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A healthy 9-years-old boy was brought to the Emergency Department for widespread abdominal pain associated with bloody diarrhoea and significant tenesmus, in the absence of fever. Blood tests were compatible with an acute gastroenteritis, even though microbiological tests on stools resulted negative. Given the haemorrhagic dysentery, the boy was hospitalized to start empiric antibiotic therapy and intravenous rehydration. Abdominal ultrasound showed a thickening of colonic walls, mimicking an inflammatory intestinal disease at the onset (subsequently denied by gastro-colonoscopy). Seven days after the onset of symptoms, blood tests revealed microangiopathic anaemia with negative Coombs test, associated with thrombocytopenia. Urine dipstick revealed haematuria and proteinuria in nephritic range. No contraction of diuresis or alteration of renal function were observed (being creatinine values always within the normal range). Laboratory tests were consistent with the diagnosis of Haemolytic Uremic Syndrome (Hus) at the onset. Approximately 1% of paediatric patients with bloody diarrhoea can develop Hus. Positivity for Escherichia coli is not always evident in the stools. Thus, the triad of haemolytic anaemia, thrombocytopenia and renal failure could be present in only 60% of Hus at the onset. The finding of haematuria and/or proteinuria on the urine dipstick may be indicative of early kidney damage, allowing for careful monitoring and a rehydration program that can prevent progression of kidney damage and extrarenal complications.
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Síndrome Hemolítico-Urêmica , Trombocitopenia , Masculino , Humanos , Criança , Hematúria/complicações , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/terapia , Diarreia/complicações , Diarreia/terapia , Trombocitopenia/complicações , Hemorragia Gastrointestinal/etiologia , Proteinúria/complicações , RimRESUMO
To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable neuromuscular diseases, or aging. Here, we showed that denervation resulting from transection of the sciatic nerve triggered a marked increase in the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle in mice, providing evidence that injury drives early expression of this aging-associated enzyme or gerozyme. Treating mice with a small-molecule inhibitor of 15-PGDH promoted regeneration of motor axons and formation of neuromuscular synapses leading to an acceleration in recovery of force after an acute nerve crush injury. In aged mice with chronic denervation of muscles, treatment with the 15-PGDH inhibitor increased motor neuron viability and restored neuromuscular junctions and function. These presynaptic changes synergized with previously reported muscle tissue remodeling to result in a marked increase in the strength of aged muscles. We further found that 15-PGDH aggregates defined the target fibers that are histopathologic hallmarks of human neurogenic myopathies, suggesting that the gerozyme may be involved in their etiology. Our data suggest that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease, or aging.
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Hidroxiprostaglandina Desidrogenases , Sinapses , Camundongos , Animais , Humanos , Idoso , Prostaglandinas , Músculo Esquelético , Denervação/métodos , Regeneração NervosaRESUMO
Miller-Fisher syndrome is a rare acquired nerve disease related to Guillain-Barré syndrome. Clinical features include asthenia, ocular muscle weakness with ophthalmoplegia, impaired limb coordination with instability, and absence of tendon reflexes. Swallowing disorders and rarely respiratory failure may be associated. The article aims to summarize, starting from the presentation of a clinical case, the latest updates which, in clinical practice, can be useful for a correct diagnosis and treatment of this condition which concerns both adult and pediatric patients.
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Síndrome de Guillain-Barré , Síndrome de Miller Fisher , Adulto , Humanos , Criança , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/terapia , Doenças RarasRESUMO
Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels' upregulation, neuromuscular junction and axonal damage, neurotrophins' receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.
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Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive blood-derived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.
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Insuficiência Renal Crônica , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Agrina , Força da Mão/fisiologia , Reprodutibilidade dos Testes , Atrofia Muscular , Biomarcadores , MúsculosRESUMO
BACKGROUND: Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. METHODS: Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. RESULTS: At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (-8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. CONCLUSIONS: The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.
