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To describe a patient with hypertensive herpetic uveitis complicated by arterial retinal occlusions and a decompression retinopathy revealing a sickle cell trait.Case report.A 24-year-old African man presented with a hypertensive herpetic keratouveitis. A brutal lowering of the intraocular pressure (IOP) by systemic acetazolamide resulted in a ocular decompression retinopathy and multiple arterial occlusions involving the macular and the mid-periphery retina. A hemoglobin electrophoresis revealed a sickle cell trait.Under rare circumstances, vaso occlusive events can occur in patients with a sickle cell trait. We identified high IOP and acetazolamide to be responsible of an increased blood viscosity and a reduction of the vessels' caliber, resulting in sickling and arterial retinal occlusions. We recommend a thorough anamnesis and a sickle cell screening for patients of African or Mediterranean descent with acute elevated IOP, especially if they have to be treated with carbonic anhydrase inhibitors.

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock. The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M. Sí

IntroductionPrevious studies have demonstrated the effectiveness of therapeutic repetitive transcranial magnetic stimulation (rTMS) to treat pharmacoresistant depression. Nevertheless, these trials have primarily focused on the therapeutic and neurophysiological effects of rTMS following a long-term treatment course. Identifying brain-based biomarkers of early rTMS therapeutic response remains an important unanswered question. In this pilot study, we examined the effects of rTMS on individuals with pharmacoresistant depression using a graph-based method, called Functional Cortical Networks (FCN), and serial electroencephalography (EEG). We hypothesized that changes in brain activity would occur early in treatment course.MethodsA total of 15 patients with pharmacoresistant depression underwent five rTMS sessions (5Hz over the left dorsolateral prefrontal cortex, 120%MT, up to 4,000 pulses/session). Five participants received additional rTMS treatment, up to 40 sessions. Resting EEG activity was measured at baseline and following every five sessions, using 64-channel EEG, for 10 minutes with eyes closed. An FCN model was constructed using time-varying graphs and motif synchronization. The primary outcome was acute changes in weighted-node degree. Secondary outcomes included serial FFT-based power spectral analysis and changes in depressive symptoms measured by the 9-Item Patient Health Questionnaire (PHQ-9) and the 30-item Inventory of Depressive Symptoms-Self Report (IDS-SR).ResultsWe found a significant acute effect over the left posterior area after five sessions, as evidenced by an increase in weighted-node degree of 37,824.59 (95% CI, 468.20 to 75,180.98) and a marginal enhancement in the left frontal region (t (14) = 2.0820, p = 0.056). One-way repeated measures ANOVA indicated a significant decrease in absolute beta power over the left prefrontal cortex (F (7, 28) = 2.37, p = 0.048) following ten rTMS sessions. Furthermore, a significant clinical improvement was observed following five rTMS sessions on both PHQ-9 (t (14) = 2.7093, p = 0.017) and IDS-SR (t (14) = 2.5278, p = 0.024) and progressed along the treatment course.DiscussionOur findings suggest that FCN models and serial EEG may contribute to a deeper understanding of mechanisms underlying rTMS treatment. Additional research is required to investigate the acute and serial effects of rTMS in pharmacoresistant depression and assess whether early EEG changes could serve as predictors of therapeutic rTMS response.

We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers’ data are close to physicians’ data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age and age at first words. Each of the two datasets provide complementary knowledge. We confirmed that symptoms are similar to those in the literature and provide more details on feeding difficulties. Caregivers considered that the symptom attention-deficit/hyperactivity disorder was most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention-deficit/hyperactivity disorder, anxiety and sleep disorders need to be treated. In addition, we demonstrate preliminary evidence of a mild genome-wide DNA methylation profile in patients carrying mutations in DDX3X.

The molecular mechanisms induced by hypoxia are misunderstood in non-small cell lung cancer (NSCLC), and above all the hypoxia and RASSF1A/Hippo signaling relationship.We confirmed that human NSCLC (n=45) as their brain metastases (BM) counterpart are hypoxic since positive with CAIX-antibody (target gene of Hypoxia-inducible factor (HIF)). A severe and prolonged hypoxia (0.2% O2, 48h) activated YAP (but not TAZ) in Human Bronchial Epithelial Cells (HBEC) lines by downregulating RASSF1A/kinases Hippo (except for NDR2) regardless their promoter methylation status. Subsequently, the NDR2-overactived HBEC cells exacerbated a HIF-1A, YAP and C-Jun-dependent-amoeboid migration, and mainly, support BM formation. Indeed, NDR2 is more expressed in human tumour of metastatic NSCLC than in human localized NSCLC while NDR2 silencing in HBEC lines (by shRNA) prevented the xenograft formation and growth in a lung cancer-derived BM model in mice.Collectively, our results indicated that NDR2 kinase is over-active in NSCLC by hypoxia and supports BM formation. NDR2 expression is thus a useful biomarker to predict the metastases risk in patients with NSCLC, easily measurable routinely by immunohistochemistry on tumour specimens.

In current sensor-based monitoring solutions, each application involves a customized deployment and requires significant configuration efforts to adapt to changes in the sensor field. This becomes particularly problematic for massive deployments of battery-powered monitoring sensors.In this paper, we propose a generic solution for LPWAN sensors emissions scheduling, to ensure overall regular sensor data emissions over time (at a rate chosen by the user), while limiting management costs incurred by sensors' arrivals and departure. Our objectives include monitoring quality that we evaluate through a ``diversity'' metric encompassing that information value depletes with time, plus management cost quantified by the number of orders sent to sensors.Modeling arrivals and departures as random processes, we compute those performance metrics as functions of the overall data reception period selected, and evaluate them against alternative scheduling methods. We show that our solution is better suited for Massive IoT contexts.

EDITORIAL Ce numéro sur les approches critiques a été longtemps désiré dans la revue. Après 13 ans d’existence, il voit enfin le jour. C’est l’occasion pour le comité de rédaction d’Entreprendre & Innover de repenser collectivement ce qui l’anime et de s’interroger sur la dimension critique du positionnement de la revue. Le comité de rédaction est composé de 22 chercheurs et 11 experts professionnels de l’entrepreneuriat et de l’innovation et se réunit 4 fois par an. Tous les membres du comité ont participé à la rédaction collective de cette tribune-manifeste, à travers une procédure d’écriture collaborative.

This study sought to assess 18 F-fludarabine ( 18 F-FLUDA) PET/CT's ability in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs).Patients harboring either PCNSL (n = 8) before any treatment, PCNSL treated using corticosteroids (PCNSLh; n = 10), or GBM (n = 13) were investigated with conventional MRI and PET/CT, using 11 C-MET and 18 F-FLUDA. The main parameters measured with each tracer were SUV T and T/N ratios for the first 30 minutes of 11 C-MET acquisition, as well as at 3 different times after 18 F-FLUDA injection. The early 18 F-FLUDA uptake within the first minute of injection was equally considered, whereas this parameter was combined with the later uptakes to obtain R FLUDA 2 and R FLUDA 3 ratios.No significant differences in 11 C-MET uptakes were observed among PCNSL, PCNSLh, and GBM. With 18 F-FLUDA, a clear difference in dynamic GBM uptake was observed, which decreased over time after an early maximum, as compared with that of PCNSL, which steadily increased over time, PCNSLh exhibiting intermediate values. The most discriminative parameters consisting of R FLUDA 2 and R FLUDA 3 integrated the early tracer uptake (first 60 seconds), thereby provided 100% specificity and sensitivity.18 F-FLUDA was shown to likely be a promising radiopharmaceutical for differentiating PCNSL from other malignancies, although a pretreatment with corticosteroids might compromise this differential diagnostic ability. The diagnostic role of 18 F-FLUDA should be further investigating, along with its potential of defining therapeutic strategies in patients with PCNSL, while assessing the treatments' effectiveness.

Robenacoxib is a veterinary-approved non-steroidal anti-inflammatory drug (NSAID) of the coxib group. It possesses anti-hyperalgesic, anti-inflammatory and anti-pyretic properties. Robenacoxib inhibits the cyclooxygenase (COX)-2 isoform of COX selectively (in vitro IC

“Living on borders and in margins, keeping intact one’s shifting and multiple identity and integrity, is like trying to swim in a new element, an alien element.”Gloria Anzaldúa, Borderlands/La Frontera: The New Mestiza, Prefacio Los artículos que constituyen este dossier nacen del encuentro científico que se realizó del 6 al 8 de julio de 2022 en Madrid en el marco de las 13as Jornadas de los Jóvenes Americanistas. Nuestr...

Cet article s’attache à l’examen du problème du caractère logiquement présaussurien d’une linguistique chronologiquement post-saussurienne: le structuralisme. Nous nous efforçons ainsi de faire apparaître la radicale différence de problématiqueséparant la théorie saussurienne de la langue, étiologique, de sa réélaboration structuraliste, qui apparaît alors, par récurrence, «analytique», donc empirique. Nous nous attachons ensuite à mettre en évidence les enjeux des concepts saussuriens de système et de valeur, à savoir la rupture avec la représentation commune de la langue comme une entité et la théorisation du rapport son/sens constitutif du signe et de la langue, avant de proposer une explication de ce recouvrement de la rupture saussurienne par le structuralisme et une large part de la linguistique ultérieure.

Background For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. Objective To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Study design Experimental study. Methods Drug plasma and urine concentrations following single intravenous (i.v.) administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 h for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the International Screening Limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/ml, urine; 100 ng/ml) RESULTS: For a regimen of 1.1 mg/kg BW q 24 h, the IPC and IUC values were 2.0 and 73.0 ng/ml, respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 h after a single 1.1 mg/kg dose administration, 149 h and 199 h after multiple doses over 5 days at either 24- or 12-h intervals, respectively. Corresponding detection times in urine were 46 h, 68 h and 104 h, respectively. Main limitation Only female horses were investigated. Conclusions Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.

Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.

INTRODUCTION We aimed to evaluate the performance of the fully automated multiparameter CN-6000 hemostasis analyzer. METHODS Performance evaluation of the CN-6000 analyzer was conducted for 10 tests including prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen level, anti-Xa activity, and antithrombin activity using a unique portfolio of liquid ready-to-use reagents. Precision, sample and reagent carryovers, throughput, and sample turnaround time (STAT) function were prospectively assessed. Results from 343 samples (normal subjects, critically ill patients, patients receiving anticoagulants, subjects with high or low fibrinogen levels, and patients with decreased levels of factor II, V, VII, and X) were compared to those obtained on the STA-R Max 2® analyzer using dedicated reagents. RESULTS Total precision (coefficient of variation) was below 7% for all parameters in both normal and pathological ranges. For all analyzed parameters, results obtained on the CN-6000 were strongly correlated with those obtained on the STA-R Max 2®analyzer. Agreement between both instruments was excellent for all assays. The CN-6000 demonstrated a 30% higher throughput compared to the STA-R Max 2® (258 vs 185 tests per hour for a panel of tests including PT, aPTT, fibrinogen, factor V, anti-Xa, and D-Dimer). STAT turnaround time for critical care samples testing was

Avec la perspective du retour de la haute intensite, et alors que l’actualisation strategique a confirme la pertinence d’un modele complet d’armee, une remontee en puissance s’impose : il s’agit de pouvoir agir avec succes dans un environnement conteste en maitrisant l’attrition, et d’operer un effet d’entrainement sur nos partenaires. Retrouver une masse critique suffisante, sans renoncer aux technologies de rupture, n’est pas un objectif irrealiste. D’abord, le rendement de la masse operationnelle peut etre optimise. Ensuite, des marges de manœuvre peuvent etre trouvees, avec une approche equilibree de la technologie, le retour a une certaine differenciation capacitaire, et une recherche de plus grandes synergies a l’international.

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Schizophreniais a severe mental disorder associated with persistent or recurrent psychosis, hallucinations, delusions, and thought disorders that affect approximately 26 million people worldwide, according to the World Health Organization (WHO). Several studies encompass machine learning and deep learning algorithms to automate the diagnosis of this mental disorder. Others study schizophrenia brain networks to get new insights into the dynamics of information processing in patients suffering from the condition. In this paper, we offer a rigorous approach with machine learning and deep learning techniques for evaluating connectivity matrices and measures of complex networks to establish an automated diagnosis and comprehend the topology and dynamics of brain networks in schizophrenia patients. For this purpose, we employed an fMRI and EEG dataset in a multimodal fashion. In addition, we combined EEG measures, i.e., Hjorth mobility and complexity, to complex network measurements to be analyzed in our model for the first time in the literature. When comparing the schizophrenia group to the control group, we found a high positive correlation between the left superior parietal lobe and the left motor cortex and a positive correlation between the left dorsal posterior cingulate cortex and the left primary motor. In terms of complex network measures, the diameter, which corresponds to the longest shortest path length in a network, may be regarded as a biomarker because it is the most important measure in a multimodal fashion. Furthermore, the schizophrenia brain networks exhibit less segregation and lower distribution of information. As a final result, EEG measures outperformed complex networks in capturing the brain alterations associated with schizophrenia. As a result, our model achieved an AUC of 100%, an accuracy of 98% for the fMRI, an AUC of 95 %, and an accuracy of 95% for the EEG data set. These are excellent classification results. Furthermore, we investigated the impact of specific brain connections and network measures for these results, which helped us better describe changes in the diseased brain.

Due to the restrictions of its use, Bisphenol A (BPA) has been replaced by many structurally related bisphenols (BPs) in consumer products. The endocrine disrupting potential similar to that of BPA has been described for several bisphenols, there is therefore an urgent need of toxicokinetic (TK) data for these emerging BPs in order to evaluate if their internal exposure could increase the risk of endocrine disruption. We investigated TK behaviors of eleven BPA substitutes (BPS, BPAF, BPB, BPF, BPM, BPZ, 3-3BPA, BP4-4, BPAP, BPP, and BPFL) by intravenous and oral administrations of mixtures of them to piglets and serial collection of blood over 72 h and urine over 24 h, to evaluate their disposition. Data were analyzed using nonlinear mixed-effects modeling and a comparison was made with TK predicted by the generic model HTTK package. The low urinary excretion of some BPs, in particular BPM, BPP and BPFL, is an important aspect to consider in predicting human exposure based on urine biomonitoring. Despite their structural similarities, for the same oral dose, all BPA analogues investigated showed a higher systemic exposure (area under the plasma concentration-time curve (AUC) of the unconjugated Bisphenol) than BPA (2 to 4 fold for 3-3BPA, BPAF, BPB and BPZ, 7-20 fold for BP4-4, BPAP, BPP, BPFL, BPF and BPM and 150 fold for BPS) due mainly to a considerable variation of oral bioavailability (proportion of BP administered by oral route that attains the systemic circulation unchanged). Given similarities in the digestive tract between pigs and humans, our TK data suggest that replacing BPA with some of its alternatives, particularly BPS, will likely lead to higher internal exposure to potential endocrine disruptive compounds. These findings are crucial for evaluating the risk of human exposure to these emerging BPs.

To report two cases of multiple evanescent white dot syndrome (MEWDS) following COVID-19 vaccination with the BNT162b2 mRNA vaccine.Two case reports. Case-1: A 40-yo Caucasian male, complained of blurred and decrease of vision in his left eye (OS) one week after the first dose of the BNT162b2 mRNA SARS-CoV-2 vaccine. Funduscopic examination OS showed multiple granular white dots with an aspect of foveal granularity. Case-2: A 23-yo woman also presented with defective and decrease of vision OS. She received her first dose of the BNT162b2 mRNA SARS-CoV-2 vaccine ten days before. Dilated fundus examination OS showed altered macular reflex with an aspect of foveal granularity.Multimodal imaging showed features of MEWDS in both cases. The anomalies found resolved spontaneously after 6 weeks.Inflammation and immune dysregulation induced by COVID-19 mRNA vaccine or its adjuvants could be involved in ocular adverse effects.

Acute ischemic stroke results in an ischemic core surrounded by a tissue at risk, named the penumbra, which is potentially salvageable. One way to differentiate the tissues is to measure the hypoxia status. The purpose of the current study is to correlate the abnormal brain tissue volume derived from magnetic resonance-based imaging of brain oxygen saturation (S

Resume Objectifs Une enquete a ete menee dans les maternites de la Guyane francaise en 2017–2018 sur les consommations de tabac, d’alcool et de pemba (argile) ainsi que sur les violences et la perception de situations negatives au cours de la grossesse. Methodes Un questionnaire a ete concu interrogeant sur les consommations, le vecu de la grossesse, les conditions sociodemographiques des femmes en post-partum. Il comporte egalement des questions du T-Ace ainsi que d’autres visant a reperer les situations a risques pendant les grossesses. Resultats Les 789 femmes interrogees etaient, en moyenne, plus jeunes a l’accouchement qu’en France metropolitaine, moins souvent mariees et scolarisees, plus frequemment etrangeres, notamment Haitiennes ou Surinamiennes. Parmi elles, 22 % avaient ete victimes de violences au cours de leur vie. Elles se distinguaient du profil moyen par leur langue maternelle, etat matrimonial, nationalite, et sources de revenus. Un groupe sur les trois degages se demarquait par la part des victimes de violences (pres 50 %). Les femmes y etaient le plus souvent etrangeres, non consommatrices de substances psychoactives, residentes de la region de Cayenne, celibataires avec des enfants, disposant d’un faible niveau d’education, et avec des difficultes a faire face a cette grossesse. Conclusion Au sein de ce groupe de femmes victimes de violences, un sous-groupe se degage cumulant des facteurs de vulnerabilite : precarite, celibat, nationalite etrangere, absence de ressources et de suivi medical, migration recente. Ayant davantage recours a des IVG repetees, elles constituent egalement un groupe plus a risques de maladies sexuellement transmissibles.

Distinction between language and languages is a common structuralist one. Not only can we find it in the hjelmslevian, jakobsonian and benvenistian theories, where it constitutes an axis of elaboration, but what is more inexpected is that it is also present in Martinet’s work, in spite of a sharp criticism of the very notion of language and of the jakobsonian and chomskyan universalist problematics. Saussurean theory shows us that this distinction is inescapable, as soon as language is presupposed instead of being defined. Saussurean definition of language (langue) implies a quite different distinction: between language (langage), the language (langue) and idioms, and this distinction throws a new light on the problematics of general grammar.

Apres la traduction en francais de la correspondance de Nicolas Troubetzkoy (1890-1938) avec Roman Jakobson (1896 1982), qui ne contient que quelques doubles ou brouillons ecrits par ce dernier, apres la publication en francais de la correspondance entre Jakobson et Claude Levi-Strauss (1908-2009) par Emmanuelle Loyer et Patrice Maniglier puis celle de 34 lettres supplementaires en langue originale par Pierre-Yves Testenoire, cet ouvrage rend accessible a la communaute scientifique une autre ...

L’objet et la problematique de Chapters of Dependency Grammar sont clairement exposes dans l’introduction de l’ouvrage, « Aspects of the theory and history of dependency grammar », redigee par les directeurs de l’ouvrage. Andras Imrenyi et Nicolas Mazziotta distinguent tout d’abord entre deux cadres possibles pour l’analyse syntaxique, respectivement fondes sur la dependance et sur la constituance, celui des grammaires de dependance et celui des grammaires de la structure de la phrase. Ces de...

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p

In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (IV) dose of 0.2 mg/kg DIA Plasma and urine samples were collected at specified intervals until 16 and 26 days post-administration, respectively. Samples were analysed by a sensitive liquid chromatography-electrospray ionization/tandem mass spectrometry method. DIA showed a triphasic elimination pattern in the horse. The mean plasma clearance of DIA was 5.9 ml/min/kg, and the plasma elimination half-life in the terminal phase was 19.9 h. Applying the Toutain model approach, an effective plasma concentration of DIA was estimated at 24 ng/ml, and irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were computed to 0.047 and 0.1 ng/ml, respectively. The detection time according to the European Horserace Scientific Liaison Committee (EHSLC), that is the time for which observed DIA plasma concentrations of all investigated horses were below the IPC was 10 days. Using Monte Carlo Simulations, it was estimated that concentrations of DIA in plasma would fall below the IPC 18 days after the DIA administration for 90% of horses. However, in the present study, a single administration of DIA could be detected for 24 days in urine via the presence of OXA, its dominant metabolite.

Heteroresistance corresponds to the presence, in a bacterial isolate, of an initial small subpopulation of bacteria characterized by a significant reduction in their sensitivity to a given antibiotic. Mechanisms of heteroresistance versus resistance are poorly understood. The aim of this study was to explore heteroresistance in