Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

BACKGROUND: Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. RESULTS: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. CONCLUSION: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Chaperone mediated autophagy contributes to the newly synthesized histones H3 and H4 quality control.

Although there are several pathways to ensure that proteins are folded properly in the cell, little is known about the molecular mechanisms regulating histone folding and proteostasis. In this work, we identified that chaperone-mediated autophagy (CMA) is the main pathway involved in the degradation of newly synthesized histones H3 and H4. This degradation is finely regulated by the interplay between HSC70 and tNASP, two histone interacting proteins. tNASP stabilizes histone H3 levels by blocking the direct transport of histone H3 into lysosomes. We further demonstrate that CMA degrades unfolded histone H3. Thus, we reveal that CMA is the main degradation pathway involved in the quality control of histone biogenesis, evidencing an additional mechanism in the intricate network of histone cellular proteostasis.

Non-invasive phrenic nerve stimulation to avoid ventilator-induced diaphragm dysfunction in critical care.

BACKGROUND: Diaphragm muscle atrophy during mechanical ventilation begins within 24 h and progresses rapidly with significant clinical consequences. Electrical stimulation of the phrenic nerves using invasive electrodes has shown promise in maintaining diaphragm condition by inducing intermittent diaphragm muscle contraction. However, the widespread application of these methods may be limited by their risks as well as the technical and environmental requirements of placement and care. Non-invasive stimulation would offer a valuable alternative method to maintain diaphragm health while overcoming these limitations. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. Respiratory pressure and flow, diaphragm electromyography and mechanomyography, and ultrasound visualization were used to assess the diaphragmatic response to stimulation. The electrode positions and stimulation parameters were systematically varied in order to investigate the influence of these parameters on the ability to induce diaphragm contraction with non-invasive stimulation. RESULTS: We demonstrate that non-invasive capture of the phrenic nerve is feasible using surface electrodes without the application of pressure, and characterize the stimulation parameters required to achieve therapeutic diaphragm contractions in healthy volunteers. We show that an optimal electrode position for phrenic nerve capture can be identified and that this position does not vary as head orientation is changed. The stimulation parameters required to produce a diaphragm response at this site are characterized and we show that burst stimulation above the activation threshold reliably produces diaphragm contractions sufficient to drive an inspired volume of over 600 ml, indicating the ability to produce significant diaphragmatic work using non-invasive stimulation. CONCLUSION: This opens the possibility of non-invasive systems, requiring minimal specialist skills to set up, for maintaining diaphragm function in the intensive care setting.

Effect of Rest Interval Between Sets in the Muscle Function During a Sequence of Strength Training Exercises for the Upper Body.

ABSTRACT: Matos, F, Ferreira, B, Guedes, J, Saavedra, F, Reis, VM, and Vilaça-Alves, J. Effect of rest interval between sets in the muscle function during a sequence of strength training exercises for the upper body. J Strength Cond Res 35(6): 1628-1635, 2021-The objective of this study was to observe the ideal recovery time between sets and exercises, for both chest and back, which allowed for maintaining muscle function with the initial load previously established. Sixty young men recreationally trained in strength training (ST) were divided into 2 groups: (a) 30 subjects were included in the GC group (the group that performed ST for the chest) and (b) 30 subjects were included in the GB group (the group that performed ST for the back). Each group was submitted to 3 experimental sessions, performing an ST sequence with 3 sets of 8 repetition maximum: GC performed a chest barbell press (CBP), an inclined CBP, and a chest butterfly; GB performed a lat pull-down, a back row, and a shoulder extension on the high pulley. The experimental sessions differed in rest time between sets performed (60, 90, and 120 seconds). For both groups in each sequence, significantly higher numbers of repetitions were observed with the rest time of 120 seconds relative to the rest time of 90 seconds (p = 0.004), 120 seconds in relation to the rest time of 60 seconds (p = 0.001), and in the rest interval of 90 seconds in relation to the rest time of 60 seconds (p < 0.0001). The results showed that 120 seconds was sufficient to maintain muscle function and perform the total number of repetitions per set. The data seem to show that for the ST methodology applied, it is not appropriate to assume that a certain relative intensity will translate into a similar number of repetitions in different exercises, especially with shorter rest intervals such as 60 and 90 seconds.