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Sarcopenia , Masculino , Feminino , Humanos , Idoso , Sarcopenia/epidemiologia , Envelhecimento/fisiologia , Exercício Físico/fisiologia , Músculo Esquelético/patologia , Absorciometria de FótonRESUMO
This study evaluates neuromechanical control and muscle-tendon interaction during energy storage and dissipation tasks in hypergravity. During parabolic flights, while 17 subjects performed drop jumps (DJs) and drop landings (DLs), electromyography (EMG) of the lower limb muscles was combined with in vivo fascicle dynamics of the gastrocnemius medialis, two-dimensional (2D) kinematics, and kinetics to measure and analyze changes in energy management. Comparisons were made between movement modalities executed in hypergravity (1.8 G) and gravity on ground (1 G). In 1.8 G, ankle dorsiflexion, knee joint flexion, and vertical center of mass (COM) displacement are lower in DJs than in DLs; within each movement modality, joint flexion amplitudes and COM displacement demonstrate higher values in 1.8 G than in 1 G. Concomitantly, negative peak ankle joint power, vertical ground reaction forces, and leg stiffness are similar between both movement modalities (1.8 G). In DJs, EMG activity in 1.8 G is lower during the COM deceleration phase than in 1 G, thus impairing quasi-isometric fascicle behavior. In DLs, EMG activity before and during the COM deceleration phase is higher, and fascicles are stretched less in 1.8 G than in 1 G. Compared with the situation in 1 G, highly task-specific neuromuscular activity is diminished in 1.8 G, resulting in fascicle lengthening in both movement modalities. Specifically, in DJs, a high magnitude of neuromuscular activity is impaired, resulting in altered energy storage. In contrast, in DLs, linear stiffening of the system due to higher neuromuscular activity combined with lower fascicle stretch enhances the buffering function of the tendon, and thus the capacity to safely dissipate energy.NEW & NOTEWORTHY For the first time, the neuromechanics of distinct movement modalities that fundamentally differ in their energy management function have been investigated during overload systematically induced by hypergravity. Parabolic flight provides a unique experimental setting that allows near-natural movement execution without the confounding effects typically associated with load variation. Our findings show that gravity-adjusted muscle activities are inversely affected within jumps and landings. Specifically, in 1.8 G, typical task-specific differences in neuromuscular activity are reduced during the center of mass deceleration phase, resulting in fascicle lengthening, which is associated with energy dissipation.
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Músculo Esquelético , Tendões , Humanos , Fenômenos Biomecânicos , Tendões/fisiologia , Músculo Esquelético/fisiologia , Eletromiografia , Perna (Membro)/fisiologia , Contração Muscular/fisiologiaRESUMO
BACKGROUND: Inactivity and unloading induce skeletal muscle atrophy, loss of strength and detrimental metabolic effects. Bed rest is a model to study the impact of inactivity on the musculoskeletal system. It not only provides information for bed-ridden patients care, but it is also a ground-based spaceflight analogue used to mimic the challenges of long space missions for the human body. In both cases, it would be desirable to develop a panel of biomarkers to monitor muscle atrophy in a minimally invasive way at point of care to limit the onset of muscle loss in a personalized fashion. METHODS: We applied mass spectrometry-based proteomics to measure plasma protein abundance changes in response to 10 days of bed rest in 10 young males. To validate the correlation between muscle atrophy and the significant hits emerging from our study, we analysed in parallel, with the same pipeline, a cohort of cancer patients with or without cachexia and age-matched controls. Our analysis resulted in the quantification of over 500 proteins. RESULTS: Unloading affected plasma concentration of proteins of the complement cascade, lipid carriers and proteins derived from tissue leakage. Among the latter, teneurin-4 increased 1.6-fold in plasma at bed rest day 10 (BR10) compared with BR0 (6.E9 vs. 4.3E9, P = 0.02) and decreased to 0.6-fold the initial abundance after 2 days of recovery at normal daily activity (R + 2, 2.7E9, P = 3.3E-4); the extracellular matrix protein lumican was decreased to 0.7-fold (1.2E9 vs. 8.5E8, P = 1.5E-4) at BR10 and remained as low at R + 2. We identified six proteins distinguishing subjects developing unloading-mediated muscle atrophy (decrease of >4% of quadriceps cross-sectional area) from those largely maintaining their initial muscle mass. Among them, transthyretin, a thyroid hormone-binding protein, was significantly less abundant at BR10 in the plasma of subjects with muscle atrophy compared with those with no atrophy (1.6E10 vs. 2.6E10, P = 0.001). Haptoglobin-related protein was also significantly reduced in the serum of cancer patients with cachexia compared with that of controls. CONCLUSIONS: Our findings highlight a combination or proteomic changes that can be explored as potential biomarkers of muscle atrophy occurring under different conditions. The panel of significant proteomic differences distinguishing atrophy-prone and atrophy-resistant subjects after 10 days of bed rest need to be tested in a larger cohort to validate their potential to predict inactivity-triggered muscle loss in humans.
