Neuromuscular drive and force production are not altered during bilateral contractions

Jakobi, J. M., and E. Cafarelli. Neuromuscular driveand force production are not altered during bilateral contractions. J. Appl. Physiol. 84(1): 200-206, 1998.Several investigators have studied the deficit in maximalvoluntary force that is said to occur when bilateral muscle groupscontract simultaneously. A true bilateral deficit (BLD) would suggest asignificant limitation of neuromuscular control; however, some of thedata from studies in the literature are equivocal. Our purpose was todetermine whether there is a BLD in the knee extensors of untrainedyoung male subjects during isometric contractions and whether thisdeficit is associated with a decreased activation of the quadriceps,increased activation of the antagonist muscle, or an alteration inmotor unit firing rates. Twenty subjects performed unilateral (UL) and bilateral (BL) isometric knee extensions at 25, 50, 75, and 100% maximal voluntary contraction. Total UL and BL force (3%) and maximal rate of force generation (2.5%) were not significantly different. Total UL and BL maximal vastus lateralis electromyographic activity (EMG; 2.7 ± 0.28 vs. 2.6 ± 0.24 mV) andcoactivation (0.17 ± 0.02 vs. 0.20 ± 0.02 mV) were also notdifferent. Similarly, the ratio of force to EMG during submaximal ULand BL contractions was not different. Analysis of force production byeach leg in UL and BL conditions showed no differences in force, rateof force generation, EMG, motor unit firing rates, and coactivation.Finally, assessment of quadriceps activity with the twitchinterpolation technique indicated no differences in the degree ofvoluntary muscle activation (UL: 93.6 ± 2.51 Hz, BL: 90.1 ± 2.43 Hz). These results provide no evidence of a significant limitationin neuromuscular control between BL and UL isometric contractions ofthe knee extensor muscles in young male subjects.

     

Differences in Supraspinal and Spinal Excitability during Various Force Outputs of the Biceps Brachii in Chronic- and Non-Resistance Trained Individuals

Motor evoked potentials (MEP) and cervicomedullary evoked potentials (CMEP) may help determine the corticospinal adaptations underlying chronic resistance training-induced increases in voluntary force production. The purpose of the study was to determine the effect of chronic resistance training on corticospinal excitability (CE) of the biceps brachii during elbow flexion contractions at various intensities and the CNS site (i.e. supraspinal or spinal) predominantly responsible for any training-induced differences in CE. Fifteen male subjects were divided into two groups: 1) chronic resistance-trained (RT), (n = 8) and 2) non-RT, (n = 7). Each group performed four sets of ∼5 s elbow flexion contractions of the dominant arm at 10 target forces (from 10%–100% MVC). During each contraction, subjects received 1) transcranial magnetic stimulation, 2) transmastoid electrical stimulation and 3) brachial plexus electrical stimulation, to determine MEP, CMEP and compound muscle action potential (M_max) amplitudes, respectively, of the biceps brachii. All MEP and CMEP amplitudes were normalized to M_max. MEP amplitudes were similar in both groups up to 50% MVC, however, beyond 50% MVC, MEP amplitudes were lower in the chronic RT group (p<0.05). CMEP amplitudes recorded from 10–100% MVC were similar for both groups. The ratio of MEP amplitude/absolute force and CMEP amplitude/absolute force were reduced (p<0.012) at all contraction intensities from 10–100% MVC in the chronic-RT compared to the non-RT group. In conclusion, chronic resistance training alters supraspinal and spinal excitability. However, adaptations in the spinal cord (i.e. motoneurone) seem to have a greater influence on the altered CE.     

Increased rate of force development and neural drive of human skeletal muscle following resistance training.

