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A control-oriented tokamak profile evolution model is crucial for the development and testing of control schemes for a fusion plasma. The RAPTOR (RApid Plasma Transport simulatOR) code was developed with this aim in mind (Felici 2011 Nucl. Fusion51 083052). The performance of the control system strongly depends on the quality of the control-oriented model predictions. In RAPTOR a semi-empirical transport model is used, instead of a first-principles physics model, to describe the electron heat diffusivity in view of computational speed. The structure of the empirical model is given by the physics knowledge, and only some unknown physics of , which is more complicated and less well understood, is captured in its model parameters. Additionally, time-averaged sawtooth behavior is modeled by an ad hoc addition to the neoclassical conductivity and electron heat diffusivity. As a result, RAPTOR contains parameters that need to be estimated for a tokamak plasma to make reliable predictions. In this paper a generic parameter estimation method, based on the nonlinear least-squares theory, was developed to estimate these model parameters. For the TCV tokamak, interpretative transport simulations that used measured profiles were performed and it was shown that the developed method is capable of finding the model parameters such that RAPTOR’s predictions agree within ten percent with the simulated q profile and twenty percent with the measured profile. The newly developed model-parameter estimation procedure now results in a better description of a fusion plasma and allows for a less ad hoc and more automated method to implement RAPTOR on a variety of tokamaks. [ABSTRACT FROM AUTHOR]

A real-time capable core turbulence tokamak transport model is developed. This model is constructed from the regularized nonlinear regression of quasilinear gyrokinetic transport code output. The regression is performed with a multilayer perceptron neural network. The transport code input for the neural network training set consists of five dimensions, and is limited to adiabatic electrons. The neural network model successfully reproduces transport fluxes predicted by the original quasilinear model, while gaining five orders of magnitude in computation time. The model is implemented in a real-time capable tokamak simulator, and simulates a 300 s ITER discharge in 10 s. This proof-of-principle for regression based transport models anticipates a significant widening of input space dimensionality and physics realism for future training sets. This aims to provide unprecedented computational speed coupled with first-principle based physics for real-time control and integrated modelling applications. [ABSTRACT FROM AUTHOR]

A controller is designed for the tokamak safety factor profile that takes real-time-varying operational and physics limits into account. This so-called model predictive controller (MPC) employs a prediction model in order to compute optimal control inputs that satisfy the given limits. The use of linearized models around a reference trajectory results in a quadratic programming problem that can easily be solved online. The performance of the controller is analysed in a set of ITER L-mode scenarios simulated with the non-linear plasma transport code RAPTOR. It is shown that the controller can reduce the tracking error due to an overestimation or underestimation of the modelled transport, while making a trade-off between residual error and amount of controller action. It is also shown that the controller can account for a sudden decrease in the available actuator power, while providing warnings ahead of time about expected violations of operational and physics limits. This controller can be extended and implemented in existing tokamaks in the near future. [ABSTRACT FROM AUTHOR]

Optimal actuator trajectories for an ITER hybrid scenario ramp-up are computed using a numerical optimization method. For both L-mode and H-mode scenarios, the time trajectory of plasma current, EC heating and current drive distribution is determined that minimizes a chosen cost function, while satisfying constraints. The cost function is formulated to reflect two desired properties of the plasma q profile at the end of the ramp-up. The first objective is to maximize the ITG turbulence threshold by maximizing the volume-averaged s/q ratio. The second objective is to achieve a stationary q profile by having a flat loop voltage profile. Actuator and physics-derived constraints are included, imposing limits on plasma current, ramp rates, internal inductance and q profile. This numerical method uses the fast control-oriented plasma profile evolution code RAPTOR, which is successfully benchmarked against more complete CRONOS simulations for L-mode and H-mode mode ITER hybrid scenarios. It is shown that the optimized trajectories computed using RAPTOR also result in an improved ramp-up scenario for CRONOS simulations using the same input trajectories. Furthermore, the optimal trajectories are shown to vary depending on the precise timing of the L–H transition. [ABSTRACT FROM AUTHOR]

Tokamak plasmas operating at high performance are limited by several MHD instabilities. The sawtooth instability limits the core plasma pressure and can drive the neoclassical tearing mode unstable, but also prevents accumulation of impurities in the core. Electron cyclotron heating and current drive systems can be used to modify the local current profile and therefore tailor the sawtooth period. This paper reports on demonstrations of continuous real time feedback control of the sawtooth period by varying the EC injection angle. [ABSTRACT FROM AUTHOR]

Starting from a standard single null X-point configuration, a second order null divertor (snowflake (SF)) has been successfully created on the Tokamak a Configuration Variable (TCV) tokamak. The magnetic properties of this innovative configuration have been analysed and compared with a standard X-point configuration. For the SF divertor, the connection length and the flux expansion close to the separatrix exceed those of the standard X-point by more than a factor of 2. The magnetic shear in the plasma edge is also larger for the SF configuration. [ABSTRACT FROM AUTHOR]

Objective: Parental counseling for fetal malformations of cortical development (MCD) is based on data from studies in children and adults undergoing imaging investigation for abnormal neurodevelopment. However, such postnatal findings may not be applicable to prenatally diagnosed cases. The aim of this study was to review the existing data on postnatal neurodevelopmental outcome for fetuses diagnosed with MCD., Methods: A literature search was conducted in PubMed, Web of Science and EMBASE for articles published between 2013 and 2023, using standardized keywords to describe fetal cortical malformations. Full-text articles were accessed for the retrieved citations and data on participant characteristics, imaging findings, and pregnancy and neonatal outcomes were extracted. Fetal MCD was defined as either complex or isolated, according to the presence or absence, respectively, of additional brain or extracranial defects., Results: Overall, 30 articles including 371 cases of fetal MCD were reviewed. The cases were classified as complex (n = 324), isolated (n = 21) or unknown (n = 26). There were 144 terminations and four stillbirths, with pregnancy outcome unreported in 149 cases. A total of 108 cases had postnatal magnetic resonance imaging or postmortem examination data available. In nine of these cases, a diagnosis of complex fetal MCD was changed to isolated MCD after birth, and one case was found not to have MCD. There were 74 live births, for which postnatal neurodevelopment data were available in only 30 cases. Normal neurodevelopmental outcome was reported in seven (23.3% (95% CI, 9.9-42.2%)) infants, with the remaining 23 exhibiting various levels of neurodevelopmental delay (three mild, seven moderate and 13 severe) from 6 months to 7 years of age., Conclusions: Most reviewed cases of fetal MCD were complex in nature and underwent termination of pregnancy. There is a paucity of data on postnatal neurological development in fetuses diagnosed with MCD. The available data suggest antenatal overdiagnosis of case severity in about 5% of cases with known outcome, and either normal neurodevelopment or mild neurodevelopmental delay in approximately one-third of liveborn cases with neurological follow-up. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

This cross-sectional study aims to elucidate the neural mechanisms underlying the control of knee extension forces in individuals with anterior cruciate ligament reconstruction (ACLR). Eleven soccer players with ACLR and nine control players performed unilateral isometric knee extensions at 10% and 30% of their maximum voluntary force (MVF). Simultaneous recordings of high-density surface electromyography (HDEMG) and force output were conducted for each lower limb, and HDEMG data from the vastus lateralis (VL) and vastus medialis (VM) muscles were decomposed into individual motor unit spike trains. Force steadiness was estimated using the coefficient of variation of force. An intramuscular coherence analysis was adopted to estimate the common synaptic input (CSI) converging to each muscle. A factor analysis was applied to investigate the neural strategies underlying the control of synergistic motor neuron clusters, referred to as motor unit modes. Force steadiness was similar between lower limbs. However, motor neurons innervating the VL on the reconstructed side received a lower proportion of CSI at low-frequency bandwidths (<5 Hz) compared with the unaffected lower limbs ( P < 0.01). Furthermore, the reconstructed side demonstrated a higher proportion of motor units associated with the neural input common to the synergistic muscle, as compared with the unaffected lower limbs ( P < 0.01). These findings indicate that the VL muscle of reconstructed lower limbs contribute marginally to force steadiness and that a plastic rearrangement in synergistic clusters of motor units involved in the control of knee extension forces is evident following ACLR. NEW & NOTEWORTHY Chronic quadriceps dysfunction is common after anterior cruciate ligament reconstruction (ACLR). We investigated voluntary force control strategies by estimating common inputs to motor neurons innervating the vastii muscles. Our results showed attenuated common inputs to the vastus lateralis and plastic rearrangements in functional clusters of motor neurons modulating knee extension forces in the reconstructed limb. These findings suggest neuroplastic adjustments following ACLR that may occur to fine-tune the control of quadriceps forces.

Purpose: In the present study, we examined how a 4-week intervention of maximal intended velocity (MIVRT) and controlled velocity resistance training (CRT)-induced task-specific responses in expert individuals., Methods: Twenty elite athletes were randomly assigned to either a MIVRT (n = 10) or CRT (n = 10) group, both following the same volume-load training based on the back-squat three times a week but with different intentions in moving load (force-exertion speed). We assessed one-repetition maximum (1RM), mean propulsive velocity (MPV), and mean propulsive power (MPP) using a progressive-loading test before and after the intervention. A linear position transducer was used to monitor propulsive velocity in training and testing sessions., Results: Both groups significantly increased their 1RM (CRT: + 12.3%, p < 0.001, d = 0.39; MIVRT: + 12.5%, p < 0.001, d = 0.45). Only the MIVRT group showed a significant improvement in MPV (p < 0.01) across different stepping loads, while both groups improved in MPP (MIVRT: + 22.4%, p < 0.001, d = 0.54; CRT: + 8.1%, p = 0.04, d = 0.17)., Conclusions: MIVRT induced significant adaptations in MPV and MPP at various loads (%1RM), underlining its specificity in targeting these parameters. Despite similar enhancements in 1RM, the distinct training protocols suggest that strength gains may stem from either maximal intent in moving loads or longer times under tension. This study highlights the role of execution speed in optimizing power outcomes, emphasizing task specificity as paramount to elicit physiological adaptations in chronically strength-trained individuals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Emerging questions in neuromuscular physiology revolve around whether males and females share similar neural control in diverse tasks across a broad range of intensities. In order to explore these features, high-density electromyography was used to record the myoelectrical activity of biceps brachii during trapezoidal isometric contractions at 35% and 70% of maximal voluntary force (MVF) on 11 male and 13 female participants. Identified motor units were then classified as lower-threshold (recruited at ≤30%MVF) and higher-threshold (recruited at >30%MVF). The discharge rate, interspike interval variability, recruitment and derecruitment thresholds, and estimates of neural drive to motor neurons were assessed. Female lower-threshold motor units showed higher neural drive (P < 0.001), accompanied by higher discharge rate at recruitment (P = 0.006), plateau (P = 0.001) and derecruitment (P = 0.001). On the other hand, male higher-threshold motor units showed greater neural drive (P = 0.04), accompanied by higher discharge rate at recruitment (P = 0.005), plateau (P = 0.04) and derecruitment (P = 0.01). Motor unit discharge rate normalised by the recruitment threshold was significantly higher in female lower-threshold motor units (P < 0.001), while no differences were observed in higher-threshold motor units. Recruitment and derecruitment thresholds are higher in males across all intensities (P < 0.01). However, males and females have similar activation and deactivation strategies, as evidenced by similar recruitment-to-derecruitment ratios (P > 0.05). This study encompasses a broad intensity range to analyse motor unit sex-related differences, highlighting higher neural drive and discharge rates in female lower-threshold motor units, elevated recruitment and derecruitment thresholds in males, and convergences in activation and deactivation strategies. HIGHLIGHTS: What is the central question of the study? Do male and female motor units behave similarly in low- and high-intensity contractions? What is the main finding and its importance? Female motor units show higher discharge rates in low-intensity tasks and lower discharge rates in high-intensity tasks, with no differences in recruitment behaviour. A broader inter-spike interval variability was also observed in females. These findings underline that there are sex-specific differences concern the firing strategies based on task intensity., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: The detection of a fetal abdominal cyst at the first-trimester ultrasound scan is a rare event, for which the natural history and prognosis are often unknown and unpredictable, owing to various underlying etiologies. The aim of this study was to evaluate the outcome of fetal abdominal cysts detected in the first trimester to better understand their possible clinical significance and improve their clinical management., Methods: We present a case report of a fetal abdominal cyst detected in the first trimester, with subsequent diagnosis of congenital multiple arthrogryposis. We also performed a systematic review of the literature to determine the incidence and outcome of similar cases, which was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and registered with PROSPERO (CRD42023491729). PubMed, Web of Science and EMBASE were searched from inception to December 2023 to identify case reports and case series documenting an ultrasound diagnosis of a single fetal abdominal cyst in the first trimester., Results: Our case presented at 12 + 6 weeks' gestation with an isolated fetal abdominal cyst, which underwent spontaneous resolution in the second trimester, when multiple congenital arthrogryposis was observed. Data on a total of 60 cases of fetal abdominal cyst detected in the first trimester were extracted from the literature. Of these, 35% were associated with concurrent or late-onset structural anomalies, as in our case, and 65% were isolated. In pregnancies with an isolated fetal abdominal cyst, 54% had a live birth with a normal outcome., Conclusions: A fetal abdominal cyst in the first trimester is usually an isolated finding with a moderate-to-good prognosis, but it could also be an early sign of other associated abnormalities, including arthrogryposis. Increased ultrasound surveillance and additional genetic testing to rule out possible associated anomalies are necessary to assess the risk of adverse pregnancy outcome and provide appropriate parental counseling. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: Our knowledge of monochorionic pregnancies' complications is largely based on the extensive ongoing research on monochorionic placental structure. Previous studies on the concordance of umbilical cord insertions are limited. This study aimed to evaluate placental anastomoses and cord insertions as independent risk factors for neonatal adverse outcomes., Methods: This was a prospective study conducted at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy from April 2021 to December 2022. Seventy-six women with a monochorionic pregnancy were enrolled at their first-trimester scan. After delivery, all placentas that were confirmed to be monochorionic were analyzed according to standard protocols, including those of complicated monochorionic twin pregnancies. The primary outcomes were a Composite Monochorionic Pregnancy Outcome (CMPO) and a Composite Neonatal Adverse Outcome (CNAO). The secondary outcome was the birth weight discordance between the neonates., Results: The CMPO occurred in 15.8 % pregnancies, and the CNAO occurred in 67.1 % pregnancies. The analysis confirmed a significant association between velamentous cord insertions and neonatal adverse events (p = 0.003). Also, a significant positive association (p = 0.0326) between twin birth weight discordance and discordance in twins umbilical cord insertions' sites was found. No significant association between the number and type of the anastomoses and both the CMPO or CNAO was detected., Discussion: Our data suggest that the routine sonographic assessment of umbilical cords' insertion sites during the first trimester could be helpful in predicting fetal and neonatal adverse events. We believe that this sonographic assessment should start to be implemented in our routine care of monochorionic pregnancies., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several whole-body vibration (WBV) effects on performance have been related to potential changes in the neural drive, motor unit firing rate, and sensorimotor integration. In the present paper, motor unit coherence analysis was performed to detect the source of neural modulation based on the frequency domain. Methods: Thirteen men [25 ± 2.1 years; Body Mass Index (BMI) = 23.9 ± 1.3 kg m2; maximal voluntary force (MVF): 324.36 ± 41.26 N] performed sustained contractions of the Tibialis Anterior (TA) at 10%MVF before and after acute WBV. The vibrating stimulus was applied barefoot through a platform to target the TA. High-Density surface Electromyography (HDsEMG) was used to record the myoelectrical activity of TA to evaluate coherence from motor unit cumulative spike-trains (CSTs). Results: Mean coherence showed a significant decrease in the alpha and low-beta bandwidths (alpha: from 0.143 ± 0.129 to 0.132 ± 0.129, p = 0.035; low-beta: from 0.117 ± 0.039 to 0.086 ± 0.03, p = 0.0001), whereas no significant changes were found in the other ones ( p > 0.05). The discharge rate (DR) and the Force Covariance (CovF%) were not significantly affected by acute WBV exposure ( p > 0.05). Discussion: According to the significant effects found in alpha and low-beta bandwidths, which reflect sensorimotor integration parameters, accompanied by no differences in the DR and CovF%, the present results underlined that possible neural mechanisms at the base of the previously reported performance enhancements following acute WBV are likely based on sensorimotor integration rather than direct neural drive modulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Lecce, Nuccio, Del Vecchio, Conti, Nicolò, Sacchetti, Felici and Bazzucchi.)

