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ABSTRACT: Miralles-Iborra, A, Del Coso, J, De Los Ríos-Calonge, J, Elvira, JLL, Barbado, D, Urban, T, and Moreno-Pérez, V. Deceleration capacity during directional change as a time-efficient (ecological) prescreening of hip adductor force status in amateur soccer players. J Strength Cond Res XX(X): 000-000, 2024-Reduced isometric adductor muscle strength has been identified as a modifiable risk factor contributing to injury in soccer players. However, the measurement of hip adductor muscle strength is habitually laboratory-based, with isolated hip movements that do not reflect soccer-specific movements that induce groin injury during match play. This study aimed to determine the usefulness of deceleration capacity during a change of direction (COD) as a time-efficient (ecological) prescreening of hip adductor force status in soccer players. Nineteen amateur soccer players completed unilateral isometric hip adductor strength assessments and a 180° COD test. Isometric hip strength assessment included the maximum peak torque (PT) and maximum rate of torque development (RTDmax) relative to players' body mass. Players' deceleration capacity during the COD test was determined for each leg through maximum deceleration normalized to the linear momentum. A linear regression analysis was performed to associate isometric hip strength variables with the deceleration capacity during the COD test at each leg. There was not a statistically significant association between deceleration capacity and hip isometric maximum PT of the dominant and nondominant legs (r ≤ 0.14, p > 0.05). Nevertheless, a moderate association was found between deceleration capacity and RTDmax for both legs (r ≥ 0.58, p < 0.05). The optimal linear regression model suggests that measuring deceleration capacity during a directional change test could explain RTDmax by 33 and 43% for the dominant and nondominant legs, respectively. During a 180° COD test, the deceleration capacity captured through GPS-accelerometer device was limited as a prescreening tool to evaluate hip adductor force status in soccer players.
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Identification of therapeutic targets for treating fibrotic diseases and cancer remains challenging. Our study aimed to investigate the effects of TGF-ß1 and TGF-ß3 on myofibroblast differentiation and extracellular matrix deposition in different types of fibroblasts, including normal/dermal, cancer-associated, and scar-derived fibroblasts. When comparing the phenotype and signaling pathways activation we observed extreme heterogeneity of studied markers across different fibroblast populations, even within those isolated from the same tissue. Specifically, the presence of myofibroblast and deposition of extracellular matrix were dependent on the origin of the fibroblasts and the type of treatment they received (TGF-ß1 vs. TGF-ß3). In parallel, we detected activation of canonical signaling (pSMAD2/3) across all studied fibroblasts, albeit to various extents. Treatment with TGF-ß1 and TGF-ß3 resulted in the activation of canonical and several non-canonical pathways, including AKT, ERK, and ROCK. Among studied cells, cancer-associated fibroblasts displayed the most heterogenic response to TGF-ß1/3 treatments. In general, TGF-ß1 demonstrated a more potent activation of signaling pathways compared to TGF-ß3, whereas TGF-ß3 exhibited rather an inhibitory effect in keloid- and hypertrophic scar-derived fibroblasts suggesting its clinical potential for scar treatment. In summary, our study has implications for comprehending the role of TGF-ß signaling in fibroblast biology, fibrotic diseases, and cancer. Future research should focus on unraveling the mechanisms beyond differential fibroblast responses to TGF-ß isomers considering inherent fibroblast heterogeneity.
