Up to 30% of the human population are asymptomatically and permanently colonized with nasal
. To successfully colonize human nares,
needs to establish solid interactions with human nasal epithelial ...cells and overcome host defense mechanisms. However, some factors like bacterial interactions in the human nose can influence
colonization and sometimes prevent colonization. On the other hand, certain host characteristics and environmental factors can predispose to colonization. Nasal colonization can cause opportunistic and sometimes life-threatening infections such as surgical site infections or other infections in non-surgical patients that increase morbidity, mortality as well as healthcare costs.
À une époque où le fait religieux prend une certaine importance dans la société contemporaine, les recherches archéologiques, en particulier préventives, ainsi que de nombreux programmes collectifs ...de recherche apportent depuis quelques années des éclairages inédits sur sa place dans les sociétés du passé. Le rapport au sacré est un phénomène universel, apparu sans doute très tôt dans l’histoire de l’humanité. Aborder cette question, c’est aborder pour une part la pensée symbolique à travers ...
Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent ...sodium current, the post-SCI increase in which contributes to spasticity. The repurposing of this drug may therefore constitute a useful potential therapeutic option for relieving SCI patients suffering from chronic traumatic spasticity.
RILUSCI is a phase 1b-2b trial designed to assess whether riluzole is a safe and biologically effective means of managing spasticity in adult patients with traumatic chronic SCI.
In this multicenter double-blind trial, adults (aged 18-65 years) suffering from spasticity after SCI (target enrollment: 90 participants) will be randomly assigned to be given either a placebo or a recommended daily oral dose of riluzole for two weeks. The latter dose will be previously determined in phase 1b of the study by performing double-blind dose-finding tests using a Bayesian continuous reassessment method. The primary endpoint of the trial will be an improvement in the Modified Ashworth Score (MAS) or the Numerical Rating Score (NRS) quantifying spasticity. The secondary outcomes will be based on the safety and pharmacokinetics of riluzole as well as its impact on muscle spasms, pain, bladder dysfunction and quality of life. Analyses will be performed before, during and after the treatment and the placebo-controlled period.
To the best of our knowledge, this clinical trial will be the first to document the safety and efficacy of riluzole as a means of reducing spasticity in patients with chronic SCI.
The clinical trial, which is already in progress, was registered on the ClinicalTrials.gov website on August 9, 2016 under the registration number NCT02859792.
Assistance Publique-Hôpitaux de Marseille.
The cortico-limbic system is critically involved in emotional responses and resulting adaptive behaviors. Within this circuit, complementary regions are believed to be involved in either the ...appraisal or the regulation of affective state. However, the respective contribution of these bottom-up and top-down mechanisms during emotion processing remains to be clarified. We used a new functional magnetic resonance imaging (fMRI) paradigm varying 3 parameters: emotional valence, emotional congruency, and allocation of attention, to distinguish the functional variation in activity and connectivity between amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Bottom-up appraisal of negative compared with positive stimuli led to a greater amygdala response and stronger functional interaction between amygdala and both dorsal ACC and DLPFC. Top-down resolution of emotional conflict was associated with increased activity within ACC and higher functional connectivity between this structure, and both the amygdala and DLPFC. Finally, increased top-down attentional control caused greater engagement of the DLPFC, accompanied by increased connectivity between DLPFC and dorsal ACC. This novel task provides an efficient tool for exploring bottom-up and top-down processes underlying emotion and may be particularly helpful for investigating the neurofunctional underpinnings of psychiatric disorders.
Les insectes, qui représentent près des quatre cinquièmes des espèces animales, ont investi tous les milieux hormis les océans (Borror et al. 1989). En 2021, l’Union européenne a lancé l’initiative « ...Liste rouge des taxinomistes » et un appel en ligne (red-list-taxinomists.eu). Le but est de constituer une base de données d’experts européens spécialistes de l’entomologie à un moment où, à l’échelle mondiale, les populations d’insectes connaissent une chute catastrophique du fait du changemen...
Therapeutic drug monitoring is recommended for several psychotropic drugs, particularly in sensitive situations such as the peripartum period. This study aimed to develop an ultra-high-performance ...liquid chromatography-tandem spectrometry method for the simultaneous quantification of 14 psychotropic drugs in human plasma and 4 in breast milk.
The samples were precipitated with methanol containing the stable isotope-labeled analogs. Chromatographic separation was performed using a Phenomenex Luna Omega Polar C18 column. Detection was performed using a triple-quadrupole mass spectrometer equipped with an electrospray ionization interface. The method was fully validated in plasma according to the European Guidelines on Bioanalytical Method Validation and partially validated in breast milk by determining the intraday precision and accuracy, linearity, lower limit of quantification, and matrix effect.
The correlation coefficients of the calibration curves were greater than 0.99. Coefficients of variation ranged from 3.05% to 14.66% and 0.62%-14.90% for internal standard-normalized matrix effect, 1.4%-14.1% and 2.1%-10.4% for intraday precision, and 3.2%-13.9% and 4.1%-9.6% for interday precision, in plasma and milk, respectively. The relative error in accuracy did not exceed ±15% for any analyte. The method was successfully applied clinically to measure the concentrations of psychotropic drugs in 952 plasma samples, among which 43% of the concentrations were out of the therapeutic range, and 13 breast milk samples, with calculated relative infant doses ranging from 0.32% to 8.18%.
To the best of the authors' knowledge, this is the first routine technique validated for the quantification of psychotropic drugs in both plasma and breast milk, allowing for treatment optimization and prevention of adherence issues, including those in breastfeeding patients.
The BDNF Val66Met gene polymorphism is a relevant factor explaining inter-individual differences to TMS responses in studies of the motor system. However, whether this variant also contributes to ...TMS-induced memory effects, as well as their underlying brain mechanisms, remains unexplored. In this investigation, we applied rTMS during encoding of a visual memory task either over the left frontal cortex (LFC; experimental condition) or the cranial vertex (control condition). Subsequently, individuals underwent a recognition memory phase during a functional MRI acquisition. We included 43 young volunteers and classified them as 19 Met allele carriers and 24 as Val/Val individuals. The results revealed that rTMS delivered over LFC compared to vertex stimulation resulted in reduced memory performance only amongst Val/Val allele carriers. This genetic group also exhibited greater fMRI brain activity during memory recognition, mainly over frontal regions, which was positively associated with cognitive performance. We concluded that BDNF Val66Met gene polymorphism, known to exert a significant effect on neuroplasticity, modulates the impact of rTMS both at the cognitive as well as at the associated brain networks expression levels. This data provides new insights on the brain mechanisms explaining cognitive inter-individual differences to TMS, and may inform future, more individually-tailored rTMS interventions.
Lithium has been used in the treatment of bipolar disorder for several decades. Treatment optimization is recommended for this drug, due to its narrow therapeutic range and a large pharmacokinetics ...(PK) variability. In addition to therapeutic drug monitoring, attempts have been made to predict individual lithium doses using population pharmacokinetics (popPK) models. This study aims to assess the clinical applicability of published lithium popPK models by testing their predictive performance on two different external datasets. Available PopPK models were identified and their predictive performance was determined using a clinical dataset (46 patients/samples) and the literature dataset (89 patients/samples). The median prediction error (PE) and median absolute PE were used to assess bias and inaccuracy. The potential factors influencing model predictability were also investigated, and the results of both external evaluations compared. Only one model met the acceptability criteria for both datasets. Overall, there was a lack of predictability of models; median PE and median absolute PE, respectively, ranged from −6.6% to 111.2% and from 24.4% to 111.2% for the literature dataset, and from −4.5% to 137.6% and from 24.9% to 137.6% for the clinical dataset. Most models underpredicted the observed concentrations (7 out of 10 models presented a negative bias). Renal status was included as a covariate of lithium’s clearance in only two models. To conclude, most of lithium’s PopPK models had limited predictive performances related to the absence of covariates of interest included, such as renal status. A solution to this problem could be to improve the models with methodologies such as metamodeling. This could be useful in the perspective of model-informed precision dosing.
Dynamic Functional Connectivity (dFC) in the resting state (rs) is considered as a correlate of cognitive processing. Describing dFC as a flow across morphing connectivity configurations, our notion ...of dFC speed quantifies the rate at which FC networks evolve in time. Here we probe the hypothesis that variations of rs dFC speed and cognitive performance are selectively interrelated within specific functional subnetworks.
In particular, we focus on Sleep Deprivation (SD) as a reversible model of cognitive dysfunction. We found that whole-brain level (global) dFC speed significantly slows down after 24h of SD. However, the reduction in global dFC speed does not correlate with variations of cognitive performance in individual tasks, which are subtle and highly heterogeneous. On the contrary, we found strong correlations between performance variations in individual tasks –including Rapid Visual Processing (RVP, assessing sustained visual attention)– and dFC speed quantified at the level of functional sub-networks of interest. Providing a compromise between classic static FC (no time) and global dFC (no space), modular dFC speed analyses allow quantifying a different speed of dFC reconfiguration independently for sub-networks overseeing different tasks. Importantly, we found that RVP performance robustly correlates with the modular dFC speed of a characteristic frontoparietal module.
•Sleep Deprivation (SD) slows down the random walk in FC space implemented by Dynamic Functional Connectivity (dFC) at rest.•Whole-brain level slowing of dFC speed does not selectively correlate with fine and task-specific changes in performance.•We quantify dFC speed separately for different link-based modules coordinated by distinct regional “meta-hubs”.•Modular dFC speed variations capture subtle and task-specific variations of cognitive performance induced by SD.
« Il n’y avait rien qui fût plus à cœur à une ville que le souvenir de sa fondation. »Numa Denis Fustel de Coulanges, La Cité antique, 1864. L’archéologie urbaine – l’archéologie de la ville – a pris ...son essor en Europe, et en France en particulier, voici une quarantaine d’années. À la suite des destructions massives de la Seconde Guerre mondiale et des travaux de reconstruction (qui ne donnèrent que très rarement lieu à observations), la politique de rénovation des centres historiques dans l...
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