Purpose: Growing evidence suggests that respiratory frequency ( f R ) is a marker of physical effort and a variable sensitive to changes in exercise tolerance. The comparison between arm+leg cycling (Arm+leg) and leg cycling (Leg) has the potential to further test this notion because a greater exercise tolerance is expected in the Arm+leg modality. We systematically compared Arm+leg vs. Leg using different performance tests. Methods: Twelve males underwent six performance tests in separate, randomized visits. Three tests were performed in each of the two exercise modalities, i.e. an incremental test and two time-to-exhaustion (TTE) tests performed at 90% or 75% of the peak power output reached in the Leg incremental test (PPO Leg ). Exercise tolerance, perceived exertion, and cardiorespiratory variables were recorded during all the tests. Results: A greater exercise tolerance ( p < 0.001) was found for Arm+leg in the incremental test (337 ± 32 W vs. 292 ± 28 W), in the TTE test at 90% of PPO Leg (638 ± 154 s vs. 307 ± 67 s), and in the TTE test at 75% of PPO Leg (1,675 ± 525 s vs. 880 ± 363 s). Unlike V ˙ O 2 and heart rate, both f R and minute ventilation were lower ( p < 0.003) at isotime in all the Arm+leg tests vs. Leg tests. Furthermore, a lower perceived exertion was observed in the Arm+leg tests, especially during the TTE tests ( p < 0.001). Conclusion: Minute ventilation, f R and perceived exertion are sensitive to the improvements in exercise tolerance observed when comparing Arm+leg vs. Leg, unlike V ˙ O 2 and heart rate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nicolò, Girardi, Bazzucchi, Sacchetti and Felici.)

Introduction: The application of neuromuscular electrical stimulation superimposed on voluntary muscle contractions (NMES+) has demonstrated a considerable potential to enhance or restore muscle function in both healthy and individuals with neurological or orthopedic disorders. Improvements in muscle strength and power have been commonly associated with specific neural adaptations. In this study, we investigated changes in the discharge characteristics of the tibialis anterior motor units, following three acute exercises consisting of NMES+, passive NMES and voluntary isometric contractions alone. Methods: Seventeen young participants participated in the study. High-density surface electromyography was used to record myoelectric activity in the tibialis anterior muscle during trapezoidal force trajectories involving isometric contractions of ankle dorsi flexors with target forces set at 35, 50% and 70% of maximal voluntary isometric contraction (MVIC). From decomposition of the electromyographic signal, motor unit discharge rate, recruitment and derecruitment thresholds were extracted and the input-output gain of the motoneuron pool was estimated. Results: Global discharge rate increased following the isometric condition compared to baseline at 35% MVIC while it increased after all experimental conditions at 50% MVIC target force. Interestingly, at 70% MVIC target force, only NMES + led to greater discharge rate compared to baseline. Recruitment threshold decreased after the isometric condition, although only at 50% MVIC. Input-output gain of the motoneurons of the tibialis anterior muscle was unaltered after the experimental conditions. Discussion: These results indicated that acute exercise involving NMES + induces an increase in motor unit discharge rate, particularly when higher forces are required. This reflects an enhanced neural drive to the muscle and might be strongly related to the distinctive motor fiber recruitment characterizing NMES+., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Borzuola, Nuccio, Scalia, Parrella, Del Vecchio, Bazzucchi, Felici and Macaluso.)

Because of the biophysical relation between muscle fibre diameter and the propagation velocity of action potentials along the muscle fibres, motor unit conduction velocity could be a non-invasive index of muscle fibre size in humans. However, the relation between motor unit conduction velocity and fibre size has been only assessed indirectly in animal models and in human patients with invasive intramuscular EMG recordings, or it has been mathematically derived from computer simulations. By combining advanced non-invasive techniques to record motor unit activity in vivo, i.e. high-density surface EMG, with the gold standard technique for muscle tissue sampling, i.e. muscle biopsy, here we investigated the relation between the conduction velocity of populations of motor units identified from the biceps brachii muscle, and muscle fibre diameter. We demonstrate the possibility of predicting muscle fibre diameter (R 2  = 0.66) and cross-sectional area (R 2  = 0.65) from conduction velocity estimates with low systematic bias (∼2% and ∼4% respectively) and a relatively low margin of individual error (∼8% and ∼16%, respectively). The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling. The non-invasive nature of high-density surface EMG for the assessment of muscle fibre size may be useful in studies monitoring child development, ageing, space and exercise physiology, although the applicability and validity of the proposed methodology need to be more directly assessed in these specific populations by future studies. KEY POINTS: Because of the biophysical relation between muscle fibre size and the propagation velocity of action potentials along the sarcolemma, motor unit conduction velocity could represent a potential non-invasive candidate for estimating muscle fibre size in vivo. This relation has been previously assessed in animal models and humans with invasive techniques, or it has been mathematically derived from simulations. By combining high-density surface EMG with muscle biopsy, here we explored the relation between the conduction velocity of populations of motor units and muscle fibre size in healthy individuals. Our results confirmed that motor unit conduction velocity can be considered as a novel biomarker of fibre size, which can be adopted to predict muscle fibre diameter and cross-sectional area with low systematic bias and margin of individual error. The proposed neuromuscular interface opens new perspectives in the use of high-density EMG as a non-invasive tool to estimate muscle fibre size without the need of surgical biopsy sampling., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Introduction: several studies have reported improved neuromuscular parameters in response to whole-body vibration (WBV). This is likely achieved by modulation of the central nervous system (CNS). Reduced recruitment threshold (RT), which is the % of Maximal Voluntary Force (%MVF) at which a given Motor Unit (MU) is recruited, may be responsible for the force/power improvements observed in several studies. Methods: 14 men (25 ± 2.3 years; BMI = 23.3 ± 1.5 kg m 2 MVF: 319.82 ± 45.74 N) performed trapezoidal isometric contractions of the tibialis anterior (TA) at 35-50-70 %MVF before and after three conditions: WBV, STAND (standing posture), and CNT (no intervention). The vibration was applied through a platform for targeting the TA. High-density surface electromyography (HDsEMG) recordings and analysis were used to detect changes in the RT and Discharge Rate (DR) of the MUs. Results: Mean motor unit recruitment threshold (MURT) reached 32.04 ± 3.28 %MVF before and 31.2 ± 3.72 %MVF after WBV, with no significant differences between conditions ( p > 0.05). Additionally, no significant changes were found in the mean motor unit discharge rate (before WBV: 21.11 ± 2.94 pps; after WBV: 21.19 ± 2.17 pps). Discussion: The present study showed no significant changes in motor unit properties at the base of neuromuscular changes documented in previous studies. Further investigations are needed to understand motor unit responses to different vibration protocols and the chronic effect of vibration exposure on motor control strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lecce, Nuccio, Del Vecchio, Conti, Nicolò, Sacchetti, Felici and Bazzucchi.)

