RESUMEN
Spinal motoneuron firing depends greatly on persistent inward currents (PICs), which in turn are facilitated by the neuromodulators serotonin and noradrenaline. The aim of this study was to determine whether jaw clenching (JC) and mental stress (MS), which may increase neuromodulator release, facilitate PICs in human motoneurons. The paired motor unit (MU) technique was used to estimate PIC contribution to motoneuron firing. Surface electromyograms were collected using a 32-channel matrix on gastrocnemius medialis (GM) during voluntary, ramp, plantar flexor contractions. MU discharges were identified, and delta frequency (ΔF), a measure of recruitment-derecruitment hysteresis, was calculated. Additionally, another technique was used (VibStim) that evokes involuntary contractions that persist after cessation of combined Achilles tendon vibration and triceps surae neuromuscular electrical stimulation. VibStim measures of plantar flexor torque and soleus activity may reflect PIC activation. ΔF was not significantly altered by JC (p = .679, n = 18, 9 females) or MS (p = .147, n = 14, 5 females). However, all VibStim variables quantifying involuntary torque and muscle activity during and after vibration cessation were significantly increased in JC (p < .011, n = 20, 10 females) and some, but not all, increased in MS (p = .017-.05, n = 19, 10 females). JC and MS significantly increased the magnitude of involuntary contractions (VibStim) but had no effect on GM ΔF during voluntary contractions. Effects of increased neuromodulator release on PIC contribution to motoneuron firing might differ between synergists or be context dependent. Based on these data, the background level of voluntary contraction and, hence, both neuromodulation and ionotropic inputs could influence neuromodulatory PIC enhancement.
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Neuronas Motoras , Músculo Esquelético , Femenino , Humanos , Músculo Esquelético/fisiología , Electromiografía , Neuronas Motoras/fisiología , Norepinefrina/farmacología , Neurotransmisores/farmacologíaRESUMEN
Persistent inward currents (PICs) are crucial for initiation, acceleration, and maintenance of motoneuron firing. As PICs are highly sensitive to synaptic inhibition and facilitated by serotonin and noradrenaline, we hypothesised that both reciprocal inhibition (RI) induced by antagonist nerve stimulation and whole-body relaxation (WBR) would reduce PICs in humans. To test this, we estimated PICs using the well-established paired motor unit (MU) technique. High-density surface electromyograms were recorded from gastrocnemius medialis during voluntary, isometric 20-s ramp, plantarflexor contractions and decomposed into MU discharges to calculate delta frequency (ΔF). Moreover, another technique (VibStim), which evokes involuntary contractions proposed to result from PIC activation, was used. Plantarflexion torque and soleus activity were recorded during 33-s Achilles tendon vibration and simultaneous 20-Hz bouts of neuromuscular electrical stimulation (NMES) of triceps surae. ΔF was decreased by RI (n = 15, 5 females) and WBR (n = 15, 7 females). In VibStim, torque during vibration at the end of NMES and sustained post-vibration torque were reduced by WBR (n = 19, 10 females), while other variables remained unchanged. All VibStim variables remained unaltered in RI (n = 20, 10 females). Analysis of multiple human MUs in this study demonstrates the ability of local, focused inhibition to attenuate the effects of PICs on motoneuron output during voluntary motor control. Moreover, it shows the potential to reduce PICs through non-pharmacological, neuromodulatory interventions such as WBR. The absence of a consistent effect in VibStim might be explained by a floor effect resulting from low-magnitude involuntary torque combined with the negative effects of the interventions. KEY POINTS: Spinal motoneurons transmit signals to skeletal muscles to regulate their contraction. Motoneuron firing partly depends on their intrinsic properties such as the strength of persistent (long-lasting) inward currents (PICs) that make motoneurons more responsive to excitatory input. In this study, we demonstrate that both reciprocal inhibition onto motoneurons and whole-body relaxation reduce the contribution of PICs to human motoneuron firing. This was observed through analysis of the firing of single motor units during voluntary contractions. However, an alternative technique that involves tendon vibration and neuromuscular electrical stimulation to evoke involuntary contractions showed less effect. Thus, it remains unclear whether this alternative technique can be used to estimate PICs under all physiological conditions. These results improve our understanding of the mechanisms of PIC depression in human motoneurons. Potentially, non-pharmacological interventions such as electrical stimulation or relaxation could attenuate unwanted PIC-induced muscle contractions in conditions characterised by motoneuron hyperexcitability.
