61 Medizin und Gesundheit
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Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-In silico approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway via cytochrome C and the activation of caspase 3 (both p < 0.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor α and receptor interaction protein 3 (p < 0.05; p < 0.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-In silico approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the in vitro experiments by using machine learning algorithms.
Intervention in the form of core-specific stability exercises is evident to improve trunk stability. The purpose was to assess the effect of an additional 6 weeks sensorimotor or resistance training on maximum isokinetic trunk strength and response to sudden dynamic trunk loading (STL) in highly trained adolescent athletes. The study was conducted as a single-blind, 3-armed randomized controlled trial. Twenty-four adolescent athletes (14f/10 m, 16 ± 1 yrs.;178 ± 10 cm; 67 ± 11 kg; training sessions/week 15±5; training h/week 22±8) were randomized into resistance training (RT; n=7), sensorimotor training (SMT; n = 10), and control group (CG; n = 7). Athletes were instructed to perform standardized, center-based training for 6 weeks, two times per week, with a duration of 1 h each session. SMT consisted of four different core-specific sensorimotor exercises using instable surfaces. RT consisted of four trunk strength exercises using strength training machines, as well as an isokinetic dynamometer. All participants in the CG received an unspecific heart frequency controlled, ergometer-based endurance training (50 min at max. heart frequency of 130HF). For each athlete, each training session was documented in an individual training diary (e.g., level of SMT exercise; 1RM for strength exercise, pain). At baseline (M1) and after 6 weeks of intervention (M2), participants’ maximum strength in trunk rotation (ROM:63°) and flexion/extension (ROM:55°) was tested on an isokinetic dynamometer (concentric/eccentric 30°/s). STL was assessed in eccentric (30°/s) mode with additional dynamometer-induced perturbation as a marker of core stability. Peak torque [Nm] was calculated as the main outcome. The primary outcome measurements (trunk rotation/extension peak torque: con, ecc, STL) were statistically analyzed by means of the two-factor repeated measures analysis of variance (α = 0.05). Out of 12 possible sessions, athletes participated between 8 and 9 sessions (SMT: 9 ± 3; RT: 8 ± 3; CG: 8 ± 4). Regarding main outcomes of trunk performance, experimental groups showed no significant pre–post difference for maximum trunk strength testing as well as for perturbation compensation (p > 0.05). It is concluded, that future interventions should exceed 6 weeks duration with at least 2 sessions per week to induce enhanced trunk strength or compensatory response to sudden, high-intensity trunk loading in already highly trained adolescent athletes, regardless of training regime.