Background: The existing evidence is insufficient to draw conclusions about the association between maternal position in labor and obstetrical outcomes., Objective: This study aimed to evaluate the effects of different maternal positions during the second stage of labor among women with and those without epidural analgesia on important obstetrical outcomes including perineal damage., Study Design: In this retrospective cohort study, we collected data of women who delivered vaginally over a 2-year period. The associations between maternal and gestational characteristics and several obstetrical outcomes were analyzed. We considered perineal damage as the primary outcome. Secondary outcomes were the incidence of operative vaginal births, duration of fetal descent, intrapartum blood loss, and 1-minute and 5-minutes Apgar scores., Results: A total of 2240 nulliparous, at-term pregnancies were included. Of those, 76.9% gave birth in a supine position and 23.1% gave birth in alternative positions. The results showed that regardless of the use of epidural analgesia, nonsupine positions in the second stage of labor are associated with a significant reduction in the risk of both episiotomy and perineal damage to any degree ( P <.0001) and to a reduction in the duration of fetal descent (Spearman rho, 9.17; confidence interval, 3.07-15.32; P =.003). No statistically significant differences were found in the 1-minute and 5-minutes Apgar score between the 2 groups., Conclusion: Our results show that nonsupine positions in the second stage of labor and at the time of birth are associated with a significant increase in having an intact perineum and a reduction in any perineal trauma and in the need for an episiotomy regardless of the use of epidural analgesia., (© 2023 The Authors.)

The COVID-19 pandemic is an unprecedented worldwide event with a massive impact on the economic system. The first Western country that had to face the COVID-19 crisis was Italy, which therefore represents a natural "case study." By using the microdata and granular policy information available at the Italian Ministry of Economy and Finance, this paper provides a macroeconomic quantitative assessment of the initial emergency fiscal measures introduced in 2020 and an analysis of the impact of the COVID-19 shock during the lockdown. We find that emergency measures avoided an additional fall of GDP of about 4.4% in 2020. The impact of public interventions on the dynamics of investments is particularly significant., (© 2022 Elsevier Inc. All rights reserved.)

Nuclear fusion using magnetic confinement, in particular in the tokamak configuration, is a promising path towards sustainable energy. A core challenge is to shape and maintain a high-temperature plasma within the tokamak vessel. This requires high-dimensional, high-frequency, closed-loop control using magnetic actuator coils, further complicated by the diverse requirements across a wide range of plasma configurations. In this work, we introduce a previously undescribed architecture for tokamak magnetic controller design that autonomously learns to command the full set of control coils. This architecture meets control objectives specified at a high level, at the same time satisfying physical and operational constraints. This approach has unprecedented flexibility and generality in problem specification and yields a notable reduction in design effort to produce new plasma configurations. We successfully produce and control a diverse set of plasma configurations on the Tokamak à Configuration Variable 1,2 , including elongated, conventional shapes, as well as advanced configurations, such as negative triangularity and 'snowflake' configurations. Our approach achieves accurate tracking of the location, current and shape for these configurations. We also demonstrate sustained 'droplets' on TCV, in which two separate plasmas are maintained simultaneously within the vessel. This represents a notable advance for tokamak feedback control, showing the potential of reinforcement learning to accelerate research in the fusion domain, and is one of the most challenging real-world systems to which reinforcement learning has been applied., (© 2022. The Author(s).)

Although maximal force increases following short-term isometric strength training, the rate of force development (RFD) may remain relatively unaffected. The underlying neural and muscular mechanisms during rapid contractions after strength training are largely unknown. Since strength training increases the neural drive to muscles, it may be hypothesized that there are distinct neural or muscular adaptations determining the change in RFD independently of an increase in maximal force. Therefore, we examined motor unit population data acquired from surface electromyography during the rapid generation of force before and after 4 wk of strength training. We observed that strength training did not change the RFD because it did not influence the number of motor units recruited per second or their initial discharge rate during rapid contractions. Although strength training did not change motoneuron behavior in the force increase phase of rapid contractions, it increased the discharge rate of motoneurons (by ∼4 spikes/s) when reaching the plateau phase (∼150 ms) of the rapid contractions, determining an increase in maximal force production. Computer simulations with a motor unit model that included neural and muscular properties, closely matched the experimental observations and demonstrated that the lack of change in RFD following training is primarily mediated by an unchanged maximal recruitment speed of motoneurons. These results demonstrate that maximal force and contraction speed are determined by different adaptations in motoneuron behavior following strength training and indicate that increases in the recruitment speed of motoneurons are required to evoke training-induced increases in RFD. NEW & NOTEWORTHY Although maximal force increases with strength training, the rate of force development may remain unaffected. For the first time, we associated motor unit population behavior during rapid force contractions before and after a 4-wk isometric strength training intervention. We found that strength training combined with slow and rapid contractions does not change rate of force development. The specific mechanisms include similar discharge rate during the initial phase of contraction and similar recruitment speed of motoneurons.

Poly-articulated hands, actuated by multiple motors and controlled by surface myoelectric technologies, represent the most advanced aids among commercial prostheses. However, simple hook-like body-powered solutions are still preferred for their robustness and control reliability, especially for challenging environments (such as those encountered in manual work or developing countries). This study presents the mechatronic implementation and the usability assessment of the SoftHand Pro-Hybrid, a family of poly-articulated, electrically-actuated, and body-controlled artificial hands, which combines the main advantages of both body-powered and myoelectric systems in a single device. An assessment of the proposed system is performed with individuals with and without limb loss, using as a benchmark the SoftHand Pro, which shares the same soft mechanical architecture, but is controlled using surface electromyographic sensors. Results indicate comparable task performance between the two control methods and suggest the potential of the SoftHand Pro-Hybrid configurations as a viable alternative to myoelectric control, especially in work and demanding environments., Competing Interests: AB, MC, and GG are cofounders and shareholders of qbrobotics s.r.l., a company producing robotic hands and components of the SoftHand Pro used in the experiments reported in this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Godfrey, Piazza, Felici, Grioli, Bicchi and Catalano.)

Background: Prolonged or unaccustomed eccentric exercise may cause muscle damage and depending from its extent, this event negatively affects physical performance., Objectives: The aim of the present investigation was to evaluate, in humans, the effect of the flavonoid quercetin on circulating levels of the anabolic insulin-like growth factor 1 (IGF-I) and insulin-like growth factor 2 (IGF-II), produced during the recovery period after an eccentric-induced muscle damage (EIMD)., Methods: A randomized, double-blind, crossover study has been performed; twelve young men ingested quercetin (1 g/day) or placebo for 14 days and then underwent an eccentric-induced muscle damaging protocol. Blood samples were collected, and cell damage markers [creatine kinase (CK), lactate dehydrogenase (LDH) and myoglobin (Mb)], the inflammatory responsive interleukin 6 (IL-6), IGF-I and IGF-II levels were evaluated before the exercise and at different recovery times from 24 hours to 7 days after EIMD., Results: We found that, in placebo treatment the increase in IGF-I (72 h) preceded IGF-II increase (7 d). After Q supplementation there was a more marked increase in IGF-I levels and notably, the IGF-II peak was found earlier, compared to placebo, at the same time of IGF-I (72 h). Quercetin significantly reduced plasma markers of cell damage [CK (p<0.005), LDH (p<0.001) and Mb (p<0.05)] and the interleukin 6 level [IL-6 (p<0.05)] during recovery period following EIMD compared to placebo., Conclusions: Our data are encouraging about the use of quercetin as dietary supplementation strategy to adopt in order to mitigate and promote a faster recovery after eccentric exercise as suggested by the increase in plasma levels of the anabolic factors IGF-I and IGF-II., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sgrò, Ceci, Lista, Patrizio, Sabatini, Felici, Sacchetti, Bazzucchi, Duranti and Di Luigi.)