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Cicatriz Hipertrófica , Factor de Crecimiento Transformador beta1 , Humanos , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta3/metabolismo , Factor de Crecimiento Transformador beta3/farmacología , Fibroblastos/metabolismo , Cicatrización de Heridas , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Factor de Crecimiento Transformador beta/metabolismo , Carcinogénesis/metabolismo , Carcinogénesis/patología , Transformación Celular Neoplásica/metabolismo , Isoformas de Proteínas/metabolismo , Células CultivadasRESUMEN
NREP (neuronal regeneration related protein homolog) plays a role in the transformation of neural, muscle, and fibroblast cells and in smooth muscle myogenesis. The NREP gene was selected for detailed study as an expressional and functional candidate gene on the basis of data from the expression microarray, which detected the differences in gene expression between Czech Large White pigs and wild boars in the longissimus lumborum et thoracis and biceps femoris muscle tissues. Quantitative real-time PCR results confirmed that porcine NREP was expressed in both skeletal muscles and significantly overexpressed in Czech Large White pigs compared with wild boars (14.5- and 11.6-fold; p < .05). We identified 9 polymorphic sites in the genomic DNA of NREP. Six of these polymorphisms were in complete linkage disequilibrium, and therefore, only 4 loci were informative. The associations of the HF571253:g.103G>A, HF571253:g.134G>A, HF571253:g.179T>C and HF571253:g.402_409delT polymorphisms with backfat thickness, lean meat content and average daily gain were assessed in Czech Large White pigs. The GG genotypes HF571253:g.103G>A and HF571253:g.134G>A, the TT genotypes HF571253:g.179T>C and 67 HF571253:g.402_409delT genotypes had favourable effects on the studied traits. Our results indicate the possibility of utilizing the variability of the NREP gene in marker-assisted selection in order to improve meat production in pigs.
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Polimorfismo de Nucleótido Simple , Sus scrofa , Animales , Genotipo , Desequilibrio de Ligamiento , Carne , Músculo Esquelético , Sus scrofa/genética , Porcinos/genéticaRESUMEN
PURPOSE: Functional electrical stimulation-assisted cycle ergometry (FESCE) enables in-bed leg exercise independently of patients' volition. We hypothesised that early use of FESCE-based progressive mobility programme improves physical function in survivors of critical care after 6 months. METHODS: We enrolled mechanically ventilated adults estimated to need >7 days of intensive care unit (ICU) stay into an assessor-blinded single centre randomised controlled trial to receive either FESCE-based protocolised or standard rehabilitation that continued up to day 28 or ICU discharge. RESULTS: We randomised in 1:1 ratio 150 patients (age 61±15 years, Acute Physiology and Chronic Health Evaluation II 21±7) at a median of 21 (IQR 19-43) hours after admission to ICU. Mean rehabilitation duration of rehabilitation delivered to intervention versus control group was 82 (IQR 66-97) versus 53 (IQR 50-57) min per treatment day, p<0.001. At 6 months 42 (56%) and 46 (61%) patients in interventional and control groups, respectively, were alive and available to follow-up (81.5% of prespecified sample size). Their Physical Component Summary of SF-36 (primary outcome) was not different at 6 months (50 (IQR 21-69) vs 49 (IQR 26-77); p=0.26). At ICU discharge, there were no differences in the ICU length of stay, functional performance, rectus femoris cross-sectional diameter or muscle power despite the daily nitrogen balance was being 0.6 (95% CI 0.2 to 1.0; p=0.004) gN/m2 less negative in the intervention group. CONCLUSION: Early delivery of FESCE-based protocolised rehabilitation to ICU patients does not improve physical functioning at 6 months in survivors. TRIAL REGISTRATION NUMBER: NCT02864745.
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Enfermedad Crítica/rehabilitación , Ergometría/métodos , Terapia por Ejercicio/métodos , Unidades de Cuidados Intensivos , Fuerza Muscular/fisiología , Debilidad Muscular/rehabilitación , Calidad de Vida , Respiración Artificial/métodos , Estimulación Eléctrica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Debilidad Muscular/fisiopatología , Estudios Prospectivos , Factores de TiempoRESUMEN
Excessive connective tissue accumulation, a hallmark of hypertrophic scaring, results in progressive deterioration of the structure and function of organs. It can also be seen during tumor growth and other fibroproliferative disorders. These processes result from a wide spectrum of cross-talks between mesenchymal, epithelial and inflammatory/immune cells that have not yet been fully understood. In the present review, we aimed to describe the molecular features of fibroblasts and their interactions with immune and epithelial cells and extracellular matrix. We also compared different types of fibroblasts and their roles in skin repair and regeneration following burn injury. In summary, here we briefly review molecular changes underlying hypertrophic scarring following burns throughout all basic wound healing stages, i.e. during inflammation, proliferation and maturation.