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Neuronas Motoras , Contracción Muscular , Electromiografía/métodos , Femenino , Humanos , Neuronas Motoras/fisiología , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , TorqueRESUMEN
Shroom is a family of related proteins linked to the actin cytoskeleton, and one of them, xShroom1, is constitutively expressed in Xenopus laevis oocytes which is required for the expression of the epithelial sodium channel (ENaC). On the other hand, ENaC and the cystic fibrosis transmembrane regulator (CFTR) are co-expressed in many types of cells with a negative or positive interaction depending on the studied tissues. Here, we measured the amiloride-sensitive ENaC currents (INaamil) and CFTR currents (ICFTR) with voltage clamp techniques in oocytes co-injected with ENaC and/or CFTR and xShroom1 antisense oligonucleotides. The objective was to study the mechanism of regulation of ENaC by CFTR when xShroom1 was suppressed and the endocytic traffic of CFTR was blocked. CFTR activation had a measurable negative effect on ENaC and this activation resulted in a greater inhibition of INaamil than with xShroom1 antisense alone. Our results with Dynasore, a drug that acts as an inhibitor of endocytic pathways, suggest that the changes in INaamil by xShroom1 downregulation were probably due to an increment in channel endocytosis. An opposite effect was observed when ICFTR was measured. Thus, when xShroom1 was downregulated, the ICFTR was larger than in the control experiments and this effect is not observed with Dynasore. A speculative explanation could be that xShroom1 exerts a dual effect on the endocytic traffic of ENaC and CFTR and these actions were canceled with Dynasore. In the presence of Dynasore, no difference in either INaamil or ICFTR was observed when xShroom1 was downregulated.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Animales , Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Canales Epiteliales de Sodio/genética , Canales Epiteliales de Sodio/metabolismo , Hidrazonas , Oocitos/metabolismo , Xenopus laevis/metabolismoRESUMEN
ABSTRACT: Gonçalves, BM, Mesquita, RNO, Tavares, F, Brito, J, Correia, P, Santos, P, and Mil-Homens, P. A new portable device to reliably measure maximal strength and rate of force development of hip adduction and abduction. J Strength Cond Res 36(9): 2465-2471, 2022-Groin injuries are a major issue in sports involving kicking or quick changes of direction. Decreased hip adduction and abduction strength have been indicated as one of the main risk factors for groin injury. The methods currently available to measure hip adduction and abduction strength are reliable but highly dependent on the evaluator skills. Furthermore, several studies have reported the reliability of maximal strength (MVIC), but very few studies investigated the reliability of explosive strength (RFD), a parameter that has been previously shown to have a higher functional value. The aim of the current investigation was to assess the reliability of a user-independent portable dynamometer that concurrently measures MVIC and RFD. Twenty-five healthy young subjects performed maximal isometric hip adduction and abduction in both sitting and supine positions. Measurements occurred in 2 different days separated by 48-72 hours. Test-retest reliability was calculated for both MVIC and RFD. Both MVIC and RFD showed good relative reliability (intraclass correlation coefficient = 0.77-0.98) with no differences between positions or muscle actions. Measurement error was similar between positions for MVIC in both hip adduction and abduction. Measurements of RFD showed higher reliability using a time window of at least 0-100 milliseconds, and lower measurement error was observed in sitting for adduction and in supine for abduction. This study shows that portable dynamometry can be used to concurrently measure hip adduction and abduction maximal and explosive strength, with levels of reliability that are similar to previously described methods.
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Fuerza Muscular , Músculo Esquelético , Humanos , Fuerza Muscular/fisiología , Dinamómetro de Fuerza Muscular , Músculo Esquelético/fisiología , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels. METHODS: We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment. RESULTS: Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine. CONCLUSIONS: Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.