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Repouso em Cama , Proteoma , Masculino , Humanos , Repouso em Cama/efeitos adversos , Voluntários Saudáveis , Caquexia , Proteômica , Atrofia Muscular/etiologiaRESUMO
AIM: We planned a cross-sectional investigation (study 1) and a longitudinal training intervention (study 2) to investigate whether recreational dancing affords greater neuroprotective effects against age-related neuromuscular junction (NMJ) degeneration compared to general fitness exercise training. METHODS: In study 1, we recruited 19 older volunteers regularly practising dancing (older dancers [OD]) and 15 recreationally physically active older individuals (OA) and physical performance, muscle morphology, muscle function, and NMJ stability (from serum C-terminal agrin fragment [CAF] concentration) were assessed. In study 2, employing a longitudinal study design in a different cohort (composed of 37 older adults), we aimed to study whether a 6-month dancing intervention decreased CAF concentration compared to general fitness exercise training in older adults. RESULTS: Our findings show that OD had a lower CAF concentration (suggesting an increased NMJ stability) compared to OA. This result was accompanied by superior functional performance despite no differences in muscle size. In study 2, we observed a reduction in CAF concentration only in the dancing group. CONCLUSION: Overall, these findings suggest that dancing is an effective training modality to promote neuroprotection and increase muscle function in healthy older individuals.
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Dança , Fármacos Neuroprotetores , Humanos , Idoso , Dança/fisiologia , Estudos Longitudinais , Estudos Transversais , EnvelhecimentoRESUMO
Experimental evidence implicates reactive oxygen species (ROS) generation in the hypoxic stabilization of hypoxia-inducible factor (HIF)-1α and in the subsequent expression of promoters of tumor invasiveness and metastatic spread. However, the role played by mitochondrial ROS in hypoxia-induced Epithelial-Mesenchymal Transition (EMT) activation is still unclear. This study was aimed at testing the hypothesis that the inhibition of hypoxia-induced mitochondrial ROS production, mainly at the mitochondrial Complex III UQCRB site, could result in the reversion of EMT, in addition to decreased HIF-1α stabilization. The role of hypoxia-induced ROS increase in HIF-1α stabilization and the ability of antioxidants, some of which directly targeting mitochondrial Complex III, to block ROS production and HIF-1α stabilization and prevent changes in EMT markers were assessed by evaluating ROS, HIF-1α and EMT markers on breast cancer cells, following 48 h treatment with the antioxidants. The specific role of UQCRB in hypoxia-induced EMT was also evaluated by silencing its expression through RNA interference and by assessing the effects of its downregulation on ROS production, HIF-1α levels, and EMT markers. Our results confirm the pivotal role of UQCRB in hypoxic signaling inducing EMT. Thus, UQCRB might be a new therapeutic target for the development of drugs able to reverse EMT by blocking mitochondrial ROS production.
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Although regular physical activity exposure leads to positive postural balance control (PBC) adaptations, few studies investigated its effects, or the one of inactivity, on PBC in populations of different age groups. Thus, this study investigated the impact of a physically active lifestyle on static and dynamic PBC in young and older adults. Thirty-five young physically active subjects (YA), 20 young sedentary subjects (YS), 16 physically active older adults (OA), and 15 sedentary older adults (OS) underwent a static and a dynamic PBC assessment. A force platform and an instrumented proprioceptive board were employed to measure the center of pressure (COP) trajectory and the anteroposterior oscillations, respectively. In static conditions, no significant differences were detected among groups considering the overall postural balance performance represented by the area of confidence ellipse values. Conversely, the YA highlighted a higher efficiency (i.e., lower sway path mean velocity) in PBC maintenance compared to the other groups (YA vs OA: p = 0.0057, Cohen's d = 0.94; YA vs OS p = 0.043, d = 1.07; YA vs YS p = 0.08, d = 0.67). OS exhibited an overall worse performance in dynamic conditions than YA and YS. Surprisingly, no differences were found between YS and OA for all the static and dynamic parameters considered. In conclusion, our results suggest that a physically active lifestyle may promote static and dynamic balance performance in young and older adults, thus with potentially positive effects on the age-related decline of postural balance performance. Dynamic PBC assessment seems more sensitive in detecting differences between groups than the static evaluation.
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Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short-term unloading and active recovery (AR). Eleven healthy males underwent a 10-day unilateral lower limb suspension (ULLS) period, followed by 21-day AR based on resistance exercise. Quadriceps femoris (QF) cross-sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c-terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA-sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10-day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR. KEY POINTS: We used integrative electrophysiological and molecular approaches to comprehensively investigate changes in neuromuscular integrity and function after a 10-day unilateral lower limb suspension (ULLS), followed by 21 days of active recovery in young healthy men, with a particular focus on neuromuscular junction (NMJ) and motor unit potential (MUP) properties alterations. After 10-day ULLS, we found significant NMJ molecular alterations in the absence of NMJ transmission stability impairment. These findings suggest that the human NMJ is functionally resilient against insults and stresses induced by short-term disuse at least at relatively low contraction intensities, at which low-threshold, slow-type motor units are recruited. Intramuscular electromyography analysis revealed that unloading caused increased MUP complexity and decreased motor unit firing rates, and these alterations could be related to the observed changes in skeletal muscle ion channel pool and initial and partial signs of fibre denervation and axonal damage. The active recovery period restored these neuromuscular changes.
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Contração Muscular , Transcriptoma , Masculino , Humanos , Contração Muscular/fisiologia , Junção Neuromuscular/fisiologia , Músculo Esquelético/fisiologia , Músculo Quadríceps/fisiologia , EletromiografiaRESUMO
BACKGROUND: A ketogenic diet (KD) is a nutritional approach, usually adopted for weight loss, that restricts daily carbohydrates under 30 g/day. KD showed contradictory results on sport performance, whilst no data are available on team sports. We sought to investigate the influence of a KD on different parameters in semi-professional soccer players. METHODS: Subjects were randomly assigned to a iso-protein (1.8 g/Kg body weight/day) ketogenic diet (KD) or western diet (WD) for 30 days. Body weight and body composition, resting energy expenditure (REE), respiratory exchange ratio (RER), cross sectional area (CSA) and isometric muscle strength of quadriceps, counter movement jump (CMJ) and yoyo intermittent recovery test time were measured. RESULTS: There was a significantly higher decrease of body fat (p = 0.0359), visceral adipose tissue (VAT) (p = 0.0018), waist circumference (p = 0.0185) and extra-cellular water (p = 0.0060) in KD compared to WD group. Lean soft tissue, quadriceps muscle area, maximal strength and REE showed no changes in both groups. RER decreased significantly in KD (p = 0.0008). Yo-yo intermittent test improved significantly (p < 0.0001) in both groups without significant differences between groups. CMJ significantly improved (p = 0.0021) only in KD. CONCLUSIONS: This is the first study investigating the effects of a KD on semi-professional soccer players. In our study KD athletes lost fat mass without any detrimental effects on strength, power and muscle mass. When the goal is a rapid weight reduction in such athletes, the use of a KD should be taken into account. TRIAL REGISTRATION: registered retrospectively on Clinical Trial registration number NCT04078971 .
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Composição Corporal , Dieta Cetogênica , Força Muscular , Músculo Esquelético/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto , Atletas , Dieta Ocidental , Humanos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
Purpose: Fascicle and sarcomere lengths are important predictors of muscle mechanical performance. However, their regulation during stretch-shortening cycle (SSC) activities in usual and challenging conditions is poorly understood. In this study, we aimed to investigate muscle fascicle and sarcomere behavior during drop jumps (a common SSC activity) in conditions of variable gravity. Methods: Fifteen volunteers performed repeated drop jumps in 1 g, hypo-gravity (0 to 1 g), and hyper-gravity (1 to 2 g) during a parabolic flight. Gastrocnemius medialis (GM) electromyographic activity and fascicle length (Lf) were measured at drop-off, ground contact (GC), minimum ankle joint angle (MAJ), and push-off. GM sarcomere number was estimated by dividing Lf, measured by ultrasound at rest, by published data on GM sarcomere length, and measured in vivo at the same joint angle. Changes in sarcomere length were estimated by dividing GM Lf in each jump phase by sarcomere number calculated individually. The sarcomere force-generating capacity in each jump phase was estimated from the sarcomere length-tension relationship previously reported in the literature. Results: The results showed that, regardless of the gravity level, GM sarcomeres operated in the ascending portion of their length-tension relationship in all the jump phases. Interestingly, although in hypo-gravity and hyper-gravity during the braking phase (GC-MAJ) GM fascicles and sarcomeres experienced a stretch (as opposed to the quasi-isometric behavior in 1 g), at MAJ they reached similar lengths as in 1 g, allowing sarcomeres to develop about the 70% of their maximum force. Conclusion: The observed fascicle behavior during drop jumping seems useful for anchoring the tendon, enabling storage of elastic energy and its release in the subsequent push-off phase for effectively re-bouncing in all gravity levels, suggesting that an innate neuromuscular wisdom enables to perform SSC movements also in challenging conditions.
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Space analogs, such as bed rest, are used to reproduce microgravity-induced morphological and physiological changes and can be used as clinical models of prolonged inactivity. Nevertheless, nonuniform decreases in muscle mass and function have been frequently reported, and peripheral nerve adaptations have been poorly studied, although some of these mechanisms may be explained. Ten young healthy males (18-33 yr) underwent 10 days of horizontal bed rest. Peripheral neurophysiological assessments were performed bilaterally for the dominant (DL) and nondominant upper and lower limbs (N-DL) on the 1st and 10th day of bed rest, including ultrasound of the median, deep peroneal nerve (DPN), and common fibular nerve (CFN) , as well as a complete nerve conduction study (NCS) of the upper and lower limbs. Consistently, reduced F waves, suggesting peripheral nerve dysfunction, of both the peroneal (DL: P = 0.005, N-DL: P = 0.013) and tibial nerves (DL: P = 0.037, N-DL: P = 0.005) were found bilaterally, whereas no changes were observed in nerve ultrasound or other parameters of the NCS of both the upper and lower limbs. In these young healthy males, only the F waves, known to respond to postural changes, were significantly affected by short-term bed rest. These preliminary results suggest that during simulated microgravity, most changes occur at the muscle or central nervous system level. Since the assessment of F waves is common in clinical neurophysiological examinations, caution should be used when testing individuals after prolonged immobility.
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Repouso em Cama , Extremidades/inervação , Sistema Nervoso Periférico/fisiologia , Simulação de Ausência de Peso , Adaptação Fisiológica , Adolescente , Adulto , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Masculino , Condução Nervosa , Exame Neurológico , Sistema Nervoso Periférico/diagnóstico por imagem , Decúbito Dorsal , Fatores de Tempo , Ultrassonografia , Adulto JovemRESUMO
Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate. Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course. Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction. Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%). Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens. Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).
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Motor neuron degeneration, denervation, neuromuscular junction (NMJ) fragmentation and loss of motor units (MUs), play a key-role in the development of sarcopenia. The aim of the present study was to investigate the beneficial effects of regular practice of dancing in physically active elders on concentration of C-terminal Agrin fragment (CAF), a marker of NMJ instability, muscle mass, strength, and physical performance in a group of 16 recreationally active older dancers (AOD; 70.1 ± 3.4 yr) compared to 15 age-matched sedentary peers (OS; 70.9 ± 6.2 yr). Circulating concentration of CAF was measured in serum, while morphology of the vastus lateralis and multifidus muscles was assessed by ultrasound imaging. In addition, the participants underwent two functional performance tests, the Timed Up and Go (TUG) and the 10-meter walk test (10-MWT), a lower and upper limb isometric strength test, a static and a dynamic balance test. Although no statistically significant differences were detected for both muscle morphology and isometric strength, higher CAF concentration (20%, p < 0.01) was found in OS. AOD showed a better performance in TUG (22%, p < 0.001), 10-MWT (17%, p < 0.001) and dynamic balance (25%, p < 0.01) than OS. Notably, CAF concentration correlated with dynamic balance performance (r = 0.3711, p < 0.05). Our results provide evidence that the regular practice of dancing in older age, together with non-structured light aerobic physical activities, is associated to lower CAF concentration and improved walking and balance performance. Our findings also suggest that NMJ instability, as indicated by elevated CAF serum concentration, seems to precede the loss of muscle size and alterations in muscle architecture normally associated with sarcopenia.
