Use of transcranial magnetic stimulation to assess relaxation rates in unfatigued and fatigued knee-extensor muscles

We examined whether transcranial magnetic stimulation (TMS) delivered to the motor cortex 13 allows assessment of muscle relaxation rates in unfatigued and fatigued knee extensors (KE). 14 We assessed the ability of this technique to measure time course of fatigue-induced changes 15 in muscle relaxation rate and compared relaxation rate from resting twitches evoked by 16 femoral nerve stimulation. Twelve healthy men performed maximal voluntary isometric 17 contractions (MVC) twice before (PRE) and once at the end of a 2-min KE MVC and five 18 more times within 8 min during recovery. Relative (intraclass correlation coefficient; ICC2,1) 19 and absolute (repeatability coefficient) reliability and variability (coefficient of variation) 20 were assessed. Time course of fatigue-induced changes in muscle relaxation rate was tested 21 with generalized estimating equations. In unfatigued KE, peak relaxation rate coefficient of 22 variation and repeatability coefficient were similar for both techniques. Mean (95% CI) 23 ICC2,1 for peak relaxation rates were [0.933 (0.724-0.982)] and [0.889 (0.603-0.968)] for 24 TMS and femoral nerve stimulation, respectively. TMS-induced normalized muscle 25 relaxation rate was -11.5 ± 2.5 s-1 at PRE, decreased to -6.9 ± 1.2 s-1 (-37 ± 17%, P < 0.001), 26 and recovered by 2 min post-exercise. Normalized peak relaxation rate for resting twitch did 27 not show a fatigue-induced change. During fatiguing KE exercise, the change in muscle 28 relaxation rate as determined by the two techniques was different. TMS provides reliable 29 values of muscle relaxation rates. Furthermore, it is sufficiently sensitive and more 30 appropriate than the resting twitch evoked by femoral nerve stimulation to reveal fatigue-31 induced changes in KE

Spinal contribution to neuromuscular recovery differs between elbow-flexor and knee-extensor muscles after a maximal sustained fatiguing task

Data from studies of elbow-flexor (EF) or knee-extensor (KE) muscles suggest that a fatigue-related decrease in motoneuron excitability only occurs in EF. It is unknown how motoneuron excitability changes after sustained fatiguing maximal voluntary isometric contractions (MVICs) in EF and KE in the same participants. In two sessions, eight healthy men performed a 2-min MVIC of EF or KE to induce fatigue with brief MVICs before and six times after the 2-min MVIC. Electromyographic responses elicited by corticospinal tract stimulation at the transmastoid [cervicomedullary motor-evoked potential (CMEP)] or thoracic [thoracic motor-evoked potential (TMEP)] level were recorded from EF and KE, respectively. To account for muscle excitability, CMEPs and TMEPs were normalized to maximal M-wave (Mmax) elicited by peripheral nerve stimulation during each brief MVIC. Immediately after the 2-min MVIC, biceps brachii and brachioradialis CMEP/Mmax were 88% (SD 11%) (P = 0.026) and 87% (SD 12%) (P = 0.029) of pre-MVIC values, respectively, and remained lower than PRE after 5 s of recovery [91% (SD 8%), P = 0.036 and 87% (SD 13%), P = 0.046, respectively]. No subsequent time points differed from PRE (all P ³ 0.253). TMEP/Mmax for rectus femoris and vastus lateralis were not different from PRE at any time during the recovery period (all P > 0.050). A different recovery pattern in motoneuron excitability occurred in EF as it recovered by 60 s whereas KE motoneurons were unaffected by the fatiguing task. The present findings may contribute to better understand muscle-specific neurophysiological differences in spinal excitability

Familial Polyposis Coli: The Management of Desmoid Tumor Bleeding

There is currently no standard treatment for desmoid tumors (DTs) associated with familial polyposis coli (FAP). Familial adenomatous polyposis in DT patients is sometimes a life-threatening condition

Isokinetic strength of foot dorsal and plantar flexor muscles in young male orienteers

Map and compass allow orienteers navigating point to point in unfamiliar and uneven grounds. High levels of fitness and running speed are requested to cover successfully long distances and climbs. Lower limb muscular strength is necessary to sustain challenging descents on rough terrains (Fong et al., 2007). Eight male junior (age, 19±1.6yr) Italian national team orienteers (OR), and 8 cross country track and fields (TF) experienced runners (20±4.5yr), all with right lower limb dominance volunteered. Ages, weights, heights, and BMI of OR and TF did not differ (ANOVA, p&gt;0.05). Each participant performed, and an isokinetic dynamometer measured 5 repetitions of right and left foot dorsal and plantar flexions at the angular speeds of 60-120-180deg/sec respectively. Each value was normalized to the body weight of the respective subject. Descriptive statistics were computed within subject, group, movement, angular speed, and side. For each movement, the effects of group and side on the peak torques at different speeds were compared by ANOVA (statistical significance 5%). On average in both groups, right foot dorsal and plantar flexor muscles were stronger than those of contralateral limb, for all the angular speeds, but no significant differences were found. OR performed peak torques larger than those obtained by TF, in both sides and movements. Differences were significant in foot plantar flexor muscles at 60-120-180deg/sec, and in foot dorsal flexor muscles at 60-120deg/sec (p≤0.04 for all comparisons). The investigation should be extended to a larger group of participants and to other muscular districts. Data could be of interest for athletes, coaches, and physicians to set a correct training planning, to prevent accidental injuries, or to quantify the effects of rehabilitation (Fong et al., 2007)