The maximal rate of rise in muscle force [rate of force development (RFD)] has important functional consequences as it determines the force that can be generated in the early phase of muscle contraction (0-200 ms). The present study examined the effect of resistance training on contractile RFD and efferent motor outflow ("neural drive") during maximal muscle contraction. Contractile RFD (slope of force-time curve), impulse (time-integrated force), electromyography (EMG) signal amplitude (mean average voltage), and rate of EMG rise (slope of EMG-time curve) were determined (1-kHz sampling rate) during maximal isometric muscle contraction (quadriceps femoris) in 15 male subjects before and after 14 wk of heavy-resistance strength training (38 sessions). Maximal isometric muscle strength [maximal voluntary contraction (MVC)] increased from 291.1 +/- 9.8 to 339.0 +/- 10.2 N. m after training. Contractile RFD determined within time intervals of 30, 50, 100, and 200 ms relative to onset of contraction increased from 1,601 +/- 117 to 2,020 +/- 119 (P < 0.05), 1,802 +/- 121 to 2,201 +/- 106 (P < 0.01), 1,543 +/- 83 to 1,806 +/- 69 (P < 0.01), and 1,141 +/- 45 to 1,363 +/- 44 N. m. s(-1) (P < 0.01), respectively. Corresponding increases were observed in contractile impulse (P < 0.01-0.05). When normalized relative to MVC, contractile RFD increased 15% after training (at zero to one-sixth MVC; P < 0.05). Furthermore, muscle EMG increased (P < 0.01-0.05) 22-143% (mean average voltage) and 41-106% (rate of EMG rise) in the early contraction phase (0-200 ms). In conclusion, increases in explosive muscle strength (contractile RFD and impulse) were observed after heavy-resistance strength training. These findings could be explained by an enhanced neural drive, as evidenced by marked increases in EMG signal amplitude and rate of EMG rise in the early phase of muscle contraction.     

Contraction type influences the human ability to use the available torque capacity of skeletal muscle during explosive efforts

The influence of contraction type on the human ability to use the torque capacity of skeletal muscle during explosive efforts has not been documented. Fourteen male participants completed explosive voluntary contractions of the knee extensors in four separate conditions: concentric (CON) and eccentric (ECC); and isometric at two knee angles (101°, ISO101 and 155°, ISO155). In each condition, torque was measured at 25 ms intervals up to 150 ms from torque onset, and then normalized to the maximum voluntary torque (MVT) specific to that joint angle and angular velocity. Explosive voluntary torque after 50 ms in each condition was also expressed as a percentage of torque generated after 50 ms during a supramaximal 300 Hz electrically evoked octet in the same condition. Explosive voluntary torque normalized to MVT was more than 60 per cent larger in CON than any other condition after the initial 25 ms. The percentage of evoked torque expressed after 50 ms of the explosive voluntary contractions was also greatest in CON (ANOVA; p < 0.001), suggesting higher concentric volitional activation. This was confirmed by greater agonist electromyography normalized to M(max) (recorded during the explosive voluntary contractions) in CON. These results provide novel evidence that the ability to use the muscle's torque capacity explosively is influenced by contraction type, with concentric contractions being more conducive to explosive performance due to a more effective neural strategy.     

Differences in stretch reflex responses of elbow flexor muscles during shortening, lengthening and isometric contractions

Stretch reflexes were evoked in elbow flexor muscles undergoing three different muscle contractions, i.e. isotonic shortening (SHO) and lengthening (LEN), and isometric (ISO) contractions. The intermuscle relationships for the magnitude of the stretch reflex component in the eletromyographic (EMG) activities of two main elbow flexor muscles, i.e. the biceps brachii (BB) and the brachioradialis (BRD), were compared among the three types of contractions. The subjects were requested to move their forearms sinusoidally (0.1 Hz) against a constant pre-load between elbow joint angles of 10° (0° = full extension) and 80° during SHO and LEN, and to keep an angle of 45° during the ISO. The perturbations were applied at the elbow angle of 45° in pseudo-random order. The EMG signals were rectified and averaged over a period of 100 ms before and 400 ms after the onset of the perturbation 40–50 times. From the ensemble averaged EMG waveform, the background activity (BGA), short (20–50 ms) and long latency (M2, 50–80, M3, 80–100 ms) reflex and voluntary activity (100–150 ms) components were measured. The results showed that both BGA and reflex EMG activity of the two elbow flexor muscles were markedly decreased during the lengthening contraction compared to the SHO and ISO contractions. Furthermore, the changes of reflex EMG components in the BRD muscle were more pronounced than those in the BB muscle, i.e. the ratios of M2 and M3 magnitudes between BRD and BB (BRD:BB) were significantly reduced during the LEN contractions. These results would suggest that the gain of long latency stretch reflex EMG activities in synergistic muscles might be modulated independently according to the model of muscle contraction. Accepted: 1 September 1997     

The rate of force development obtained at early contraction phase is not influenced by active static stretching