PP32 and SET/TAF-Iß proteins regulate the acetylation of newly synthesized histone H4.

Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade. In addition to known binding partners Hsp90 and Hsp70, we also identify for the first time two subunits of the histone acetyltransferase inhibitor complex (INHAT): PP32 and SET/TAF-Iß. We show that both proteins function to prevent HAT1-mediated H4 acetylation in vitro. When PP32 and SET/TAF-Iß protein levels are down-regulated in vivo, we detect hyperacetylation on lysines 5 and 12 and other H4 lysine residues. Notably, aberrantly acetylated H4 is less stable and this reduces the interaction with Hsp90. As a consequence, PP32 and SET/TAF-Iß depleted cells show an S-phase arrest. Our data demonstrate a novel function of PP32 and SET/TAF-Iß and provide new insight into the mechanisms regulating acetylation of newly synthesized histone H4.

New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival.

Comparative modeling of the DNA-binding domain of human HSF1 facilitated the prediction of possible binding pockets for small molecules and definition of corresponding pharmacophores. In silico screening of a large library of lead-like compounds identified a set of compounds that satisfied the pharmacophoric criteria, a selection of which compounds was purchased to populate a biased sublibrary. A discriminating cell-based screening assay identified compound 001, which was subjected to systematic analysis of structure-activity relationships, resulting in the development of compound 115 (IHSF115). IHSF115 bound to an isolated HSF1 DNA-binding domain fragment. The compound did not affect heat-induced oligomerization, nuclear localization and specific DNA binding but inhibited the transcriptional activity of human HSF1, interfering with the assembly of ATF1-containing transcription complexes. IHSF115 was employed to probe the human heat shock response at the transcriptome level. In contrast to earlier studies of differential regulation in HSF1-naïve and -depleted cells, our results suggest that a large majority of heat-induced genes is positively regulated by HSF1. That IHSF115 effectively countermanded repression in a significant fraction of heat-repressed genes suggests that repression of these genes is mediated by transcriptionally active HSF1. IHSF115 is cytotoxic for a variety of human cancer cell lines, multiple myeloma lines consistently exhibiting high sensitivity.

Use of a Single Wireless IMU for the Segmentation and Automatic Analysis of Activities Performed in the 3-m Timed Up & Go Test.

Falls represent a major public health problem in the elderly population. The Timed Up & Go test (TU & Go) is the most used tool to measure this risk of falling, which offers a unique parameter in seconds that represents the dynamic balance. However, it is not determined in which activity the subject presents greater difficulties. For this, a feature-based segmentation method using a single wireless Inertial Measurement Unit (IMU) is proposed in order to analyze data of the inertial sensors to provide a complete report on risks of falls. Twenty-five young subjects and 12 older adults were measured to validate the method proposed with an IMU in the back and with video recording. The measurement system showed similar data compared to the conventional test video recorded, with a Pearson correlation coefficient of 0.9884 and a mean error of 0.17 ± 0.13 s for young subjects, as well as a correlation coefficient of 0.9878 and a mean error of 0.2 ± 0.22 s for older adults. Our methodology allows for identifying all the TU & Go sub­tasks with a single IMU automatically providing information about variables such as: duration of sub⁻tasks, standing and sitting accelerations, rotation velocity of turning, number of steps during walking and turns, and the inclination degrees of the trunk during standing and sitting.

Effect of Cold-Water Immersion on Elbow Flexors Muscle Thickness After Resistance Training.