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Quemaduras/genética , Cicatriz Hipertrófica/genética , Inflamación/genética , Cicatrización de Heridas/genética , Quemaduras/patología , Proliferación Celular/genética , Cicatriz Hipertrófica/inmunología , Cicatriz Hipertrófica/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Inflamación/patologíaRESUMEN
Classification is a hot topic in Paralympic sport, making the development of evidence-based and sport-specific classification systems mandatory. However, the development of measurements for exploring the relationships between the athletes' impairment and their activity limitation is a considerable scientific challenge in team Paralympic sport such as 7-side football (ie, CP Football). The aims of this study were 1) to describe the activity limitation and external match load (ML) differences among impairment profiles (FT) in international level footballers with cerebral palsy (CPFP) and 2) to analyze the relationship among the activity limitation and external ML variables. Forty-eight international male CPFP (23 ± 7 y; 174.7 ± 7.2 cm; 69.4 ± 9.2 kg; 22.7 ± 2.6 kg·m-2 ) participated in this study and were divided according to their impairment profile (FT5/6, FT7, and FT8). Significant differences (P < .05) have been observed among FT profiles in the activity limitation tests (ie, static balance, coordination, vertical jump, horizontal jump, acceleration capacity, and change of direction ability). Additionally, significant differences have been observed among FT profiles in certain ML values (ie, Velmax , High Acc and in Mod and High Dec), where generally, FT8 players reported the best performance values. On the other hand, especially in the FT5/6 and in the FT8 profiles, a large-to-very large significant relationship was observed between the CPFP activity limitation and the ML values. In general, the results of the present study show that players with a lower impairment have less activity limitation and better ML. This study concludes that the potential relationships between the impairments of hypertonia, ataxia, or athetosis and performance in this para-sport might be impairment-specific.
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Parálisis Cerebral/fisiopatología , Limitación de la Movilidad , Fútbol , Deportes para Personas con Discapacidad , Adolescente , Adulto , Atletas , Rendimiento Atlético , Estudios Transversales , Personas con Discapacidad , Prueba de Esfuerzo , Humanos , Masculino , Adulto JovenRESUMEN
Nowadays, the irradiation methodology in proton therapy is switching from the use of passively scattered beams to active pencil beams due to the possibility of more conformal dose distributions. The dose rates of active pencil beams are much higher than those of passive beams. The purpose of this study was to investigate whether there is any difference in the biological effectiveness of these passive and active irradiation modes. The beam qualities of double scattering and pencil beam scanning were measured dosimetrically and simulated using the Monte Carlo code. Using the medulloblastoma cell line DAOY, we performed an in vitro comparison of the two modes in two positions along the dose-deposition curve plateau and inside the Bragg peak. We followed the clonogenic cell survival, apoptosis, micronuclei, and γH2AX assays as biological endpoints. The Monte Carlo simulations did not reveal any difference between the beam qualities of the two modes. Furthermore, we did not observe any statistically significant difference between the two modes in the in vitro comparison of any of the examined biological endpoints. Our results do not show any biologically relevant differences related to the different dose rates of passive and active proton beams.
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Terapia de Protones , Apoptosis/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Simulación por Computador , Histonas/metabolismo , Humanos , Transferencia Lineal de Energía , Pruebas de Micronúcleos , Método de Montecarlo , NeutronesRESUMEN
Postural control is considered a key variable in team sports, such as handball, which require abilities strongly related to balance. However, postural control and its relationship to the performance of handball skills according to the players' skill level and age has not been evaluated to date. This study analyzes the relationship between balance ability and team-handball performance according to age and expertise, applying a non-linear approach to balance assessment. Postural control from 114 male team-handball players was analyzed through the center of pressure (COP) during a balance task. Sport performance was measured by the accuracy and speed in throwing. Expert players threw faster, but not more accurately than recreational players. Balance performance was better for 18+ players (older than 18 years old) than those U12 (under 12 years old), but no differences were found according to their skill level. Players who threw with less accuracy showed slower COP velocity during the balance task and their moves were less irregular. Players who threw faster displayed more irregular and less auto-correlated COP movements. In conclusion, experienced team-handball players exhibited better balance performance, and this seems to be related to the maturation of the motor system more than to sport performance level. Nevertheless, non-linear measures of COP excursion revealed an exploratory behavior during balance in expert players, exhibiting more motion adjustments to reduce motor output error. Traditional variables measuring balance performance did not show sensitivity to this motor control process. A non-linear approach to balance assessment revealed functional variability during balance as an intrinsic characteristic of individuals' motor control according to age and skill level.