The objective of this study was to investigate the influence of active static stretching on the maximal isometric muscle strength (maximal voluntary contraction [MVC]) and rate of force development (RFD) determined within time intervals of 30, 50, 100, and 200 milliseconds relative to the onset of muscle contraction. Fifteen men (aged 21.3 ± 2.4 years) were submitted on different days to the following tests: (a) familiarization session to the isokinetic dynamometer; (b) 2 maximal isometric contractions for knee extensors in the isokinetic dynamometer to determine MVC and RFD (control); and (c) 2 active static stretching exercises for the dominant leg extensors (10 × 30 seconds for each exercise with a 20-second rest interval between bouts). After stretching, the isokinetic test was repeated (poststretching). Conditions 2 and 3 were performed in random order. The RFD was considered as the mean slope of the moment-time curve at time intervals of 0-30, 0-50, 0-100; 0-150; and 0200 milliseconds relative to the onset of muscle contraction. The MVC was reduced after stretching (285 ± 59 vs. 271 ± 56 N · m, p < 0.01). The RFD at intervals of 0-30, 0-50, and 0-100 milliseconds was unchanged after stretching (p > 0.05). However, the RFD measured at intervals of 0-150 and 0-200 milliseconds was significantly lower after stretching (p < 0.01). It can be concluded that explosive muscular actions of a very short duration (<100 milliseconds) seem less affected by active static stretching when compared with actions using maximal muscle strength.     

Neuromuscular Activation of the Vastus Intermedius Muscle during Isometric Hip Flexion

Although activity of the rectus femoris (RF) differs from that of the other synergists in quadriceps femoris muscle group during physical activities in humans, it has been suggested that the activation pattern of the vastus intermedius (VI) is similar to that of the RF. The purpose of present study was to examine activation of the VI during isometric hip flexion. Ten healthy men performed isometric hip flexion contractions at 25%, 50%, 75%, and 100% of maximal voluntary contraction at hip joint angles of 90°, 110° and 130°. Surface electromyography (EMG) was used to record activity of the four quadriceps femoris muscles and EMG signals were root mean square processed and normalized to EMG amplitude during an isometric knee extension with maximal voluntary contraction. The normalized EMG was significantly higher for the VI than for the vastus medialis during hip flexion at 100% of maximal voluntary contraction at hip joint angles of 110° and 130° (P < 0.05). The onset of VI activation was 230–240 ms later than the onset of RF activation during hip flexion at each hip joint angle, which was significantly later than during knee extension at 100% of maximal voluntary contraction (P < 0.05). These results suggest that the VI is activated later than the RF during hip flexion. Activity of the VI during hip flexion might contribute to stabilize the knee joint as an antagonist and might help to smooth knee joint motion, such as in the transition from hip flexion to knee extension during walking, running and pedaling.     

Force Control Is Related to Low-Frequency Oscillations in Force and Surface EMG

Force variability during constant force tasks is directly related to oscillations below 0.5 Hz in force. However, it is unknown whether such oscillations exist in muscle activity. The purpose of this paper, therefore, was to determine whether oscillations below 0.5 Hz in force are evident in the activation of muscle. Fourteen young adults (21.07±2.76 years, 7 women) performed constant isometric force tasks at 5% and 30% MVC by abducting the left index finger. We recorded the force output from the index finger and surface EMG from the first dorsal interosseous (FDI) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) power spectrum of force below 2 Hz; 3) EMG bursts; 4) power spectrum of EMG bursts below 2 Hz; and 5) power spectrum of the interference EMG from 10–300 Hz. The SD of force increased significantly from 5 to 30% MVC and this increase was significantly related to the increase in force oscillations below 0.5 Hz (R ² = 0.82). For both force levels, the power spectrum for force and EMG burst was similar and contained most of the power from 0–0.5 Hz. Force and EMG burst oscillations below 0.5 Hz were highly coherent (coherence = 0.68). The increase in force oscillations below 0.5 Hz from 5 to 30% MVC was related to an increase in EMG burst oscillations below 0.5 Hz (R ² = 0.51). Finally, there was a strong association between the increase in EMG burst oscillations below 0.5 Hz and the interference EMG from 35–60 Hz (R ² = 0.95). In conclusion, this finding demonstrates that bursting of the EMG signal contains low-frequency oscillations below 0.5 Hz, which are associated with oscillations in force below 0.5 Hz.     

Hamstring Muscle Fatigue and Central Motor Output during a Simulated Soccer Match

Purpose

To examine changes in hamstring muscle fatigue and central motor output during a 90-minute simulated soccer match, and the concomitant changes in hamstring maximal torque and rate of torque development.

