The Long COVID experience from a patient's perspective: a clustering analysis of 27,216 Reddit posts

ObjectiveThis work aims to study the profiles of Long COVID from the perspective of the patients spontaneously sharing their experiences and symptoms on Reddit.MethodsWe collected 27,216 posts shared between July 2020 and July 2022 on Long COVID-related Reddit forums. Natural language processing, clustering techniques and a Long COVID symptoms lexicon were used to extract the different symptoms and categories of symptoms and to study the co-occurrences and correlation between them.ResultsMore than 78% of the posts mentioned at least one Long COVID symptom. Fatigue (29.4%), pain (22%), clouded consciousness (19.1%), anxiety (17.7%) and headaches (15.6%) were the most prevalent symptoms. They also highly co-occurred with a variety of other symptoms (e.g., fever, sinonasal congestion). Different categories of symptoms were found: general (45.5%), neurological/ocular (42.9%), mental health/psychological/behavioral (35.2%), body pain/mobility (35.1%) and cardiorespiratory (31.2%). Posts focusing on other concerns of the community such as vaccine, recovery and relapse and, symptom triggers were detected.ConclusionsWe demonstrated the benefits of leveraging large volumes of data from Reddit to characterize the heterogeneity of Long COVID profiles. General symptoms, particularly fatigue, have been reported to be the most prevalent and frequently co-occurred with other symptoms. Other concerns, such as vaccination and relapse following recovery, were also addressed by the Long COVID community

A Decision Support Tool based on microbial safety prediction for a better dimensioning of modified atmosphere packaging

Predicting microbial safety of fresh products in Modified Atmosphere Packaging (MAP) systems implies to take into account the dynamic of O2 and CO2 exchanges in the system and its effect on microbial growth. In this purpose we coupled mathematical models of gas transfer (permeation through packaging and solubilisation / diffusion within food) with predictive microbiology models that take into account the effect of CO2 and O2 partial pressure in headspace and corresponding dissolved concentrations in the food. This mechanistic model was validated in simplified and in real conditions using dedicated challenge-tests performed on poultry meat, fresh salmon and processed cheese, inoculated with either Listeria monocytogenes or Pseudomonas fluorescens.Once validated, this model could be used as a Decision Support Tool in order to optimize the initial packaging atmosphere (level of O2 and CO2) and / or the geometry (ratio headspace volume to food mass). This tool could also be used to identify the packaging gas permeability the most suitable for maintaining the targeted % of gas initially flushed in the pack within a given tolerance. This approach permits a better dimensioning of MAP of fresh produce by selecting the packaging material fitted to “just necessary” (and not by default the most barrier one). The connexion of this model with dedicated databases gathering gas permeabilities of commonly used packaging materials allows us to obtain as output a ranking of the most suitable materials. This tool would be very useful for all stakeholders of the fresh produce chain. A demonstration of this Decision Support Tool is here proposed with the pipeline between mathematical models and related databases

Genomic and ecogenomic characterisation of Proteus mirabilis bacteriophage

Proteus mirabilis often complicates the care of catheterized patients through the formation of crystalline biofilms which block urine flow. Bacteriophage therapy has been highlighted as a promising approach to control this problem, but relatively few phages infecting P. mirabilis have been characterized. Here we characterize five phages capable of infecting P. mirabilis, including those shown to reduce biofilm formation, and provide insights regarding the wider ecological and evolutionary relationships of these phages. Transmission electron microscopy (TEM) imaging of phages vB_PmiP_RS1pmA, vB_PmiP_RS1pmB, vB_PmiP_RS3pmA, and vB_PmiP_RS8pmA showed that all share morphologies characteristic of the Podoviridae family. The genome sequences of vB_PmiP_RS1pmA, vB_PmiP_RS1pmB, and vB_PmiP_RS3pmA showed these are species of the same phage differing only by point mutations, and are closely related to vB_PmiP_RS8pmA. Podophages characterized in this study were also found to share similarity in genome architecture and composition to other previously described P. mirabilis podophages (PM16 and PM75). In contrast, vB_PimP_RS51pmB showed morphology characteristic of the Myoviridae family, with no notable similarity to other phage genomes examined. Ecogenomic profiling of all phages revealed no association with human urinary tract viromes, but sequences similar to vB_PimP_RS51pmB were found within human gut, and human oral microbiomes. Investigation of wider host-phage evolutionary relationships through tetranucleotide profiling of phage genomes and bacterial chromosomes, indicated vB_PimP_RS51pmB has a relatively recent association with Morganella morganii and other non-Proteus members of the Morganellaceae family. Subsequent host range assays confirmed vB_PimP_RS51pmB can infect M. morganii

Identification de biomarqueurs biochimiques des états de mal épileptiques

Status epilepticus (SE) is a life-threatening prolonged epileptic seizure for which survivors frequently had neurological sequels at discharge. The objectives of my thesis work were to identify diagnosis and outcome predictive biochemical biomarkers for SE. I first found that serum S100-beta protein levels have both a good positive predictive value and a good specificity for the diagnosis of SE. Furthermore, daily serum Neuron Specific Enolase measurements revealed its ability to reflect electroencephalographic abnormalities and to predict the risk of seizure recurrence in patients admitted with refractory SE. Secondly, I evidenced, by a translational and multimodal approach, that SE is followed by disturbances in cholesterol homeostasis including a first decrease of 24-hydroxycholesterol levels and a deleterious secondary increase of the cholesterol synthesis. Finally, I applied machine learning models to clinico-biological data to predict accurately the outcome at discharge and after several months for any patient admitted to intensive care unit for a SE. My thesis work highlighted the interest of biochemical biomarkers to help in diagnosing SE, to monitor SE patients over time and to predict SE outcome.L’état de mal épileptique (EME) se définit par l’absence d’arrêt spontané d’une crise d’épilepsie et est associé à une importante mortalité et morbidité. Mon travail de thèse a consisté à rechercher des biomarqueurs biochimiques diagnostiques et pronostiques de l’EME. J’ai premièrement montré que la protéine S100-bêta dosée au niveau sérique possède une bonne valeur prédictive positive et une bonne spécificité pour le diagnostic de l’EME. De plus, des dosages quotidiens de la Neuron Specific Enolase sérique ont révélé sa capacité à refléter les anomalies électroencéphalographiques et à prédire le risque de recrudescence de crises, chez des patients admis en réanimation pour un EME réfractaire. J’ai évalué l’impact de l’EME sur le métabolisme du cholestérol chez l’homme et dans un modèle murin et montré que l’EME s’accompagnait d’une diminution précoce des concentrations de 24-hydroxycholestérol et d’une synthèse accrue secondaire délétère de cholestérol. J’ai développé à l’aide d’outils de machine learning de nouveaux modèles clinico-biologiques permettant d’optimiser l’évaluation pronostique à la sortie de réanimation et après plusieurs mois, pour tout patient admis en réanimation pour un EME. Mon travail de thèse a permis de démontrer l’intérêt des biomarqueurs biochimiques pour faciliter le diagnostic, le suivi et l’évaluation pronostique des patients en EME

Identification et caractérisation des gènes induits in vivo chez Enterococcus faecalis

Enterocoocus faecalis fait partie du microbiote commensal humain, son habitat principal étant le tractus gastro-intestinal. S il est inoffensif pour des individus en bonne santé, E. faecalis a récemment émergé en tant que cause majeure d infections nosocomiales. Dans le but de mieux comprendre le passage de la bactérie d un état commensal à celui de pathogène, nous avons développé une approche de type R-IVET (Recombination-based in vivo expression technology) pour ce microorganisme. Deux systèmes R-IVET avec différents niveaux de sensibilité ont été construits dans une souche dérivée d E. faecalis V583 et testés chez l insecte Galleria mellonella, dans des modèles murins de septicémie ou de péritonite ainsi que lors d une croissance en urine. L ensemble des résultats a conduit à l identification de 79 gènes dont l expression est activée in vivo. Parmi ceux-ci, l opéron ef_3197/6 a été montré comme étant fortement induit chez l insecte. La délétion de cette structure opéronique a démontré que le système à deux composants codé par ces gènes est essentiel au potentiel pathogène d E. faecalis chez G. mellonella. Le gène ef_0377, induit à la fois dans les modèles insecte et murins a également été étudié plus en détail, ce qui a permis de montrer que ce gène codant une protéine ankyrine était également impliqué dans la virulence. Il en est de même pour le gène ef_3282, codant la sous-unité de liaison à l ATP ClpC du complexe protéolytique Clp. Ainsi, les différents criblages R-IVET ont permis la mise en évidence de nouveaux facteurs d E. faecalis impliqués dans la persistance in vivo et le potentiel de virulence de ce pathogène opportuniste.Enterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has recently emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a R-IVET approach (Recombination-based in vivo expression technology) for this microorganism. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, in mouse bacteremia and peritonitis models and during growth in urine. Our combined results led to the identification of 79 in vivo activated genes. Among them, the ef_3197/6 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system encoded by these genes was essential to the E. faecalis pathogenic potential in G. mellonella. Gene ef_0377, induced in both insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Gene ef_3282, encoding the ATP-binding subunit ClpC from the Clp proteolytic complexe, has also been demonstrated to be involved in the pathogenic potential of this organism. Thus these different R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen.CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

Modélisation de l'impact d'un consortium microbien de fromages à pâte molle sur la croissance de L. monocytogenes et E. coli O157:H7

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Treatment with disinfectants may induce an increase in viable but non culturable populations of Listeria monocytogenes in biofilms formed in smoked salmon processing environments

International audienceThe objectives of this study were 1) to evaluate the impact of two industrial disinfectants on the viability ofListeria monocytogenespopulations in biofilm and 2) to investigate the viability state ofL. monocytogenescellspresent on contact surfaces in the smoked salmon processing environment. In thefirst step, we cultured monospecies and mixed species biofilms containingL. monocytogeneson stainless steel or polyvinyl chloride (PVC) at8 °C for 48h. The biofilms were then exposed to quaternary ammonium- and hydrogen peroxide-based disin-fectants. Residual total populations ofL. monocytogeneswere measured by qPCR, and viable culturable (VC) cellpopulations were quantified using standard microbiological culture-based techniques and by a quantitative PCR(qPCR) assay coupled with a propidium monoazide treatment. Decreases in VC populations and the appearanceof viable but non culturable (VBNC) populations were observed in response to treatment with the disinfectants.An 8 month sampling campaign in 4 smoked salmon processing plants was also carried out to detectL. mono-cytogenesin environmental samples. VBNC cells were detected mainly after the cleaning and disinfection op-erations. This study showed that industrial disinfectants did not inactivate allL. monocytogenescells on inertsurfaces. The presence of VBNC populations ofL. monocytogenesin the smoked salmon processing environment isa public health concern.1

Continuous EEG monitoring in the follow-up of convulsive status epilepticus patients: A proposal and preliminary validation of an EEG-based seizure build-up score (EaSiBUSSEs)

International audienceContinuous electroencephalography (EEG) is a major tool for monitoring patients admitted to the intensive care unit after refractory convulsive status epilepticus, following control of convulsive movements. We review the values of different EEG patterns observed in critically ill patients for prognosis and seizure risk, together with proposed criteria for non-convulsive status epilepticus diagnosis (Salzburg Criteria), the EEG scores for prognosis (Epidemiology-based Mortality score in Status Epilepticus, EMSE) and for seizure risk (2HELPS2B). These criteria and scores, based partially on continuous EEG, are not tailored to repetitively monitor the progressive build-up leading to seizure or status epilepticus recurrence. Therefore, we propose a new EEG-based seizure build-up score in status epilepticus (EaSiBUSSEs), based on the morphology and the prevalence of the EEG patterns observed in the follow-up of convulsive status epilepticus patients. It displays subscores from the least (no interictal activity) to the most associated with seizures (focal or generalized status epilepticus). We then evaluated the performance of the EaSiBUSSEs in a cohort of eleven patients who were admitted to intensive care unit for convulsive status epilepticus and who underwent continuous EEG recording. The receiver operating curve revealed good accuracy in identifying patients who would have seizures in the next 24 h, with excellent intra- and inter-rater reliability. We believe that this score is simple to perform, and suitable for repeated monitoring of EEG following refractory convulsive status epilepticus, with quantitative description of major EEG changes leading to seizures

SlyA regulator is involved in bile salts stress response of Enterococcus faecalis

International audienceSlyA is a newly transcriptional regulator identified in Enterococcus faecalis that is involved in the virulence, persistence in mouse kidneys and liver, and survival inside peritoneal macrophages. In this study we searched for environmental conditions that affect expression of the corresponding gene. Of the several stress conditions tested, only bile salts (0.08%) significantly induced transcription of slyA. In addition, the growth of ΔslyA mutant strain was significantly impaired in the presence of bile salts. To increase knowledge of SlyA regulon, real-time quantitative PCR was performed and revealed that expression of EF_3005, which encodes a choloylglycine hydrolase, is negatively regulated by SlyA

Screening of In Vivo Activated Genes in Enterococcus faecalis during Insect and Mouse Infections and Growth in Urine

International audienceEnterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a Recombination-based In Vivo Expression Technology for E. faecalis. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, during growth in urine, in a mouse bacteremia and in a mouse peritonitis model. Our combined results led to the identification of 81 in vivo activated genes. Among them, the ef_3196/7 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system was essential to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Thus these R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen