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Institut
- Department Sport- und Gesundheitswissenschaften (43) (entfernen)
The aim of this study was to investigate the effect of a 6-week sensorimotor or resistance training on maximum trunk strength and response to sudden, high-intensity loading in athletes. Interventions showed no significant difference for maximum strength in concentric and eccentric testing (p>0.05). For perturbation compensation, higher peak torque response following SMT (Extension: +24Nm 95%CI +/- 19Nm; Rotation: + 19Nm 95%CI +/- 13Nm) and RT (Extension: +35Nm 95%CI +/- 16Nm; Rotation: +5Nm 95%CI +/- 4Nm) compared to CG (Extension: -4Nm 95%CI +/- 16Nm; Rotation: -2Nm 95%CI +/- 4Nm) was present (p<0.05).
Background and objective Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort (R) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency. Methods Cortisol and binding protein concentrations were evaluated in the absence and presence of dexamethasone in healthy volunteers (n = 30). Dexamethasone was used to suppress endogenous cortisol concentrations prior to and after single doses of 0.5, 2, 5 and 10 mg of Infacort (R) or 20 mg of Infacort (R)/hydrocortisone tablet/hydrocortisone intravenously. A plasma protein binding model was established using unbound and total cortisol concentrations, and sequentially integrated into the pharmacokinetic model. Results Both specific (non-linear) and non-specific (linear) protein binding were included in the cortisol binding model. A two-compartment disposition model with saturable absorption and constant endogenous cortisol baseline (Baseline (cort),15.5 nmol/L) described the data accurately. The predicted cortisol exposure for a given dose varied considerably within a small body weight range in individuals weighing < 20 kg. Conclusions Our semi-mechanistic population pharmacokinetic model for hydrocortisone captures the complex pharmacokinetics of hydrocortisone in a simplified but comprehensive framework. The predicted cortisol exposure indicated the importance of defining an accurate hydrocortisone dose to mimic physiological concentrations for neonates and infants weighing < 20 kg.
Objective: The aim of the present study was to examine the effect of Cold Water Immersion (CWI) on the recovery of physical performance, hematological stress markers and perceived wellness (i.e., Hooper scores) following a simulated Mixed Martial Arts (MMA) competition. Methods: Participants completed two experimental sessions in a counter-balanced order (CWI or passive recovery for control condition: CON), after a simulated MMAs competition (3 x 5-min MMA rounds separated by 1-min of passive rest). During CWI, athletes were required to submerge their bodies, except the trunk, neck and head, in the seated position in a temperature-controlled bath (similar to 10 degrees C) for 15-min. During CON, athletes were required to be in a seated position for 15-min in same room ambient temperature. Venous blood samples (creatine kinase, cortisol, and testosterone concentrations) were collected at rest (PRE-EX, i.e., before MMAs), immediately following MMAs (POST-EX), immediately following recovery (POST-R) and 24 h post MMAs (POST-24), whilst physical fitness (squat jump, countermovement-jump and 5- and 10-m sprints) and perceptual measures (well-being Hooper index: fatigue, stress, delayed onset muscle soreness (DOMS), and sleep) were collected at PRE-EX, POST-R and POST-24, and at PRE-EX and POST-24, respectively. Conclusion: The use of CWI resulted in an enhanced recovery of 10-m sprint performance, as well as improved perceived wellness 24-h following simulated MMA competition.
Farber disease (FD) is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of FD is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of FD and ceramide accumulation. Asah1(tmEx1) mice were generated by deletion of the acid ceramidase signal peptide sequence. The effects on lysosomal targeting and activity of the enzyme were assessed. Ceramide and sphingomyelin levels were quantified by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and disease manifestations in several organ systems were analyzed by histology and biochemistry. We show that deletion of the signal peptide sequence disrupts lysosomal targeting and enzyme activity, resulting in ceramide and sphingomyelin accumulation. The affected mice fail to thrive and die early. Histiocytic infiltrations were observed in many tissues, as well as lung inflammation, liver fibrosis, muscular disease manifestations and mild kidney injury. Our new mouse model mirrors human FD and thus offers further insights into the pathogenesis of this disease. In the future, it may also facilitate the development of urgently needed therapies.
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD’s extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity response-element-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.