Method

Eight amateur male soccer players performed a 90-minute simulated soccer match, with measures performed at the start of and every 15-minutes during each half. Maximal torque (Nm) and rate of torque development (RTD; Nm.s^–1) were calculated from maximal isometric knee flexor contractions performed at 10° of flexion. Hamstring peripheral fatigue was assessed from changes in the size and shape of the resting twitch (RT). Hamstring central motor output was quantified from voluntary activation (%) and normalized biceps femoris (BF) and medial hamstrings (MH) electromyographic amplitudes (EMG/M).

Results

Maximal torque was reduced at 45-minutes by 7.6±9.4% (p<0.05). RTD in time intervals of 0–25, 0–50, and 0–75 ms post-contraction onset were reduced after 15-minutes in the first-half between 29.6 to 46.2% (p<0.05), and were further reduced at the end of the second-half (p<0.05). Maximal EMG/M was reduced for biceps femoris only concomitant to the time-course of reductions in maximal torque (p = 0.007). The rate of EMG rise for BF and MH was reduced in early time periods (0–75 ms) post-contraction onset (p<0.05). No changes were observed for the size and shape of the RT, indicating no hamstring peripheral fatigue.

Conclusion

Centrally mediated reductions in maximal torque and rate of torque development provide insight into factors that may explain hamstring injury risk during soccer. Of particular interest were early reductions during the first-half of hamstring rate of torque development, and the decline in maximal EMG/M of biceps femoris in the latter stages of the half. These are important findings that may help explain why the hamstrings are particularly vulnerable to strain injury during soccer.     

Electromechanical delay in isometric muscle contractions evoked by voluntary, reflex and electrical stimulation

Electromechanical delay (EMD) in isometric contractions of knee extensors evoked by voluntary, tendon reflex (TR) and electrical stimulation (ES) was investigated in 21 healthy young subjects. The subject performed voluntary knee extensions with maximum effort (maximal voluntary contraction, MVC), and at 30%, 60% and 80% MVC. Patellar tendon reflexes were evoked with the reflex hammer being dropped from 60°, 75° and 90° positions. In the percutaneous ES evoked contractions, single switches were triggered with pulses of duration 1.0 ms and of intensities 90, 120 and 150 V. Electromyograms of the vastus lateralis and rectus femoris muscles were recorded using surface electrodes. The isometric knee extension force was recorded using a load cell force transducer connected to the subject's lower leg. The major finding of this study was that EMD of the involuntary contractions [e.g. mean 22.1 (SEM 1.32) ms in TR 90°; mean 17.2 (SEM 0.62) ms in ES 150 V] was significantly shorter than that of the voluntary contractions [e.g. mean 38.7 (SEM 1.18) ms in MVC,P < 0.05]. The relationships between EMD, muscle contractile properties and muscle fibre conduction velocity were also investigated. Further study is needed to explain fully the EMD differences found between the voluntary and involuntary contractions.     

Fluid Overload,Pulse Wave Velocity,and Ratio of Brachial Pre-Ejection Period to Ejection Time in Diabetic and Non-Diabetic Chronic Kidney Disease

Fluid overload is one of the characteristics in chronic kidney disease (CKD). Changes in extracellular fluid volume are associated with progression of diabetic nephropathy. Not only diabetes but also fluid overload is associated with cardiovascular risk factors The aim of the study was to assess the interaction between fluid overload, diabetes, and cardiovascular risk factors, including arterial stiffness and left ventricular function in 480 patients with stages 4–5 CKD. Fluid status was determined by bioimpedance spectroscopy method, Body Composition Monitor. Brachial-ankle pulse wave velocity (baPWV), as a good parameter of arterial stiffness, and brachial pre-ejection period (bPEP)/brachial ejection time (bET), correlated with impaired left ventricular function were measured by ankle-brachial index (ABI)-form device. Of all patients, 207 (43.9%) were diabetic and 240 (50%) had fluid overload. For non-diabetic CKD, fluid overload was associated with being female (β = –2.87, P = 0.003), heart disease (β = 2.69, P = 0.04), high baPWV (β = 0.27, P = 0.04), low hemoglobin (β = –1.10, P<0.001), and low serum albumin (β = –5.21, P<0.001) in multivariate analysis. For diabetic CKD, fluid overload was associated with diuretics use (β = 3.69, P = 0.003), high mean arterial pressure (β = 0.14, P = 0.01), low bPEP/ET (β = –0.19, P = 0.03), low hemoglobin (β = –1.55, P = 0.001), and low serum albumin (β = –9.46, P<0.001). In conclusion, baPWV is associated with fluid overload in non-diabetic CKD and bPEP/bET is associated with fluid overload in diabetic CKD. Early and accurate assessment of these associated cardiovascular risk factors may improve the effects of entire care in late CKD.     

