Articles de revues : « Interindividual difference »

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Boobis, Alan R., Nigel J. Gooderham, Robert J. Edwards et Donald S. Davies. « Isozymle and interindividual difference in human metabollsm of heterocyclle aminee ». Toxicology Letters 78 (août 1995) : 4. http://dx.doi.org/10.1016/0378-4274(95)94611-j.

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Ambrosini, Ettore, et Antonino Vallesi. « Domain-general Stroop Performance and Hemispheric Asymmetries : A Resting-state EEG Study ». Journal of Cognitive Neuroscience 29, n^o 5 (mai 2017) : 769–79. http://dx.doi.org/10.1162/jocn_a_01076.

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The ability to suppress irrelevant information while executing a task, also known as interference resistance ability, is a function of pFC that is critical for successful goal-directed human behavior. In the study of interference resistance and, more generally, executive functions, two key questions are still open: Does pFC contribute to cognitive control abilities through lateralized but domain-general mechanisms or through hemispheric specialization of domain-specific processes? And what are the underlying causes of interindividual differences in executive control performance? To shed light on these issues, here we employed an interindividual difference approach to investigate whether participants' hemispheric asymmetry in resting-state electrophysiological brain dynamics may reflect their variability in domain-general interference resistance. We recorded participants' resting-state electroencephalographic activity and performed spectral power analyses on the estimated cortical source activity. To measure participants' lateralized brain dynamics at rest, we computed the right–left hemispheric asymmetry score for the β/α power ratio. To measure their domain-general interference resistance ability, verbal and spatial Stroop tasks were used. Robust correlations followed by intersection analyses showed that participants with stronger resting-state-related left-lateralized activity in different pFC regions, namely the mid-posterior superior frontal gyrus, middle and posterior middle frontal gyrus, and inferior frontal junction, were more able to inhibit irrelevant information in both domains. The present results confirm and extend previous findings showing that neurophysiological difference factors may explain interindividual differences in executive functioning. They also provide support for the hypothesis of a left pFC hemispheric specialization for domain-independent phasic cognitive control processes mediating Stroop performance.

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Hayashi, Shin-ichi, Junko Watanabe, Kei Nakachi, Hidetaka Eguchi, Osamu Gotoh et kaname Kawajiri. « Interindividual difference in expression of human Ah receptor and related P450 genes ». Carcinogenesis 15, n^o 5 (1994) : 801–6. http://dx.doi.org/10.1093/carcin/15.5.801.

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Miura, M., T. Niioka, H. Kagaya, M. Saito, M. Hayakari, T. Habuchi et S. Satoh. « Pharmacogenetic determinants for interindividual difference of tacrolimus pharmacokinetics 1 year after renal transplantation ». Journal of Clinical Pharmacy and Therapeutics 36, n^o 2 (1 mars 2011) : 208–16. http://dx.doi.org/10.1111/j.1365-2710.2010.01163.x.

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Ito, Shin-ichi, Yasue Mitsukura, Katsuya Sato, Shoichiro Fujisawa et Minoru Fukumi. « Interindividual Difference Analysis in Prefrontal Cortex EEGs Based on the Relationship with Personality ». Journal of Signal Processing 16, n^o 5 (2012) : 443–50. http://dx.doi.org/10.2299/jsp.16.443.

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Fiamoncini, Jarlei, Andrianos M. Yiorkas, Kurt Gedrich, Milena Rundle, Sanne I. Alsters, Guus Roeselers, Tim J. van den Broek et al. « Determinants of postprandial plasma bile acid kinetics in human volunteers ». American Journal of Physiology-Gastrointestinal and Liver Physiology 313, n^o 4 (1 octobre 2017) : G300—G312. http://dx.doi.org/10.1152/ajpgi.00157.2017.

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Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women ( n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention. BA were quantified in plasma by liquid chromatography-tandem mass spectrometry combined with whole genome exome sequencing and fecal microbiota profiling. Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma BA profiles. Fasting and postprandial BA profiles revealed high interindividual variability, and three main patterns in postprandial BA response were identified using multivariate analysis. Although the women enrolled were postmenopausal, effects of sex difference in BA response were evident. Exome data revealed the contribution of preselected genes to the observed interindividual variability. In particular, a variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases. Fecal microbiota analysis did not reveal evidence for a significant influence of bacterial diversity and/or composition on plasma BA profiles. The analysis of plasma BA profiles in response to two different dietary challenges revealed a high interindividual variability, which was mainly determined by genetics and sex difference of host with minimal effects of the microbiota. NEW & NOTEWORTHY Considering the average response of all 72 subjects, no effect of the successful weight loss intervention was found on plasma bile acid (BA) profiles. Despite high interindividual variability, three main patterns in postprandial BA response were identified using multivariate analysis. A variant in the SLCO1A2 gene, encoding the small intestinal BA transporter organic anion-transporting polypeptide-1A2 (OATP1A2), was associated with delayed postprandial BA increases in response to both the oral glucose tolerance test and the mixed-meal tolerance test.

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Nishioka, Alessandra, Eric de Castro Tobaruela, Layanne Nascimento Fraga, Francisco A. Tomás-Barberán, Franco Maria Lajolo et Neuza Mariko Aymoto Hassimotto. « Stratification of Volunteers According to Flavanone Metabolite Excretion and Phase II Metabolism Profile after Single Doses of ‘Pera’ Orange and ‘Moro’ Blood Orange Juices ». Nutrients 13, n^o 2 (30 janvier 2021) : 473. http://dx.doi.org/10.3390/nu13020473.

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Large interindividual variations in the biological response to citrus flavanones have been observed, and this could be associated with high variations in their bioavailability. The aim of this study was to identify the main determinants underlying interindividual differences in citrus flavanone metabolism and excretion. In a randomized cross-over study, non-obese and obese volunteers, aged 19–40 years, ingested single doses of Pera and Moro orange juices, and urine was collected for 24 h. A large difference in the recovery of the urinary flavanone phase II metabolites was observed, with hesperetin-sulfate and hesperetin-sulfo-O-glucuronide being the major metabolites. Subjects were stratified according to their total excretion of flavanone metabolites as high, medium, and low excretors, but the expected correlation with the microbiome was not observed at the genus level. A second stratification was proposed according to phase II flavanone metabolism, whereby participants were divided into two excretion groups: Profiles A and B. Profile B individuals showed greater biotransformation of hesperetin-sulfate to hesperetin-sulfo-O-glucuronide, as well as transformation of flavanone-monoglucuronide to the respective diglucuronides, suggestive of an influence of polymorphisms on UDP-glucuronosyltransferase. In conclusion, this study proposes a new stratification of volunteers based on their metabolic profiles. Gut microbiota composition and polymorphisms of phase II enzymes may be related to the interindividual variability of metabolism.

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Brothers, R. Matthew, David M. Keller, Jonathan E. Wingo, Matthew S. Ganio et Craig G. Crandall. « Heat-stress-induced changes in central venous pressure do not explain interindividual differences in orthostatic tolerance during heat stress ». Journal of Applied Physiology 110, n^o 5 (mai 2011) : 1283–89. http://dx.doi.org/10.1152/japplphysiol.00035.2011.

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The extent to which heat stress compromises blood pressure control is variable among individuals, with some individuals becoming very intolerant to a hypotensive challenge, such as lower body negative pressure (LBNP) while heat stressed, while others are relatively tolerant. Heat stress itself reduces indexes of ventricular filling pressure, including central venous pressure, which may be reflective of reductions in tolerance in this thermal condition. This study tested the hypothesis that the magnitude of the reduction in central venous pressure in response to heat stress alone is related to the subsequent decrement in LBNP tolerance. In 19 subjects, central hypovolemia was imposed via LBNP to presyncope in both normothermic and heat-stress conditions. Tolerance to LBNP was quantified using a cumulative stress index (CSI), and the difference between normothermic CSI and heat-stress CSI was calculated for each individual. The eight individuals with the greatest CSI difference between normothermic and heat-stress tolerances (LargeDif), and the eight individuals with the smallest CSI difference (SmallDif), were grouped together. By design, the difference in CSI between thermal conditions was greater in the LargeDif group (969 vs. 382 mmHg × min; P < 0.001). Despite this profound difference in the effect of heat stress in decreasing LBNP tolerance between groups, coupled with no difference in the rise in core body temperatures to the heat stress (LargeDif, 1.4 ± 0.1°C vs. SmallDif, 1.4 ± 0.1°C; interaction P = 0.89), the reduction in central venous pressure during heat stress alone was similar between groups (LargeDif: 5.7 ± 1.9 mmHg vs. SmallDif: 5.2 ± 2.0 mmHg; interaction P = 0.85). Contrary to the proposed hypothesis, differences in blood pressure control during LBNP are not related to differences in the magnitude of the heat-stress-induced reductions in central venous pressure.

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Sakata, Seiichiro, Junichiro Hayano, Seiji Mukai, Akiyoshi Okada et Takao Fujinami. « Aging and spectral characteristics of the nonharmonic component of 24-h heart rate variability ». American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 276, n^o 6 (1 juin 1999) : R1724—R1731. http://dx.doi.org/10.1152/ajpregu.1999.276.6.r1724.

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To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21–79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (β) was greater in the region below than above the break point (1.63 ± 0.23 vs. 0.96 ± 0.21, P < 0.001). The break point frequency increased with age ( r = 0.51, P < 0.001) and β correlated with age negatively below the break point ( r = 0.39) and positively above the break point ( r = 0.70). The contribution to interindividual difference in total power was greater from the differences in the power spectral density at frequencies closer to both ends of the frequency axis and minimal from that at −3.25 log(Hz), suggesting hingelike movement of the spectral shape at this frequency with the difference in total power. These characteristics of the 24-h HRV spectrum were simulated by an artificial signal generated by adding two noises with different β values. Given that the power law assumption is fundamental to the analysis of dynamics through the log-log scaled spectrum, our observations are substantial for physiological and clinical studies of the heartbeat dynamic during daily life and suggest that the nonharmonic component of HRV in normal subjects during daily life may include at least two 1/ f β fluctuations that differ in dynamics and age dependency.

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He, Ruo-Hui, Yi-Jing He, Yong-Jun Tang, Hong-Hao Zhou, Howard L. McLeod et Jie Liu. « The potential anticancer effect of beta-blockers and the genetic variations involved in the interindividual difference ». Pharmacogenomics 17, n^o 1 (janvier 2016) : 74–9. http://dx.doi.org/10.2217/pgs.15.152.

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Metcalfe, Richard S., Nicolas Tardif, Dylan Thompson et Niels B. J. Vollaard. « Changes in aerobic capacity and glycaemic control in response to reduced-exertion high-intensity interval training (REHIT) are not different between sedentary men and women ». Applied Physiology, Nutrition, and Metabolism 41, n^o 11 (novembre 2016) : 1117–23. http://dx.doi.org/10.1139/apnm-2016-0253.

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Previously it has been reported that reduced-exertion high-intensity interval training (REHIT; total training time of 3 × 10 min per week) improves maximal aerobic capacity in both sedentary men and women, but improves insulin sensitivity in men only. The aim of the present study was to determine whether there is a true sex difference in response to REHIT, or that these findings can be explained by the large interindividual variability in response inherent to all exercise training. Thirty-five sedentary participants (18 women; mean ± SD age for men and women, respectively: age, 33 ± 9 and 36 ± 9 years; body mass index, 25.1 ± 2.1 and 24.1 ± 3.5 kg·m−2; maximal aerobic capacity, 38.6 ± 8.3 and 31.6 ± 4.6 mL·kg−1·min−1) completed a 6-week REHIT programme consisting of eighteen 10-min unloaded cycling sessions with 1 (first session) or 2 (all other sessions) “all-out” 10–20-s sprints against a resistance of 5% of body mass. Maximal aerobic capacity and oral glucose tolerance test-derived insulin sensitivity were determined before and after training. REHIT was associated with an increase in maximal aerobic capacity (2.54 ± 0.65 vs. 2.78 ± 0.68 L·min−1, main effect of time: p < 0.01), a trend toward reduced plasma insulin area-under-the-curve (AUC; 6.7 ± 4.8 vs. 6.1 ± 4.0 IU·min−1·mL−1, p = 0.096), but no significant change in plasma glucose AUC or the Cederholm index of insulin sensitivity. Substantial interindividual variability in response to REHIT was observed for all variables, but there was no significant effect of sex. In conclusion, REHIT improves the key health marker of aerobic capacity within a minimal total training time-commitment. There is large interindividual variability in responses to REHIT, but sex differences in the responses are not apparent.

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Strelcyk, Olaf, Pavel Zahorik, James Shehorn, Chhayakanta Patro et Ralph Peter Derleth. « Sensitivity to Interaural Phase in Older Hearing-Impaired Listeners Correlates With Nonauditory Trail Making Scores and With a Spatial Auditory Task of Unrelated Peripheral Origin ». Trends in Hearing 23 (janvier 2019) : 233121651986449. http://dx.doi.org/10.1177/2331216519864499.

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Interaural phase difference (IPD) discrimination upper frequency limits and just-noticeable differences (JNDs), interaural level difference (ILD) JNDs, and diotic intensity JNDs were measured for 20 older hearing-impaired listeners with matched moderate sloping to severe sensorineural hearing losses. The JNDs were measured using tone stimuli at 500 Hz. In addition to these auditory tests, the participants completed a cognitive test (Trail Making Test). Significant performance improvements in IPD discrimination were observed across test sessions. Strong correlations were found between IPD and ILD discrimination performance. Very strong correlations were observed between IPD discrimination and Trail Making performance as well as strong correlations between ILD discrimination and Trail Making performance. These relationships indicate that interindividual variability in IPD discrimination performance did not exclusively reflect deficits specific to any auditory processing, including early auditory processing of temporal information. The observed relationships between spatial audition and cognition may instead be attributable to a modality-general spatial processing deficit and/or individual differences in global processing speed.

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Berthoz, Alain, et Bérangère Thirioux. « A Spatial and Perspective Change Theory of the Difference Between Sympathy and Empathy ». Paragrana 19, n^o 1 (novembre 2010) : 32–61. http://dx.doi.org/10.1524/para.2010.0003.

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AbstractEmpathy is a multicomponent faculty of the human brain which is funda-mental for social interactions.Understanding its behavioural, cognitive, emotional neural mechanisms and pathology is a major interdisciplinary challenge..Here we propose, in relation with a modern conception of the Philosophical tradition of Phenomenology and a primary role of cognitive embodiement, a new theory in which we give an important although not exclusive, role to the brain mechanisms which also are involved in spatial cognition: we show, that there is a basic difference between *sympathy* and *empathy*. Whether sympathy is akin to emotional contagion and does not require the siubject to adopt the point of view of others, empathy requires a dynamic and complex manipulation of spatial reference frames. We give an example of an experiment using virtual reality in which a subject interacts with an artificial tight rope walker and discuss also the possible interindividual differences, and gender differences, in the different strategies used by subjects to have an empathic relationship.

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Lee, SoJung, Ian Janssen et Robert Ross. « Interindividual variation in abdominal subcutaneous and visceral adipose tissue : influence of measurement site ». Journal of Applied Physiology 97, n^o 3 (septembre 2004) : 948–54. http://dx.doi.org/10.1152/japplphysiol.01200.2003.

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We evaluated the influence of measurement site on the ranking (low to high) of abdominal subcutaneous (SAT) and visceral (VAT) adipose tissue. We also determined the influence of measurement site on the prediction of abdominal SAT and VAT mass. The subjects included 100 men with computed tomography (CT) measurements at L4–L5 and L3–L4 levels and 100 men with magnetic resonance imaging (MRI) measurements at L4–L5 and 5 cm above L4–L5 (L4–L5 +5 cm). Corresponding mass values were determined by using multiple-image protocols. For SAT, 90 and 92 of the 100 subjects for CT and MRI, respectively, had a difference in rank position at the two levels. The change in rank position exceeded the error or measurement for ∼75% of the subjects for both methods. For VAT, 91 and 95 of the 100 subjects for CT and MRI, respectively, had a difference in rank position at the two levels. The change in rank position exceeded the error of measurement for 36% of the subjects for CT and for 8% of the subjects for MRI. For both imaging modalities, the variance explained in SAT and VAT mass (kg) was comparable for L4–L5, L4–L5 +5 cm, and L3–L4 levels. In conclusion, the ranking of subjects for abdominal SAT and VAT quantity is influenced by measurement location. However, the ability to predict SAT and VAT mass by using single images obtained at the L4–L5, L4–L5 +5 cm, or L3–L4 levels is comparable.

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Nishigami, Tomohiko, Hideki Nakano, Michihiro Osumi, Morihiro Tsujishita, Akira Mibu et Takahiro Ushida. « Central neural mechanisms of interindividual difference in discomfort during sensorimotor incongruence in healthy volunteers : an experimental study ». Rheumatology 53, n^o 7 (3 mars 2014) : 1194–99. http://dx.doi.org/10.1093/rheumatology/ket494.

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Gayles, Jochebed G., et Peter C. M. Molenaar. « The utility of person-specific analyses for investigating developmental processes ». International Journal of Behavioral Development 37, n^o 6 (novembre 2013) : 549–62. http://dx.doi.org/10.1177/0165025413504857.

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The fields of psychology and human development are experiencing a resurgence of scientific inquiries about phenomena that unfold at the level of the individual. This article addresses the issues of analyzing intraindividual psychological/developmental phenomena using standard analytical techniques for interindividual variation. When phenomena are characterized by intraindividual variation, analyses must be done at the level of the individual. Research on these processes generally uses methods analyzing interindividual variation, rather than intraindividual, however, a noteworthy fundamental difference exists between the two. The current article provides theoretical and empirical illustrations of the fundamental contrast between variation within subjects and variation between subjects. First, we explain this distinction through the classical ergodic theorems. Next, we discuss the utility of analysis of intraindividual variation for developmental processes. We then provide an empirical example, using recently-developed methods for analyzing person-specific developmental processes. This article presents for the first time a methodological approach in which first the factor model is determined by exploratory and confirmatory P-technique, and then in a separate second phase the dynamic model for the latent factor series is determined.

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Vande Casteele, Niels, Filip Baert, Sumin Bian, Erwin Dreesen, Griet Compernolle, Gert Van Assche, Marc Ferrante, Severine Vermeire et Ann Gils. « Subcutaneous Absorption Contributes to Observed Interindividual Variability in Adalimumab Serum Concentrations in Crohn’s Disease : A Prospective Multicentre Study ». Journal of Crohn's and Colitis 13, n^o 10 (1 mars 2019) : 1248–56. http://dx.doi.org/10.1093/ecco-jcc/jjz050.

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Abstract Background and Aim Therapeutic drug monitoring is used to optimise adalimumab therapy in patients with Crohn’s disease [CD]. However, the interindividual variability in drug absorption and the quantitative effect on drug clearance of anti-adalimumab antibodies [AAA], measured with a drug-resistant assay, are unclear. We aimed to characterise adalimumab population pharmacokinetics [PopPK] and identify determinants of interindividual variability in patients with CD. Methods In a prospective multicentre open-label cohort study in 28 patients with CD starting adalimumab therapy peak, intermediate, and trough serum samples were analysed for adalimumab and AAA concentrations using a drug resistant assay. Adalimumab concentration-time data were analysed by non-linear mixed effects modelling and were adequately described by a PopPK model with first-order absorption and one-compartment disposition with linear elimination. Clinical remission at Week 12 [W12] was defined as a Harvey-Bradshaw index ≤4. Results The absorption rate, volume of distribution, and clearance estimates of a typical patient were respectively 0.343 /day, 7.8 L, and 0.330 L/day. A 4-fold difference in the range of adalimumab concentrations was observed 7 days after the first dose and found to be inversely correlated with baseline lean body weight [LBW], soluble tumour necrosis factor [s-TNF], and s-TNF receptor-1 whereas positive AAA and higher LBW were found to be important predictors of accelerated clearance. An adalimumab concentration at W12 of >7.3 µg/mL was significantly associated with achieving clinical remission at W12. Conclusion Variability in subcutaneous drug absorption is an important contributor to the observed interindividual variability in adalimumab concentrations, in addition to drug clearance [ClinicalTrials.gov NCT02450513].

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Abd-El-Atti, E., F. Nevens, G. van Roey et J. Fevery. « A wide interindividual difference between portal and variceal pressureexplains the lack of correlation between portal pressure andvariceal haemorrhage ». Journal of Hepatology 32 (2000) : 72. http://dx.doi.org/10.1016/s0168-8278(00)80612-1.

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Liu, Haiyan, Xiaowei Xing, Lihua Huang, Zhijun Huang et Hong Yuan. « The expression level of myocardial β1-adrenergic receptor affects metoprolol antihypertensive effects : A novel mechanism for interindividual difference ». Medical Hypotheses 81, n^o 1 (juillet 2013) : 71–72. http://dx.doi.org/10.1016/j.mehy.2013.02.014.

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Keevil, Brian G., Eric S. Kilpatrick, Simon P. Nichols et Paul W. Maylor. « Biological variation of cystatin C : implications for the assessment of glomerular filtration rate ». Clinical Chemistry 44, n^o 7 (1 juillet 1998) : 1535–39. http://dx.doi.org/10.1093/clinchem/44.7.1535.

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Abstract To assess the inherent potential for detecting mild to moderate reductions in glomerular filtration rate, this study determined the biological variability of serum cystatin C and creatinine in 12 healthy subjects. After accounting for analytical variation, interindividual variance accounted for 93% and intraindividual variance accounted for 7% of serum creatinine biological variation. As such, to lie outside the assay reference interval, some subjects must exceed 13 SD from their usual mean value, whereas in others, a change of only 2 SD would be sufficient. For cystatin C, interindividual variation explained 25% and intraindividual variance explained 75% of biological variability. Therefore, the upper limit of the population reference interval for cystatin C is seldom more than 3–4 SD from the mean value of any healthy individual. The critical difference for sequential values significant at P ≤0.05 was calculated as 37% for serum cystatin C and 14% for serum creatinine. We conclude that cystatin C is potentially a better marker for detecting impaired renal function than serum creatinine, but serum creatinine is probably still the better marker for detecting temporal changes of renal function in individuals with established renal disease.

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Leertouwer, IJsbrand, Noémi K. Schuurman et Jeroen K. Vermunt. « Are retrospective assessments means of people’s experiences ? Accounting for interpersonal and intrapersonal variability when comparing retrospective assessment data to ecological momentary assessment data. » Journal for Person-Oriented Research 8, n^o 2 (11 décembre 2022) : 52–70. http://dx.doi.org/10.17505/jpor.2022.24855.

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Retrospective Assessment (RA) scores are often found to be higher than the mean of Ecological Momentary Assessment (EMA) scores about a concurrent period. This difference is generally interpreted as bias towards salient experiences in RA. During RA participants are often asked to summarize their experiences in unspecific terms, leaving room for personal interpretation. As a result, participants may use various strategies to summarize their experiences. In this study, we reanalyzed an existing dataset (N = 92) using a repeated N = 1 approach. We assessed for each participant whether it was likely that their RA score was an approximation of the mean of their experiences as captured by their EMA scores. We found considerable interpersonal differences in the difference between EMA scores and RA scores, as well as some extreme cases. Furthermore, for a considerable part of the sample (n = 46 for positive affect, n = 56 for negative affect), we did not reject the null hypothesis that their RA score represented the mean of their experiences as captured by their EMA scores. We conclude that in its current unspecific form RA may facilitate bias, although not for everyone. Future studies may determine whether differences between RA and EMA are mitigated using more specific forms of RA, while acknowledging interindividual differences.

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Castrogiovanni, Paolo, Fulvio Pieraccini, Sonia Iapichino, Claudia Pacchierotti, Letizia Bossini, Elisabetta Truglia, Claudio Malpassi et Bruno Natale. « Electroretinogram B-Wave Amplitude in Panic Disorder ». CNS Spectrums 6, n^o 3 (mars 2001) : 210–13. http://dx.doi.org/10.1017/s1092852900008580.

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AbstractAbnormal light-related behaviors have been described for patients with panic disorder (PD). The present study was undertaken to investigate the retinal light response in PD using electroretinography (ERG). The authors conducted bwave ERG measurements with a bright light (after dark adaptation) in 28 patients with PD and 28 control subjects. There were no significant differences in the mean b-wave amplitude between the two groups, but the retinal response to light in PD patients was generally lower than in healthy subjects. A large interindividual variability was found; also noted was a significant difference in the mean b-wave amplitude between the right and left eyes in the control group. The data indicate subtle variation of retinal photosensitivity in a subgroup of patients with PD. Because dopaminergic retinal activity affects b-ERG amplitude, the authors hypothesize that the dopaminergic system is involved in the response to light in PD patients.

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Meier, Tabea, Ryan L. Boyd, Matthias R. Mehl, Anne Milek, James W. Pennebaker, Mike Martin, Markus Wolf et Andrea B. Horn. « (Not) Lost in Translation : Psychological Adaptation Occurs During Speech Translation ». Social Psychological and Personality Science 12, n^o 1 (12 mars 2020) : 131–42. http://dx.doi.org/10.1177/1948550619899258.

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While language style is considered to be automatic and relatively stable, its plasticity has not yet been studied in translations that require the translator to “step into the shoes of another person.” In the present study, we propose a psychological model of language adaptation in translations. Focusing on an established interindividual difference marker of language style, that is, gender, we examined whether translators assimilate to the original gendered style or implicitly project their own gendered language style. In a preregistered study, we investigated gender differences in language use in TED Talks ( N = 1,647) and their translations ( N = 544) in same- versus opposite-gender speaker/translator dyads. The results showed that translators assimilated to gendered language styles even when in mismatch to their own gender. This challenges predominating views on language style as fixed and fosters a more dynamic view of language style as also being shaped by social context.

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Hauraix, Hugo, Antoine Nordez, Gaël Guilhem, Giuseppe Rabita et Sylvain Dorel. « In vivo maximal fascicle-shortening velocity during plantar flexion in humans ». Journal of Applied Physiology 119, n^o 11 (1 décembre 2015) : 1262–71. http://dx.doi.org/10.1152/japplphysiol.00542.2015.

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Interindividual variability in performance of fast movements is commonly explained by a difference in maximal muscle-shortening velocity due to differences in the proportion of fast-twitch fibers. To provide a better understanding of the capacity to generate fast motion, this study aimed to 1) measure for the first time in vivo the maximal fascicle-shortening velocity of human muscle; 2) evaluate the relationship between angular velocity and fascicle-shortening velocity from low to maximal angular velocities; and 3) investigate the influence of musculo-articular features (moment arm, tendinous tissues stiffness, and muscle architecture) on maximal angular velocity. Ultrafast ultrasound images of the gastrocnemius medialis were obtained from 31 participants during maximal isokinetic and light-loaded plantar flexions. A strong linear relationship between fascicle-shortening velocity and angular velocity was reported for all subjects (mean R2 = 0.97). The maximal shortening velocity (VFmax) obtained during the no-load condition (NLc) ranged between 18.8 and 43.3 cm/s. VFmax values were very close to those of the maximal shortening velocity (Vmax), which was extrapolated from the F-V curve (the Hill model). Angular velocity reached during the NLc was significantly correlated with this VFmax ( r = 0.57; P < 0.001). This finding was in agreement with assumptions about the role of muscle fiber type, whereas interindividual comparisons clearly support the fact that other parameters may also contribute to performance during fast movements. Nevertheless, none of the biomechanical features considered in the present study were found to be directly related to the highest angular velocity, highlighting the complexity of the upstream mechanics that lead to maximal-velocity muscle contraction.

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Paluch, Katarzyna, Katarzyna Jurewicz et Andrzej Wróbel. « Beyond Difference in Reaction Time : Understanding Neuronal Activity during the Preparatory Period of the Decision Process ». Journal of Cognitive Neuroscience 33, n^o 2 (février 2021) : 263–78. http://dx.doi.org/10.1162/jocn_a_01648.

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Even the simplest perceptual tasks are executed with significant interindividual differences in accuracy and RT. In this work, we used the diffusion decision model and multi-electrode EEG signals to study the impact of neuronal activity during the preparatory period on the following decision process in an attention task. Two groups were defined by fast and slow responses during the performance of control trials. A third, control group performed the same experiment but with instructions defining signal for response execution. We observed that the fast-responding group had a shorter duration of nondecision processes (describing both stimulus encoding and response preparation) preceded by lower power of the frontal upper alpha (10–15 Hz) and central beta (21–26 Hz) activities during the preparatory period. To determine whether these differences were followed by a shortening of the early perceptual or late motor process, we analyzed lateralized readiness potential (LRP). The time from LRP onset until response execution (LRP-RT interval) was similar in all three groups, enabling us to interpret shortening of nondecision time as reflecting faster stimulus encoding.

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Hagberg, James M., Robert E. Ferrell, Steve D. McCole, Kenneth R. Wilund et Geoffrey E. Moore. « V˙o 2 max is associated with ACE genotype in postmenopausal women ». Journal of Applied Physiology 85, n^o 5 (1 novembre 1998) : 1842–46. http://dx.doi.org/10.1152/jappl.1998.85.5.1842.

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Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (V˙o 2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml ⋅ kg−1 ⋅ min−1higher V˙o 2 max( P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml ⋅ kg−1 ⋅ min−1higher V˙o 2 max( P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher V˙o 2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation inV˙o 2 max among women after accounting for the effect of habitual physical activity levels. The entire difference inV˙o 2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDo 2). ACE genotype accounted for 17% of the variation in maximal a-vDo 2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences inV˙o 2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDo 2 and not of maximal stroke volume and maximal cardiac output.

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Taguchi, Masato. « Analysis of Interindividual Variability and Race Difference in the Pharmacokinetics of .BETA.-blocker for Personalized Medicine in Heart Failure Patients ». Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) 35, n^o 5 (2009) : 301–15. http://dx.doi.org/10.5649/jjphcs.35.301.

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Reinberg, Alain E., Alena Bicakova-Rocher, Antoine Gorceix, Israel E. Ashkenazi et Michael H. Smolensky. « Placebo Effect on the Circadian Rhythm Period τ of Temperature and Hand-Grip Strength Rhythms : Interindividual and Gender-Related Difference ». Chronobiology International 11, n^o 1 (janvier 1994) : 45–53. http://dx.doi.org/10.3109/07420529409057230.

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Mikacenic, C., A. P. Reiner, T. D. Holden, D. A. Nickerson et M. M. Wurfel. « Variation in the TLR10/TLR1/TLR6 locus is the major genetic determinant of interindividual difference in TLR1/2-mediated responses ». Genes & ; Immunity 14, n^o 1 (15 novembre 2012) : 52–57. http://dx.doi.org/10.1038/gene.2012.53.

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Li, Fangfang, Jing Jin, Ivonne M. C. M. Rietjens et Fuguo Xing. « Interindividual Differences in In Vitro Human Intestinal Microbial Conversion of 3-Acetyl-DON and 15-Acetyl-DON ». Toxins 14, n^o 3 (7 mars 2022) : 199. http://dx.doi.org/10.3390/toxins14030199.

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In order to evaluate the potential differences between 3-Ac-DON and 15-Ac-DON in the human intestinal microbial metabolism, human fecal samples were anaerobically cultured in vitro. Quantitative fecal microbiota characteristics were obtained by 16S rRNA sequencing, and the data revealed several genera that may be relevant for the transformation of the acetylated DONs. Significant differences in the level of 3-Ac-DON and 15-Ac-DON conversion were observed among microbiota from different human individuals. 3-Ac-DON could be rapidly hydrolyzed; a ten-fold difference was observed between the highest and lowest in vitro conversion after 4 h. However, 15-Ac-DON was not fully transformed in the 4 h culture of all the individual samples. In all cases, the conversion rate of 3-Ac-DON was higher than that of 15-Ac-DON, and the conversion rate of 3-Ac-DON into DON varied from 1.3- to 8.4-fold that of 15-Ac-DON. Based on in vitro conversion rates, it was estimated that 45–452 min is required to convert all 3-Ac-DON to DON, implying that deacetylation of 3-Ac-DON is likely to occur completely in all human individuals during intestinal transit. However, for conversion of 15-Ac-DON, DON formation was undetectable at 4 h incubation in 8 out of the 25 human samples, while for 7 of these 8 samples conversion to DON was detected at 24 h incubation. The conversion rates obtained for these seven samples indicated that it would take 1925–4805 min to convert all 15-Ac-DON to DON, while the other 17 samples required 173–734 min. From these results it followed that for eight of the 25 individuals, conversion of 15-Ac-DON to DON was estimated to be incomplete during the 1848 min intestinal transit time. The results thus indicate substantial interindividual as well as compound specific differences in the deconjugation of acetylated DONs. A spearman correlation analysis showed a statistically significant relationship between deconjugation of both acetyl-DONs at 4 h and 24 h incubation. Based on the in vitro kinetic parameters and their scaling to the in vivo situation, it was concluded that for a substantial number of human individuals the deconjugation of 15-Ac-DON may not be complete upon intestinal transit.

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Franken, Willeke P. J., Steven Thijsen, Ron Wolterbeek, John J. M. Bouwman, Hanane el Bannoudi, Sandra V. Kik, Jaap T. van Dissel et Sandra M. Arend. « Variation in T-SPOT.TB Spot Interpretation between Independent Observers from Different Laboratories ». Clinical and Vaccine Immunology 16, n^o 10 (26 août 2009) : 1439–42. http://dx.doi.org/10.1128/cvi.00456-08.

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ABSTRACT T-SPOT.TB is a specific assay for the diagnosis of tuberculosis. The assay needs to be performed with freshly isolated cells, and interpretation requires training. T-SPOT.TB has been used in various clinical-epidemiological settings, but so far no studies have evaluated the effect of interobserver variation in test reading. Our aim was to evaluate variation between different observers in reading T-SPOT.TB results. The study was nested within an ongoing cohort study, in which part of the T-SPOT.TB had been performed with frozen material. Culture plates were read visually by four different observers from two laboratories and by two automated readers. Of 313 T-SPOT.TB assays, 235 were performed with fresh cells and 78 were performed with frozen cells. No significant difference was found between results obtained with fresh cells and those obtained with frozen cells. The percentage of positive results varied between readers by maximally 15%; five/six raters were within a 6% difference in positive results. Analysis of the observed interrater differences showed that some individuals systematically counted more spots than others did. Because test interpretation includes subtraction of background values, this systematic variance had little influence on interindividual differences. The test result as positive or negative varied between independent raters, mainly due to samples with values around the cutoff. This warrants further study regarding determinants affecting the reading of T-SPOT.TB.

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Todt, I., R. Guerkov, H. B. Gehl et H. Sudhoff. « Comparison of Cochlear Implant Magnets and Their MRI Artifact Size ». BioMed Research International 2020 (10 janvier 2020) : 1–8. http://dx.doi.org/10.1155/2020/5086291.

