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BACKGROUND AND OBJECTIVE: Previously, we developed a pharmacokinetic-pharmacodynamic model of allopurinol, oxypurinol, and biomarkers, hypoxanthine, xanthine, and uric acid, in neonates with hypoxic-ischemic encephalopathy, in which high initial biomarker levels were observed suggesting an impact of hypoxia. However, the full pharmacodynamics could not be elucidated in our previous study. The current study included additional data from the ALBINO study (NCT03162653) placebo group, aiming to characterize the dynamics of hypoxanthine, xanthine, and uric acid in neonates with hypoxic-ischemic encephalopathy. METHODS: Neonates from the ALBINO study who received allopurinol or placebo mannitol were included. An extended population pharmacokinetic-pharmacodynamic model was developed based on the mechanism of purine metabolism, where synthesis, salvage, and degradation via xanthine oxidoreductase pathways were described. The initial level of the biomarkers was a combination of endogenous turnover and high disease-related amounts. Model development was accomplished by nonlinear mixed-effects modeling (NONMEM®, version 7.5). RESULTS: In total, 20 neonates treated with allopurinol and 17 neonates treated with mannitol were included in this analysis. Endogenous synthesis of the biomarkers reduced with 0.43% per hour because of precursor exhaustion. Hypoxanthine was readily salvaged or degraded to xanthine with rate constants of 0.5 1/h (95% confidence interval 0.33-0.77) and 0.2 1/h (95% confidence interval 0.09-0.31), respectively. A greater salvage was found in the allopurinol treatment group consistent with its mechanism of action. High hypoxia-induced initial levels of biomarkers were quantified, and were 1.2-fold to 2.9-fold higher in neonates with moderate-to-severe hypoxic-ischemic encephalopathy compared with those with mild hypoxic-ischemic encephalopathy. Half-maximal xanthine oxidoreductase inhibition was achieved with a combined allopurinol and oxypurinol concentration of 0.68 mg/L (95% confidence interval 0.48-0.92), suggesting full xanthine oxidoreductase inhibition during the period studied. CONCLUSIONS: This extended pharmacokinetic-pharmacodynamic model provided an adequate description of the complex hypoxanthine, xanthine, and uric acid metabolism in neonates with hypoxic-ischemic encephalopathy, suggesting a positive allopurinol effect on these biomarkers. The impact of hypoxia on their dynamics was characterized, underlining higher hypoxia-related initial exposure with a more severe hypoxic-ischemic encephalopathy status. ispartof: CLINICAL PHARMACOKINETICS vol:61 issue:11 pages:1545-1558 ispartof: location:Switzerland status: published

Gaze behavior and performance of internationally ranked players and “near”-expert players were investigated under field conditions for the game situation service-return in badminton. According to the literature, it was assumed that expert players focus more frequently on the racket arm, wrist, and racket of the opponent, while less experienced players focus on the shuttle. Thus, gaze strategy would have an influence on performance. The results contradicted the initial hypotheses: the higher the performance level of the athletes, the more frequently they directed their gaze to the shuttle. Non-professional players were found to focus more often on the upper body and face. To improve gaze behavior in the service situation, on-court drills with focusing on the shuttle region are assumed to be advantageous for athletes of all skill levels. Our research showed that players use other visual search strategies when observing a real opponent then when confronted with a two-dimensional stimulus., La conducta de la mirada y el desempeño de jugadores de categoría internacional y “casi” expertos fueron investigados en condiciones de campo para la situación de juego servicio-devolución en bádminton. Según la literatura, se asumía que los jugadores expertos se enfocan con más frecuencia en el brazo de la raqueta, la muñeca y la raqueta del oponente, mientras que los jugadores menos experimentados se enfocan en el volante. Por tanto, la estrategia de la mirada tendría una influencia en el desempeño. Los resultados contradicen las hipótesis iniciales: entre más alto sea el nivel de desempeño de los atletas, más dirigen la mirada al volante. Los jugadores no profesionales se enfocaron más en la parte superior del cuerpo y el rostro. Se supone que los ejercicios en campo enfocados en el área del volante sirven para mejorar la conducta de la mirada en la situación de servicio en los atletas de todos los niveles de habilidad. Nuestra investigación demuestra que los jugadores usan unas estrategias de búsqueda visual al observar a un oponente real diferentes a las que usan con un estímulo de dos dimensiones.