Hepatitis B Vaccine Responsiveness and Clinical Outcomes in HIV Controllers

Background

Hepatitis B virus (HBV) vaccine responsiveness is associated with reduced risk of AIDS or death in HIV-infected individuals. Although HIV controllers (HIC) typically have favorable immunologic and clinical characteristics compared to non-controllers, vaccine responsiveness has not been studied.

Methods and Findings

In the U.S. Military HIV Natural History Study, HBV vaccine response was defined as antibody to hepatitis B surface antigen (anti-HBs) ≥10 IU/L after last vaccination. For determination of vaccine responsiveness, HIC (n = 44) and treatment-naïve non-controllers (n = 476) were not on highly active antiretroviral therapy (HAART) when vaccinated while treated non-controllers (n = 284) received all HBV vaccine doses during viral load (VL)-suppressive HAART. Progression to AIDS or death was also compared for all HIC (n = 143) and non-controllers (n = 1566) with documented anti-HBs regardless of the timing of HBV vaccination. Positive vaccine responses were more common in HIC (65.9%) compared to HAART-naïve non-controllers (36.6%; P<0.001), but similar to non-controllers on HAART (59.9%; P = 0.549). Factors associated with vaccine response for HIC compared to HAART-naïve non-controllers include HIC status (OR 2.65, 95% CI 1.23–5.89; P = 0.014), CD4 count at last vaccination (OR 1.28, 1.15–1.45 for every 100 cells/uL; P<0.001), and number of vaccine doses administered (OR 0.56, 0.35–0.88; P = 0.011). When HIC were compared to non-controllers on HAART, only CD4 count at last vaccination was significant (OR 1.23, 1.1–1.38 for every 100 cells/uL; P<0.001). The rate of AIDS or death per 100 person/years for HIC compared to non-controllers was 0.14 (95% CI 0–0.76) versus 0.98 (95% CI 0.74–1.28) for vaccine responders and 0 (95% CI 0–2.22) versus 4.11 (95% CI 3.38–4.96) for non-responders, respectively.

Conclusions

HIC have improved HBV vaccine responsiveness compared to treatment-naïve non-controllers, but similar to those on VL-suppressive HAART. Progression to AIDS or death can be predicted by HBV vaccine responder status for non-controllers, however these events are rarely observed in HIC.     

Downregulated E-Cadherin Expression Indicates Worse Prognosis in Asian Patients with Colorectal Cancer: Evidence from Meta-Analysis

Background

Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive.

Methodology

Eligible studies were searched from the PubMed, Embase and Web of Science databases. Correlation between E-cadherin expression and clinicopathological features and prognosis was analyzed. Subgroup analysis was also performed according to study location, number of patients, quality score of studies and cut-off value.

Principal Findings

A total of 27 studies comprising 4244 cases met the inclusion criteria. Meta-analysis suggested that downregulated E-cadherin expression had an unfavorable impact on overall survival (OS) of CRC (n = 2730 in 14 studies; HR = 2.27, 95%CI: 1.63–3.17; Z = 4.83; P = 0.000). Subgroup analysis indicated that low E-cadherin expression was significantly associated with worse OS in Asian patients (n = 1054 in 9 studies; HR = 2.86, 95%CI: 2.13–3.7, Z = 7.11; P = 0.000) but not in European patients (n = 1552 in 4 studies; HR = 1.14, 95%CI: 0.95–1.35, Z = 1.39; P = 0.165). In addition, reduced E-cadherin expression indicated an unfavorable OS only when the cut off value of low E-cadherin expression was >50% (n = 512 in 4 studies; HR = 2.08, 95%CI 1.45–2.94, Z = 4.05; P = 0.000). Downregulated E-cadherin expression was greatly related with differentiation grade, Dukes'' stages, lymphnode status and metastasis. The pooled OR was 0.36(95%CI: 0.19–0.7, Z = 3.03, P = 0.002), 0.34(95%CI: 0.21–0.55, Z = 6.61, P = 0.000), 0.49(95%CI: 0.32–0.74, Z = 3.02, P = 0.002) and 0.45(95%CI: 0.22–0.91, Z = 3.43, P = 0.001), respectively.

