quantum‐dot light‐emitting synaptic transistor capable of dual output of optoelectronic signals by integrating the functions of light‐emitting transistor and synaptic transistor into a single device is demonstrated for the first time. Based on the novel working mechanism and the excellent optoelectronic properties of quantum dots, the device can exhibit dual responses of electrical and optical signals under electrical pulse stimulation. More importantly, some key synaptic functions such as excitatory postsynaptic current, paired pulse facilitation, high‐pass filtering properties, and the transition from short‐term memory to long‐term memory are successfully simulated in the device. In addition, classical conditioned reflex experiments as well as the processes of learning and forgetting are optically and electrically simulated. This work provides a feasible way to realize multivariate artificial neural networks with high integration and optoelectronic interconnection to transmit information, showing great potential in the development of neuromorphic computing in the future.

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation.

Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24h to human myotubes isolated and differentiated from biopsy samples from six morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24h thereafter. Size and concentration of EV subtypes were characterized by nanoparticle tracking analysis, surface markers were examined by flow cytometry and Western blotting, and morphology was confirmed by transmission electron microscopy. Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray, and selected microRNAs (miRs) validated by real time RT-qPCR. The size and concentration of exosomes and MV were unaffected by EPS. Of the 400 miRs identified in the EVs, EPS significantly changed the level of 15 exosome miRs, of which miR-1233-5p showed the highest fold change. The miR pattern of MV was unaffected by EPS. Totally, about 1000 proteins were identified in exosomes and 2000 in MV. EPS changed the content of 73 proteins in exosomes, 97 in MVs, and of these four were changed in both exosomes and MV (GANAB, HSPA9, CNDP2, and ATP5B). By matching the EPS-changed miRs and proteins in exosomes, 31 targets were identified, and among these several promising signaling factors. Of particular interest were CNDP2, an enzyme that generates the appetite regulatory metabolite Lac-Phe, and miR-4433b-3p, which targets CNDP2. Several of the regulated miRs, such as miR-92b-5p, miR-320b, and miR-1233-5p might also mediate interesting signaling functions. In conclusion, we have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of EVs derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.

Transthyretin knockdown recapitulates the insulin-sensitizing effects of exercise and promotes skeletal muscle adaptation to exercise endurance.

Liver transthyretin (TTR) synthesis and release are exacerbated in insulin-resistant states but are decreased by exercise training, in relation to the insulin-sensitizing effects of exercise. We hypothesized that TTR knockdown (TTR-KD) may mimic this exercise-induced metabolic improvement and skeletal muscle remodeling. Adeno-associated virus-mediated TTR-KD and control mice were trained for 8 weeks on treadmills. Their metabolism status and exercise capacity were investigated and then compared with sedentary controls. After treadmill training, the mice showed improved glucose and insulin tolerance, hepatic steatosis, and exercise endurance. Sedentary TTR-KD mice displayed metabolic improvements comparable to the improvements in trained mice. Both exercise training and TTR-KD promoted the oxidative myofiber compositions of MyHC I and MyHC IIa in the quadriceps and gastrocnemius skeletal muscles. Furthermore, training and TTR-KD had an additive effect on running performance, accompanied by substantial increases in oxidative myofiber composition, Ca2+-dependent Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, and the downstream expression of PGC1α as well as the unfolded protein response (UPR) segment of PERK-p-eIF2a pathway activity. Consistent with these findings, electrical pulse stimulation of an in vitro model of chronic exercise (with differentiated C2C12 myoblasts) showed that exogenous TTR protein was internalized and localized in the endoplasmic reticulum, where it disrupted Ca2+ dynamics; this led to decreases in intracellular Ca2+ concentration and downstream pathway activity. TTR-KD may function as an exercise/Ca2+-dependent CaMKII-PGC1α-UPR regulator that upregulates the oxidative myofiber composition of fast-type muscles; it appears to mimic the effect of exercise training on insulin sensitivity-related metabolic improvement and endurance capacity.

Mimicking exercise in vitro - effects of myotube contractions and mechanical stretch on omics.

The number of studies using skeletal muscle (SkM) cell culture models to study exercise in vitro are rapidly expanding. Progressively, more comprehensive analysis methods, such as different omics approaches including transcriptomics, proteomics and metabolomics have been used to examine the intra- and extracellular molecular responses to exercise mimicking stimuli in cultured myotubes. Among other techniques, exercise-like electrical pulse stimulation (EL-EPS) and mechanical stretch of SkM cells are the two most commonly used methods to mimic exercise in vitro. In this mini-review we focus on these two approaches and their effects on the omics of myotubes and/or cell culture media. Furthermore, besides traditional two-dimensional (2D) methods, the use of three-dimensional (3D) SkM approaches are increasing in the field of in vitro exercise mimicry. Our aim with this mini-review is to provide the reader with an up-to-date overview of the 2D and 3D models and the use of omics approaches to study the molecular response to exercise in vitro.

Stimulation of spinal cord according to recorded theta hippocampal rhythm during rat move on treadmill.

Several studies have revealed that after spinal cord injury (SCI), in acute and sub-acute phase the spinal cord neurons below the injury are alive and could stimulate by use of electrical pulses. Spinal cord electrical stimulation could generate movement for paralyzed limbs and is a rehabilitation strategy for paralyzed patients. An innovative idea for controlling spinal cord electrical stimulation onset time is presented in current study. In our method, the time of applying electrical pulse on the spinal cord is according to rat behavioral movement and two movements behaviors are recognized only based on rat EEG theta rhythm on the treadmill line. Briefly, 5 rats were placed on the treadmill and the animals experienced zero or 12m/min speeds. These speeds were recognized based on EEG signals and off-line periodogram analysis. Finally, the electrical stimulation pulses had been applied to the spinal cord if the results of the EEG analysis had detected running behavior. These findings may guide future research in utilizing theta rhythms for the recognition of animal motor behavior and designing electrical stimulation systems based on it.

Effects of Long-Term Physical Activity and BCAA Availability on the Subcellular Associations between Intramyocellular Lipids, Perilipins and PGC-1α.

Cellular skeletal muscle lipid metabolism is of paramount importance for metabolic health, specifically through its connection to branched-chain amino acids (BCAA) metabolism and through its modulation by exercise. In this study, we aimed at better understanding intramyocellular lipids (IMCL) and their related key proteins in response to physical activity and BCAA deprivation. By means of confocal microscopy, we examined IMCL and the lipid droplet coating proteins PLIN2 and PLIN5 in human twin pairs discordant for physical activity. Additionally, in order to study IMCLs, PLINs and their association to peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in cytosolic and nuclear pools, we mimicked exercise-induced contractions in C2C12 myotubes by electrical pulse stimulation (EPS), with or without BCAA deprivation. The life-long physically active twins displayed an increased IMCL signal in type I fibers when compared to their inactive twin pair. Moreover, the inactive twins showed a decreased association between PLIN2 and IMCL. Similarly, in the C2C12 cell line, PLIN2 dissociated from IMCL when myotubes were deprived of BCAA, especially when contracting. In addition, in myotubes, EPS led to an increase in nuclear PLIN5 signal and its associations with IMCL and PGC-1α. This study demonstrates how physical activity and BCAA availability affects IMCL and their associated proteins, providing further and novel evidence for the link between the BCAA, energy and lipid metabolisms.

Versatile electrical stimulator for cardiac tissue engineering-Investigation of charge-balanced monophasic and biphasic electrical stimulations.

The application of biomimetic physical stimuli replicating the in vivo dynamic microenvironment is crucial for the in vitro development of functional cardiac tissues. In particular, pulsed electrical stimulation (ES) has been shown to improve the functional properties of in vitro cultured cardiomyocytes. However, commercially available electrical stimulators are expensive and cumbersome devices while customized solutions often allow limited parameter tunability, constraining the investigation of different ES protocols. The goal of this study was to develop a versatile compact electrical stimulator (ELETTRA) for biomimetic cardiac tissue engineering approaches, designed for delivering controlled parallelizable ES at a competitive cost. ELETTRA is based on an open-source micro-controller running custom software and is combinable with different cell/tissue culture set-ups, allowing simultaneously testing different ES patterns on multiple samples. In particular, customized culture chambers were appositely designed and manufactured for investigating the influence of monophasic and biphasic pulsed ES on cardiac cell monolayers. Finite element analysis was performed for characterizing the spatial distributions of the electrical field and the current density within the culture chamber. Performance tests confirmed the accuracy, compliance, and reliability of the ES parameters delivered by ELETTRA. Biological tests were performed on neonatal rat cardiac cells, electrically stimulated for 4days, by comparing, for the first time, the monophasic waveform (electric field = 5V/cm) to biphasic waveforms by matching either the absolute value of the electric field variation (biphasic ES at ±2.5V/cm) or the total delivered charge (biphasic ES at ±5V/cm). Findings suggested that monophasic ES at 5V/cm and, particularly, charge-balanced biphasic ES at ±5V/cm were effective in enhancing electrical functionality of stimulated cardiac cells and in promoting synchronous contraction.

Phase-based novel quantification of effective connectivity with single pulse electrical stimulations

Phase-based novel quantification of effective connectivity with single pulse electrical stimulations

Loss of differentiation and complexity in the sleeping human brain: a multi-scale analysis

Abstract Complexity, defined as the coexistence of functional differentiation and functional integration is a general property of thalamo-cortical circuits that can be characterized at a multiscale level. Previous studies suggest that local dynamics occurring at the micro/meso-scale, such as sleep-like neuronal bistability, can be responsible for the collapse/emergence of global patterns of complex interactions among brain areas at the macro-scale. Here, we link the two scales by combining, for the first time, intracerebral single pulse electrical stimulation (SPES) with simultaneous invasive recordings (stereo-EEG, SEEG) and scalp high-density EEG (hdEEG) during both wakefulness and sleep. This work includes data collected during presurgical evaluation from 30 epileptic subjects. SEEG was recorded trough ∼150 intracerebral contacts connected to a 192-channel amplifier together with simultaneous scalp recordings using a 256 channels hdEEG. Recordings of simultaneous SEEG and hd-EEG activity were combined with SPES (5 mA, 1/0.5ms, 0.5Hz).100 stimulation sessions were performed by delivering SPES during wakefulness at rest in different areas. 66 stimulation sessions were repeated during NREM sleep (stages N2 or N3). We show that (1) the overall complexity, as assessed by the Perturbational Complexity Index, was significantly higher in wakefulness with respect to NREM (p<0.05) and that (2) the differentiation of the response to SPES, evaluated by performing the Principal Component Analysis across all sessions and comparing the ensuing number of components across states, was significantly higher in wakefulness with respect to NREM over the parietal areas (p<0.05). These results allow linking bistable dynamics (neuronal downstates in the Local Field Potential) and their effects on local cortico-cortical interactions with the overall connectivity and complexity assessed at the scalp level. Importantly, combining multiple stimulation sites across different states strongly suggests that during NREM sleep the reduction of complexity is mainly due to loss of differentiation. Research Category and Technology and Methods Basic Research: 15. Electroencephalography (EEG) Keywords: SEEG, Bistability, Sleep, hd-EEG

Epidural Spinal Cord Stimulation Helps Restore Locomotion in an Individual with Subacute Combined Degeneration: A Case Report

Background: Subacute combined degeneration (SCD) of the spinal cord with corticospinal tract involvement can impair motor functions below the level of the lesion. Case Report: A 63-year-old man developed progressive bilateral lower extremity weakness marked by difficulty standing for more than a second and the inability to ambulate, causing him to become wheelchair-bound. He was diagnosed with SCD. His vitamin B12 level was corrected and he underwent physical therapy. Despite these interventions, he experienced an overall deterioration in his strength examination. He later underwent an epidural spinal cord stimulator trial with pulsed electrical stimulation. With this, he experienced improvement in his lower extremity strength and regained the ability to ambulate independently. Permanent leads were placed with the retained faculty to ambulate with the stimulator turned on. Conclusion: Epidural spinal cord stimulation (SCS) has the potential to improve motor function and restore locomotion in individuals with spinal cord injury from SCD. Key words: Case report, epidural spinal cord stimulation, spinal cord injury, subacute combined degeneration

Variability of Single Pulse Electrical Stimulation Responses Recorded with Intracranial Electroencephalography in Epileptic Patients