To avoid the drawbacks of optical video-based motion capture systems and due to the ongoing miniaturization of integrated sensors, an increasing variety of sensor-based systems has been used for motion capture in sports. Meanwhile, there are ready-made, commercially available solutions that claim to be capable of recording reliable kinematic data. This research project focuses on the question of whether a commercially available badminton racket with an integrated sensor device (Oliver® Plasma TX 5) provides meaningful data for diagnostic and training purposes in elite sports. Therefore, 16 elite badminton players executed jump smashes using this sensor racket while the kinematics of the stroke technique were recorded using a high speed video-based system. Bland-Altman plots were applied to analyze the agreement between the two systems. The plots revealed a systematic bias and 95% limits of agreement ranging from 6% to 23%: The detection of stroke techniques showed a 42% rate of success. These data show that the measurement accuracy of the sensor racket is not sufficient for use in diagnostics or training. Future development of the sensor racket could include a method to calibrate the system prior to a measurement, in addition to correcting the underlying algorithm to reduce the bias., Para evitar las desventajas de los sistemas ópticos de captura de movimiento basados en video y debido a la continua miniaturización de los sensores integrados, una creciente variedad de sistemas basados en sensores se ha usado para la captura de movimiento en deportes. Entretanto, existen soluciones ya terminadas y comercialmente disponibles que afirman ser capaces de registrar datos cinemáticos confiables. Este proyecto de investigación se enfoca en la pregunta de si una raqueta de bádminton disponible comercialmente con un sensor integrado (Oliver® Plasma TX 5) proporciona datos relevantes para el diagnóstico y entrenamiento en deportes de élite. Por tanto, 16 jugadores de bádminton de élite ejecutaron remates en salto usando la raqueta con sensor mientras la cinemática de la técnica del golpe era grabada con un sistema de alta velocidad basado en video. Los gráficos de Bland-Altman se usaron para analizar la concordancia entre los dos sistemas. Los gráficos revelaron un sesgo sistemático y límites de concordancia del 95% entre 6% y 23%. La detección de las técnicas del golpe evidenció una tasa de éxito del 42%. Estos datos demuestran que la precisión en la medición de la raqueta con sensor no es suficiente para usarla en diagnóstico o entrenamiento. El desarrollo futuro de la raqueta con sensor podría incluir un método para calibrar el sistema antes de hacer una medición, además de corregir el algoritmo subyacente para reducir el sesgo.

This dataset contains motion analysis data from five female persons (age: 24.8 ± 1.9 y, height: 168.6 ± 6.8 cm, body mass: 66.4 ± 10.3 kg, body mass index: 23.2 ± 2.4 kg∙m-2) and 13 male persons (age: 31.3 ± 7.3 y, height: 182.6 ± 6.7 cm, body mass: 78.0 ± 11.7 kg, body mass index: 23.3 ± 2.3 kg∙m-2) using a motion capture system. Participants completed a total of three measurements with alternating three-minute motion activities (walking at 4 km/h, hiking at 6 km/h, running at 9 km/h, running at 12 km/h) in different orders on a treadmill lasting between 11 and 16 minutes. A total of 40 minutes was recorded for each participant. In addition to the camera system, two force plates, two pressure measurement insoles, and three IMUs were also used for data acquisition. Funded by the Deutsche Forschungsgemeinschaft (DFG, German ResearchFoundation) – Project-ID 416228727 – SFB 1410.

BACKGROUND: Allopurinol, an xanthine oxidase (XO) inhibitor, is a promising intervention that may provide neuroprotection for neonates with hypoxic-ischemic encephalopathy (HIE). Currently, a double-blind, placebo-controlled study (ALBINO, NCT03162653) is investigating the neuroprotective effect of allopurinol in HIE neonates. OBJECTIVE: The aim of the current study was to establish the pharmacokinetics (PK) of allopurinol and oxypurinol, and the pharmacodynamics (PD) of both compounds on hypoxanthine, xanthine, and uric acid in HIE neonates. The dosage used and the effect of allopurinol in this population, either or not undergoing therapeutic hypothermia (TH), were evaluated. METHODS: Forty-six neonates from the ALBINO study and two historical clinical studies were included. All doses were administered on the first day of life. In the ALBINO study (n = 20), neonates received a first dose of allopurinol 20 mg/kg, and, in the case of TH (n = 13), a second dose of allopurinol 10 mg/kg. In the historical cohorts (n = 26), neonates (all without TH) received two doses of allopurinol 20 mg/kg in total. Allopurinol and oxypurinol population PK, and their effects on inhibiting conversions of hypoxanthine and xanthine to uric acid, were assessed using nonlinear mixed-effects modelling. RESULTS: Allopurinol and oxypurinol PK were described by two sequential one-compartment models with an autoinhibition effect on allopurinol metabolism by oxypurinol. For allopurinol, clearance (CL) was 0.83 L/h (95% confidence interval [CI] 0.62-1.09) and volume of distribution (Vd) was 2.43 L (95% CI 2.25-2.63). For metabolite oxypurinol, CL and Vd relative to a formation fraction (fm) were 0.26 L/h (95% CI 0.23-0.3) and 11 L (95% CI 9.9-12.2), respectively. No difference in allopurinol and oxypurinol CL was found between TH and non-TH patients. The effect of allopurinol and oxypurinol on XO inhibition was described by a turnover model of hypoxanthine with sequential metabolites xanthine and uric acid. The combined allopurinol and oxypurinol concentration at the half-maximal XO inhibition was 0.36 mg/L (95% CI 0.31-0.42). CONCLUSION: The PK and PD of allopurinol, oxypurinol, hypoxanthine, xanthine, and uric acid in neonates with HIE were described. The dosing regimen applied in the ALBINO trial leads to the targeted XO inhibition in neonates treated with or without TH. ispartof: CLINICAL PHARMACOKINETICS vol:61 issue:2 pages:321-333 ispartof: location:Switzerland status: published

Background Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration NCT03162653, www.ClinicalTrials.gov, May 22, 2017.

BMC pediatrics 19(1), 363 (2019). doi:10.1186/s12887-019-1735-9, Published by BioMed Central, London

Background Most extremely low gestational age neonates (ELGANS, postmenstrual age at birth (PMA)