Place des nouvelles technologies dans l'enseignement de la physique-chimie

Après avoir replacé l'évolution de l'utilisation de l'ordinateur dans le contexte des programmes, deux exemples montrent des aspects pédagogiques différents des usages de l'outil informatique tel qu'il s'est intégré dans les pratiques des enseignants. Cette évolution se poursuit avec des produits beaucoup plus riches, en images en particulier, et des moyens de communications à grande échelle. Ces changements ont conduit à s'interroger sur les connaissances indispensables des élèves ainsi que sur les possibilités de transférer les expériences acquises au travers des formations des enseignants

Effect of aneurysm size on procedure-related rupture in patients with subarachnoid hemorrhage treated with coil occlusion

Objective: Procedure-related rupture is one of the most feared complications in treating patients with cerebral aneurysm. The primary aim of this study was to estimate the effect of aneurysm size on procedure-related rupture. We also estimated its effect on peri-procedural thromboembolic events. Methods: This observational study was conducted using routinely-collected health data on patients admitted for subarachnoid hemorrhage and treated with aneurysm coil occlusion in the CHU de Québec — Enfant-Jésus hospital from January 1st, 2000 until sample size was reached. Patients were identified from the Discharge Abstract Database using the Canadian Classification of Health codes. Assessment of complications was blind to aneurysm size. Logistic regression models were performed to test associations between aneurysm size and procedure-related rupture or peri-procedural thromboembolic events, and between both procedure-related rupture and thromboembolic events and patients' outcomes. Results: This study included 532 aneurysms treated with coil occlusion in 505 patients. Procedure-related rupture occurred in 34 patients (6.7%) and thromboembolic events in 53 (10.5%) patients. Aneurysms of 2 to 3 mm inclusively were not more significantly associated with procedure-related rupture or thromboembolic events than those larger than 3 mm (OR 1.02, 95% CI: 0.9–1.16, p = 0.78 and OR 1.06, 95% CI: 0.96–1.17, p = 0.3, respectively). However, procedure-related rupture had a significant effect on patient mortality (OR 3.86, 95% CI: 1.42–10.53, p < 0.01). Conclusions: Very small aneurysm size should not preclude aneurysm coil occlusion. Every measure should be taken to prevent procedure-related rupture as it is strongly associated with higher mortality

Les impacts des changements climatiques sur la santé au Québec : l’exemple de l’Estrie

L’Organisation mondiale de la Santé (OMS) soutient que les changements climatiques représentent la plus grande menace pour la santé dans le monde au 21e siècle. Ceux-ci influencent négativement plusieurs déterminants sociaux et environnementaux de la santé comme l’accessibilité à la nourriture et la qualité de cette dernière, l’eau et l’air. Blessures, impacts psychosociaux, aggravation de maladies respiratoires, malnutrition, maladies infectieuses, décès : les conséquences sanitaires sont susceptibles d’affecter les populations sur tous les continents. Le Canada se réchauffe deux fois plus rapidement que la moyenne mondiale en raison de sa proximité au pôle Arctique, où le réchauffement est accéléré comparativement à l’équateur (Bush et Lemmen, 2019). Ainsi, le Québec n’est certainement pas à l’abri des changements climatiques. Dans le Sud de la province, les températures moyennes observées ont augmenté de plus d’un degré depuis 1970 et des répercussions se font déjà sentir dans notre environnement. Ce réchauffement, accompagné d’une plus grande variabilité du climat (augmentation du risque d’orages, de tempêtes et d’extrêmes hydrométéorologiques en général), représente un défi grandissant pour les professionnel.le.s de la santé. Dans la région de l’Estrie, les professionnel.le.s de santé publique ont effectué une analyse qui leur ont permis d’identifier quatre principaux problèmes environnementaux associés aux changements climatiques, soit : les vagues de chaleur; les inondations; les tiques à pattes noires; le pollen de l’herbe à poux. Ces problèmes ont des impacts importants sur la santé, c’est-à-dire potentiellement graves ou qui touchent un grand nombre de personnes. Le stress et les pertes (humaines et matérielles) engendrées par ces différents problèmes environnementaux peuvent aussi représenter une source majeure de problèmes psychologiques significatifs pouvant persister dans le temps. De plus, ces impacts sont variables selon les différents contextes sociaux des individus et des communautés, générant des inégalités sociales de santé

Theranostic 64Cu-DOTHA2-PSMA allows low toxicity radioligand therapy in mice prostate cancer model

IntroductionWe have previously shown that copper-64 (64Cu)-DOTHA2-PSMA can be used for positron emission tomography (PET) imaging of prostate cancer. Owing to the long-lasting, high tumoral uptake of 64Cu-DOTHA2-PSMA, the objective of the current study was to evaluate the therapeutic potential of 64Cu-DOTHA2-PSMA in vivo.MethodsLNCaP tumor-bearing NOD-Rag1nullIL2rgnull (NRG) mice were treated with an intraveinous single-dose of 64Cu-DOTHA2-PSMA at maximal tolerated injected activity, natCu-DOTHA2-PSMA at equimolar amount (control) or lutetium-177 (177Lu)-PSMA-617 at 120 MBq to assess their impact on survival. Weight, well-being and tumor size were followed until mice reached 62 days post-injection or ethical limits. Toxicity was assessed through weight, red blood cells (RBCs) counts, pathology and dosimetry calculations.ResultsSurvival was longer with 64Cu-DOTHA2-PSMA than with natCu-DOTHA2-PSMA (p &lt; 0.001). Likewise, survival was also longer when compared to 177Lu-PSMA-617, although it did not reach statistical significance (p = 0.09). RBCs counts remained within normal range for the 64Cu-DOTHA2-PSMA group. 64Cu-DOTHA2-PSMA treated mice showed non-pathological fibrosis and no other signs of radiation injury. Human extrapolation of dosimetry yielded an effective dose of 3.14 × 10-2 mSv/MBq, with highest organs doses to gastrointestinal tract and liver.DiscussionCollectively, our data showed that 64Cu-DOTHA2-PSMA-directed radioligand therapy was effective for the treatment of LNCaP tumor-bearing NRG mice with acceptable toxicity and dosimetry. The main potential challenge is the hepatic and gastrointestinal irradiation

Preclinical evaluation of the radioligands 64Cu-DOTHA2-PSMA and 64Cu/177Lu-CT-PCTA-PSMA as theranostic agents for prostate cancer

L’antigène membranaire prostatique spécifique (PSMA) peut être ciblé par des radioligands pour réaliser une imagerie sensible par tomographie par émission de positrons (TEP) du cancer de la prostate ou pour le traiter par endoradiothérapie. Le 64Cu est un émetteur de positrons (imagerie) et d’électrons β- et Auger (thérapie) de demi-vie de 12,7h produit par cyclotron. L’objectif général de cette thèse était de faire l’évaluation préclinique de deux nouveaux radioligands théranostiques pour le cancer de la prostate, le 64Cu-DOTHA2-PSMA et la paire 64Cu/lutétium-177 (177Lu)-CT-PCTA-PSMA, afin de surmonter les défis rencontrés par les précédents radioligands au 64Cu ciblant le PSMA. Tout d’abord, la caractérisation du 64Cu-DOTHA2-PSMA a montré sa stabilité. En TEP, sa captation tumorale est spécifique et a atteint un maximum de 23,8 % de l’activité injectée par centimètre cube (%AI/cc) 4h après l’injection. Sa captation rénale était faible et sa clairance urinaire rapide en opposition à une captation hépatique plus importante et une clairance hépatobiliaire plus lente. Le 64Cu-DOTHA2-PSMA a prolongé significativement la survie en comparaison à l’agent contrôle non radioactif et sans différence significative avec le produit le plus utilisé en clinique, le 177Lu-PSMA-617. Le suivi de l’état général et des globules rouges ainsi que l’analyse pathologique des reins, du foie et des glandes salivaires des souris de l’étude de survie ont montré peu de signes de toxicité. La dose efficace du 64Cu-DOTHA2-PSMA a été estimée à 3,14 × 10-2 mSv/MBq chez l’humain et les doses aux organes sont comparables à celles rapportées en littérature. En ce qui concerne la paire 64Cu/177Lu-CT-PCTA-PSMA, les produits étaient également stables, mais l’agent marqué au 64Cu a montré une faible captation tumorale en imagerie (2,92 %AI/cc après 1h et 1,26 %AI/cc après 4h). L’imagerie par TEP au gallium-68 (68Ga)-CT-PCTA-PSMA a été explorée et a montré une captation tumorale similaire (2,81 %AI/cc après 1h). La principale retombée possible de ce projet est la translation clinique d’agents théranostiques pour améliorer la prise en charge du cancer de la prostate. Le 64Cu-DOTHA2-PSMA a montré des résultats plus intéressants, ayant notamment un potentiel pour l’imagerie de la loge prostatique et la thérapie. Limiter l’impact de sa distribution hépatique et gastro-intestinale élevée sera un défi à surmonter pour son application théranostique. Malgré les résultats moins prometteurs de la paire 64Cu/177Lu-CT-PCTA-PSMA, des avenues pourront être explorées pour en améliorer le potentiel.Abstract : Prostate specific membrane antigen (PSMA) can be targeted by radioligands in order to achieve sensible imaging by positron emission tomography (PET) of prostate cancer or to achieve its endoradiotherapy. Copper-64 (64Cu) is a positron (imaging), and β- and Auger electron emitter (therapy) with a 12.7h half-life produced by cyclotron. The broad objective of this thesis was to preclinically evaluate novel theranostic radioligands, 64Cu-DOTHA2-PSMA and the pair 64Cu/lutetium-177 (177Lu)-CT-PCTA-PSMA, to overcome challenges faced by precedent 64Cu PSMA radioligands. Firstly, 64Cu-DOTHA2-PSMA’s characterization showed its stability. On PET imaging, its tumoral uptake was specific and reached a maximum of 23.8% of injected activity per centimeter cube (%IA/cc) at 4h post-injection. Renal uptake was low and urinary clearance was fast in opposition to high liver uptake and slow hepatobiliary clearance. 64Cu-DOTHA2-PSMA increased survival significantly in comparison to the control agent and non significantly in comparison to the most clinically used agent, 177Lu-PSMA-617. General well-being, red blood cells counts and pathology analysis of kidney, liver and salivary glands in survival assays mice showed low signs of toxicity. The effective dose was estimated to 3.14 × 10-2 mSv/MBq in human with organ doses comparable to the values reported in the literature. Regarding the 64Cu/177Lu-CT-PCTA-PSMA pair, both agents were stable, but 64Cu-CT-PCTA-PSMA showed low tumoral uptake on PET imaging (2.92 %AI/cc after 1h p.i. and 1.26 %IA/cc after 4h). Gallium-68 (68Ga)-CT-PCTA-PSMA PET imaging was explored and showed a similar tumoral uptake (2.81 %IA/cc at 1h p.i.). The main possible impact of this project is the clinical translation of novel theranostic agents to improve prostate cancer care. 64Cu-DOTHA2-PSMA showed the most interesting results, notably for prostate bed imaging and for endoradiotherapy. For its application, the main challenge to overcome will be the possible consequences of its high hepatic and gastrointestinal distribution. 64Cu/177Lu-CT-PCTA-PSMA imaging results were less promising, but it could be possible to improve the compound’s potential