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Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Melanoma/genética , ARN Mensajero/metabolismo , Sertralina/farmacología , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Antineoplásicos Alquilantes/uso terapéutico , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/genética , Supervivencia Celular/efectos de los fármacos , Dacarbazina/uso terapéutico , Femenino , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Silenciador del Gen , Humanos , Melanoma/metabolismo , Melanoma Experimental/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , ARN Interferente Pequeño/genética , Sertralina/uso terapéutico , Transfección , Proteína Tumoral Controlada Traslacionalmente 1 , Ensayo de Tumor de Célula Madre , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Shroom is a family of related proteins linked to the actin cytoskeleton. xShroom1 is constitutively expressed in Xenopus laevis oocytes, and it is required for the expression of the epithelial sodium channel (ENaC). As there is a close relationship between ENaC and the cystic fibrosis transmembrane regulator (CFTR), we examined the action of xShroom1 on CFTR expression and activity. Biotinylation was used to measure CFTR surface expression, and currents were registered with voltage clamp when stimulated with forskolin and 3-isobutyl-1-methylxanthine. Oocytes were coinjected with CFTR complementary RNAs (cRNAs) and xShroom1 sense or antisense oligonucleotides. We observed an increment in CFTR currents and CFTR surface expression in oocytes coinjected with CFTR and xShroom1 antisense oligonucleotides. MG-132, a proteasome inhibitor, did not prevent the increment in currents when xShroom1 was suppressed by antisense oligonucleotides. In addition, we inhibited the delivery of newly synthesized proteins to the plasma membrane with BFA and we found that the half-life of plasma membrane CFTR was prolonged when coinjected with the xShroom1 antisense oligonucleotides. Chloroquine, an inhibitor of the late endosome/lysosome, did not significantly increase CFTR currents when xShroom1 expression was inhibited. The higher expression of CFTR when xShroom1 is suppressed is in concordance with the functional studies suggesting that the suppression of the xShroom1 protein resulted in an increment in CFTR currents by promoting the increase of the half-life of CFTR in the plasma membrane. The role of xShroom1 in regulating CFTR expression could be relevant in the understanding of the channel malfunction in several diseases.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Canales de Sodio/metabolismo , Proteínas de Xenopus/metabolismo , Potenciales de Acción , Animales , Membrana Celular/metabolismo , Membrana Celular/fisiología , Endosomas/metabolismo , Transporte de Proteínas , XenopusRESUMEN
Cystic fibrosis is caused by dysfunction or lack of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that has a key role in maintaining ion and water homoeostasis in different tissues. CFTR is a cyclic AMP-activated Cl- channel found in the apical and basal plasma membrane of airway, intestinal, and exocrine epithelial cells. One of CFTR's primary roles in the lungs is to maintain homoeostasis of the airway surface liquid layer through its function as a chloride channel and its regulation of the epithelial sodium channel ENaC. More than 1900 CFTR mutations have been identified in the cftr gene. The disease is characterized by viscous secretions of the exocrine glands in multiple organs and elevated levels of sweat sodium chloride. In cystic fibrosis, salt and fluid absorption is prevented by the loss of CFTR and ENaC is not appropriately regulated, resulting in increased fluid and sodium resorption from the airways and formation of a contracted viscous surface liquid layer. In the sweat glands both Na+ and Cl- ions are retained in the lumen, causing significant loss of electrolytes during sweating. Thus, elevated sweat NaCl concentration is the basis of the classic pilocarpine-induced sweat test as a diagnostic feature of the disease. Here we discuss the ion movement of Cl- and Na+ ions in two tissues, sweat glands and in the air surface as well as the role of ENaC in the pathogenesis of cystic fibrosis.
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Transporte Biológico/fisiología , Permeabilidad de la Membrana Celular/fisiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Fibrosis Quística/fisiopatología , Canales Epiteliales de Sodio/fisiología , HumanosRESUMEN
PURPOSE: Sprinting often provokes hip pain in individuals with femoroacetabular impingement syndrome (FAIS). Asphericity of the femoral head-neck junction (cam morphology) characteristic of FAIS can increase the risk of anterior-superior acetabular cartilage damage. This study aimed to 1) compare hip contact forces (magnitude and direction) during sprinting between individuals with FAIS, asymptomatic cam morphology (CAM), and controls without cam morphology, and 2) identify the phases of sprinting with high levels of anteriorly directed hip contact forces. METHODS: Forty-six recreationally active individuals with comparable levels of physical activity were divided into three groups (FAIS, 14; CAM, 15; control, 17) based on their history of hip/groin pain, results of clinical impingement tests, and presence of cam morphology (alpha angle >55°). Three-dimensional marker trajectories, ground reaction forces, and electromyograms from 12 lower-limb muscles were recorded during 10-m overground sprinting trials. A linearly scaled electromyogram-informed neuromusculoskeletal model was used to calculate hip contact force magnitude (resultant, anterior-posterior, inferior-superior, medio-lateral) and angle (sagittal and frontal planes). Between-group comparisons were made using two-sample t -tests via statistical parametric mapping ( P < 0.05). RESULTS: No significant differences in magnitude or direction of hip contact forces were observed between FAIS and CAM or between FAIS and control groups during any phase of the sprint cycle. The highest anteriorly directed hip contact forces were observed during the initial swing phase of the sprint cycle. CONCLUSIONS: Hip contact forces during sprinting do not differentiate recreationally active individuals with FAIS from asymptomatic individuals with and without cam morphology. Hip loading during early swing, where peak anterior loading occurs, may be a potential mechanism for cartilage damage during sprinting-related sports in individuals with FAIS and/or asymptomatic cam morphology.