Neural and morphological adaptations combine to underpin the enhanced muscle strength following prolonged exposure to strength training, although their relative importance remains unclear. We investigated the contribution of motor unit (MU) behavior and muscle size to submaximal force production in chronically strength-trained athletes (ST) versus untrained controls (UT). Sixteen ST (age: 22.9 ± 3.5 yr; training experience: 5.9 ± 3.5 yr) and 14 UT (age: 20.4 ± 2.3 yr) performed maximal voluntary isometric force (MViF) and ramp contractions (at 15%, 35%, 50%, and 70% MViF) with elbow flexors, whilst high-density surface electromyography (HDsEMG) was recorded from the biceps brachii (BB). Recruitment thresholds (RTs) and discharge rates (DRs) of MUs identified from the submaximal contractions were assessed. The neural drive-to-muscle gain was estimated from the relation between changes in force (ΔFORCE, i.e. muscle output) relative to changes in MU DR (ΔDR, i.e. neural input). BB maximum anatomical cross-sectional area (ACSA MAX ) was also assessed by MRI. MViF (+64.8% vs. UT, P < 0.001) and BB ACSA MAX (+71.9%, P < 0.001) were higher in ST. Absolute MU RT was higher in ST (+62.6%, P < 0.001), but occurred at similar normalized forces. MU DR did not differ between groups at the same normalized forces. The absolute slope of the ΔFORCE - ΔDR relationship was higher in ST (+66.9%, P = 0.002), whereas it did not differ for normalized values. We observed similar MU behavior between ST athletes and UT controls. The greater absolute force-generating capacity of ST for the same neural input demonstrates that morphological, rather than neural, factors are the predominant mechanism for their enhanced force generation during submaximal efforts. NEW & NOTEWORTHY In this study, we observed that recruitment strategies and discharge characteristics of large populations of motor units identified from biceps brachii of strength-trained athletes were similar to those observed in untrained individuals during submaximal force tasks. We also found that for the same neural input, strength-trained athletes are able to produce greater absolute muscle forces (i.e., neural drive-to-muscle gain). This demonstrates that morphological factors are the predominant mechanism for the enhanced force generation during submaximal efforts.

The persistence of quadriceps weakness represents a major concern following anterior cruciate ligament reconstruction (ACLR). The underlying adaptations occurring in the activity of spinal motoneurons are still unexplored. This study examined the discharge patterns of large populations of motor units (MUs) in the vastus lateralis (VL) and vastus medialis muscles following ACLR. Nine ACLR individuals and 10 controls performed unilateral trapezoidal contractions of the knee extensor muscles at 35%, 50% and 70% of the maximal voluntary isometric force (MVIF). High-density surface electromyography (HDsEMG) was used to record the myoelectrical activity of the vasti muscles in both limbs. HDsEMG signals were decomposed with a convolutive blind source separation method and MU properties were extracted and compared between sides and groups. The ACLR group showed a lower MVIF on the reconstructed side compared to the contralateral side (28.1%; P < 0.001). This force deficit was accompanied by reduced MU discharge rates (∼21%; P < 0.05), lower absolute MU recruitment and derecruitment thresholds (∼22% and ∼22.5%, respectively; P < 0.05) and lower input-output gain of motoneurons (27.3%; P = 0.009). Deficits in MU discharge rates of the VL and in absolute recruitment and derecruitment thresholds of both vasti MUs were associated with deficits in MVIF (P < 0.05). A strong between-side correlation was found for MU discharge rates of the VL of ACLR individuals (P < 0.01). There were no significant between-group differences (P > 0.05). These results indicate that mid- to long-term strength deficits following ACLR may be attributable to a reduced neural drive to vasti muscles, with potential changes in excitatory and inhibitory synaptic inputs. KEY POINTS: Impaired expression and control of knee extension forces is common after anterior cruciate ligament reconstruction and is related to high risk of a second injury. To provide novel insights into the neural basis of this impairment, the discharge patterns of motor units in the vastus lateralis and vastus medialis were investigated during voluntary force contractions. There was lower knee extensor strength on the reconstructed side with respect to the contralateral side, which was explained by deficits in motor unit discharge rate and an altered motoneuronal input-output gain. Insufficient excitatory inputs to motoneurons and increased inhibitory afferent signals potentially contributed to these alterations. These results further our understanding of the neural underpinnings of quadriceps weakness following anterior cruciate ligament reconstruction and can help to develop effective rehabilitation protocols to regain muscle strength and reduce the risk of a second injury., (© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.)

Purpose: To assess subclinical markers of endothelial inflammation in young survivors from acute lymphoblastic leukemia (ALL) treated with chemotherapy without cranial irradiation. Methods: Anthropometric parameters [height (H), body mass index (BMI), waist circumference (WC), hip circumference (HC), WC/H, and WC/HC ratio], blood pressure, lipid profile, serum markers of inflammation and endothelial dysfunction [Interleukin 6 (IL-6), vascular cell adhesion molecule, intercellular adhesion molecule, tumor necrosis factor-alfa (TNF-α), Endogenous secretory Receptor for Advanced Glycation Endproducts (Es-RAGE)], and carotid intima-media thickness (c-IMT) were assessed in a group of young ALL survivors and in matched controls. Local Ethics Committee approved the study (code 56/13) on June 24, 2013. Results: 28 ALL survivors (71% male, 18% prepubertal, aged 15.98 ± 4.41 years, mean follow-up 8.57 ± 3.14 years) exhibited lower levels of Es-RAGE than controls (0.18 ± 0.07 vs. 0.27 ± 0.08 ng/mL, p  < 0.001). Among survivors, Es-RAGE values significantly correlated with BMI-SD off-therapy ( R 2 -0.42), WC/H ratio ( R 2 -0.41), WC/HC ratio ( R 2 -0.38), and low-density-lipoprotein cholesterol (LDL-C; R 2 -0.43). Most of the ALL survivors (78%) presented c-IMT above the 95th centile if compared with gender and age standard. Mean c-IMT value correlated with blood pressure ( R 2 0.56) and with LDL-C levels ( R 2 0.56). Metabolic syndrome (MetS) was fully detected only in one ALL survivor. Nevertheless, 18% ALL survivors presented more than one MetS diagnostic criteria: 14% insulin resistance, 25% dyslipidemia, and 17.8% hypertension. Conclusion: We demonstrated an initial functional vascular alteration in young ALL survivors even when treated with standard risk protocols. Our data already support the activation at endothelial level of glycosylation and oxidation processes that are persistent long after the end of the treatment.

Purpose: Survival after whole brain radiation therapy (WBRT) in patients with multiple brain metastases (BM) is currently predicted by group-based scoring systems with limited usability for decision. We aimed to develop a more relevant individualized predictive model than Radiation Therapy Oncology Group - Recursive Partitioning Analysis (RTOG-RPA) and Diagnosis - Specific Graded Prognostic Assessment (DS-GPA) for patients with limited life-expectancy., Methods: Based on a Discovery cohort of patients undergoing WBRT, multivariable piecewise Cox regression models with time cut-offs at 1 and 3 months were developed to predict overall survival (OS). A final parsimonious model was defined, and an external validation cohort was used to assess its discrimination and calibration at one, six, and 12 months., Results: In the 173-patient Discovery cohort, the majority of patients had primary lung cancer (56%), presence of extracranial disease (ECD) (75%), Eastern Cooperative Oncolgy Group - Performance Status (ECOG-PS) score 1 (41%) and no intracranial hypertension (ICH) (74%). Most patients were classified as the RPA class II (48%). The final piecewise Cox model was based on primary site, age, ECD, ECOG-PS and ICH. An external validation of the model was carried out using a cohort of 79 patients. Individualized survival estimates obtained with this model outperformed the RPA and DS-GPA scores for overall survival prediction at 1-month, 6-months and 12- months in both Discovery and Validation cohorts. A R/Shiny web application was developed to obtain individualized predictions for new patients, providing an easy-to-use tool for clinicians and researchers., Conclusion: Our model provides individualized estimates of survival for poor prognosis patients undergoing WBRT, outperforming actual scoring systems., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

In magnetic confinement thermonuclear fusion the exhaust of heat and particles from the core remains a major challenge. Heat and particles leaving the core are transported via open magnetic field lines to a region of the reactor wall, called the divertor. Unabated, the heat and particle fluxes may become intolerable and damage the divertor. Controlled 'plasma detachment', a regime characterized by both a large reduction in plasma pressure and temperature at the divertor target, is required to reduce fluxes onto the divertor. Here we report a systematic approach towards achieving this critical need through feedback control of impurity emission front locations and its experimental demonstration. Our approach comprises a combination of real-time plasma diagnostic utilization, dynamic characterization of the plasma in proximity to the divertor, and efficient, reliable offline feedback controller design.