Ethical Issues in the Use of Suboptimal Kidneys for Transplants: an Italian Point of View

The shortage of organs leads to the need for utilizing suboptimal kidneys for transplantation. The distinction between optimal, marginal, and suboptimal kidneys leads surgeons to face not only technical problems but also ethical and legal issues related to clinical advantages offered by the transplant of a nonstandard kidney and the acquisition of consent. Between 1999 and 2015, we performed 658 transplants, 49 (7.5%) using suboptimal kidneys. All patients were alive and with vital graft throughout follow-up. We did not encounter any major surgical complications. From a technical point of view, our experience and literature review confirm that transplant of suboptimal kidney leads to good clinical results but exposes patients to a increased risks of surgical complications. Therefore, these interventions must take place in hospitals fully prepared for this type of surgery and performed by experienced transplant surgeons with proper matching between organ and recipient. Considering the insufficient resources available, from an ethical and legal point of view, doctors play an essential role in optimizing the use of these kidneys by avoiding wastage of organs, ensuring that transplants are done in suitable patients, and that patients are fully informed and aware of the risks and benefits associated with the specific suboptimal kidney being transplanted. We believe that, in highly specialized centers, the number of suboptimal kidney transplants should be increased, as their use has shown good clinical results and carries fewer ethical issues compared with marginal kidneys. Further, suboptimal kidneys may also be proposed for use in young patients with end-stage renal disease

Sex differences in neuromuscular and biological determinants of isometric maximal force

Aim: Force expression is characterized by an interplay of biological and molecular determinants that are expected to differentiate males and females in terms of maximal performance. These include muscle characteristics (muscle size, fiber type, contractility), neuromuscular regulation (central and peripheral factors of force expression), and individual genetic factors (miRNAs and gene/protein expression). This research aims to comprehensively assess these physiological variables and their role as determinants of maximal force difference between sexes. Methods: Experimental evaluations include neuromuscular components of isometric contraction, intrinsic muscle characteristics (proteins and fiber type), and some biomarkers associated with muscle function (circulating miRNAs and gut microbiome) in 12 young and healthy males and 12 females. Results: Male strength superiority appears to stem primarily from muscle size while muscle fiber-type distribution plays a crucial role in contractile properties. Moderate-to-strong pooled correlations between these muscle parameters were established with specific circulating miRNAs, as well as muscle and plasma proteins. Conclusion: Muscle size is crucial in explaining the differences in maximal voluntary isometric force generation between males and females with similar fiber type distribution. Potential physiological mechanisms are seen from associations between maximal force, skeletal muscle contractile properties, and biological markers

MiR-320a as a Potential Novel Circulating Biomarker of Arrhythmogenic CardioMyopathy

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53\u2009\ub1\u20090.04 fold expression difference in ACM vs. HC (p\u2009<\u20090.01). A similar trend was observed when comparing ACM (n\u2009=\u200913) and HC (n\u2009=\u200917) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78\u2009\ub1\u20090.05 fold expression change vs. IVT (p\u2009=\u20090.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation

Do aerobic characteristics explain isometric exercise-induced neuromuscular fatigue and recovery in upper and lower limbs?

This study investigated the relationships between aerobic characteristics and (i) neuromuscular fatigue induced by 2-min sustained isometric maximal voluntary contractions (MVC) and (ii) subsequent recovery, in the upper and lower limbs. In a pseudo-randomized order, eleven healthy males completed four sessions on different days: maximal incremental cycling test (100 W + 40 W every 2 min); maximal arm-cranking test (50 W + 20 W every 2 min); and 2-min sustained isometric MVCs of the knee extensors (KE) and elbow flexors (EF). Neuromuscular assessment was performed with transcranial magnetic and peripheral nerve stimulation to evaluate central and peripheral neuromuscular factors of fatigue and the subsequent recovery. Peak oxygen uptake, gas exchange threshold and the corresponding power outputs were correlated with recovery of voluntary force after the 2-min KE MVC. Regression analysis showed that power output at the gas exchange threshold alone explained 72% of the variability in ∆recovery of KE voluntary force. No relationships with fatigue or recovery in EF were observed. These results suggest that participants with greater aerobic capacities experience the same amount of fatigue and faster recovery of voluntary force in KE but not EF. The potential reasons behind the relationship in KE but not EF are discussed

Model of CD45 isoforms-mediated IL-6 signaling in multiple myeloma cells.

<p>Engagement of IL-6R with IL-6 leads to complex formation of IL-6R, gp130, Lyn as well as CD45RO/RB in raft microdomains. In response to IL-6 stimulation, CD45RO/RB moves into lipid rafts to induce dephosphorylation of the negative regulatory of Tyr507, phosphorylation of Tyr396, and subsequent conformation change and Lyn activation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119780#pone.0119780.ref017" target="_blank">17</a>]. We confirmed our hypothesis that lipid rafts-targeted CD45RO/RB facilitates IL-6-induced STAT3 and Lyn/PKC/NF-κB activation in rafts microdomains, while raft-excluded CD45RA remains outside of lipid rafts after IL-6 stimulation and negatively regulates ERK-activation.</p