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Pinzamiento Femoroacetabular , Humanos , Articulación de la Cadera , Acetábulo/fisiología , Cadera , Dolor , ArtralgiaRESUMEN
The regulation of the epithelial Na⺠channel (ENaC) during cell swelling is relevant in cellular processes in which cell volume changes occur, i.e., migration, proliferation and cell absorption. Its sensitivity to hypotonically induced swelling was investigated in the Xenopus oocyte expression system with the injection of the three subunits of mouse ENaC. We used voltage-clamp techniques to study the amiloride-sensitive Na⺠currents (INa(amil)) and video microscopic methodologies to assess oocyte volume changes. Under conditions of mild swelling (25 % reduced hypotonicity) inward current amplitude decreased rapidly over 1.5 min. In contrast, there was no change in current amplitude of H2O-injected oocytes to the osmotic insult. INa(amil) kinetics analysis revealed a decrease in the slower inactivation time constant during the hypotonic stimuli. Currents from ENaC-injected oocytes were not sensitive to external Clâ» reduction. Neither short- nor long-term cytochalasin D treatment affected the observed response. Oocytes expressing a DEG mutant ß-ENaC subunit (ß-S518K) with an open probability of 1 had reduced INa(amil) hypotonic response compared to oocytes injected with wild-type ENaC subunits. Finally, during the hypotonic response ENaC-injected oocytes did not show a cell volume difference compared with water-injected oocytes. On this basis we suggest that hypotonicity-dependent ENaC inhibition is principally mediated through an effect on open probability of channels in the membrane.
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Canales Epiteliales de Sodio/metabolismo , Presión Osmótica , Actinas/metabolismo , Animales , Transporte Biológico , Canales Epiteliales de Sodio/genética , Femenino , Expresión Génica , Cinética , Potenciales de la Membrana , Ratones , Oocitos/metabolismo , Sodio/metabolismo , Xenopus laevisRESUMEN
BACKGROUND: People with femoroacetabular with femoroacetabular impingement syndrome (FAIS) often report pain during sports involving repeated sprinting. It remains unclear how sports participation influences running biomechanics in individuals with FAIS. HYPOTHESIS: Changes in running biomechanics and/or isometric hip strength after repeated sprint exercise would be greatest in individuals with FAIS compared with asymptomatic individuals with (CAM) and without cam morphology (Control). STUDY DESIGN: Controlled laboratory study. LEVEL OF EVIDENCE: Level 3. METHODS: Three-dimensional hip biomechanics during maximal running (10 m) and hip strength were measured in 49 recreationally active individuals (FAIS = 15; CAM = 16; Control = 18) before and after repeated sprint exercise performed on a nonmotorized treadmill (8-16 × 30 m). Effects of group and time were assessed for biomechanics and strength variables with repeated-measures analyses of variance. Relationships between hip pain (Copenhagen Hip and Groin Outcome Score) and changes in hip moments and strength after repeated sprint exercise were determined using Spearman's correlation coefficients (ρ). RESULTS: Running speed, hip flexion angles, hip flexion and extension moments, and hip strength in all muscle groups were significantly reduced from pre to post. No significant between-group differences were observed before or after repeated sprint exercise. No significant relationships (ρ = 0.04-0.30) were observed between hip pain and changes in hip moments or strength in the FAIS group. CONCLUSION: Changes in running biomechanics and strength after repeated sprint exercise did not differ between participants with FAIS and asymptomatic participants with and without cam morphology. Self-reported pain did not appear to influence biomechanics during running or strength after repeated sprint exercise in participants with FAIS. CLINICAL RELEVANCE: A short bout of repeated sprinting may not elicit changes in running biomechanics in FAIS beyond what occurs in those without symptoms. Longer duration activities or activities requiring greater hip flexion angles may better provoke pathology-related changes in running biomechanics in people with FAIS.