Conclusions

This study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC. However, downregulated E-cadherin expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients. Additionally, this meta-analysis suggested that the negative threshold of E-cadherin should be >50% when we detected its expression in the immunohistochemistry stain.     

Inter-Individual Difference in the Effect of Mirror Reflection-Induced Visual Feedback on Phantom Limb Awareness in Forearm Amputees

Objective

To test whether the phantom limb awareness could be altered by observing mirror reflection-induced visual feedback (MVF) in unilateral forearm amputees.

Methods

Ten unilateral forearm amputees were asked to perform bilateral (intact and phantom) synchronous wrist motions with and without MVF. During wrist motion, electromyographic activities in the extensor digitorum longus (EDL) and flexor carpi radialis muscles (FCR) were recorded with bipolar electrodes. Degree of wrist range of motion (ROM) was also recorded by electrogoniometry attached to the wrist joint of intact side. Subjects were asked to answer the degree of attainment of phantom limb motion using a visual analog scale (VAS: ranging from 0 (hard) to 10 (easy)).

Results

VAS and ROM were significantly increased by utilizing MVF, and the extent of an enhancement of the VAS and wrist ROM was positively correlated (r = 0.72, p<0.05). Although FCR EMG activity also showed significant enhancement by MVF, this was not correlated with the changes of VAS and ROM. Interestingly, while we found negative correlation between EDL EMG activity and wrist ROM, MVF generally affected to be increasing both EDL EMG and ROM.

Conclusions

Although there was larger extent of variability in the effect of MVF on phantom limb awareness, MVF has a potential to enhance phantom limb awareness, in case those who has a difficulty for the phantom limb motion. The present result suggests that the motor command to the missing limb can be re-activated by an appropriate therapeutic strategy such as mirror therapy.     

Effect of Hypohydration on Peripheral and Corticospinal Excitability and Voluntary Activation

We investigated whether altered peripheral and/or corticospinal excitatory output and voluntary activation are implicated in hypohydration-induced reductions in muscle isometric and isokinetic (90°.s⁻¹) strength. Nine male athletes completed two trials (hypohydrated, euhydrated) comprising 90 min cycling at 40°C, with body weight losses replaced in euhydrated trial. Peripheral nerve and transcranial magnetic stimulations were applied during voluntary contractions pre- and 40 min post-exercise to quantify voluntary activation and peripheral (M-wave) and corticospinal (motor evoked potential) evoked responses in m. vastus medialis. Both maximum isometric (−15.3±3.1 vs −5.4±3.5%) and isokinetic eccentric (−24.8±4.6 vs −7.3±7.2%) torque decreased to a greater extent in hypohydrated than euhydrated trials (p<0.05). Half relaxation time of the twitch evoked by peripheral nerve stimulation during maximal contractions increased after exercise in the hypohydrated (21.8±9.3%) but stayed constant in the euhydrated (1.6±10.7%; p = 0.017) condition. M-wave amplitude during maximum voluntary contraction increased after exercise in the heat in hypohydrated (10.7±18.0%) but decreased in euhydrated condition (−17.4±16.9%; p = 0.067). Neither peripheral nor cortical voluntary activation were significantly different between conditions. Motor evoked potential amplitude increased similarly in both conditions (hypohydrated: 25.7±28.5%; euhydrated: 52.9±33.5%) and was accompanied by lengthening of the cortical silent period in euhydrated but not hypohydrated condition (p = 0.019). Different neural strategies seem to be adopted to regulate neural drive in the two conditions, with increases in inhibitory input of either intracortical or corticospinal origin during the euhydrated trial. Such changes were absent in the hypohydrated condition, yet voluntary activation was similar to the euhydrated condition, perhaps due to smaller increases in excitatory drive rather than increased inhibition. Despite this maximal isometric and eccentric strength were impaired in the hypohydrated condition. The increase in peripheral muscle excitability evident in the hypohydrated condition was not sufficient to preserve performance in the face of reduced muscle contractility or impaired excitation-contraction coupling.     