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OBJECTIVES: Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. DESIGN: In vitro study on human skeletal muscle cells. SETTINGS: University research laboratories. SUBJECTS: Patients undergoing hip surgery and healthy volunteers. INTERVENTIONS: Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 µg/mL propofol for 96 hours. MEASUREMENTS AND MAIN RESULTS: Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 µg/mL of propofol, concentrations as low as 1 µg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. CONCLUSIONS: Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.
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Hipnóticos y Sedantes/efectos adversos , Músculo Esquelético/efectos de los fármacos , Propofol/efectos adversos , Anciano , Células Cultivadas , Metabolismo Energético , Humanos , Hipnóticos y Sedantes/farmacología , Técnicas In Vitro , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Propofol/farmacologíaRESUMEN
Variable practice has been shown to be an effective strategy to improve open motor skills. However, the usefulness of this procedure in closed motor skills remains controversial. The following study has the objective of analysing the effects of variability practice in the improvement of a closed skill. The skill studied has been the tennis serve. Thirty young tennis players (13 ± 1.52 years), divided in two groups, took part in this study. One group practiced in variable conditions and the other group in consistency conditions. Both groups performed 12 training sessions (60 serves/session). The variable practice group improved their accuracy significantly compared with the consistency group (F3.25 = 3.078; P = 0.035). The velocity of serve increased after training in both groups (F3.25 = 15.890; P = 0.001). The practice in variable conditions seems to be effective in improving the performance of the tennis serve.
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Rendimiento Atlético , Destreza Motora , Movimiento , Educación y Entrenamiento Físico , Práctica Psicológica , Análisis y Desempeño de Tareas , Tenis , Adolescente , Niño , Femenino , Humanos , MasculinoRESUMEN
The study aimed to analyze the genetic diversity in the Czech population of Apis mellifera using mitochondrial DNA markers, tRNAleu-cox2 intergenic region and cox1 gene. A total of 308 samples of bees were collected from the entire Czech Republic (from colonies and flowers in 13 different regions). Following sequencing, several polymorphisms and haplotypes were identified. Analysis of tRNAleu-cox2 sequences revealed three DraI haplotypes (C, A1, and A4). The tRNAleu-cox2 region yielded 10 C lineage haplotypes, one of which is a newly described variant. Three A lineage haplotypes were identified, two of which were novel. A similar analysis of cox1 sequences yielded 16 distinct haplotypes (7 new) within the population. The most prevalent tRNAleu-cox2 haplotype identified was C1a, followed by C2a, C2c, C2l, and C2d. For the cox1 locus, the most frequent haplotypes were HpB02, HpB01, HpB03, and HpB04. The haplotype and nucleotide diversity indices were high in both loci, in tRNAleu-cox2 with values of 0.682 and 0.00172, respectively, and in cox1 0.789 and 0.00203, respectively. The Tajima's D values were negative and lower in tRNAleu-cox2 than in cox1. The most frequent haplotypes were uniformly distributed across all regions of the Czech Republic. No haplotype of the indigenous M lineage was identified. High diversity and the occurrence of rare haplotypes indicate population expansion and continuous import of tribal material of the C lineage.