Purpose: Pedalling cadence influences respiratory frequency (f R ) during exercise, with group III/IV muscle afferents possibly mediating its effect. However, it is unclear how exercise intensity affects the link between cadence and f R . We aimed to test the hypothesis that the effect of cadence on f R is moderated by exercise intensity, with interest in the underlying mechanisms., Methods: Ten male cyclists performed a preliminary ramp incremental test and three sinusoidal experimental tests on separate visits. The experimental tests consisted of 16 min of sinusoidal variations in cadence between 115 and 55 rpm (sinusoidal period of 4 min) performed during passive exercise (PE), moderate exercise (ME) and heavy exercise (HE). The amplitude (A) and phase lag (φ) of the dependent variables were calculated., Results: During PE, f R changed in proportion to variations in cadence (r = 0.85, P < 0.001; A = 3.9 ± 1.4 breaths·min -1 ; φ = - 5.3 ± 13.9 degrees). Conversely, the effect of cadence on f R was reduced during ME (r = 0.73, P < 0.001; A = 2.6 ± 1.3 breaths·min -1 ; φ = - 25.4 ± 26.3 degrees) and even more reduced during HE (r = 0.26, P < 0.001; A = 1.8 ± 1.0 breaths·min -1 ; φ = - 70.1 ± 44.5 degrees). No entrainment was found in any of the sinusoidal tests., Conclusion: The effect of pedalling cadence on f R is moderated by exercise intensity-it decreases with the increase in work rate-and seems to be mediated primarily by group III/IV muscle afferents, at least during passive exercise.

The aim of the present paper is to examine to what extent the application of surface electromyography (sEMG) in the field of exercise and, more in general, of human movement, is adopted by professionals on a regular basis. For this purpose, a brief history of the recent developments of modern sEMG techniques will be assessed and evaluated for a potential use in exercise physiology and clinical biomechanics. The idea is to understand what are the limitations that impede the translation of sEMG to applied fields such as exercise physiology. A cost/benefits evaluation will be drawn in order to understand possible causes that prevents sEMG from being routinely adopted. Among the possible causative factors, educational, economic and technical issues will be considered. Possible corrective interventions will be proposed. We will also give an overview of the parameters that can be extracted from the decomposition of the sHDEMG signals and how this can be related by professionals for assessing the health and disease of the neuromuscular system. We discuss how the decomposition of surface EMG signals might be adopted as a new non-invasive tool for assessing the status of the neuromuscular system. Recent evidences show that is possible to monitor the changes in neuromuscular function after training of longitudinally tracked populations of motoneurons, predict the maximal rate of force development by an individual via motoneuron interfacing, and identify possible causal relations between aging and the decrease in motor performance. These technologies will guide our understanding of motor control and provide a new window for the investigation of the underlying physiological processes determining force control, which is essential for the sport and exercise physiologist. We will also illustrate the challenges related to extraction of neuromuscular parameters from global EMG analysis (i.e., root-mean-square, and other global EMG metrics) and when the decomposition is needed. We posit that the main limitation in the application of sEMG techniques to the applied field is associated to problems in education and teaching, and that most of the novel technologies are not open source., (Copyright © 2020 Felici and Del Vecchio.)

Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.

The neural factors underlying the persistency of quadriceps weakness after anterior cruciate ligament reconstruction (ACLR) have been only partially explained. This study examined muscle fiber conduction velocity (MFCV) as an indirect parameter of motor unit recruitment strategies in the vastus lateralis (VL) and medialis (VM) muscles of soccer players with ACLR. High-density surface electromyography (HDsEMG) was acquired from VL and VM in nine soccer players (22.7 ± 2.9 years; BMI: 22.08 ± 1.72 kg·m -2 ; 7.7 ± 2.2 months post-surgery). Voluntary muscle force and the relative myoelectrical activity from the reconstructed and contralateral sides were recorded during linearly increasing isometric knee extension contractions up to 70% of maximal voluntary isometric force (MVIF). The relation of MFCV and force was examined by linear regression analysis at the individual subject level. The initial (intercept), peak (MFCV 70 ), and rate of change (slope) of MFCV related to force were compared between limbs and muscles. The MVIF was lower in the reconstructed side than in the contralateral side (-%20.5; P < .05). MFCV intercept was similar among limbs and muscles (P > .05). MFCV 70 and MFCV slope were lower in the reconstructed side compared to the contralateral for both VL (-28.5% and -10.1%, respectively; P < .001) and VM (-22.6% and -8.1%, respectively; P < .001). The slope of MFCV was lower in the VL than VM, but only in the reconstructed side (-12.4%; P < .001). These results suggest possible impairments in recruitment strategies of high-threshold motor units (HTMUs) as well as deficits in sarcolemmal excitability, fiber diameter, and discharge rate of knee extensor muscles following ACLR., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Muscle fibre conduction velocity (MFCV) is a basic physiological parameter biophysically related to the diameter of muscle fibres and properties of the sarcolemma. The aim of this study was to assess the intersession reproducibility of the relation between voluntary force and estimates of average muscle fibre conduction velocity (MFCV) from multichannel high-density surface electromyographic recordings (HDsEMG). Ten healthy men performed six linearly increasing isometric ankle dorsiflexions on two separate experimental sessions, 4 weeks apart. Each session involved the recordings of voluntary force during maximal isometric (MViF) and submaximal ramp contractions at 35-50-70% of MViF. Concurrently, the HDsEMG activity was detected from the tibialis anterior muscle and MFCV estimates were derived in 250-ms epochs. Absolute and relative reproducibility of MFCV initial value (intercept) and rate of change (regression slope) as a function of force were assessed by within-subject coefficient of correlation (CV w ) and with intraclass correlation coefficient (ICC). MFCV was positively correlated with voluntary force (R 2  = 0.75 ± 0.12) in all individuals and test conditions (P < 0.001). Average CV w for MFCV intercept and slope were of 2.6 ± 2.0% and 11.9 ± 3.2% and ICC values of 0.96 and 0.94, respectively. Overall, MFCV regression coefficients showed a high degree of intersession reproducibility in both absolute and relative terms. These results may have important practical implications in the tracking of training-induced neuromuscular changes and/or in the monitoring of the progress of neuromuscular disorders when a full sEMG signal decomposition is problematic or not possible., (Copyright © 2020. Published by Elsevier Ltd.)