Matos, F, Neves, EB, Rosa, C, Reis, VM, Saavedra, F, Silva, S, Tavares, F, and Vilaça-Alves, J. Effect of cold-water immersion on elbow flexors muscle thickness after resistance training. J Strength Cond Res 32(3): 756-763, 2018-Cold-water immersion (CWI) is commonly applied to speed up the recovery process after exercise. Muscle damage may induce a performance reduction and consequence of the intramuscular pressure induced by the muscular swelling. The aim of the study was to verify the CWI effects on muscle thickness (MT) behavior of the elbow flexors after a strength training (ST) protocol. Eleven men were submitted to an ST, performed in 2 different weeks. In one of the weeks, subjects experienced a passive recovery. In the other, subjects were submitted to a CWI (20 minutes at 5-10° C). Ultrasound (US) images were taken before, after, as well as 24, 48, and 72 hours after exercise, to evaluate the MT. Muscle thickness in both exercise arm (EA) and control arm (CA) was significantly higher 48 and 72 hours after exercise when subjects were submitted to a passive recovery compared with the CWI (p = 0.029, p = 0.028, p = 0.009, and p = 0.001, 48 hours, 72 hours, EA, and CA, respectively). When each arm was analyzed with or without using CWI individually, significantly higher MT was observed in the EA with CWI: before exercise in relation to 72 hours after exercise (p = 0.042) and after exercise in relation to the other measurements (p = 0.003, p = 0.003, p = 0.038, and p < 0.0001, before exercise and 24, 48, 72 hours after exercise, respectively). The evaluation of MT by US provides evidence that CWI after ST (and 24 hours after exercise) may reduce muscle swelling in the postexercise days when compared with a passive recovery. Seems to be a paradox between the uses of CWI for an acute reduction of muscle swelling.

Methylation of histone H3 lysine 9 occurs during translation.

Histone post-translational modifications are key contributors to chromatin structure and function, and participate in the maintenance of genome stability. Understanding the establishment and maintenance of these marks, along with their misregulation in pathologies is thus a major focus in the field. While we have learned a great deal about the enzymes regulating histone modifications on nucleosomal histones, much less is known about the mechanisms establishing modifications on soluble newly synthesized histones. This includes methylation of lysine 9 on histone H3 (H3K9), a mark that primes the formation of heterochromatin, a critical chromatin landmark for genome stability. Here, we report that H3K9 mono- and dimethylation is imposed during translation by the methyltransferase SetDB1. We discuss the importance of these results in the context of heterochromatin establishment and maintenance and new therapeutic opportunities in pathologies where heterochromatin is perturbed.

Influence of a Personal Trainer on Self-selected Loading During Resistance Exercise.

Dias, MRC, Simao, RF, Saavedra, FJF, and Ratamess, NA. Influence of a personal trainer on self-selected loading during resistance exercise. J Strength Cond Res 31(7): 1925-1930, 2017-The purpose of this study was to compare differences in muscle strength and self-selected resistance training intensities between trained subjects who trained under the supervision of a personal trainer (PT) and those who trained without supervision (WoPT). Twenty-one trained subjects, men (n = 12) and women (n = 9), completed 3 sessions (separated by 48 hours) in the following sequence: first session, self-selected intensity assessment consisting of performance of 3 sets of 10 repetitions for the leg press (LP), bench press (BP), leg extension (LE), and arm curl (AC) exercises with self-selected load; second session, a 1 repetition maximum (1RM) test to determine subjects' maximal strength in the 4 exercises; and third session, a 10RM test to determine the maximum load completed for 10 repetitions for each exercise. Self-selected training loads were significantly higher in PT compared with WoPT for the LP (by 15.6%), BP (by 26.6%), LE (by 12.1%), and AC (by 22.2%) exercises. Self-selected training loads expressed relative to 1RM and 10RM data were significantly higher in PT (49-59.5% of 1RM; 62.7-77.3% of 10RM) than WoPT (41-58.7% of 1RM; 58.7-76.2% of 10RM) with largest difference observed in the lower-body exercises. Ratings of perceived exertion values were significantly higher in PT compared with WoPT. The results of the present study indicated that supervised resistance training with a personal trainer was advantageous in trained subjects although self-selected loading was still considerably lower than 1RM and 10RM percentage values.

Influence of strength and flexibility training, combined or isolated, on strength and flexibility gains.

The aim of this study was to analyze the strength and flexibility gains after 12 weeks of strength and flexibility training (FLEX), isolated or combined. Twenty-eight trained women (age = 46 ± 6.52 years; body mass = 56.8 ± 5.02 kg; height = 162 ± 5.58 cm; mean ± SD) were randomly divided into 4 groups: strength training (ST) (n = 7), FLEX (n = 7), combination of strength and flexibility (ST + FLEX) (n = 7), and combination of flexibility and strength (FLEX + ST) (n = 7). All groups were assessed before and after training for the sit and reach test, goniometry, and 10 repetition maximum in bench press (BP) and leg press (LP) exercises. The training protocol for all groups included training sessions on alternate days and was composed of 8 exercises performed at periodized intensities. The FLEX consisted of dynamic stretching performed for a total duration of 60 minutes. The results demonstrated significant strength gains in all groups in the LP exercise (FLEX: p = 0.0187; ST: p = 0.0001; FLEX + ST: p = 0.0034; ST + FLEX: p = 0.0021). All groups except the FLEX improved in BP strength (FLEX: p = 0.1757; ST: p = 0.0001; FLEX + ST: p = 0.0017; ST + FLEX: p = 0.0035). Statistical analyses did not show significant differences between groups; however, effect sizes demonstrated slightly different treatment effects for each group. Largest treatment effects were calculated for the ST group (LP: 2.72; BP: 1.25) and the lowest effects in the FLEX group (LP: 0.41; BP: -0.06). Both combination groups demonstrated lower effect sizes for both LP and BP as compared with the ST group. No significant differences in flexibility were seen in any group, in any of the comparisons (p > 0.05). In conclusion, these findings suggest that combining strength and FLEX is not detrimental to flexibility development; however, combined training may slightly reduce strength development, with little influence of order in which these exercises are performed.

Order effects of combined strength and endurance training on testosterone, cortisol, growth hormone, and IGF-1 binding protein 3 in concurrently trained men.

Concurrent training (CT) has been widely used in fitness centers to simultaneously optimize cardiovascular and neuromuscular fitness, and induce a high-energy expenditure. Therefore, the aim of this study was to compare the acute effects of 2 different orders of CT on hormonal responses in concurrently trained men. Fourteen men (mean ± SD: 24.7 ± 5.1 years) were randomly divided into 2 groups: endurance training followed by strength (ES, n = 7) and strength training followed by endurance (SE, n = 7). Serum concentrations of testosterone, cortisol, growth hormone, and IGF-1 binding protein 3 (IGFBP-3) were measured before and after both training orders. A significant interaction between exercise order and time was only found in the IGFBP-3 levels (p = 0.022). The testosterone and IGFBP-3 concentrations significantly increased in the ES group after the exercise trainings (57.7 ± 35.1%, p = 0.013 and 17.0 ± 15.5%, p = 0.032, respectively) but did not change significantly in the SE group (15.5 ± 36.6%, p = 0.527 and -4.2 ± 13.9%, p = 0.421, respectively). Conversely, cortisol and growth hormone concentrations significantly increased in both ES (169.2 ± 191.0%, p = 0.021 and 13,296.8 ± 13,009.5%, p = 0.013, respectively) and SE (92.2 ± 81.5%, p = 0.017 and 12,346.2 ± 9714.1%, p = 0.001, respectively) groups compared with baseline values. No significant correlations were found between the changes in the hormonal concentrations. In conclusion, these results suggest that immediately postexercise testosterone and IGFPB-3 responses are significantly increased only after the ES order. Therefore, an ES training order should be prescribed if the main focus of the training intervention is to induce an acute postexercise anabolic environment.

Ecological, historical and evolutionary determinants of modularity in weighted seed-dispersal networks.

Modularity is a recurrent and important property of bipartite ecological networks. Although well-resolved ecological networks describe interaction frequencies between species pairs, modularity of bipartite networks has been analysed only on the basis of binary presence-absence data. We employ a new algorithm to detect modularity in weighted bipartite networks in a global analysis of avian seed-dispersal networks. We define roles of species, such as connector values, for weighted and binary networks and associate them with avian species traits and phylogeny. The weighted, but not binary, analysis identified a positive relationship between climatic seasonality and modularity, whereas past climate stability and phylogenetic signal were only weakly related to modularity. Connector values were associated with foraging behaviour and were phylogenetically conserved. The weighted modularity analysis demonstrates the dominating impact of ecological factors on the structure of seed-dispersal networks, but also underscores the relevance of evolutionary history in shaping species roles in ecological communities.

Functional importance of avian seed dispersers changes in response to human-induced forest edges in tropical seed-dispersal networks.

Although seed-dispersal networks are increasingly used to infer the functioning of ecosystems, few studies have investigated the link between the properties of these networks and the ecosystem function of seed dispersal by animals. We investigate how frugivore communities and seed dispersal change with habitat disturbance and test whether relationships between morphological traits and functional roles of seed dispersers change in response to human-induced forest edges. We recorded interaction frequencies between fleshy fruited plants and frugivorous bird species in tropical montane forests in the Bolivian Andes and recorded functional bird traits (body mass, gape width and wing tip length) associated with quantitative (seed-removal rate) and qualitative (seed-deposition pattern) components of seed-dispersal effectiveness. We found that the abundance and richness of frugivorous birds were higher at forest edges. More fruits were removed and dispersed seeds were less clustered at edges than in the interior. Additionally, functional and interaction diversity were higher at edges than in the interior, but functional and interaction evenness did not differ. Interaction strength of bird species increased with body mass, gape width and wing tip length in the forest interior, but was not related to bird morphologies at forest edges. Our study suggests that increases in functional and interaction diversity and an even distribution of interaction strength across bird morphologies lead to enhanced quantity and tentatively enhanced quality of seed dispersal. It also suggests that the effects of species traits on ecosystem functions can vary along small-scale gradients of human disturbance.

Birds optimize fruit size consumed near their geographic range limits.

Animals can adjust their diet to maximize energy or nutritional intake. For example, birds often target fruits that match their beak size because those fruits can be consumed more efficiently. We hypothesized that pressure to optimize diet-measured as matching between fruit and beak size-increases under stressful environments, such as those that determine species' range edges. Using fruit-consumption and trait information for 97 frugivorous bird and 831 plant species across six continents, we demonstrate that birds feed more frequently on closely size-matched fruits near their geographic range limits. This pattern was particularly strong for highly frugivorous birds, whereas opportunistic frugivores showed no such tendency. These findings highlight how frugivore interactions might respond to stressful conditions and reveal that trait matching may not predict resource use consistently.

Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity.

We explore the synergistic effect of photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells (NS) or hollow gold nanoparticles (HGNPs) in human HeLa cells following near-infrared (NIR) light irradiation. Thermal transfer from NS was higher than that displayed by HGNPs, owing to a differential interaction of the nanomaterial with the biological environment. Under sublethal photothermal conditions, NS and HGNPs effectively modulated the expression levels of a DsRed-monomer reporter gene controlled by the highly heat-inducible human HSP70B promoter, as a function of nanomaterial concentration and length of laser exposure. Hyperthermia treatments at doses that do not promote cell death generated a lethal outcome in HeLa cells harboring the fusogenic GALV-FMG transgene under the control of the HSP70B promoter. Combination of lethal photothermia with the triggering of the cytotoxic transgene resulted in a dramatic increase of the cell-ablation area as a result of the synergistic activity established. FROM THE CLINICAL EDITOR: In this study photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells or hollow gold nanoparticles, was investigated in human HeLa cells following near-infrared (NIR) light irradiation. It is shown that the combination of lethal photothermia with the triggering of the cytotoxic transgene at sublethal levels results in a synergistic cytotoxic effect in vitro.

Remote control of transgene expression using noninvasive near-infrared irradiation.

This study investigated whether noninvasive near-infrared (NIR) energy could be transduced into heat in deep-seated organs in which adenovirus type-5 vectors tend to accumulate, thereby activating heat shock protein (HSP) promoter-mediated transgene expression, without local administration of photothermal agents. NIR irradiation of the subdiaphragmatic and left dorsocranial part of the abdominal cavity of adult immunocompetent C3H/HeNRj mice with an 808-nm laser effectively increased the temperature of the irradiated regions of the liver and spleen, respectively, resulting in the accumulation of the heat-inducible HSP70 protein. Spatial control of transgene expression was achieved in the NIR-irradiated regions of the mice administered an adenoviral vector carrying a firefly luciferase (fLuc) coding sequence controlled by a human HSP70B promoter, as assessed by bioluminescence and immunohistochemistry analyses. Levels of reporter gene expression were modulated by controlling NIR power density. Spatial control of transgene expression through NIR-focused activation of the HSP70B promoter, as well as temporal regulation by administering rapamycin was achieved in the spleens of mice inoculated with an adenoviral vector encoding a rapamycin-dependent transactivator driven by the HSP70B promoter and an adenoviral vector carrying a fLuc coding sequence controlled by the rapamycin-activated transactivator. Mice that were administered rapamycin and exposed to NIR light expressed fLuc activity in the splenic region, whereas no activity was detected in mice that were only administered rapamycin or vehicle or only NIR-irradiated. Thus, in the absence of any exogenously supplied photothermal material, remote control of heat-induced transgene expression can be achieved in the liver and spleen by means of noninvasive NIR irradiation.

Does aerobic and strength exercise sequence in the same session affect the oxygen uptake during and postexercise?

Concurrent training is a strategy employed in both general fitness and sports conditioning. The purpose of this study was to compare the responses of VO2 in different combinations of strength exercise with aerobic interval exercise. Eight men (23.6 ± 4.2 years, 178 ± 6.3 cm, 77 ± 7.9 kg, 7.67 ± 1.95% body fat) completed 3 combinations of strength training (ST) and aerobic training (AT) in a randomized order with a 7-day recovery period: AT before ST exercises, AT between 2 blocks of ST exercises, and AT after ST exercises. The ST comprised 4 exercises performed in 3 sets of 10 reps and 2 exercises, abdominal crunch and lumbar extension, performed in 3 sets of 30 and 20 reps, respectively. The AT consisted of a 20-minute interval cycling. There were no significant differences in the values of absolute or relative VO2, in the heart rate (HR) and in the respiratory exchange ratio (RER) when the 3 sessions (during + postexercise measurements) were compared (values are mean ± SD). Analyzing only ST in each session, differences were detected in the RER values (F = 4.714; p < 0.05; η2 = 0.308) between AT before ST and AT in the middle of ST (1.01 ± 0.97 vs. 1.11 ± 0.07, respectively). In all sequences, there was a significant increase (p < 0.05) in the values of relative and absolute VO2 and HR, and a significant decrease in RER values (p < 0.05) from the first to the second part of the ST session. The values of absolute or relative VO2, HR, and RER did not vary significantly among the 3 sessions as compared with the AT after ST. These data support the hypothesis that ST and AT, when performed in sequence in the same session, do not seem to affect the overall oxygen consumption during the exercise session. Therefore, training sessions may incorporate both modalities without apparent impact on aerobic exercise.

Computation of Activating Fields for Approximation of the Orientation-Specific Neural Response to Electrical Stimulation.

Computational methods of determining the response of neural tissue to electrical stimulation have demonstrated value for the development of novel devices and the programming of neuromodulation therapies. Detailed biophysical models are excessively computationally intensive for many applications; simple metrics to approximate activation can speed up progress in this area. The activating function provides such a useful metric. However, this measure, defined for a specific axon orientation, is not immediately applicable to computed electric fields to assess their effects. We demonstrate a method for computation of the activating function generalized to a field in order to allow rapid computation of the effects of stimulation on neural tissue while preserving information on axon orientation. Clinical Relevance- This demonstrates a useful method of approximating the effect of electrical stimulation on nervous tissue for the development of devices and the optimization of parameters for electrical neuromodulation.

Effect of the Current Intensity and Inter-Electrode Distance in Surface Electrical Stimulation: A FEM Simulation Study.

In functional electric stimulation, variables such as electrode size, shape, and inter-electrodes distance can produce different neural and functional responses. In this work, a computational model combining FEM and MRG axon models is implemented to replicate two experimental studies that compare the effect of changing inter-electrode distance when applying FES to induce knee flexion. One work affirms that the stronger torque happens for greater distances, while the other obtain its maximum at lower distances. Using a simplified computational model gave another study perspective to understand why these two stimulation methodologies obtain different results. According to our results, an anodic stimulation occurs with greater current intensities and inter-electrode distances. This anodic effect can activate other nerve or motor points in the vicinity of the anode, explaining that more muscle fibers are recruited and generate an increased torque. Clinical Relevance - This work gives another view to understanding how the distance between electrodes affects neural activation, which has implications for optimizing clinical and exercise protocols using electrical stimulation techniques.