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INTRODUCTION: Patients who have sustained extensive burns frequently exhibit substantial damage to skeletal muscle and associated complications. The rehabilitation of these patients can be challenging due to the nature of the injury and the subsequent complications. Nevertheless, there is a possibility that functional proprioceptive stimulation (illusory movements) may facilitate effective rehabilitation in patients with limited physiotherapy options. Nevertheless, this approach has yet to be tested in patients with burn injuries. MATERIAL AND METHODOLOGY: A prospective, randomised, crossover trial was conducted at a burn centre in a tertiary teaching hospital. The objective was to assess the effects of illusory movements on energy metabolism, insulin sensitivity, and skeletal muscle biology in adult critically ill patients with deep burns covering 30 % or more of the total body surface area. Two 30-minute daily sessions of functional proprioceptive stimulation were administered in addition to the standard physical therapy or physical activity regimen. Subsequently, the patients proceeded to the next stage of the trial, which involved a two-week crossover period. MEASUREMENTS AND MAIN RESULTS: Daily indirect calorimetry and calculation of nitrogen balance. Skeletal muscle biopsies from vastus lateralis for high resolution respirometry and euglycemic clamps to assess whole body glucose disposal were performed three times: at baseline and then fortnightly after each intervention period. The intervention was feasible and well tolerated in both early and late stages of burn disease. It did not change energy expenditure (mean change -33 [95 % CI: -292;+227] kcal .24 h-1, p = 0.79), nitrogen balance (+2.0 [95 % CI: -3.1;+7.1] g N .1.73 m-2 BSA .24 h-1), or insulin sensitivity (mean change of insulin-mediated glucose disposal -0.33 [95 % CI: -1.18;+0.53] mmol.h-1). At the cellular level, the intervention increased the capacity of mitochondria to synthesize ATP by aerobic phosphorylation and tended to increase mitochondrial coupling. Functional capacities of fatty acid oxidation and electron transfer chain complexes I, II, and IV were unaffected. CONCLUSIONS: Compared to physical therapy alone, two daily sessions of functional proprioceptive stimulation in addition to usual physical therapy in patients with extensive burns did not change energy expenditure, insulin sensitivity, nitrogen balance, or energy substrate oxidation. At cellular level, the intervention improved the capacity of aerobic phosphorylation in skeletal muscle mitochondria. Clinical effects remain to be demonstrated in adequately powered trials.
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Induced variability by the use of unstable surfaces has been proposed to enhance proprioceptive control to deal with perturbations in the support base better. However, there is a lack of evidence about its benefits facilitating motor adaptions in upper body skills. In this experiment, practice on an unstable surface was applied to analyze the adaptations in an upper limb precision throwing skill. After a pretest, twenty-one participants were randomly allocated into two groups: one group practiced the throwing task on a stable surface and the other group practiced the same task on an unstable support base. Differences in throwing performance between pre- and post-practice were analyzed in accuracy, hand movement kinematics and variability of the throw in both surface conditions. Fuzzy entropy of the horizontal force was calculated to assess the complexity dynamics of postural sway. Participants improved their performance on the stable and the unstable surface. Induced variability using an unstable surface reduced participants' variability and the complexity of postural sway, but it did not facilitate a superior adaptation of the throwing task. The results suggest that the variations induced by unstable surfaces would fall far from the family of specific motor solutions and would not facilitate additional motor performance of the throwing task.
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Destreza Motora , Extremidad Superior , Humanos , Mano , Movimiento , AclimataciónRESUMEN
To assess the influence of age and skill level on handball throwing kinematics and performance, 126 participants were distributed into groups according to their skill level (elite or recreational) and age group (U12, U16 or +18). Each participant performed three sets of 10 throws, aiming to hit a target (40 × 40 cm) located in the right corner of the goal. During testing, kinematic data were recorded and throwing performance (accuracy and velocity) was measured. Results showed greater throwing velocity in the elite compared to recreational groups, whereas no differences were found for throwing accuracy. The elite U16 and +18 groups displayed higher segment velocities (hand, arm and pelvis) than the recreational groups. The participation of proximal segments was higher in older groups, showing the more skilled players (U16 and +18) greater pelvis velocities (1.62-1.75 vs 1.02-1.22 m/s). The increased velocity of the distal joints (hand peak velocity: 13.56 ± 1.65 vs 10.67 ± 1.98 m/s) are responsible for the difference in throwing velocity between the elite and recreational U12 groups. Several correlations were found between joint kinematics and throwing velocity. Coaches could use these results during training, to optimise specific throwing training.
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Rendimiento Atlético , Humanos , Anciano , Fenómenos Biomecánicos , Extremidad SuperiorRESUMEN
The aim of this work is to propose methodology for estimations the characteristics of the radiation fields (and derived quantities from the field of dosimetry and radiation protection) in knowledge of a distribution of radionuclides released into the main production unit (or just a containment) area after a nuclear reactor accident. For such task stochastic Monte Carlo method has been chosen. Because of dimensions and thick shielding (concrete) barriers in the facility, application of the variance reduction techniques has been necessary. Monte Carlo code Monaco in sequence MAVRIC (from package SCALE 6.2.3) with variance reduction techniques using CADIS methodology has been employed for designing the proposed methodology. Procedure has been tested on a simulation model of a main production unit described by inspiration from the block of a nuclear power plant with a VVER-1000 reactor (installed in the Czech Republic, Central Europe).