Recent work demonstrated that it is possible to identify motor unit discharge times from high-density surface EMG (HDEMG) decomposition. Since then, the number of studies that use HDEMG decomposition for motor unit investigations has increased considerably. Although HDEMG decomposition is a semi-automatic process, the analysis and interpretation of the motor unit pulse trains requires a thorough inspection of the output of the decomposition result. Here, we report guidelines to perform an accurate extraction of motor unit discharge times and interpretation of the signals. This tutorial includes a discussion of the differences between the extraction of global EMG signal features versus the identification of motor unit activity for physiological investigations followed by a comprehensive guide on how to acquire, inspect, and decompose HDEMG signals, and robust extraction of motor unit discharge characteristics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Muscular spasticity represents one of the most common motor disorder associated to lesions of the Central Nervous System, such as Stroke, and affects joint mobility up to the complete prevention of skeletal muscle voluntary control. Its clinical evaluation is hence of fundamental relevance for an effective rehabilitation of the affected subjects. Standard assessment protocols are usually manually performed by humans, and hence their reliability strongly depends on the capabilities of the clinical operator performing the procedures. To overcome this limitation, one solution is the usage of mechatronic devices based on the estimation of the Tonic Stretch Reflex Threshold, which allows for a quite reliable and operator-independent evaluation. In this work, we present the design and characterization of a novel mechatronic device that targets the estimation of the Tonic Stretch Reflex Threshold at the elbow level, and, at the same time, it can potentially act as a rehabilitative system. Our device can deliver controllable torque/velocity stimulation and record functional parameters of the musculo-skeletal system (joint position, torque, and multi-channel ElectroMyoGraphyc patterns), with the ultimate goals of: i) providing significant information for the diagnosis and the classification of muscular spasticity, ii) enhancing the recovery evaluation of patients undergoing through therapeutic rehabilitation procedures and iii) enabling a future active usage of this device also as therapeutic tool.Clinical relevance- The contribution presented in this work proposes a technological advancement for a device-based evaluation of motion impairment related to spasticity, with a major potential impact on both the clinical appraisal and the rehabilitation procedures.

Purpose: Motor unit conduction velocity (MUCV) represents the propagation velocity of action potentials along the muscle fibers innervated by individual motor neurons and indirectly reflects the electrophysiological properties of the sarcolemma. In this study, we investigated the effect of a 4-wk strength training intervention on the peripheral properties (MUCV and motor unit action potential amplitude, RMSMU) of populations of longitudinally tracked motor units (MU)., Methods: The adjustments exhibited by 12 individuals who participated in the training (INT) were compared with 12 controls (CON). Strength training involved ballistic (4 × 10) and sustained (3 × 10) isometric ankle dorsiflexions. Measurement sessions involved the recordings of maximal voluntary isometric force and submaximal isometric ramp contractions, whereas high-density surface EMG was recorded from the tibialis anterior. High-density surface EMG signals were decomposed into individual MU discharge timings, and MU was tracked across the intervention., Results: Maximal voluntary isometric force (+14.1%, P = 0.003) and average MUCV (+3.0%, P = 0.028) increased in the INT group, whereas normalized MU recruitment threshold (RT) decreased (-14.9%, P = 0.001). The slope (rate of change) of the regression between MUCV and MU RT increased only in the INT group (+32.6%, P = 0.028), indicating a progressive greater increase in MUCV for higher-threshold MU. The intercept (initial value) of MUCV did not change after the intervention (P = 0.568). The association between RMSMU and MU RT was not altered by the training., Conclusion: The increase in the rate of change in MUCV as a function of MU RT, but not the initial value of MUCV, suggests that short-term strength training elicits specific adaptations in the electrophysiological properties of the muscle fiber membrane in high-threshold MU.

Purpose: Variables currently used in soccer training monitoring fail to represent the physiological demand of the player during movements like accelerations, decelerations, and directional changes performed at high intensity. We tested the hypothesis that respiratory frequency (fR) is a marker of physical effort during soccer-related high-intensity exercise., Methods: A total of 12 male soccer players performed a preliminary intermittent incremental test and 2 shuttle-run high-intensity interval training (HIIT) protocols, in separate visits. The 2 HIIT protocols consisted of 12 repetitions over 9 minutes and differed in the work-to-recovery ratio (15:30 vs 30:15 s). Work rate was self-paced by participants to achieve the longest possible total distance in each HIIT protocol., Results: Work-phase average metabolic power was higher (P < .001) in the 15:30-second protocol (31.7 [3.0] W·kg-1) compared with the 30:15-second protocol (22.8 [2.0] W·kg-1). Unlike heart rate and oxygen uptake, fR showed a fast response to the work-recovery alternation during both HIIT protocols, resembling changes in metabolic power even at supramaximal intensities. Large correlations (P < .001) were observed between fR and rating of perceived exertion during both 15:30-second (r = .87) and 30:15-second protocols (r = .85)., Conclusions: Our findings suggest that fR is a good marker of physical effort during shuttle-run HIIT in soccer players. These findings have implications for monitoring training in soccer and other team sports.

Background and Purpose: Recurrent middle ear cholesteatomas are commonly preoperatively assessed using MR imaging (non-EPI-DWI) and CT. Both modalities are used with the aim of distinguishing scar tissue from cholesteatoma and determining the extent of bone erosions. Inflammation and scar tissue associated with the lesions might hamper a proper delineation of the corresponding extensions on CT images. Using surgical findings as the criterion standard, we assessed the recurrent middle ear cholesteatoma extent using either uncoregistered or fused CT-MR imaging datasets and determined the corresponding accuracy and repeatability., Materials and Methods: Twenty consecutive patients with suspected recurrent middle ear cholesteatoma and preoperative CT-MR imaging datasets were prospectively included. A double-blind assessment and coregistration of the recurrent middle ear cholesteatoma extent and manual delineation of 18 presumed recurrent middle ear cholesteatomas were performed by 2 radiologists and compared with the criterion standard. "Reliability score" was defined to qualify radiologists' confidence. For each volume, segmentation repeatability was assessed on the basis of intraclass correlation coefficient and overlap indices., Results: For the whole set of patients, recurrent middle ear cholesteatoma was further supported by surgical results. Two lesions were excluded from the analysis, given that MR imaging did not show a restricted diffusion. Lesions were accurately localized using the fused datasets, whereas significantly fewer lesions (85%) were correctly localized using uncoregistered images. Reliability scores were larger for fused datasets. Segmentation repeatability showed an almost perfect intraclass correlation coefficient regarding volumes, while overlaps were significantly lower in uncoregistered (52%) compared with fused (60%, P < .001) datasets., Conclusions: The use of coregistered CT-MR images significantly improved the assessment of recurrent middle ear cholesteatoma with a greater accuracy and better reliability and repeatability., (© 2019 by American Journal of Neuroradiology.)

Correlation between motor unit discharge times, often referred to as motor unit synchronization, is determined by common synaptic input to motor neurons. Although it has been largely speculated that synchronization should influence the rate of force development, the association between the degree of motor unit synchronization and rapid force generation has not been determined. In this study, we examined this association with both simulations and experimental motor unit recordings. The analysis of experimental motor unit discharges from the tibialis anterior muscle of 20 healthy individuals during rapid isometric contractions revealed that the average motor unit discharge rate was associated with the rate of force development. Moreover, the extent of motor unit synchronization was entirely determined by the average motor unit discharge rate ( R > 0.7, P < 0.0001). The simulation model demonstrated that the relative proportion of common synaptic input received by motor neurons, which determines motor unit synchronization, does not influence the rate of force development ( R  = 0.03, P > 0.05). Nonetheless, the estimates of correlation between motor unit spike trains were significantly correlated with the rate of force generation ( R > 0.8, P < 0.0001). These results indicate that the average motor unit discharge rate, but not the degree of motor unit synchronization, contributes to most of the variance of human contractile speed among individuals. In addition, estimates of correlation between motor unit discharge times depend strongly on the number of identified motor units and therefore are not indicative of the strength of common input. NEW & NOTEWORTHY It is commonly assumed that motor unit synchronization has an impact on the rate of force development of a muscle. Here we present computer simulations and experimental data of human tibialis anterior motor units during rapid contractions that show that motor unit synchronization is not a determinant of the rate of force production. This conclusion clarifies the neural determinants of rapid force generation.