Change in the Ipsilateral Motor Cortex Excitability Is Independent from a Muscle Contraction Phase during Unilateral Repetitive Isometric Contractions

The aim of this study was to investigate the difference in a muscle contraction phase dependence between ipsilateral (ipsi)- and contralateral (contra)-primary motor cortex (M1) excitability during repetitive isometric contractions of unilateral index finger abduction using a transcranial magnetic stimulation (TMS) technique. Ten healthy right-handed subjects participated in this study. We instructed them to perform repetitive isometric contractions of the left index finger abduction following auditory cues at 1 Hz. The force outputs were set at 10, 30, and 50% of maximal voluntary contraction (MVC). Motor evoked potentials (MEP) were obtained from the right and left first dorsal interosseous muscles (FDI). To examine the muscle contraction phase dependence, TMS of ipsi-M1 or contra-M1 was triggered at eight different intervals (0, 20, 40, 60, 80, 100, 300, or 500 ms) after electromyogram (EMG) onset when each interval had reached the setup triggering level. Furthermore, to demonstrate the relationships between the integrated EMG (iEMG) in the active left FDI and the ipsi-M1 excitability, we assessed the correlation between the iEMG in the left FDI for the 100 ms preceding TMS onset and the MEP amplitude in the resting/active FDI for each force output condition. Although contra-M1 excitability was significantly changed after the EMG onset that depends on the muscle contraction phase, the modulation of ipsi-M1 excitability did not differ in response to any muscle contraction phase at the 10% of MVC condition. Also, we found that contra-M1 excitability was significantly correlated with iEMG in all force output conditions, but ipsi-M1 excitability was not at force output levels of below 30% of MVC. Consequently, the modulation of ipsi-M1 excitability was independent from the contraction phase of unilateral repetitive isometric contractions at least low force output.     

Prognostic Significance of E-Cadherin Expression in Hepatocellular Carcinoma: A Meta-Analysis

Backgrounds

Hepatocellular Carcinoma (HCC) is one of the most common malignancy of liver and HCC-related morbidity and mortality remains at high level. Researchers had investigated whether and how reduced E-cadherin expression impacted the prognosis of patients with HCC but the results reported by different teams remain inconclusive.

Methods

A systematic literature search was performed in all available databases to retrieve eligible studies and identify all relevant data, which could be used to evaluate the correlation between reduced E-cadherin expression and clinicopathological features and prognosis for HCC patients. A fixed or random effects model was used in this meta-analysis to calculate the pooled odds ratios (OR) and weighted mean differences (WMD) with 95% confidence intervals (CI).

Results

Total 2439 patients in thirty studies matched the selection criteria. Aggregation of the data suggested that reduced E-cadherin expression in HCC patients correlated with poor 1-, 3- and 5-year overall survival. The combined ORs were 0.50 (n = 13 studies, 95% CI: 0.37–0.67, Z = 4.49, P<0.00001), 0.39 (n = 13 studies, 95% CI: 0.28–0.56, Z = 5.12, P<0.00001), 0.40 (n = 11 studies, 95% CI: 0.25–0.64, Z = 3.82, P = 0.0001), respectively. Additionally, the pooled analysis denoted that reduced E-cadherin expression negatively impacts recurrence-free survival (RSF) with no significant heterogeneity. The pooled ORs for 1-, 3- and 5- year RSF affected by down-regulated E-cadherin were 0.73 (n = 6 studies, 95% CI: 0.54–1.00, Z = 1.95, P = 0.05), 0.70 (n = 6 studies, 95% CI: 0.52–0.95, Z = 2.32, P = 0.02), 0.66 (n = 5 studies, 95% CI: 0.48–0.90, Z = 2.64, P = 0.008). And what’s more, reduced E-cadherin expression tended to be significantly associated with metastasis (OR = 0.31, 95% CI: 0.16–0.60, Z = 3.50, P = 0.0005), vascular invasion (OR = 0.76, 95% CI: 0.59–0.98, Z = 2.14, P = 0.03), advanced differentiation grade (OR = 0.31, 95% CI: 0.21–0.45, Z = 6.04, P<0.00001) and advanced TMN stage (T3/T4 versus T1/T2) (OR = 0.61,95% CI:0.38–0.98, Z = 2.05, P = 0.04).

Conclusions

Reduced E-cadherin expression indicates a poor prognosis for patients with HCC, and it may have predictive potential for prognosis of HCC patients.     