Assuntos
Agrina , Sarcopenia , Idoso , Marcha , Humanos , Força Muscular , Músculo Esquelético , Fragmentos de Peptídeos , Equilíbrio PosturalRESUMO
BACKGROUND: The assessment of muscle mass is a key determinant of the diagnosis of sarcopenia. We introduce for the first time an ultrasound imaging method for diagnosing sarcopenia based on changes in muscle geometric proportions. METHODS: Vastus lateralis muscle fascicle length (Lf) and thickness (Tm) were measured at 35% distal femur length by ultrasonography in a population of 279 individuals classified as moderately active elderly (MAE), sedentary elderly (SE) (n = 109), mobility impaired elderly (MIE) (n = 43), and in adult young controls (YC) (n = 60). The ratio of Lf/Tm was calculated to obtain an ultrasound index of the loss of muscle mass associated with sarcopenia (USI). In a subsample of elderly male individuals (n = 76) in which corresponding DXA measurements were available (MAE, n = 52 and SE, n = 24), DXA-derived skeletal muscle index (SMI, appendicular limb mass/height2 ) was compared with corresponding USI values. RESULTS: For both young and older participants, USI values were found to be independent of sex, height and body mass. USI values were 3.70 ± 0.52 for YC, 4.50 ± 0.72 for the MAE, 5.05 ± 1.11 for the SE and 6.31 ± 1.38 for the MIE, all significantly different between each other (P < 0.0001). Based on the USI Z-scores, with reference to the YC population, the 219 elderly participants were stratified according to their muscle sarcopenic status. Individuals with USI values within a range of 3.70 < USI ≥ 4.23 were classified as non-sarcopenic (prevalence 23.7%), those with USI values within 4.23 < USI ≥ 4.76 were classified as pre-sarcopenic (prevalence 23.7%), those with USI values within 4.76 < USI ≥ 5.29 were classified as moderately sarcopenic (prevalence 15.1%), those with USI values within range 5.29 < USI ≥ 5.82 were classified as sarcopenic (prevalence 27.9%), and those with USI values >5.82 were classified as severely sarcopenic (prevalence 9.6%). The DXA-derived SMI was found to be significantly correlated with USI (r = 0.61, P < 0.0001). Notably, the USI cut-off value for moderate sarcopenia (4.76 a.u.) was found to coincide with the DXA cut-off value of sarcopenia (7.26 kg/m2 ). CONCLUSIONS: We propose a novel, practical, and inexpensive imaging marker of the loss of muscle mass associated with sarcopenia, called the ultrasound sarcopenic index (USI), based on changes in muscle geometric proportions. These changes provide a useful 'signature of sarcopenia' and allow the stratification of individuals according to the presence and severity of muscle sarcopenia. We are convinced that the USI will be a useful clinical tool for confirming the diagnosis of sarcopenia, of which the assessment of muscle mass is a key-component.
Assuntos
Sarcopenia , Adulto , Idoso , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Prevalência , Músculo Quadríceps , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , UltrassonografiaRESUMO
PURPOSE: This study aimed to investigate the changes in fascicle length (Lf) of biceps femoris long head (BFlh) after 10 d of bed rest (BR) by comparing four different ultrasound (US) methods. METHODS: Ten healthy men participated in 10-d BR. Before (BR0) and after (BR10) the BR period, BFlh Lf values were obtained using 1) extended-field-of-view (EFOV) technique, 2) the manual linear extrapolation (MLE) method, and 3) two trigonometric equations (equations A and B) from a single US image. RESULTS: After BR10, decreased Lf values were observed by EFOV (P < 0.001; Hedges' g = 0.29) and MLE (P = 0.0082; g = 0.22) methods, but not with equations A and B. Differences between equation A and the other US methods were detected at both time points. The percentage of changes in Lf between BR0 and BR10 was influenced by the US methods applied, with difference detected between the changes measured by EFOV and the ones estimated by equation A (P = 0.04; g = 0.53). Bland-Altman analyses revealed relevant average absolute biases in Lf between EFOV and other methods at both time points (range BR0-BR10: MLE, 0.3-0.37 cm (3.4%-4.32%); equation B, 0.3-0.48 cm (3.24%-5.41%); equation A, 2.44-2.97 cm (24.05%-29.2%)). A significant correlation (r = 0.83) in percentage of change in Lf values was observed only between EFOV and MLE. CONCLUSIONS: We showed that four distinct US methods lead to different results in the assessment of BFlh Lf changes after a short-term period of unloading. The implementation of EFOV technique (or alternatively MLE) to assess Lf changes in BFlh during longitudinal studies is warranted.