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PURPOSE: This study aimed to compare and rank gluteal muscle forces in eight hip-focused exercises performed with and without external resistance and describe the underlying fiber lengths, velocities, and muscle activations. METHODS: Motion capture, ground reaction forces, and electromyography (EMG) were used as input to an EMG-informed neuromusculoskeletal model to estimate gluteus maximus, medius, and minimus muscle forces. Participants were 14 female footballers (18-32 yr old) with at least 3 months of lower limb strength training experience. Each participant performed eight hip-focused exercises (single-leg squat, split squat, single-leg Romanian deadlift [RDL], single-leg hip thrust, banded side step, hip hike, side plank, and side-lying leg raise) with and without 12 repetition maximum (RM) resistance. For each muscle, exercises were ranked by peak muscle force, and k-means clustering separated exercises into four tiers. RESULTS: The tier 1 exercises for gluteus maximus were loaded split squat (95% confidence interval [CI] = 495-688 N), loaded single-leg RDL (95% CI = 500-655 N), and loaded single-leg hip thrust (95% CI = 505-640 N). The tier 1 exercises for gluteus medius were body weight side plank (95% CI = 338-483 N), loaded single-leg squat (95% CI = 278-422 N), and loaded single-leg RDL (95% CI = 283-405 N). The tier 1 exercises for gluteus minimus were loaded single-leg RDL (95% CI = 267-389 N) and body weight side plank (95% CI = 272-382 N). Peak gluteal muscle forces increased by 28-150 N when exercises were performed with 12RM external resistance compared with body weight only. Peak muscle force coincided with maximum fiber length for most exercises. CONCLUSIONS: Gluteal muscle forces were exercise specific, and peak muscle forces increased by varying amounts when adding a 12RM external resistance. These findings may inform exercise selection by facilitating the targeting of individual gluteal muscles and optimization of mechanical loads to match performance, injury prevention, or rehabilitation training goals.
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Lesiones de la Cadera , Músculo Esquelético , Humanos , Femenino , Músculo Esquelético/fisiología , Terapia por Ejercicio , Nalgas/fisiología , Electromiografía , MusloAsunto(s)
Miastenia Gravis/historia , Argentina , Inhibidores de la Colinesterasa/historia , Inhibidores de la Colinesterasa/uso terapéutico , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Londres , Miastenia Gravis/tratamiento farmacológico , Nigeria , Fisostigmina/historia , Fisostigmina/uso terapéutico , TaiwánRESUMEN
For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3ß and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.
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Antimaníacos/uso terapéutico , Acuaporina 2/fisiología , Canales Epiteliales de Sodio/fisiología , Compuestos de Litio/uso terapéutico , Animales , Antimaníacos/efectos adversos , Antimaníacos/metabolismo , Trastorno Bipolar/tratamiento farmacológico , Diabetes Insípida Nefrogénica/inducido químicamente , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/fisiopatología , Litio/efectos adversos , Litio/metabolismo , Litio/farmacología , Compuestos de Litio/efectos adversos , Compuestos de Litio/metabolismoRESUMEN
OBJECTIVE: This study determined the contribution of the deep hip muscles to hip stability. METHODS: Hip stability was defined as rotational hip stiffness in the sagittal plane, which was calculated for walking trials for 12 participants via an electromyography (EMG)-informed neuromusculoskeletal model which included all 22 hip spanning muscles. Three model configurations which differed in deep hip muscle excitations but had identical excitations for all other muscles were compared: (1) deep hip muscles informed by intramuscular EMG measurements (assisted activation); (2) deep hip muscles with simulated zero activation (no activation); (3) deep hip muscles with simulated maximal activation (maximal activation). Sagittal plane rotational hip stiffness across the gait cycle was compared between the three model configurations using a within-participant analysis of variance via statistical parametric mapping (p < 0.05). RESULTS: Compared to the assisted activation configuration, hip stiffness (mean (95% confidence interval)) was 0.8% (0.7 to 0.9) lower in the no activation configuration, and 3.2% (3.0 to 3.4) higher in the maximal activation configuration. CONCLUSION: Regardless of activation level, deep hip muscles contributed little to sagittal plane rotational hip stiffness, which casts doubt on their assumed function as hip stabilizers. SIGNIFICANCE: The merit of targeted deep hip muscle strengthening to improve hip stability in rehabilitation programs remains unclear.