Decreased rate of leg extensor force development in independently ambulant patients with acute stroke with mild paresis

We aimed to examine the rate of force development (RFD) of knee extensors on both sides in independently ambulant patients with acute stroke with mild paresis compared with that in age-matched healthy adults. A total 31 patients with acute stroke history (patient group: 67 ± 12 years) and 54 age-matched healthy, community-dwelling adults (control group: 67 ± 8 years) were included. Maximum voluntary contraction (MVC) and RFD were assessed <1 month post-stroke during isometric knee extension (sitting position; 90° knee flexion) using a hand-held dynamometer. RFD was measured as the average slope of the torque–time curve over time intervals of 0–50 ms and 0–200 ms from contraction onset. In the patient group, MVC and RFD for 0–50 ms were significantly lower on the affected side than on the unaffected side (p < 0.01). RFD was significantly decreased in the patient group, to 32%–38% and 62%–71% of that in the control group, over 0–50 ms and 0–200 ms, respectively, regardless of the affected side (p < 0.01). No significant differences in MVC between patient and control groups were observed for either side. RFD of the knee extensors significantly decreased without MVC reduction in patients with acute stroke history compared with that in age-matched healthy adults in both the affected and unaffected sides. These results suggest that decrease in RFD was initiated from the acute phase of stroke, even in patients with stroke who had good motor function.     

Effects of Common Polymorphism rs11614913 in Hsa-miR-196a2 on Lung Cancer Risk

Background

Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the pathogenesis of lung cancer by altering the expression of tumor-related microRNAs. Several studies were investigated in recent years to evaluate the association between hsa-miR-196a2 rs11614913 polymorphism and increased/decreased lung cancer risk. In the present study, we performed a meta-analysis to systematically summarize the possible association.

Methodology/Principal Findings

We performed a meta-analysis of 4 case-control studies that included 2219 lung-cancer cases and 2232 cancer-free controls. We evaluated the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In the overall analysis, it was found that the rs11614913 polymorphism significantly elevated the risk of lung cancer (CC versus (vs.) TT OR = 1.26, 95% CI 1.07–1.49, P = 0.007; CC/CT vs. TT: OR = 1.13, 95% CI 0.98–1.29, P = 0.007; C vs. T: OR = 1.12, 95% CI 1.03–1.22, P = 0.008). In the subgroup analysis by ethnicity, statistically significantly increased cancer risk was found among Asians (CC vs. TT: OR = 1.30, 95% CI 1.10–1.54, P = 0.003; CT vs. TT: OR = 1.16, 95% CI 1.01–1.34, P = 0.039; CC vs. CT/TT: OR = 1.21, 95% CI 1.04–1.41, P = 0.012; C vs. T: OR = 1.14, 95% CI 1.05–1.25, P = 0.002). For Europeans, a significant association with lung cancer risk was found in recessive model (CC vs. CT/TT: OR = 0.63, 95% CI 0.40–0.98, P = 0.040). No publication bias was found in this study.

Conclusions/Significance

Our meta-analysis suggests that the rs11614913 polymorphism is significant associated with the increased risk of lung cancer, especially in Asians. Besides, the C allele of rs11614913 polymorphism may contribute to increased lung cancer risk.     

Effects of Heavy-Resistance Strength and Balance Training on Unilateral and Bilateral Leg Strength Performance in Old Adults

The term “bilateral deficit” (BLD) has been used to describe a reduction in performance during bilateral contractions when compared to the sum of identical unilateral contractions. In old age, maximal isometric force production (MIF) decreases and BLD increases indicating the need for training interventions to mitigate this impact in seniors. In a cross-sectional approach, we examined age-related differences in MIF and BLD in young (age: 20–30 years) and old adults (age: >65 years). In addition, a randomized-controlled trial was conducted to investigate training-specific effects of resistance vs. balance training on MIF and BLD of the leg extensors in old adults. Subjects were randomly assigned to resistance training (n = 19), balance training (n = 14), or a control group (n = 20). Bilateral heavy-resistance training for the lower extremities was performed for 13 weeks (3 × / week) at 80% of the one repetition maximum. Balance training was conducted using predominately unilateral exercises on wobble boards, soft mats, and uneven surfaces for the same duration. Pre- and post-tests included uni- and bilateral measurements of maximal isometric leg extension force. At baseline, young subjects outperformed older adults in uni- and bilateral MIF (all p < .001; d = 2.61–3.37) and in measures of BLD (p < .001; d = 2.04). We also found significant increases in uni- and bilateral MIF after resistance training (all p < .001, d = 1.8-5.7) and balance training (all p < .05, d = 1.3-3.2). In addition, BLD decreased following resistance (p < .001, d = 3.4) and balance training (p < .001, d = 2.6). It can be concluded that both training regimens resulted in increased MIF and decreased BLD of the leg extensors (HRT-group more than BAL-group), almost reaching the levels of young adults.