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Introduction. Recent developments regarding cochlear implant magnets (e.g., a bipolar diametral magnet) and refined surgical techniques (e.g., implant positioning) have had a significant impact on the relation between cochlear implants and MRIs, making the reproducible visibility of cochlea and IAC possible. MRI scanning has changed from a contraindication to a diagnostic tool. Magnet artifact size plays a central role in the visual assessment of the cochlea and IAC. Objective. The aim of this study is to compare the CI magnet-related maximum artifact sizes of various cochlea implant systems. Materials and Methods. We performed an in vivo measurement of MRI artifacts at 1.5 and 3 Tesla with three cochlear implant magnet systems (AB 3D, Medel Synchrony, and Oticon ZTI). The implant, including the magnet, was positioned with a head bandage 7.0 cm and 120° from the nasion, external auditory canal. We used a TSE T2w MRI sequence on the axial and coronal plains and compared the artifacts in two volunteers for each tesla strength. Results. Intraindividual artifact size differences between the three magnets are smaller than interindividual maximum artifact size differences. 3 T MRI scans, in comparison to 1.5 T MRI scans, show a difference between soft artifact areas. Conclusion. We observed no major difference between maximum implant magnet artifact sizes of the three implant magnet types.

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KREMERS, JAN, NEIL R. A. PARRY, ATHANASIOS PANORGIAS et IAN J. MURRAY. « The influence of retinal illuminance on L- and M-cone driven electroretinograms ». Visual Neuroscience 28, n^o 2 (23 février 2011) : 129–35. http://dx.doi.org/10.1017/s0952523810000556.

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AbstractThe electroretinographic response to L- and M-cone isolating stimuli was measured at different luminance levels to study the effect of retinal illuminance on amplitude and phase, and how this may influence estimates of L:M ratios in the retina. It was found that the amplitude of L- and M-cone driven responses increases differently with increasing retinal illuminance: L-cone responses increase more quickly than those of M-cones. The L:M ratio does not change strongly with retinal illuminance. The phase of both L- and M-cone driven responses advances with increasing retinal illuminance. There is considerable interindividual variability in the phase difference between the two, but generally M-cone driven responses are phase advanced.

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Schlüter, Caroline, Larissa Arning, Christoph Fraenz, Patrick Friedrich, Marlies Pinnow, Onur Güntürkün, Christian Beste, Sebastian Ocklenburg et Erhan Genc. « Genetic variation in dopamine availability modulates the self-reported level of action control in a sex-dependent manner ». Social Cognitive and Affective Neuroscience 14, n^o 7 (juillet 2019) : 759–68. http://dx.doi.org/10.1093/scan/nsz049.

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Abstract Although procrastination is a widespread phenomenon with significant influence on our personal and professional life, its genetic foundation is somewhat unknown. An important factor that influences our ability to tackle specific goals directly instead of putting them off is our ability to initiate cognitive, motivational and emotional control mechanisms, so-called metacontrol. These metacontrol mechanisms have been frequently related to dopaminergic signaling. To gain deeper insight into the genetic components of procrastination, we examined whether genetically induced differences in the dopaminergic system are associated with interindividual differences in trait-like procrastination, measured as decision-related action control (AOD). Analyzing the data of 278 healthy adults, we found a sex-dependent effect of TH genotype on AOD. Interestingly, only in women, T-allele carriers showed lower AOD values and were therefore more likely to procrastinate. Additionally, we investigated whether differences in the morphology and functional connectivity of the amygdala that were previously associated with AOD happen to be related to differences in the TH genotype and thus to differences in the dopaminergic system. However, there was no significant amygdala volume or connectivity difference between the TH genotype groups. Therefore, this study is the first to suggest that genetic, anatomical and functional differences affect trait-like procrastination independently.

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Goran, M. I., W. H. Carpenter et E. T. Poehlman. « Total energy expenditure in 4- to 6-yr-old children ». American Journal of Physiology-Endocrinology and Metabolism 264, n^o 5 (1 mai 1993) : E706—E711. http://dx.doi.org/10.1152/ajpendo.1993.264.5.e706.

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There is a sparsity of data on energy expenditure in young children. We therefore examined the components of daily energy expenditure in a group of 30 children (16 boys, 14 girls; age 4–6 yr) characterized for body weight, height, heart rate, and body composition from bioelectrical resistance. Total energy expenditure (TEE) was measured over 14 days under free living conditions by doubly labeled water, resting energy expenditure (REE) from indirect calorimetry, and activity energy expenditure was estimated from the difference between TEE and REE. Mean TEE was 1,379 +/- 290 kcal/day, which was 475 +/- 202 kcal/day lower than energy intake recommendations for this age group. Activity-related energy expenditure was estimated to be 267 +/- 203 kcal/day. TEE was most significantly related to fat-free mass (FFM; r = 0.86; P < 0.001), body weight (r = 0.83; P < 0.001), and REE (r = 0.80; P < 0.001). When TEE was adjusted for FFM, a significant correlation with heart rate was observed (partial r = 0.54; P = 0.002). Collectively, 86% of interindividual variation in TEE was accounted for by FFM, heart rate, and REE. We conclude that, in young 4- to 6-yr-old children, 1) TEE is approximately 25% lower than current recommendations for energy intake and 2) combined measurement of FFM, heart rate, and REE explain 86% of interindividual variation in TEE, thus providing a possible alternative method to estimate TEE in young children.

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Massa, Guy G., Inge Gys, Anniek Op ‘t Eyndt, Esmiralda Bevilacqua, Anne Wijnands, Peter Declercq et Renate Zeevaert. « Evaluation of the FreeStyle® Libre Flash Glucose Monitoring System in Children and Adolescents with Type 1 Diabetes ». Hormone Research in Paediatrics 89, n^o 3 (2018) : 189–99. http://dx.doi.org/10.1159/000487361.

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Background/Aims: The FreeStyle® Libre Flash Glucose Monitoring System (FGM, Abbott) measures glucose concentrations in the interstitial fluid for up to 14 days. It has been approved for use in children aged > 4 years in January 2016. Experience in children is still limited. We evaluated the accuracy and usability of the FGM in children with type 1 diabetes mellitus (DM). Methods: 67 children with type 1 DM (35 girls), aged 4–18 years, were included. Subjects wore a sensor on the back of their upper arm. For the first 14 days, they regularly measured capillary blood glucose (BG) with their usual BG meter (Accu-Chek® Mobile [ACM], Roche [n = 24]; Contour® Next Link [CNL], Bayer [n = 26]; OneTouch® Verio® IQ [OTV], LifeScan [n = 17]) followed by a sensor glucose (SG) scanning. SG readings were compared to BG measurements by consensus error grid (CEG) analysis; the mean difference (MD), the mean relative difference (MRD), the mean absolute difference (MAD), and the mean absolute relative difference (MARD) were calculated. After 14 days, subjects were asked to fill in a questionnaire on the usability of the FGM. Results: 2,626 SG readings were paired with BG results. FGM readings were highly correlated with BG (r = 0.926, p < 0.001). 80.3% of the data pairs were in zone A (= no effect on clinical action) and 18.4% were in zone B (= altered clinical action with little or no effect on the clinical outcome) of the CEG. Overall MD was +7.5 mg/dL; MD varied with the BG meter: ACM +10.4 mg/dL, CNL +14.2 mg/dL, OTV –3.6 mg/dL (p < 0.001). Overall, MARD was 16.7%. We observed a large interindividual variability in the accuracy parameters. MD and MRD were inversely related to BMI (r = –0.261 [p < 0.05]; r = –0.266 [p < 0.05], respectively). MARD was inversely related to age (r = –0.266 [p < 0.05]). Twenty-nine patients (43.3%) reported sensor problems, mainly early detachment of the sensor. Nonetheless, the usability questionnaire indicated high levels of satisfaction. Conclusions: Our results showed a reasonable agreement between the FGM SG readings and capillary BG measurements in children. There was, however, a large interindividual variability. The wearing of the sensor requires special attention. Further studies in children are imperative in order to document the accuracy and safety of the FGM in the paediatric population.

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Rajičić, Marija, Ivana Budinski, Milan Miljević, Branka Bajić, Milan Paunović, Mladen Vujošević et Jelena Blagojević. « The new highest number of B chromosomes (Bs) in Leisler’s bat Nyctalus leisleri (Kuhl, 1817) ». Comparative Cytogenetics 16, n^o 3 (30 septembre 2022) : 173–84. http://dx.doi.org/10.3897/compcytogen.v16i3.89911.

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B chromosomes (Bs) are supernumerary to the standard chromosome set, from which they prevalently derive. Variation in numbers both among individuals or populations and among cells within individuals is their constant feature. Leisler’s bat Nyctalus leisleri (Kuhl, 1817) is one of only four species of Chiroptera with detected Bs. Four males of N. leisleri were collected from two localities on the territory of Serbia and cytogenetically analysed. All animals had Bs with interindividual variability ranging from two to five heterochromatic micro Bs. The highest number of Bs was detected in this species. Among mammals, Rodentia and Chiroptera are orders with the largest number of species, but Bs frequently appear in rodents and rarely in chiropterans. Possible explanations for this difference are offered.

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Wang, Qiao, Lingsen You, Zeyu Li, Leiyi Zhang, Xueqi Li et Xuesong Yang. « Influence of AGTR1 and ABCB1 Gene Polymorphism on the Curative Effect of Irbesartan ». International Journal of Hypertension 2022 (9 novembre 2022) : 1–8. http://dx.doi.org/10.1155/2022/4278675.

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The interindividual heterogeneity in response to the antihypertensive effect of irbesartan has received considerable attention because of gene polymorphism. In this study, we investigated the new combinational influences of AGTR1 and ABCB1 gene polymorphism on the therapeutic effect of irbesartan among Chinese hypertensive patients. A total of 353 samples including 168 normal people and 185 hypertensive patients were adopted, and genotypes comprise ABCB1 (CC, CT, and TT) and AGTR1 (AA and AC) in this study. The results of multiple linear regression models showed that no statistically significant differences were observed in blood pressure change following irbesartan administration in each genotype from either ABCB1 (CC, CT, and TT) or AGTR1 (AA and AC). However, spline smoothing analysis demonstrated that the blood pressure therapeutic responses of irbesartan presented a noticeable difference among different ABCB1 genotypes when irbesartan doses reached over 300 ng/mL. Eventually, we assumed that the different drug responses of irbesartan among various AGTR1 genotypes were due to the diversity of the irbesartan-conjugated protein, which is responsible for crossing-coupled intracellular G-protein-coupled receptors (GPCRs).

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Lefebvre, Germain, Aurélien Nioche, Sacha Bourgeois-Gironde et Stefano Palminteri. « Contrasting temporal difference and opportunity cost reinforcement learning in an empirical money-emergence paradigm ». Proceedings of the National Academy of Sciences 115, n^o 49 (15 novembre 2018) : E11446—E11454. http://dx.doi.org/10.1073/pnas.1813197115.

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Money is a fundamental and ubiquitous institution in modern economies. However, the question of its emergence remains a central one for economists. The monetary search-theoretic approach studies the conditions under which commodity money emerges as a solution to override frictions inherent to interindividual exchanges in a decentralized economy. Although among these conditions, agents’ rationality is classically essential and a prerequisite to any theoretical monetary equilibrium, human subjects often fail to adopt optimal strategies in tasks implementing a search-theoretic paradigm when these strategies are speculative, i.e., involve the use of a costly medium of exchange to increase the probability of subsequent and successful trades. In the present work, we hypothesize that implementing such speculative behaviors relies on reinforcement learning instead of lifetime utility calculations, as supposed by classical economic theory. To test this hypothesis, we operationalized the Kiyotaki and Wright paradigm of money emergence in a multistep exchange task and fitted behavioral data regarding human subjects performing this task with two reinforcement learning models. Each of them implements a distinct cognitive hypothesis regarding the weight of future or counterfactual rewards in current decisions. We found that both models outperformed theoretical predictions about subjects’ behaviors regarding the implementation of speculative strategies and that the latter relies on the degree of the opportunity costs consideration in the learning process. Speculating about the marketability advantage of money thus seems to depend on mental simulations of counterfactual events that agents are performing in exchange situations.

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Curran, Aoife M., Katy Horner, Victoria O'Sullivan, Alice B. Nongonierma, Solène Le Maux, Eoin Murphy, Phil Kelly, Richard J. FitzGerald et Lorraine Brennan. « Variable Glycemic Responses to Intact and Hydrolyzed Milk Proteins in Overweight and Obese Adults Reveal the Need for Precision Nutrition ». Journal of Nutrition 149, n^o 1 (1 janvier 2019) : 88–97. http://dx.doi.org/10.1093/jn/nxy226.

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ABSTRACT Background Dietary modifications can contribute to improved pancreatic β cell function and enhance glycemic control. Objectives The objectives of this study were as follows: 1) to investigate the potential of milk protein hydrolysates to modulate postprandial glucose response; 2) to assess individual responses; and 3) to explore the inter- and intraindividual reproducibility of the response. Methods A 14-d randomized crossover study investigated interstitial glucose levels of participants in response to 12% w/v milk protein drinks (intact caseinate and casein hydrolysate A and B) consumed in random order with a 2-d washout between treatments. Milk protein drinks were consumed immediately prior to study breakfast and evening meals. Twenty participants (11 men, 9 women) aged 50 ± 8 y with a body mass index (in kg/m2) of 30.2 ± 3.1 were recruited. Primary outcome was glucose levels assessed at 15-min intervals with the use of glucose monitors. Results Repeated-measures ANOVA revealed that for breakfast there was a significant difference across the 3 treatment groups (P = 0.037). The ability to reduce postprandial glucose was specific to casein hydrolysate B in comparison with intact caseinate (P = 0.039). However, despite this significant difference, further examination revealed that only 3 out of 18 individuals were classified as responders (P < 0.05). High intraclass correlation coefficients were obtained for glucose response to study meals (intraclass correlation coefficient: 0.892 for breakfast with intact caseinate). The interindividual CVs were higher than the intraindividual CVs. Mean inter- and intraindividual CVs were 19.4% and 5.7%, respectively, for breakfast with intact caseinate. Conclusion Ingestion of a specific casein hydrolysate successfully reduced the postprandial glucose response; however, at an individual level only 3 participants were classified as responders, highlighting the need for precision nutrition. Exploration of high interindividual responses to nutrition interventions is needed, in combination with the development of precision nutrition, potentially through an n-of-1 approach. This clinical trial was registered as ISRCTN61079365 (https://www.isrctn.com/).

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Mayrhofer, Helen C., Felix Duecker, Vincent van de Ven, Heidi I. L. Jacobs et Alexander T. Sack. « Hemifield-specific Correlations between Cue-related Blood Oxygen Level Dependent Activity in Bilateral Nodes of the Dorsal Attention Network and Attentional Benefits in a Spatial Orienting Paradigm ». Journal of Cognitive Neuroscience 31, n^o 5 (mai 2019) : 625–38. http://dx.doi.org/10.1162/jocn_a_01338.

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The dorsal attention network (DAN) is known to be involved in shifts of spatial attention or in orienting. However, the involvement of each hemisphere in shifts to either hemifield is still a matter of debate. In this study, interindividual hemifield-specific attentional benefits in RTs were correlated with cue-related BOLD responses specific to directive cues in the left and right frontal and posterior nodes of the DAN, measured in a Spatial Orienting Paradigm. The pattern of correlations was analyzed with respect to its fit with three existing hypotheses of spatial attention control: the contralateral, right dominance, and hybrid hypotheses. Results showed that activation in frontal and parietal nodes of the DAN could explain a significant proportion of the interindividual variance in attentional benefits. Although we found that benefits in the right hemifield correlated with cue-related activity in the left, as well as the right, DAN and that the pattern of correlations fit best with the right dominance hypothesis, there were no significant correlations between left benefits and activation in the right (as well as left) DAN, which precludes the conclusion that our data support the right dominance hypothesis and might instead point toward a potential qualitative difference between leftward and rightward shifts of attention. In conclusion, this study demonstrates that behavioral effects of orienting can be linked to activation changes in the DAN, and it raises new questions with respect to the involvement of the frontal and parietal nodes in each hemisphere in hemifield-specific orienting.

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Mahfouz, Reda Z., Ania Jankowska, Quteba Ebrahem, Zhenbo Hu, Kenneth K. Chan, Donald Lavelle, Joseph DeSimone et al. « Gender Is A Major Determinant of Cytidine Analogue Metabolism and May Contribute to Differences in Treatment Outcomes ». Blood 118, n^o 21 (18 novembre 2011) : 1434. http://dx.doi.org/10.1182/blood.v118.21.1434.1434.

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Abstract Abstract 1434 Cytidine analogues are mainstays in hematologic malignancy therapy. One documented limitation of therapy is interindividual variability in cytidine analogue pharmacokinetics that compromises predictability, safety and efficacy. Causes of interindividual variability include single nucleotide polymorphisms (SNPs) in cytidine metabolizing enzymes, particularly cytidine deaminase (CDA): the CDA SNP A79C (rs2072671) is present in >70% of Caucasians and decreases CDA enzyme activity. Gender is another known genetic determinant of cytidine analogue clinical activity, although the pathway is unknown (Dimopoulou et al, Ann Oncol 2004). With high dose cytarabine therapy, CDA may be saturated, dampening the clinical impact of CDA SNPs. However, the recently approved cytidine analogues 5-azacytidine and decitabine are used as single agents at relatively low doses, and interindividual variability could have greater clinical significance, since drug levels may be close to minimum thresholds required for efficacy. To evaluate this possibility, the impact of A79C and gender on treatment outcomes was examined in a cohort of patients with myelodysplastic syndrome (MDS, n=127) and acute myeloid leukemia (AML, n=74) classified by WHO criteria, initiated on treatment between 1/2002 and 12/2007, with IRB approved tissue-banked bone marrow samples available for analysis for the A79C SNP by sequencing and SNP array, and with verifiable follow-up and survival annotation. Other variables analyzed were those known to have major prognostic importance in patients with MDS and AML (bone marrow myeloblast percentage, karyotype, age). Patients were analyzed in three treatment groups: (i) did not receive cytidine analogues (n=35), (ii) treated with cytarabine (n=76), (iii) treated with 5-azacytidine or decitabine (n=90). In all three treatment groups, heterozygosity or homozygosity for A79C was not associated with significant differences in overall survival (OS). Similarly, there was no significant difference in overall survival in females versus males who were treated with cytarabine or who did not receive cytidine analogues. However, in the 5-azacytidine/decitabine treatment group, females had significantly longer overall survival than males (median 1033 v 563 days, Log Rank p=0.014). In multivariate analysis incorporating age, karyotype, bone marrow blast percentage and A79C, only age, gender and karyotype were significantly (Cox Proportional Hazards p<0.01) associated with survival, with the hazard ratio for female gender 0.356 (95%CI 0.165–0.766). An important caveat is that MDS in females has a less aggressive natural history (Nosslinger et al, Ann Oncol 2010), therefore, it is possible that gender differences in cytidine analogue metabolism do not underlie the difference in overall survival. Nonetheless, in AML myeloblasts (GSE15434) and normal liver tissue (measured by microarray), CDA mRNA expression in females was significantly lower than in males (Wilcoxon test p=0.005 and p=0.025 respectively). To measure functional CDA activity, uridine conversion from cytidine by plasma was measured by uHPLC (Dionex). As expected, there was a significant 2-fold decrease in mean enzyme activity in individuals homozygous for the A79C variant (CC, n=32) compared to individuals homozygous for the ancestral allele (AA, n=32, t-test p=0.02). However, the decrease in mean enzyme activity in females (n=48) compared to males (n=48) was even greater (3-fold, t-test p<0.001). In an analysis of decitabine pharmacokinetics after administration of oral decitabine 1 mg/kg to female (n=18) and male (n=18) adult mice, plasma levels of decitabine measured by LCMSMS were consistently higher in females at all time-points (1.169-4.375 fold at the different time points, paired t-test p=0.001). In conclusion, decreased cytidine analogue conversion to uridine counterparts in females, most likely from differences in CDA expression, could be relevant to gender differences in treatment outcomes with 5-azacytidine or decitabine. Disclosures: No relevant conflicts of interest to declare.

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Goemans, Bianca F., Gertjan J. L. Kaspers, Susanne J. H. Vijverberg, Anne H. Loonen, Ursula Creutzig, Karel Hahlen, Dirk Reinhardt, Brenda E. S. Gibson, Jacqueline Cloos et Christian M. Zwaan. « Large Interindividual Differences in In Vitro Calicheamicin Sensitivity May Underly Gemtuzumab Ozogamicin Resistance in Acute Myeloid Leukemia (AML). » Blood 106, n^o 11 (16 novembre 2005) : 107. http://dx.doi.org/10.1182/blood.v106.11.107.107.

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Abstract Gemtuzumab ozogamicin (GO or Mylotarg®) is increasingly being used in the treatment of AML. GO consists of a cytotoxic drug - calicheamicin which is conjugated to an anti-CD33 antibody. Most AML patients highly express CD33 on their blasts. Studies relating CD33 expression to response to GO have failed to show an association. Although 30–50% of patients respond to Mylotarg®, the causes of primary resistance to this drug remain unclear. Previous reports have studied P-gp status and CD33 expression as a cause of resistance to GO. Another factor that might determine response to GO is cellular drug resistance to calicheamicin. In this study we examined in vitro resistance to calicheamicin in 90 initially diagnosed and 32 relapsed pediatric AML samples using the 4 day MTT assay (concentration range 0.000004 – 0.4 μg/ml). The LC50 value, the drug concentration at which 50% of the cells is killed by the drug, is used as a measure of sensitivity. In addition to calicheamicin, some samples were also tested successfully for in vitro sensitivity to etoposide, cytarabine, daunorubicin, idarubicin, mitoxantrone, 6-thioguanine, vincristine and L-asparaginase. The characteristics of the 122 pediatric AML samples included are as follows: 62% boys, median age 9.6 years, median WBC 53.0*109/L, FAB types M0 n=9, M1 n=10, M2 n=18, M3 n=9, M4 n=33, M5 n=24, M7 n=3, unknown n=16. There was a more than 100,000 fold difference in calicheamicin sensitivity between the most sensitive and the most resistant patient samples. FAB M2 samples taken at initial diagnosis (n=13) were significantly more resistant to calicheamicin compared to the other FAB types (Resistance Ratio (RR)=2.5, median LC50 0.033 vs. 0.013 μg/ml, p=0.008). Newly diagnosed AML samples were significantly more sensitive to calicheamicin compared to relapsed AML samples (RR=0.68, median LC50 0.023 vs. 0.034 μg/ml, p=0.042) (although these patients had not been treated with calicheamicin). There was strong cross-resistance between calicheamicin and the anthracyclines idarubicin (Spearmans rho = 0.73, p<0.0001, n=23), daunorubicin (rho=0.61, p<0.0001, n=103) and mitoxantrone (rho=0.52, p=0.039, n=16). In addition, there was moderate cross-resistance with etoposide (rho=0.42, p<0.0001, n=101). No cross-resistance was observed between calicheamicin and cytarabine (rho=0.11, p=0.28, n=106), 6-thioguanine (rho=0.20, p=0.054, n=97), vincristine (rho=0.12, p=0.44, n=46) or L-asparaginase (rho=0.21, p=0.16, n=45). In conclusion, the interpatient differences in calicheamicin sensitivity are the largest differences in in vitro drug sensitivity we have ever observed in pediatric AML. FAB M2 samples are 2.5 fold more resistant to calicheamicin than samples with other FAB types. Initially diagnosed pediatric AML samples are 1.5 fold more sensitive to calicheamicin than relapsed AML samples. There is marked cross-resistance between calicheamicin and the related anthracyclin compounds. Given the large differences in sensitivity to calicheamicin in pediatric AML samples, it is likely that calicheamicin resistance plays a role in resistance to Mylotarg®.

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Heinrich, Sven P., Torben Blechenberg, Christoph Reichel et Michael Bach. « The “speed” of acuity in scotopic vs. photopic vision ». Graefe's Archive for Clinical and Experimental Ophthalmology 258, n^o 12 (15 août 2020) : 2791–98. http://dx.doi.org/10.1007/s00417-020-04867-6.

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Abstract Purpose The effect of duration of optotype presentation on visual acuity measures has been extensively studied under photopic conditions. However, systematic data on duration dependence of acuity values under mesopic and scotopic conditions is scarce, despite being highly relevant for many visual tasks including night driving, and for clinical diagnostic applications. The present study aims to address this void. Methods We measured Landolt C acuity under photopic (90 cd/m2), mesopic (0.7 cd/m2), and scotopic (0.009 cd/m2) conditions for several optotype presentation durations ranging from 0.1 to 10 s using the Freiburg Acuity and Contrast Test. Two age groups were tested (young, 18–29 years, and older, 61–74 years). Results As expected, under all luminance conditions, better acuity values were found for longer presentation durations. Photopic acuity in young participants decreased by about 0.25 log units from 0.1 to 10 s; mesopic vision mimicked the photopic visual behavior. Scotopic acuities depended more strongly on presentation duration (difference > 0.78 log units) than photopic values. There was no consistent pattern of correlation between luminance conditions across participants. We found a qualitative similarity between younger and older participants, despite higher variability among the latter and differences in absolute acuity: Photopic acuity difference (0.1 vs. 10 s) for the older participants was 0.19 log units, and scotopic difference was > 0.62 log units. Conclusion Scotopic acuity is more susceptible to changes in stimulus duration than photopic vision, with considerable interindividual variability. The latter may reflect differences in aging and sub-clinical pathophysiological processes and might have consequences for visual performance during nocturnal activities such as driving at night. Acuity testing with briefly presented scotopic stimuli might increase the usefulness of acuity assessment for tracking of the health state of the visual system.

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Heinonen, E., M. Blennow, M. Blomdahl-Wetterholm, M. Hovstadius, J. Nasiell, A. Pohanka, L. L. Gustafsson et K. Wide. « Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low ». European Journal of Clinical Pharmacology 77, n^o 9 (22 mars 2021) : 1323–31. http://dx.doi.org/10.1007/s00228-021-03122-z.

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Abstract Purpose Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. Method Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. Results Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. Conclusion Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. Trial registration The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

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Garcia-Barceló, Mercè, Lok Yee Chow, Helen Fung Kum Chiu, Yun Kowk Wing, Dominic Tak Shing Lee, Kwok Lim Lam et Mary Miu Yee Waye. « Genetic Analysis of the CYP2D6 Locus in a Hong Kong Chinese Population ». Clinical Chemistry 46, n^o 1 (1 janvier 2000) : 18–23. http://dx.doi.org/10.1093/clinchem/46.1.18.