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Protección Radiológica , Liberación de Radiactividad Peligrosa , Simulación por Computador , Método de Montecarlo , Plantas de Energía Nuclear , Dosis de Radiación , Protección Radiológica/métodosRESUMEN
The aim of this contribution is to provide an overview of comparison of two types of eye lens dosemeter systems. The comparison was performed at the Department of Intravenous Cardiology using patient and physician phantoms and supplemented by dose simulation using the Monte Carlo method. The tests were performed in several specific geometries and in addition to eye lens dosemeters the value of a personal dosemeter located at the reference point was also monitored. The value of Hp(3) and Hp(10) was monitored. It is clear from the results that film dosemeters achieve more correct results in most cases. It is probably due to a better correction for the angle of exposure. This assumption must be verified by more detailed measurements in laboratory conditions.
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Cardiología , Cristalino , Exposición Profesional , Protección Radiológica , Cardiología/métodos , Humanos , Exposición Profesional/análisis , Dosis de Radiación , Protección Radiológica/métodos , Radiología Intervencionista/métodosRESUMEN
BACKGROUND: Mitochondrial dysfunction is a hallmark of both critical illness and propofol infusion syndrome and its severity seems to be proportional to the doses of noradrenaline, which patients are receiving. We comprehensively studied the effects of noradrenaline on cellular bioenergetics and mitochondrial biology in human skeletal muscle cells with and without propofol-induced mitochondrial dysfunction. METHODS: Human skeletal muscle cells were isolated from vastus lateralis biopsies from patients undergoing elective hip replacement surgery (n = 14) or healthy volunteers (n = 4). After long-term (96 h) exposure to propofol (10 µg/mL), noradrenaline (100 µM), or both, energy metabolism was assessed by extracellular flux analysis and substrate oxidation assays using [14C] palmitic and [14C(U)] lactic acid. Mitochondrial membrane potential, morphology and reactive oxygen species production were analysed by confocal laser scanning microscopy. Mitochondrial mass was assessed both spectrophotometrically and by confocal laser scanning microscopy. RESULTS: Propofol moderately reduced mitochondrial mass and induced bioenergetic dysfunction, such as a reduction of maximum electron transfer chain capacity, ATP synthesis and profound inhibition of exogenous fatty acid oxidation. Noradrenaline exposure increased mitochondrial network size and turnover in both propofol treated and untreated cells as apparent from increased co-localization with lysosomes. After adjustment to mitochondrial mass, noradrenaline did not affect mitochondrial functional parameters in naïve cells, but it significantly reduced the degree of mitochondrial dysfunction induced by propofol co-exposure. The fatty acid oxidation capacity was restored almost completely by noradrenaline co-exposure, most likely due to restoration of the capacity to transfer long-chain fatty acid to mitochondria. Both propofol and noradrenaline reduced mitochondrial membrane potential and increased reactive oxygen species production, but their effects were not additive. CONCLUSIONS: Noradrenaline prevents rather than aggravates propofol-induced impairment of mitochondrial functions in human skeletal muscle cells. Its effects on bioenergetic dysfunctions of other origins, such as sepsis, remain to be demonstrated.