Ramirez-Campillo, R, Alvarez, C, García-Pinillos, F, Sanchez-Sanchez, J, Yanci, J, Castillo, D, Loturco, I, Chaabene, H, Moran, J, and Izquierdo, M. Optimal reactive strength index: is it an accurate variable to optimize plyometric training effects on measures of physical fitness in young soccer players? J Strength Cond Res 32(4): 885–893, 2018—This study aimed to compare the effects of drop-jump training using a fixed drop-box height (i.e., 30-cm [FIXED]) vs. an optimal (OPT) drop-box height (i.e., 10-cm to 40-cm: generating an OPT reactive strength index [RSI]) in youth soccer players' physical fitness. Athletes were randomly allocated to a control group (n = 24; age = 13.7 years), a fixed drop-box height group (FIXED, n = 25; age = 13.9 years), or an OPT drop-box height group (OPT, n = 24; age = 13.1 years). Before and after 7 weeks of training, tests for the assessment of jumping (countermovement jump [CMJ], 5 multiple bounds), speed (20-m sprint time), change of direction ability (CODA [Illinois test]), strength {RSI and 5 maximal squat repetition test (5 repetition maximum [RM])}, endurance (2.4-km time trial), and kicking ability (maximal kicking distance) were undertaken. Analyses revealed main effects of time for all dependent variables (p < 0.001, d = 0.24–0.72), except for 20-m sprint time. Analyses also revealed group × time interactions for CMJ (p < 0.001, d = 0.51), depth jump (DJ) (p < 0.001, d = 0.30), 20-m sprint time (p < 0.001, d = 0.25), CODA (p < 0.001, d = 0.22), and 5RM (p < 0.01, d = 0.16). Post hoc analyses revealed increases for the FIXED group (CMJ: 7.4%, d = 0.36; DJ: 19.2%, d = 0.49; CODA: −3.1%, d = −0.21; 5RM: 10.5%, d = 0.32) and the OPT group (CMJ: 16.7%, d = 0.76; DJ: 36.1%, d = 0.79; CODA: −4.4%, d = −0.34; 5RM: 18.1%, d = 0.47). Post hoc analyses also revealed increases for the OPT group in 20-m sprint time (−3.7%, d = 0.27). Therefore, to maximize the effects of plyometric training, an OPT approach is recommended. However, using adequate fixed drop-box heights may provide a rational and practical alternative.
The aim of the study was to determine pre-interventional predictors for all-cause mortality in patients after transcatheter aortic valve implantation (TAVI) with a 12-month follow-up. From 10/2013 to 07/2015, 344 patients (80.9 +/- 5.0 years, 44.5% male) with an elective TAVI were consecutively enrolled prospectively in a multicentre cohort study. Prior to the intervention, sociodemographic parameters, echocardiographic data and comorbidities were documented. All patients performed a 6-min walk test, Short Form 12 and a Frailty Index (score consisting of activities of daily living, cognition, nutrition and mobility). Peri-interventional complications were documented. Vital status was assessed over telephone 12 months after TAVI. Predictors for all-cause mortality were identified using a multivariate regression model. At discharge, 333 patients were alive (in-hospital mortality 3.2%; n = 11). During a follow-up of 381.0 +/- 41.9 days, 46 patients (13.8%) died. The non-survivors were older (82.3 +/- 5.0 vs. 80.6 +/- 5.1 years; p = 0.035), had a higher number of comorbidities (2.6 +/- 1.3 vs. 2.1 +/- 1.3; p = 0.026) and a lower left ventricular ejection fraction (51.0 +/- 13.6 vs. 54.6 +/- 10.6%; p = 0.048). Additionally, more suffered from diabetes mellitus (60.9 vs. 44.6%; p = 0.040). While the global Frailty Index had no predictive power, its individual components, particularly nutrition (OR 0.83 per 1 pt., CI 0.72-0.95; p = 0.006) and mobility (OR 5.12, CI 1.64-16.01; p = 0.005) had a prognostic impact. Likewise, diabetes mellitus (OR 2.18, CI 1.10-4.32; p = 0.026) and EuroSCORE (OR 1.21 per 5%, CI 1.07-1.36; p = 0.002) were associated with a higher risk of all-cause mortality. Besides EuroSCORE and diabetes mellitus, nutrition status and mobility of patients scheduled for TAVI offer prognostic information for 1-year all-cause mortality and should be advocated in the creation of contemporary TAVI risk scores.
The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = -3.86, p < .001), but not in healthy controls (t = -0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t((30)) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.
Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.
The purpose of this study was to estimate the optimal body size, limb-segment length, girth or breadth ratios for 100-m backstroke mean speed performance in young swimmers. Sixty-three young swimmers (boys [n = 30; age: 13.98 ± 0.58 years]; girls [n = 33; age: 13.02 ± 1.20 years]) participated in this study. To identify the optimal body size and body composition components associated with 100-m backstroke speed performance, we adopted a multiplicative allometric log-linear regression model, which was refined using backward elimination. The multiplicative allometric model exploring the association between 100-m backstroke mean speed performance and the different somatic measurements estimated that biological age, sitting height, leg length for the lower-limbs, and two girths (forearm and arm relaxed girth) are the key predictors. Stature and body mass did not contribute to the model, suggesting that the advantage of longer levers was limb-specific rather than a general whole-body advantage. In fact, it is only by adopting multiplicative allometric models that the abovementioned ratios could have been derived. These findings highlighted the importance of considering somatic characteristics of young backstroke swimmers and can help swimming coaches to classify their swimmers and enable them to suggest what might be the swimmers’ most appropriate stroke (talent identification).