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Abstract Background: The cytochrome P450 CYP2D6 enzyme debrisoquine 4-hydroxylase metabolizes many different classes of commonly used drugs, such as tricyclic antidepressants and neuroleptics. Genetic polymorphism of the CYP2D6 gene is responsible for pronounced interindividual and interracial differences in the metabolism of these drugs. The CYP2D6*10 allele and its variants are the most frequent alleles found in Orientals, and they are responsible for diminished debrisoquine 4-hydroxylase activity because of the presence of a C188→T mutation in exon 1. Methods: One hundred nineteen Hong Kong Chinese subjects were genotyped by means of allele-specific PCR, PCR, and restriction enzyme analysis for 10 CYP2D6 alleles (CYP2D6*1, *2, *4D, *5, *8/*14, *10A, *10B, *15, *16, and J9). Results: CYP2D6*10B was the most prevalent allele, and CYP2D6*10/CYP2D6*10 was the most frequent genotype, representing 46.22% of the population. Conclusions: There was no significant difference in the prevalence of the alleles analyzed between our study and the Chinese populations genotyped previously. This is the largest study in terms of the number of CYP2D6 alleles analyzed in an Oriental population and the first one conducted in a Hong Kong Chinese population.

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Lee, Joshua F., Michelle L. Harrison, Skyler R. Brown et R. Matthew Brothers. « The magnitude of heat stress-induced reductions in cerebral perfusion does not predict heat stress-induced reductions in tolerance to a simulated hemorrhage ». Journal of Applied Physiology 114, n^o 1 (1 janvier 2013) : 37–44. http://dx.doi.org/10.1152/japplphysiol.00878.2012.

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The mechanisms responsible for heat stress-induced reductions in tolerance to a simulated hemorrhage are unclear. Although a high degree of variability exists in the level of reduction in tolerance amongst individuals, syncope will always occur when cerebral perfusion is inadequate. This study tested the hypothesis that the magnitude of reduction in cerebral perfusion during heat stress is related to the reduction in tolerance to a lower body negative pressure (LBNP) challenge. On different days (one during normothermia and the other after a 1.5°C rise in internal temperature), 20 individuals were exposed to a LBNP challenge to presyncope. Tolerance was quantified as a cumulative stress index, and the difference in cumulative stress index between thermal conditions was used to categorize individuals most (large difference) and least (small difference) affected by the heat stress. Cerebral perfusion, as indexed by middle cerebral artery blood velocity, was reduced during heat stress compared with normothermia ( P < 0.001); however, the magnitude of reduction did not differ between groups ( P = 0.51). In the initial stage of LBNP during heat stress (LBNP 20 mmHg), middle cerebral artery blood velocity and end-tidal Pco2 were lower; whereas, heart rate was higher in the large difference group compared with small difference group ( P < 0.05 for all). These data indicate that variability in heat stress-induced reductions in tolerance to a simulated hemorrhage is not related to reductions in cerebral perfusion in this thermal condition. However, responses affecting cerebral perfusion during LBNP may explain the interindividual variability in tolerance to a simulated hemorrhage when heat stressed.

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Canal, P., C. Gay, A. Dezeuze, J. Y. Douillard, R. Bugat, R. Brunet, A. Adenis, P. Herait, F. Lokiec et A. Mathieu-Boue. « Pharmacokinetics and pharmacodynamics of irinotecan during a phase II clinical trial in colorectal cancer. Pharmacology and Molecular Mechanisms Group of the European Organization for Research and Treatment of Cancer. » Journal of Clinical Oncology 14, n^o 10 (octobre 1996) : 2688–95. http://dx.doi.org/10.1200/jco.1996.14.10.2688.

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PURPOSE A pharmacokinetic study was performed during a phase II clinical trial of irinotecan (CPT-11) to confirm the pharmacokinetic profile of this drug and its metabolite and to investigate interpatient and intrapatient pharmacokinetic variations and pharmacokinetic-pharmacodynamic relationships. PATIENTS AND METHODS Twenty-six men and 21 women (mean age, 61 years) with metastatic colorectal cancer, performance status less than 3 (World Health Organization [WHO] scale), and normal renal and hepatic function were administered CPT-11 (350 mg/m2) by 30-minute intravenous (IV) infusion every 21 days. CPT-11 and its metabolites SN-38 and SN-38 glucuronide (SN-38G) were determined by high-performance liquid chromatography (HPLC) using fluorimetric detection. RESULTS The mean CPT-11 clearance and area under the concentration-time curve (AUC) were 15.2 L/h. m2 and 24,769ng. h/mL, respectively. The large difference in SN-38 and SN-38G AUCs (559 v 2,283 ng. h/mL) was suggestive of extensive glucuronidation of SN-38. Interindividual variation in the metabolic ratio ([AUCSN-38 + AUCSN-38Gl/AUCCPT-11) was marked (coefficient of variation [CV] = 51.6%] compared with intrapatient variation in this variable (CV = 32.6%). A significant relationship existed between percentage reduction in neutrophil count and the AUC of CPT-11 (r = .597, P < .001) and SN-38 (r = .559, P < .001). No relationship was identified between any pharmacokinetic parameter and delayed diarrhea or therapeutic outcome. CONCLUSION Interindividual variations in the metabolic ratio suggest interpatient variation in carboxylesterase activity. Furthermore, glucuronidation of SN-38 may also be in part responsible for the large interpatient variability in the total SN-38 AUC. Conversely, low intrapatient variation of this parameter was observed in this study, which indicates a lack of autoinduction of the carboxylesterase system. The relationship between neutropenia and both CPT-11 and SN-38 pharmacokinetic parameters confirms the results of previous studies.

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te Brake, L. H. M., R. Ruslami, H. Later-Nijland, F. Mooren, M. Teulen, L. Apriani, J. B. Koenderink et al. « Exposure to Total and Protein-Unbound Rifampin Is Not Affected by Malnutrition in Indonesian Tuberculosis Patients ». Antimicrobial Agents and Chemotherapy 59, n^o 6 (23 mars 2015) : 3233–39. http://dx.doi.org/10.1128/aac.03485-14.

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ABSTRACTNutritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis (TB) drugs. As malnutrition occurs frequently among TB patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of TB treatment. In a descriptive pharmacokinetic study in Bandung, Indonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of TB treatment. A full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. Rifampin pharmacokinetic parameters were compared between severely malnourished (BMI of <16.0 kg/m2), malnourished (BMI of <18.5 kg/m2), and well-nourished (BMI of ≥18.5 kg/m2) individuals. No difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n= 7), malnourished (n= 11), and well-nourished (n= 25) patients could be demonstrated. In addition, no significant correlation between BMI and exposure (area under the concentration-time curve from 0 to 24 h [AUC0–24] and maximum concentration of drug in serum [Cmax]) was found. Females had significantly higher total AUC0–24(geometric mean, 59.2 versus 48.2 h · mg/liter;P= 0.02) and higher unbound AUC0–24(geometric mean, 6.2 versus 4.8 h · mg/liter;P= 0.02) than males. Overall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%;n= 36). Nutritional status and BMI do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in Indonesian subjects. The large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships.

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Nazir, Shabnam, Kashif Adnan, Rukhsana Gul, Gowhar Ali, Shamim Saleha et Amjad Khan. « The effect of gender and ABCB1 gene polymorphism on the pharmacokinetics of azithromycin in healthy male and female Pakistani subjects ». Canadian Journal of Physiology and Pharmacology 98, n^o 8 (août 2020) : 506–10. http://dx.doi.org/10.1139/cjpp-2019-0569.

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In the current study, the possible outcome of gender difference and genotypic polymorphism of the ABCB1 gene encoding P-glycoprotein on the pharmacokinetics of azithromycin has been evaluated. An open-label, comparative pharmacokinetic study was done in healthy Pakistani volunteers (females (n = 8) and males (n = 8)). They were administered a single 500 mg oral dose of azithromycin. Blood samples (≈5 mL) were collected in heparinized tubes and the HPLC/MS/MS method was used to determine azithromycin plasma levels. ABCB1 polymorphism (single nucleotide polymorphisms) at C3435T, G26SST was performed using the RFLP–PCR method. The Student t test was applied to compare pharmacokinetic parameters of azithromycin between male and female human subjects (at 95% CI) using GraphPad Prism-8. A significant difference was observed in pharmacokinetic parameters between males and females, as Cmax in males (230 ± 80.2 ng/mL) was significantly higher than in females (224.9 ± 75.5 ng/mL), while [Formula: see text] was also significantly higher (p < 0.05) in males (2102 ± 200.3 ng·h−1·mL−1) compared to females (1825.7 ± 225.4 ng·h−1·mL–1). There was a significant variation in Cmax and AUC in three ABCB1 genotyping groups as well. Gender difference and ABCB1 gene polymorphisms have a significant impact on the pharmacokinetics of azithromycin, as they contribute to interindividual variability in therapeutic response.

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