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BACKGROUND: Functional electrical stimulation-assisted cycle ergometry (FESCE) can deliver active exercise to critically ill patients, including those who are sedated. Aerobic exercise is known to stimulate skeletal muscle glucose uptake. We asked whether FESCE can reduce intravenous insulin requirements and improve insulin sensitivity in intensive care unit (ICU) patients. METHOD: We performed an a priori-planned secondary analysis of data from an outcome-based randomized controlled trial (NCT02864745) of FESCE-based early-mobility program vs standard of care in mechanically ventilated patients. We analyzed glucose profile, glucose intake, and insulin requirements during ICU stay in all enrolled patients. In a nested subgroup, we performed hyperinsulinemic (120 mIU/min/m2 ) euglycemic clamps at days 0, 7, and 180 (n = 30, 23, and 11, respectively). RESULTS: We randomized 150 patients 1:1 to receive intervention or standard of care. Seventeen (23%) patients in each study arm had a history of diabetes. During ICU stay, patients received 137 ± 65 and 137 ± 88 g/day carbohydrate (P = .97), and 31 vs 35 (P = .62) of them required insulin infusion to maintain blood glucose 8.61 ± 2.82 vs 8.73 ± 2.67 mM (P = .75, n = 11,254). In those treated with insulin, median daily dose was 53 IU (interquartile range [IQR], 25-95) vs 62 IU (IQR, 26-96) in the intervention and control arm, respectively (P = .44). In the subgroup of patients undergoing hyperglycemic clamps, insulin sensitivities improved similarly and significantly from acute and protracted critical illness to 6 months after discharge. CONCLUSION: The FESCE-based early-mobility program does not significantly reduce insulin requirements in critically ill patients on mechanical ventilation.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Estimulación Eléctrica , Ergometría , Estudios de Seguimiento , Humanos , Insulina , Respiración ArtificialRESUMEN
PURPOSE: This study aimed (1) to explore the validity and reliability of a new and specific change-of-direction (COD) test that requires dribbling skills to classify international footballers with cerebral palsy (CP) and compare it with another valid and reliable COD test without ball dribbling and (2) to probe whether both tests can discriminate between the new CP football classes (ie, FT1, FT2, and FT3) established worldwide in 2018. METHODS: This study involved 180 international para-footballers with CP from 23 national teams at the 3 regional competitions held in 2018. They performed 2 COD tests, the modified agility test (no dribbling skills) and the dribbling speed test (DST). RESULTS: Reliability was excellent for both the modified agility test (intraclass correlation coefficient [ICC]2,1 = .91, SEM = 5.75%) and the DST (ICC2,1 = .92, SEM = 4.66%). The modified agility test and DST results were highly to very highly correlated to one another for the whole group and considering the sport classes (r = .60-.80; P < .001). A 1-way analysis of variance showed significant differences between sport classes in both tests (P < .001). However, among classes, there were significant differences between FT1 and FT2 and FT3 (P < .01, effect size = large) and low to moderate effect sizes between FT2 and FT3 for either test. CONCLUSION: The DST appears to be valid and reliable to classify CP football players within the new classification system. Regression analysis revealed that 18.2% of the variance in the new sport classes could be explained by the 2 examined tests.
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Rendimiento Atlético , Parálisis Cerebral , Prueba de Esfuerzo/normas , Fútbol , Deportes para Personas con Discapacidad , Humanos , Reproducibilidad de los ResultadosRESUMEN
Cardiac side effects of some pulmonary drugs are observed in clinical practice. Aminophylline, a methylxanthine bronchodilator with documented proarrhythmic action, may serve as an example. Data on the action of aminophylline on cardiac cell electrophysiology and contractility are not available. Hence, this study was focused on the analysis of changes in the beat rate and contraction force of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and HL-1 cardiomyocytes in the presence of increasing concentrations of aminophylline (10 µM-10 mM in hPSC-CM and 8-512 µM in HL-1 cardiomyocytes). Basic biomedical parameters, namely, the beat rate (BR) and contraction force, were assessed in hPSC-CMs using an atomic force microscope (AFM). The beat rate changes under aminophylline were also examined on the HL-1 cardiac muscle cell line via a multielectrode array (MEA). Additionally, calcium imaging was used to evaluate the effect of aminophylline on intracellular Ca2+ dynamics in HL-1 cardiomyocytes. The BR was significantly increased after the application of aminophylline both in hPSC-CMs (with 10 mM aminophylline) and in HL-1 cardiomyocytes (with 256 and 512 µM aminophylline) in comparison with controls. A significant increase in the contraction force was also observed in hPSC-CMs with 10 µM aminophylline (a similar trend was visible at higher concentrations as well). We demonstrated that all aminophylline concentrations significantly increased the frequency of rhythm irregularities (extreme interbeat intervals) both in hPSC-CMs and HL-1 cells. The occurrence of the calcium sparks in HL-1 cardiomyocytes was significantly increased with the presence of 512 µM aminophylline. We conclude that the observed aberrant cardiomyocyte response to aminophylline suggests an arrhythmogenic potential of the drug. The acquired data represent a missing link between the arrhythmic events related to the aminophylline/theophylline treatment in clinical practice and describe cellular mechanisms of methylxanthine arrhythmogenesis. An AFM combined with hPSC-CMs may serve as a robust platform for direct drug effect screening.