Influence of normal and radial contributions of local current density on local electrochemical impedance spectroscopy.

A new tri-electrode probe is presented and applied to local electrochemical impedance spectroscopy (LEIS) measurements. As opposed to two-probe systems, the three-probe one allows measurement not only of normal, but also of radial contributions of local current densities to the local impedance values. The results concerning the cases of the blocking electrode and the electrode with faradaic reaction are discussed from the theoretical point of view for a disk electrode. Numerical simulations and experimental results are compared for the case of the ferri/ferrocyanide electrode reaction at the Pt working electrode disk. At the centre of the disk, the impedance taking into account both normal and radial contributions was in good agreement with the local impedance measured in terms of only the normal contribution. At the periphery of the electrode, the impedance taking into account both normal and radial contributions differed significantly from the local impedance measured in terms of only the normal contribution. The radial impedance results at the periphery of the electrode are in good agreement with the usual explanation that the associated larger current density is attributed to the geometry of the electrode, which exhibits a greater accessibility at the electrode edge

Comparison Between Anaerobic Threshold Determined By Ventilatory Variables And Blood Lactate Response In Cyclists [comparação Entre Limiar Anaeróbio Determinado Por Variáveis Ventilatórias E Pela Resposta Do Lactato Sanguíneo Em Ciclistas]

Many investigations have shown that the coincidence between the ventilatory thresholds and those thresholds using the lactate response does not happen all of the time, suggesting that there is no relationship between the cause-effect between these phenomena. Thus, the present study had as main purpose to compare and correlate the Oxygen consumption (V̇O2), the power (W), and the heart rate (HR) values attained using protocols to determine the Ventilatory Threshold (VT) and the Individual Anaerobic Threshold (IAT). The sampling was constituted by eight State and National level cyclists (age: 27.88 ± 8.77 years; body mass: 65.19 ± 4.40 kg; height: 169.31 ± 5,77 cm). The IAT was determined starting from a three minutes 50 W warm up with progressive increases of 50 W.3min-1 up to achieving the voluntary exhaustion, when the blood was collected in the last 20 seconds of each phase, and during the recovering period. In order to determine the VT, it was used the same protocol used to determine the IAT, but without performing the blood collection. The VT was identified through the changes in the pulmonary ventilation, as well as of the ventilatory equivalent of the O2 and CO2. The t-Student test showed no significant statistical difference in any of the attained variables. The associations found were high and significant. The V̇O2 (ml.kg-1.min.-1), P (W), and HR (bpm) corresponding to the VT and IAT, as well as the associations between variables were respectively: 48.00 ± 3.82 vs. 48.08 ± 3.71 (r = 0.90); 256.25 ± 32.04 vs. 246.88 ± 33.91 (r = 0.84); 173.75 ± 9.18 vs. 171.25 ± 12.02 (r = 0.97). According to the results attained, it can be concluded that the IAT and the VT produce similar V̇O2, W, and HR values, favoring the adoption of the VT because it is a non-invasive method to determine the anaerobic threshold in cyclists.12134e38eJacobs, I., Blood lactate. 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1552-1557Wasserman, K., McIlroy, M.B., Detecting the threshold of anaerobic metabolism in cardiac patients during exercise (1964) Am J Cardiol, 14, pp. 844-852Heck, H., Mader, A., Hess, G., Mucke, S., Muller, R., Hollmann, W., Justification of the 4-mmol/l lactate threshold (1985) Int J Sports Med, 6, pp. 117-130McLellan, T.M., Ventilatory and plasma lactate response with different exercise protocols: A comparison of methods (1985) Int J Sports Med, 6, pp. 30-35Mader, A., Liesen, H., Heck, H., Philippi, H., Schürch, P.M., Hollmann, W., Zur beurteilung der sportartspezifischen Ausdauerleinstungsfähigkeit im Labor (1976) Sportarzt Sportmed, 26, pp. 109-112Mader, A., Liesen, H., Heck, H., Philippi, H., Schürch, P.M., Hollmann, W., Zur beurteilung der sportartspezifischen Ausdauerleinstungsfähigkeit im Labor (1976) Sportarzt Sportmed, 24, pp. 80-88Sjodin, B., Jacobs, I., Onset of blood lactate accumulation and marathon running performance (1981) Int J Sports Med, 2, pp. 23-26Hollmann, W., Historical remarks on the development of the aerobic-anaerobic threshold up to 1966 (1985) Int J Sports Med, 6, pp. 109-116Stegmann, H., Kindermann, W., Schnabel, A., Lactate kinetics and individual anaerobic threshold (1981) Int J Sports Med, 2, pp. 160-165Coen, B., Schwarz, L., Urhausen, A., Kindermann, W., Control of training in middle-and long-distance running by means of the individual anaerobic threshold (1991) Int J Sports Med, 12, pp. 519-524McLellan, T.M., Cheung, K.S., Jacobs, I., Incremental test protocol, recovery mode and the individual anaerobic threshold (1991) Int J Sports Med, 12, pp. 190-195McLellan, T.M., Cheung, K.S., A comparative evaluation of the individual anaerobic threshold and the critical power (1992) Med Sci Sports Exerc, 24, pp. 543-550Urhausen, A., Coen, B., Weiler, B., Kindermann, W., Individual anaerobic threshold and maximum lactate steady state (1993) Int J Sports Med, 14, pp. 134-139Urhausen, A., Weiler, B., Coen, B., Kindermann, W., Plasma catecholamines during endurance exercise of different intensities as related to the individual anaerobic threshold (1994) Eur J Appl Physiol Occup Physiol, 69, pp. 16-20Beneke, R., Anaerobic threshold, individual anaerobic threshold, and maximal lactate steady state in rowing (1995) Med Sci Sports Exerc, 27, pp. 863-867Bourgois, J., Vrijens, J., Metabolic and cardiorespiratory responses in young oarsmen during prolonged exercise tests on a rowing ergometer at power outputs corresponding to two concepts of anaerobic threshold (1998) Eur J Appl Physiol Occup Physiol, 77, pp. 164-169Baldari, C., Guidetti, L., A simple method for individual anaerobic threshold as predictor of max lactate steady state (2000) Med Sci Sports Exerc, 32, pp. 1798-1802Guidetti, L., Musulin, A., Baldari, C., Physiological factors in middleweight boxing performance (2002) J Sports Med Phys Fitness, 42, pp. 309-314Stegmann, H., Kindermann, W., Comparison of prolonged exercise tests at the individual anaerobic threshold and the fixed anaerobic threshold of 4 mmol.l(-1) lactate (1982) Int J Sports Med, 3, pp. 105-110Bourgois, J., Vrijens, J., The Conconi test: A controversial concept for the determination of the anaerobic threshold in young rowers (1998) Int J Sports Med, 19, pp. 553-559Dickhuth, H.H., Yin, L., Niess, A., Rocker, K., Mayer, F., Heitkamp, H.C., Ventilatory, lactate-derived and catecholamine thresholds during incremental treadmill running: Relationship and reproducibility (1999) Int J Sports Med, 20, pp. 122-127McNaughton, L., Wakefield, G., Fasset, R., Bentley, D., A comparison of lactate kinetics, minute ventilation and acid-base balance as measure of the anaerobic threshold (2001) Journal of Human Moviment Studies, 41, pp. 247-261Hughes, E.F., Turner, S.C., Brooks, G.A., Effects of glycogen depletion and pedaling speed on anaerobic threshold" (1982) J Appl Physiol, 52, pp. 1598-1607Yoshida, T., Effect of dietary modifications on lactate threshold and onset of blood lactate accumulation during incremental exercise (1984) Eur J Appl Physiol Occup Physiol, 53, pp. 200-205Berry, M.J., Stoneman, J.V., Weyrich, A.S., Burney, B., Dissociation of the ventilatory and lactate thresholds following caffeine ingestion (1991) Med Sci Sports Exerc, 23, pp. 463-469McLellan, T.M., Jacobs, I., Active recovery, endurance training, and the calculation of the individual anaerobic threshold (1989) Med Sci Sports Exerc, 21, pp. 586-592Aunola, S., Rusko, H., Does anaerobic threshold correlate with maximal lactate steady-state? (1992) J Sports Sci, 10, pp. 309-323Ribeiro, J.P., Hughes, V., Fielding, R.A., Holden, W., Evans, W., Knuttgen, H.G., Metabolic and ventilatory responses to steady state exercise relative to lactate thresholds (1986) Eur J Appl Physiol Occup Physiol, 55, pp. 215-221Yamamoto, Y., Miyashita, M., Hughson, R.L., Tamura, S., Shinohara, M., Mutoh, Y., The ventilatory threshold gives maximal lactate steady state (1991) Eur J Appl Physiol Occup Physiol, 63, pp. 55-59Wyatt, F.B., Comparison of lactate and ventilatory threshold to maximal oxygen consumption: A meta analysis (1999) Journal of Strength and Conditioning Research, 13, pp. 67-71Ahmaidi, S., Hardy, J.M., Varray, A., Collomp, K., Mercier, J., Prefaut, C., Respiratory gas exchange indices used to detect the blood lactate accumulation threshold during an incremental exercise test in young athletes (1993) Eur J Appl Physiol Occup Physiol, 66, pp. 31-36Dickstein, K., Barvik, S., Aarsland, T., Snapinn, S., Karlsson, J., A comparison of methodologies in detection of the anaerobic threshold (1990) Circulation, 81, pp. II38-II46Davis, J.A., Frank, M.H., Whipp, B.J., Wasserman, K., Anaerobic threshold alterations caused by endurance training in middle-aged men (1979) J Appl Physiol, 46, pp. 1039-1046Beaver, W.L., Wasserman, K., Whipp, B.J., A new method for detecting anaerobic threshold by gas exchange (1986) J Appl Physiol, 60, pp. 2020-2027Simon, J., Young, J.L., Blood, D.K., Segal, K.R., Case, R.B., Gutin, B., Plasma lactate and ventilation thresholds in trained and untrained cyclists (1986) J Appl Physiol, 60, pp. 777-781Davis, J.A., Anaerobic threshold: Review of the concept and directions for future research (1985) Med Sci Sports Exerc, 17, pp. 6-21Stone, M.H., Sands, W.A., Stone, M.E., The downfall of sports science in the United States (2004) Strength Cond J, 26, pp. 72-7

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary: We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction: The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods: We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n?=?181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 ?g/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results: Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions: This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs. <br/

The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder

De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause “neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities.” Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.). Using 3D protein structure analysis and an innovative dual Drosophila gain-of-function assay, we demonstrated a disruptive effect of 11 missense/in-frame indels located in or near the enzymatic JmJC or Zn-containing domain of KDM6B. Consistent with the role of KDM6B in human cognition, we demonstrated a role for the Drosophila KDM6B ortholog in memory and behavior. Taken together, we accurately define the broad clinical spectrum of the KDM6B-related NDD, introduce an innovative functional testing paradigm for the assessment of KDM6B variants, and demonstrate a conserved role for KDM6B in cognition and behavior. Our study demonstrates the critical importance of international collaboration, sharing of clinical data, and rigorous functional analysis of genetic variants to ensure correct disease diagnosis for rare disorders.Genetics of disease, diagnosis and treatmen