Cohort studies of brain stimulations performed with stereo-electroencephalographic (SEEG) electrodes in epileptic patients allow to derive large scale functional connectivity. It is known, however, that brain responses to electrical or magnetic stimulation techniques are not always reproducible. Here, we study variability of responses to single pulse SEEG electrical stimulation. We introduce a second-order probability analysis, i.e. we extend estimation of connection probabilities, defined as the proportion of responses trespassing a statistical threshold (determined in terms of Z-score with respect to spontaneous neuronal activity before stimulation) over all responses and derived from a number of individual measurements, to an analysis of pairs of measurements.Data from 445 patients were processed. We found that variability between two equivalent measurements is substantial in particular conditions. For long ( > ~ 90 mm) distances between stimulating and recording sites, and threshold value Z = 3, correlation between measurements drops almost to zero. In general, it remains below 0.5 when the threshold is smaller than Z = 4 or the stimulating current intensity is 1 mA. It grows with an increase of either of these factors. Variability is independent of interictal spiking rates in the stimulating and recording sites.We conclude that responses to SEEG stimulation in the human brain are variable, i.e. in a subject at rest, two stimulation trains performed at the same electrode contacts and with the same protocol can give discrepant results. Our findings highlight an advantage of probabilistic interpretation of such results even in the context of a single individual.

Genome-wide analysis of a cellular exercise model based on electrical pulse stimulation

Skeletal muscle communicates with other organs via myokines, which are secreted by muscle during exercise and exert various effects. Despite much investigation of the exercise, the underlying molecular mechanisms are still not fully understood. Here, we applied an in vitro exercise model in which cultured C2C12 myotubes were subjected to electrical pulse stimulation (EPS), which mimics contracting muscle. Based on the significantly up- and down-regulated genes in EPS, we constructed an in silico model to predict exercise responses at the transcriptional level. The in silico model revealed similarities in the transcriptomes of the EPS and exercised animals. Comparative analysis of the EPS data and exercised mouse muscle identified putative biomarkers in exercise signaling pathways and enabled to discover novel exercise-induced myokines. Biochemical analysis of selected exercise signature genes in muscle from exercised mice showed that EPS mimics in vivo exercise, at least in part, at the transcriptional level. Consequently, we provide a novel myokine, Amphiregulin (AREG), up-regulated both in vitro and in vivo, that would be a potential target for exercise mimetics.

The management of a Bell's Palsy Diagnosis in a Geriatric Patient Following COVID-19 Vaccination

<h3>Research Objectives</h3> To educate health care professionals about and document the potential unique incidence of Bell's Palsy diagnosis following COVID-19 vaccination during the pandemic while documenting significance of high-volt pulsed electrical stimulation intervention strategies by a physical therapist. <h3>Design</h3> Single subject retrospective case study. <h3>Setting</h3> Private practice physical therapy out patient clinic. <h3>Participants</h3> Retrospective single subject case study, based on diagnosis. <h3>Interventions</h3> A 72-year-old female, independent in all activities of daily living, experienced significant symptoms of Bell's Palsy following a COVID-19 vaccine. Past medical history included idiopathic Bell's Palsy on the contralateral side. Functional difficulties were documented and Facial Disability Index scores obtained. Physical therapy was initiated and utilized electrical stimulation protocol, active and active assistive exercise, and patient education/support. Focus for electrical stimulation included Frontalis, Orbicularis Oculi, Zygomaticus Major and Orbicularis Oris. Significant improvement and a full return to function was documented in 7 weeks. <h3>Main Outcome Measures</h3> Functional tolerances (patient reported), visual/strength improvements, and Facial Disability Index scores. <h3>Results</h3> Patient participation in physical therapy for the treatment of Bell's Palsy following a first dose vaccine for COVIID-19 is documented, with the outcome being full return to function and all social activities. FDI scores improved significantly as well as patient satisfaction scales, and the patient reported full credit to the physical therapy for the recovery, while refusing other interventions that were offered. <h3>Conclusions</h3> This case study presents a unique onset and etiology for a Bell's Palsy in a geriatric patient and contributes to the literature by offering physical therapy interventions with outcome findings. Patient advocacy for obtaining physical therapy was critical and significantly meaningful. Given the unique case of a single subject control, this case may be valuable for clinicians who may be presented with cases in the clinic, or for educational purposes in the classroom. <h3>Author(s) Disclosures</h3> None.