Key Points: We propose and validate a method for accurately identifying the activity of populations of motor neurons during contractions at maximal rate of force development in humans. The behaviour of the motor neuron pool during rapid voluntary contractions in humans is presented. We show with this approach that the motor neuron recruitment speed and maximal motor unit discharge rate largely explains the individual ability in generating rapid force contractions. The results also indicate that the synaptic inputs received by the motor neurons before force is generated dictate human potential to generate force rapidly. This is the first characterization of the discharge behaviour of a representative sample of human motor neurons during rapid contractions., Abstract: During rapid contractions, motor neurons are recruited in a short burst and begin to discharge at high frequencies (up to >200 Hz). In the present study, we investigated the behaviour of relatively large populations of motor neurons during rapid (explosive) contractions in humans, applying a new approach to accurately identify motor neuron activity simultaneous to measuring the rate of force development. The activity of spinal motor neurons was assessed by high-density electromyographic decomposition from the tibialis anterior muscle of 20 men during isometric explosive contractions. The speed of motor neuron recruitment and the instantaneous motor unit discharge rate were analysed as a function of the impulse (the time-force integral) and the maximal rate of force development. The peak of motor unit discharge rate occurred before force generation and discharge rates decreased thereafter. The maximal motor unit discharge rate was associated with the explosive force variables, at the whole population level (r 2  = 0.71 ± 0.12; P < 0.001). Moreover, the peak motor unit discharge and maximal rate of force variables were correlated with an estimate of the supraspinal drive, which was measured as the speed of motor unit recruitment before the generation of afferent feedback (P < 0.05). We show for the first time the full association between the effective neural drive to the muscle and human maximal rate of force development. The results obtained in the present study indicate that the variability in the maximal contractile explosive force of the human tibialis anterior muscle is determined by the neural activation preceding force generation., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Key Points: Previous studies have indicated that several weeks of strength training is sufficient to elicit significant adaptations in the neural drive sent to the muscles. There are few data, however, on the changes elicited by strength training in the recruitment and rate coding of motor units during voluntary contractions. We show for the first time that the discharge characteristics of motor units in the tibialis anterior muscle tracked across the intervention are changed by 4 weeks of strength training with isometric voluntary contractions. The specific adaptations included significant increases in motor unit discharge rate, decreases in the recruitment-threshold force of motor units and a similar input-output gain of the motor neurons. The findings suggest that the adaptations in motor unit function may be attributable to changes in synaptic input to the motor neuron pool or to adaptations in intrinsic motor neuron properties., Abstract: The strength of a muscle typically begins to increase after only a few sessions of strength training. This increase is usually attributed to changes in the neural drive to muscle as a result of adaptations at the cortical or spinal level. We investigated the change in the discharge characteristics of large populations of longitudinally tracked motor units in tibialis anterior before and after 4 weeks of strength training the ankle-dorsiflexor muscles with isometric contractions. The adaptations exhibited by 14 individuals were compared with 14 control subjects. High-density electromyogram grids with 128 electrodes recorded the myoelectric activity during isometric ramp contractions to the target forces of 35%, 50% and 70% of maximal voluntary force. The motor unit recruitment and derecruitment thresholds, discharge rate, interspike intervals and estimates of synaptic inputs to motor neurons were assessed. The normalized recruitment-threshold forces of the motor units were decreased after strength training (P < 0.05). Moreover, discharge rate increased by 3.3 ± 2.5 pps (average across subjects and motor units) during the plateau phase of the submaximal isometric contractions (P < 0.001). Discharge rates at recruitment and derecruitment were not modified by training (P < 0.05). The association between force and motor unit discharge rate during the ramp-phase of the contractions was also not altered by training (P < 0.05). These results demonstrate for the first time that the increase in muscle force after 4 weeks of strength training is the result of an increase in motor neuron output from the spinal cord to the muscle., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

The aim of the present investigation was to test the hypothesis that quercetin (Q) may prevent the strength loss and neuromuscular impairment associated with eccentric exercise-induced muscle damage (EEIMD). Twelve young men (26.1 ± 3.1 years) ingested either Q (1000 mg/day) or placebo (PLA) for 14 days using a randomized, double-blind, crossover study design. Participants completed a comprehensive neuromuscular (NM) evaluation before, during and after an eccentric protocol able to induce a severe muscle damage (10 sets of 10 maximal lengthening contractions). The NM evaluation comprised maximal voluntary isometric contraction (MVIC) and force⁻velocity relationship assessments with simultaneous recording of electromyographic signals (EMG) from the elbow flexor muscles. Soreness, resting arm angle, arm circumference, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) were also assessed. Q supplementation significantly increased the isometric strength recorded during MVIC compared to baseline (+4.7%, p < 0.05). Moreover, the torque and muscle fiber conduction velocity (MFCV) decay recorded during the eccentric exercise was significant lower in Q compared to PLA. Immediately after the EEIMD, isometric strength, the force⁻velocity relationship and MFCV were significantly lower when participants were given PLA rather than Q. Fourteen days of Q supplementation seems able to attenuate the severity of muscle weakness caused by eccentric-induced myofibrillar disruption and sarcolemmal action potential propagation impairment.

Introduction: One aim of the long-term care in survivors from acute lymphoblastic leukemia (ALL) during childhood is to avoid or limit complications caused by aggressive therapeutic strategies., Areas Covered: ALL survivors are a heterogeneous group according to therapeutic protocols. In the last decades, cranial radiotherapy (cRT) has been largely replaced by intrathecal chemotherapy (CT) with a reduction of endocrine sequelae. Published studies are generally difficult to be interpreted because patients were treated according to different risk-adapted protocols and results are conflicting. We perform this review on endocrine long-term effects in childhood ALL survivors focusing on studies published in the last decades. Articles were selected using the following terms (Mesh terms): 'acute lymphoblastic leukemia' AND 'survivors' AND 'childhood' AND 'growth/puberty/fertility/obesity/metabolic syndrome/bone'., Expert Commentary: Most childhood ALL survivors treated with CT alone attain normal height and have adequate pubertal development. Despite recent protocols improvements, ALL survivors still develop long-term metabolic complications (overweight, obesity, and cardiovascular disease) especially the female gender and patients with an increased body mass index (BMI) at diagnosis. The aim of this review is to describe the state of the art on these topics. We should be able to anticipate, prevent, and treat endocrine long-term morbidities through a well-established follow-up strategy.

Differentiating between respiratory frequency (f R ) and tidal volume (V T ) may improve our understanding of exercise hyperpnoea because f R and V T seem to be regulated by different inputs. We designed a series of exercise manipulations to improve our understanding of how f R and V T are regulated during exercise. Twelve cyclists performed an incremental test and three randomized experimental sessions in separate visits. In two of the three experimental visits, participants performed a moderate-intensity sinusoidal test followed, after recovery, by a moderate-to-severe-intensity sinusoidal test. These two visits differed in the period of the sinusoid (2 min vs. 8 min). In the third experimental visit, participants performed a trapezoidal test where the workload was self-paced in order to match a predefined trapezoidal template of rating of perceived exertion (RPE). The results collectively reveal that f R changes more with RPE than with workload, gas exchange, V T or the amount of muscle activation. However, f R dissociates from RPE during moderate exercise. Both V T and minute ventilation ( V ˙ E ) showed a similar time course and a large correlation with V ˙ CO 2 in all the tests. Nevertheless, V ˙ CO 2 was associated more with V ˙ E than with V T because V T seems to adjust continuously on the basis of f R levels to match V ˙ E with V ˙ CO 2 . The present findings provide novel insight into the differential control of f R and V T - and their unbalanced interdependence - during exercise. The emerging conceptual framework is expected to guide future research on the mechanisms underlying the long-debated issue of exercise hyperpnoea., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)