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Articulación de la Cadera , Caminata , Fenómenos Biomecánicos , Electromiografía , Marcha/fisiología , Articulación de la Cadera/fisiología , Humanos , Músculo Esquelético/fisiología , Caminata/fisiologíaRESUMEN
The deep hip muscles are often omitted in studies investigating hip contact forces using neuromusculoskeletal modelling methods. However, recent evidence indicates the deep hip muscles have potential to change the direction of hip contact force and could have relevance for hip contact loading estimates. Further, it is not known whether deep hip muscle excitation patterns can be accurately estimated using neuromusculoskeletal modelling or require measurement (through invasive and time-consuming methods) to inform models used to estimate hip contact forces. We calculated hip contact forces during walking, squatting, and squat-jumping for 17 participants using electromyography (EMG)-informed neuromusculoskeletal modelling with (informed) and without (synthesized) intramuscular EMG for the deep hip muscles (piriformis, obturator internus, quadratus femoris). Hip contact force magnitude and direction, calculated as the angle between hip contact force and vector from femoral head to acetabular center, were compared between configurations using a paired t-test deployed through statistical parametric mapping (P < 0.05). Additionally, root mean square error, correlation coefficients (R2), and timing accuracy between measured and modelled deep hip muscle excitation patterns were computed. No significant between-configuration differences in hip contact force magnitude or direction were found for any task. However, the synthesized method poorly predicted (R2-range 0.02-0.3) deep hip muscle excitation patterns for all tasks. Consequently, intramuscular EMG of the deep hip muscles may be unnecessary when estimating hip contact force magnitude or direction using EMG-informed neuromusculoskeletal modelling, though is likely essential for investigations of deep hip muscle function.
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Cadera , Músculo Esquelético , Fenómenos Biomecánicos , Electromiografía , Humanos , Músculo Esquelético/fisiología , Muslo , Caminata/fisiologíaRESUMEN
Shroom is a family of related proteins linked to the actin cytoskeleton. xShroom1 is constitutively expressed in X. oocytes and is required for the expression of amiloride sensitive sodium channels (ENaC). Oocytes were injected with α, ß, and γ mENaC and xShroom1 sense or antisense oligonucleotides. We used voltage clamp techniques to study the amiloride-sensitive Na(+) currents (INa((amil))). We observed a marked reduction in INa((amil)) in oocytes co-injected with xShroom1 antisense. Oocytes expressing a DEG mutant ß-mENaC subunit (ß-S518K) with an open probability of 1 had enhanced INa((amil)) although these currents were also reduced when co-injected with xShroom1 antisense. Addition of low concentration (20 ng/ml) of trypsin which activates the membrane-resident ENaC channels led to a slow increase in INa((amil)) in oocytes with xShroom1 sense but had no effect on the currents in oocytes coinjected with ENaC and xShroom1 antisense. The same results were obtained with higher concentrations of trypsin (2 µg/ml) exposed during 2.5 min. In addition, fluorescence positive staining of plasma membrane in the oocytes expressing α, ß and γ mENaC and xShroom1 sense were observed but not in oocytes coinjected with ENaC and xShroom1 antisense oligonucleotides. On this basis, we suggest that xShroom1-dependent ENaC inhibition may be through the number of channels inserted in the membrane.
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Canales Epiteliales de Sodio/metabolismo , Canales de Sodio/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Animales , Canales Epiteliales de Sodio/genética , Femenino , Mutación , Oligonucleótidos Antisentido/metabolismo , Oocitos/metabolismo , Oocitos/patología , Oocitos/fisiología , Técnicas de Placa-Clamp , Canales de Sodio/genética , Tripsina/farmacología , Proteínas de Xenopus/genéticaRESUMEN
The aim of this paper was to provide quantitative data about clinical investigation in Argentina. We searched MEDLINE which is the U.S. National Library of Medicine's bibliographic database that contains more than 18 million references to journal articles in life sciences; 5400 journals in 39 languages are listed. In 2009 almost 850,000 papers were cited in MEDLINE and Argentina provided 0.33% of them, 90% of these in English. The number of papers published in Spanish is diminishing every year and similar results are observed with the German, French and other languages. Using the tools provided by MEDLINE we searched for papers that could be classified as clinical. We restricted our search to the word "patients" in the text and "hospital" in the address provided by the authors. Along the last 10 years, from 2000 to 2009, about 16% of the papers published from Argentina contain the word "patient" and this percentage is reduced to half if we combine the word "patient" with the word "hospital" in the address. If we search for papers written in Spanish with these two restrictions the number is much lower. The number of articles from Argentina followed the upward trend in the total of articles cited in MEDLINE in the last 10 years. This local increase was due to basic investigation papers because the percentage of clinical articles was relatively constant during these years. In conclusion, these data provide a survey of an area with scanty quantitative information.