Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liège University Hospital (CHU) of Liège in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naïve (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN- on peripheral blood lymphocytes using the QuantiFERON Human IFN- SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naïve HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses

Phylogenetic classification of the world's tropical forests

Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.</p

Pneumopathies interstitielles diffuses rapidement progressives (Docetaxe Amiodarone)

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocNANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Conséquences articulaires de la sélectivité d'inhibition des COXs par les AINS dans des modèles expérimentaux d'arthropathie

Les AINS constituent l'une des classes thérapeutiques les plus utilisées et restent le traitementsymptomatique de première intention dans les pathologies articulaires, inflammatoires (arthrite) ou dégénérative (arthrose). Il est largement admis que leur principal mécanisme d'action consiste à inhiber la biosynthèse des PGs par la COX. Cependant, leur utilisation s'accompagne d'effets secondaires importants, notamment au niveau gastro-intestinal. La mise en évidence de deux isoformes de COX aux fonctions distinctes a permis de décrire des profils de sélectivité d'inhibition des deux isoformes de COX différents pour les AINSclassiques (d'après des modèles d'étude cellulaire). Ceci a également permis d'émettre unehypothèse pouvant paraître simpliste: l'inhibition de COX-l, isoforme constitutive est délétère alors que l'inhibition de COX-2 inductible, notamment au cours de l'inflammation, est bénéfique. COX-2 est donc devenue une cible thérapeutique de choix et de nouvellesmolécules ont été développées avec des pouvoirs inhibiteurs de COX-2 très importants, et par conséquent avec une tolérance notamment digestive accrue. La première partie de ce travail s'est attachée à étudier la pertinence de la sélectivité d'inhibition des isoenzymes de la COX dans des modèles mimant des conditions cliniquesd'utilisation des AINS, c'est-à-dire une administration orale réitérée du médicament au coursdu processus arthritique. Cette approche devait permettre d'étudier l'influence de la maladie arthritique sur la tolérance digestive aux AINS et de poyvoir mesurer les pouvoirs inhibiteurs des molécules dans les tissus cibles. Nous avons également mesuré l' effet de ces traitements sur l'anabolisme des protéoglycanes du cartilage. Une approche comparative entre des AINS classiques et des inhibiteurs plus ou moins sélectifs de COX-2 a été entreprise. Un inhibiteur réputé préférentiel de COX-2 (Méloxicam) et un inhibiteur réputé sélectif de COX-2 (Célécoxib) ont été comparés au naproxène, AINS classique dans des modèles d'arthrite aiguë ou chronique, avec des composantes locale ou sysémique. La seconde partie de cette étude avait pour principal objectif d'étudier les conséquences d'une inhibition plus ou moins sélective de la COX sur le cartilage articulaire au cours du processus arthrosique. Cette étude s'est plus particulièrement intéressée aux effets des traitements sur la sévérité de l' atteinte arthrosique, la survie chondrocytaire et l'anabolisme du cartilage dans la mesure où des AINS ayant une tolérance digestive améliorée sont susceptibles d'être administrés au long cours chez des patients souffrant d'arthrose. Les inhibiteurs sélectifs de COX-2,se positionnent, en effet, plus que jamais, comme une alternative au paracétamol. Cependant, ils ne doivent pas produire d'effets délétères sur le cartilage. Dans cette partie de l'étude, nous souhaitions mesurer l' impact des AINS sur le métabolisme du cartilage in vivo. Nous nous sommes intéressés aux effets de deux molécules, le rofécoxib, inhibiteur sélectif de COX-2 et le ML-3000, inhibiteur mixte COX/5-LOX, sur le cartilage. Pour cela, nous avons fait appel à des modèles expérimentaux mimant une atteinte dégénérative du cartilage articulaire (arthrose induite par section ligamentaire ou par injection de monoiodoacétate ). Nous avons plus particulièrement étudié les modifications métaboliques du cartilage (synthèse des protéoglycanes) et la survie cellulaire (apoptose chondrocytaire) Cette étude a permis de démontrer l'équivalence d'efficacité d'inhibiteurs ayant des profils de sélectivité différents pour COX-2 dans des modèles expérimentaux d'arthrite. Il a été possible de mettre en évidence la chondroneutralité de ces inhibiteurs sur le cartilage articulaire dans ces mêmes modèles. L'inhibiteur sélectif de COX-2 s'est avéré chondroneutre dans le modèle d'arthrose au MIA et sans effet aggravant sur la composante apoptotique. Par contre, l'inhibiteur mixte COX/5-LOX nous a permis de créer une chondroprotection expérimentale dans le modèle d'arthrose par section ligamentaire, avec un effet anti-apoptotique marqué.NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocSudocFranceF

Genotoxic pressure of vineyard pesticides in fish : field and mesocosm surveys

International audienc

Development of a strategy to study toxicodynamic of pollutants in spawning sea turtles from the French West Indies

Sea turtles including the green turtle Chelonia mydas and the hawksbill turtle Eretmochelys imbricata are critically endangered species, facing different factors as marine pollution. There is a blatant lack of data dealing with toxicants such as metals and persistent organic pollutants (POPs) in sea turtles. We developed a strategy to apprehend levels, effects and transfer to offspring of several pollutants in sea turtles. Sampling of blood, subcutaneous tissue and eggs of 15 gravid C. mydas and E. imbricata was carried out between July and September 2008 in Martinique (Diamant’s beach) and Guadeloupe (Petite Terre and Marie-Galante). Blood was collected from the dorso-cervical sinus and subcutaneous tissue was sampled in shoulder of the spawning females using a 5 mm biopsy punch (Kai Europe GmbH, Germany). Total blood and serum were successfully taken for metal, POP and biomarker investigations. T-mercury was analyzed by DMA milestones while PCBs, DDT and chlordecone were analyzed by EDC Ni63 high performance gas chromatography HPLC. Samples of serum were analyzed for vitamins (A and E) by HPLC and for thyroid hormones (triiodothyronine and thyroxine) by radioimmunoassay. In parallel to this field study, a cell model using 3T3-L1 cell line was built up to test in vitro effects of PCBs and mercury as well as the relationship between in vitro exposure and fat mobilization. Preliminary results showed a dose-response relationship between increased Aroclor 1234 and 1252 concentrations (0.5 ppb, 1 ppb and 1.5 ppb) and adipocyte mortality (Nucleocounter). The strategy we propose here will bring further insights on levels and potential impact of pollutants on female sea turtles and their offspring.Toxicodynamic of pollutants in poikilotherm species (turtles

Utilisation de l’humour par les soignants : un lien avec la confrontation à la mort ?

International audienc

Développement d'une stratégie afin d'étudier la toxicodynamique des polluants chez les tortues marines gestantes

Toxicodynamique des polluants chez les Amniotes Sauropsidés (Chéloniens

Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey.

peer reviewedThis study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liege, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 +/- 10.4 % vs. 90.3 +/- 6.6 %, p = 0.0013; antibiotics documented 87.9 +/- 9.0 % vs. 95.6 +/- 5.1 %, p < 0.0001; and duration or review date documented 31.9 +/- 15.4 % vs. 67.7 +/- 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators