Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth

EFFECTS OF STACK HEIGHT ON RUNNING BIOMECHANICS DURING LEVEL, UPHILL, AND DOWNHILL RUNNING AT DIFFERENT SPEEDS

This study aimed to investigate the effects of shoe stack height on comfort assessment, step frequency and lower limb joint range of motions (ROMs) during level, downhill and uphill running with different running speeds since stack height is one of the highly discussed key features of running shoes and was not intensively investigated for sloped running conditions. Seventeen male experienced runners completed the running protocol by wearing three running shoes with different stack heights. The kinematics were collected with a 3D motion capturing system. A comfort questionnaire was asked for each shoe. The lowest stack height resulted in the highest perceived stability and the lowest cushioning. Decrease in stack height resulted in increased step frequency and sagittal ROM in lower body joints (up to 10% change due to different stack heights) particularly in sloped running conditions. The results of this study can help to understand the effects of footwear technologies on running biomechanics and ultimately to improve running shoes to maximize their benefits in terms of running performance as well as injury risk

Changes in Key Biomechanical Parameters according to the Expertise Level in Runners at Different Running Speeds

Running has become increasingly popular worldwide. Among runners, there exists a wide range of expertise levels. Investigating the differences between runners at two extreme levels, that is novices and experts, is crucial to understand the changes that occur as a result of multiple years of training. Vertical oscillation of center of mass (CoM), stride frequency normalized to the leg length, and duty factor, which describes the step time relative to the flight time, are key biomechan- ical parameters that have been shown to be closely related to the running economy and are used to characterize the running style. The variability characteristics of these parameters may reveal valua- ble information concerning the control of human locomotion. However, how the expertise level and running speed affect the variability of these key biomechanical parameters has not yet been inves- tigated. The aim of this study was to analyze the effects of expertise level (novice vs. expert) and running speed (10 km/h vs. 15 km/h) on these parameters and their variability. It was hypothesized that expert runners would have lower vertical oscillation of CoM, normalized stride frequency, and duty factor and show less variability in these parameters. The parameters’ variability was opera- tionalized by the coefficient of variation. The mean values and variability of these key biomechani- cal parameters according to expertise level and running speed were compared with rmANOVAs. The results showed that the experts had a lower duty factor and less variable vertical oscillation of CoM and normalized stride frequency, independently of the running speed. At a higher running speed, the variability of vertical oscillation of CoM was higher, whereas that of normalized stride frequency and duty factor did not change significantly. To the best of our knowledge, this is the first study analyzing the effects of expertise level and running speed on the variability of key biomechanical parameters

EFFECTS OF RUNNING SHOE STACK HEIGHT ON MOVEMENT VARIABILITY - A SHARED BIOMECHANICAL AND MOTOR CONTROL PERSPECTIVE

Understanding how shoe features affect motor control processes is crucial for designing targeted running shoes. The purpose of this study was to investigate adaptations of coupled movement components, i.e. kinematic synergies (kSYNs), when running with different shoe stack heights (19 mm, 35 mm, and 50 mm). The applied analysis combined a principal component analysis, support vector machine classifiers, and stride-to-stride variability (SSV) calculations. The results showed classification rates ranging from 82.9% to 94.4% across different stack heights. Notably, only the 50 mm stack height demonstrated increased SSV for the kSYNs that highly contribute to separating the two stack heights when compared to the 19 mm condition. The findings suggest that the motor control system adjusts to variations in stack height within certain limits by regulating task-relevant kSYNs

Running-Induced Fatigue Changes the Structure of Motor Variability in Novice Runners

Understanding the effects of fatigue is a central issue in the context of endurance sports. Given the popularity of running, there are numerous novices among runners. Therefore, under- standing the effects of fatigue in novice runners is an important issue. Various studies have drawn conclusions about the control of certain variables by analyzing motor variability. One variable that plays a crucial role during running is the center of mass (CoM), as it reflects the movement of the whole body in a simplified way. Therefore, the aim of this study was to analyze the effects of fatigue on the motor variability structure that stabilizes the CoM trajectory in novice runners. To do so, the uncontrolled manifold approach was applied to a 3D whole-body model using the CoM as the result variable. It was found that motor variability increased with fatigue (UCMꓕ). However, the UCMRatio did not change. This indicates that the control of the CoM decreased, whereas the stability was not affected. The decreases in control were correlated with the degree of exhaustion, as indicated by the Borg scale (during breaking and flight phase). It can be summarized that running-induced fatigue increases the step-to-step variability in novice runners and affects the control of their CoM

Influence of Controlled Stomatognathic Motor Activity on Sway, Control and Stability of the Center of Mass During Dynamic Steady-State Balance—An Uncontrolled Manifold Analysis

Multiple sensory signals from visual, somatosensory and vestibular systems are used for human postural control. To maintain postural stability, the central nervous system keeps the center of mass (CoM) within the base of support. The influence of the stomatognathic motor system on postural control has been established under static conditions, but it has not yet been investigated during dynamic steady-state balance. The purpose of the study was to investigate the effects of controlled stomatognathic motor activity on the control and stability of the CoM during dynamic steady-state balance. A total of 48 physically active and healthy adults were assigned to three groups with different stomatognathic motor conditions: jaw clenching, tongue pressing and habitual stomatognathic behavior. Dynamic steady-state balance was assessed using an oscillating platform and the kinematic data were collected with a 3D motion capturing system. The path length (PL) of the 3D CoM trajectory was used for quantifying CoM sway. Temporal dynamics of the CoM movement was assessed with a detrended fluctuation analysis (DFA). An uncontrolled manifold (UCM) analysis was applied to assess the stability and control of the CoM with a subject-specific anthropometric 3D model. The statistical analysis revealed that the groups did not differ significantly in PL, DFA scaling exponents or UCM parameters. The results indicated that deliberate jaw clenching or tongue pressing did not seem to affect the sway, control or stability of the CoM on an oscillating platform significantly. Because of the task-specificity of balance, further research investigating the effects of stomatognathic motor activities on dynamic steady-state balance with different movement tasks are needed. Additionally, further analysis by use of muscle synergies or co-contractions may reveal effects on the level of muscles, which were not visible on the level of kinematics. This study can contribute to the understanding of postural control mechanisms, particularly in relation to stomatognathic motor activities and under dynamic conditions

Persisting effects of jaw clenching on dynamic steady-state balance

The effects of jaw clenching on balance has been shown under static steady-state conditions but the effects on dynamic steady-state balance have not yet been investigated. On this basis, the research questions were: 1) if jaw clenching improves dynamic steady-state balance; 2) if the effects persist when the jaw clenching task loses its novelty and the increased attention associated with it; 3) if the improved dynamic steady-state balance performance is associated with decreased muscle activity. A total of 48 physically active healthy adults were assigned to three groups differing in intervention (Jaw clenching and balance training (JBT), only balance training (OBT) or the no-training control group (CON)) and attending two measurement points separated by two weeks. A stabilometer was used to assess the dynamic steady-state balance performance in a jaw clenching and non-clenching condition. Dynamic steady-state balance performance was measured by the time at equilibrium (TAE). The activities of tibialis anterior (TA), gastrocnemius medialis (GM), rectus femoris (RF), biceps femoris (BF) and masseter (MA) muscles were recorded by a wireless EMG system. Integrated EMG (iEMG) was calculated to quantify the muscle activities. All groups had better dynamic steady-state balance performance in the jaw clenching condition than non-clenching at T1, and the positive effects persisted at T2 even though the jaw clenching task lost its novelty and attention associated with it after balance training with simultaneous jaw clenching. Independent of the intervention, all groups had better dynamic steady-state balance performances at T2. Moreover, reductions in muscle activities were observed at T2 parallel to the dynamic steady-state balance performance improvement. Previous studies showed that jaw clenching alters balance during upright standing, predictable perturbations when standing on the ground and unpredictable perturbations when standing on an oscillating platform. This study complemented the previous findings by showing positive effects of jaw clenching on dynamic steady-state balance performance