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Gruson, D.

Publications and source records attributed to Gruson, D..

3 recordsLinked to original sources

Distance-to-optimum biological drift as a new framework for interpreting routine laboratory results: a benchmark against Reference Change Values across 62 routine biomarkers

BackgroundWe propose the biological drift framework for the interpretation of biological test results: a z-score-like frame-work based on optimized and personalized reference populations and a distance-to-optimum drift metric for longitudinal interpretation relative to an estimated individual optimum. We benchmarked biological drifts against Reference Change Values (RCVs), which are used to interpret serial laboratory results by defining the minimum change expected to exceed normal within-subject biological variation (CVi). ObjectivesTo benchmark biological drifts against the classical biological-variation framework and assess their consistency with RCV thresholds across routine biomarkers. MethodsFor 62 routine biomarkers, biological drift levels were compared with RCVs after transformation to test the consistency between the two frameworks. ResultsSevere biological drifts mostly exceeded the 95% RCV threshold, indicating changes unlikely to be explained by short-term biological variation alone. In contrast, moderate drifts reached the 95% RCV threshold for approximately one in two biomarkers, suggesting that many moderate distance-to-optimum deviations may remain within expected variability, particularly for biomarkers with large within-subject variation (CVi). Results are particularly interesting for the follow-up of people with diabetes and for the management of thyroid and hepatic disorders. ConclusionsBiological drifts derived from optimized personalized reference populations are broadly consistent with the RCV framework for identifying biologically meaningful deviations from the optimum and may therefore be relevant for the monitoring of certain biomarkers across several medical conditions in clinical practice.

biochemistry↗

Cytokine profiles in adults with imported malaria: insights from the PALUREA cohort study

The increase in worldwide travel is making imported malaria a growing health concern in nonendemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. We report cytokine profiles in adults with Plasmodium falciparum malaria included in PALUREA, a prospective cohort study conducted in France between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex technology: interleukin (IL)-1, IL-1{beta}, IL-2, IL-4, IL-10, tumor necrosis factor (TNF), interferon (IFN){gamma}, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1, IL-1 {beta}, IL-2, IL-4, IFN {gamma}, and TNF, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R=0.32 [0.16-0.46]; P=0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Author SummaryPlasmodium falciparum malaria is increasingly common in nonendemic areas. Improved understanding of its pathophysiology might help to decrease mortality. We therefore routinely assayed eight cytokines in 278 adults with imported P. falciparum malaria at hospital admission; in the group with severe malaria (n=144), we repeated the assays on the next two days. The cytokine levels were often undetectable, suggesting that cytokine storm might not be a driving mechanism at the time of clinical presentation. IL-10 and macrophage migration inhibitory factor (MIF) were significantly higher in the group with severe vs. uncomplicated disease. Thus, the roles for these two cytokines in severe malaria, may deserve further investigation. A complicating factor is that greater IL-10 elevation may be a response to a heavy parasite burden and/or may promote parasite replication. IL-10 elevation that persisted over the first 2 days after admission was significantly associated with subsequent nosocomial infections in the group with severe malaria suggesting its possible role in acquired immune suppression syndrome.

immunology↗

The modulation of acute stress on Model-Free and Model-Based reinforcement learning in Gambling Disorder

Background and aimsExperiencing acute stress is common in behavioral addictions such as gambling disorder. Additionally, like most substance-induced addictions, aberrant decision-making wherein a reactive habit-induced response (conceptualized as a Model-free [MF] in reinforcement learning) suppresses a flexible goal-directed response (conceptualized as a Model-based [MB]) is also common in gambling disorder. In the current study we investigated the influence of acute stress on the balance between habitual response and the goal-directed system. MethodsA sample of N = 116 pathological gamblers (PG) and healthy controls (HC) performed an acute stress task - the Socially Evaluated Cold pressure task (SECPT) - or a control task. Self-reported stress and salivary cortisol were collected as measures of acute stress. Following the SECPT, participants performed the Two-Step Markov Task to account for the relative contribution of MB and MF strategies. Additionally, verbal working-memory and IQ measures were collected to account for their mediating effects on the orchestration between MB/MF and the impact of stress. ResultsBoth groups had comparable baseline and stress-induced cortisol response to the SECPT. Non-stressed PG displayed lower MB learning than HC. MANOVA and regression analyses showed a deleterious effect of stress-induced cortisol response on the orchestration between MB and MF learning in HC but not in PG. Neither working memory nor IQ mediated these effects. Discussion and ConclusionsDespite normal cortisol response to stress, we found an abnormal pattern of modulation of stress on the orchestration between MB and MF learning among PG.

neuroscience↗