Place des nouvelles technologies dans l'enseignement de la physique-chimie

After presenting the evolution of computer use in the context of the official curriculum, we give two examples showing the different pedagogical aspects of uses of the computer tool within teaching practices. This evolution continues with products which are richer in images and ways of communication at a large scale. These changes lead to ask questions about pupils’ essential knowledge and about the possibilities to transfer experiences acquired through teacher training.Après avoir replacé l’évolution de l’utilisation de l’ordinateur dans le contexte des programmes, deux exemples montrent des aspects pédagogiques différents des usages de l’outil informatique tel qu’il s’est intégré dans les pratiques des enseignants. Cette évolution se poursuit avec des produits beaucoup plus riches, en images en particulier, et des moyens de communications à grande échelle. Ces changements ont conduit à s’interroger sur les connaissances indispensables des élèves ainsi que sur les possibilités de transférer les expériences acquises au travers des formations des enseignants.Después de haber reubicado la evolución de la utilización del computador en el contexto de los programas, dos ejemplos muestran los diferentes aspectos pedagógicos del uso de la herramienta informática tal como está integrada en las prácticas de los enseñantes. Esta evolución se prosigue con productos mucho más ricos en imágenes en particular y en medios de comunicación a gran escala. Estos cambios han conducido a plantear preguntas sobre los conocimientos indispensables de los alumnos y las posibilidades de transferir las experiencias adquiridas a través de la formación de los enseñantes.Granotier-Milot Marie-Christine. Place des nouvelles technologies dans l'enseignement de la physique-chimie. In: Didaskalia, n°8, 1996. Nouvelles technologies dans l'enseignement des sciences et des techniques. pp. 97-109

Liquid Chromatography/Mass Spectrometry (LC/MS) for the Detection and Quantification of N-Acyl-L-Homoserine Lactones (AHLs) and 4-Hydroxy-2-Alkylquinolines (HAQs).

International audienceHigh-performance liquid chromatography (HPLC) coupled in-line with mass spectrometry (MS) permits rapid and specific identification and quantification of N-acyl-L-homoserine lactones (AHLs) and 4-hydroxy-2-alkylquinolines (HAQs). We are presenting here methods for the analysis of these molecules directly from biological samples using LC/MS

Interplay between 4-Hydroxy-3-Methyl-2-Alkylquinoline and N-Acyl-Homoserine Lactone Signaling in a Burkholderia cepacia Complex Clinical Strain.

International audienceSpecies from the Burkholderia cepacia complex (Bcc) share a canonical LuxI/LuxR quorum sensing (QS) regulation system named CepI/CepR, which mainly relies on the acyl-homoserine lactone (AHL), octanoyl-homoserine lactone (C8-HSL) as signaling molecule. Burkholderia ambifaria is one of the least virulent Bcc species, more often isolated from rhizospheres where it exerts a plant growth-promoting activity. However, clinical strains of B. ambifaria display distinct features, such as phase variation and higher virulence properties. Notably, we previously reported that under laboratory conditions, only clinical strains of the B. ambifaria species produced 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs) via expression of the hmqABCDEFG operon. HMAQs are the methylated counterparts of the 4-hydroxy-2-alkylquinolines (HAQs) produced by the opportunistic human pathogen Pseudomonas aeruginosa, in which they globally contribute to the bacterial virulence and survival. We have found that unlike P. aeruginosa's HAQs, HMAQs do not induce their own production. However, they indirectly regulate the expression of the hmqABCDEFG operon. In B. ambifaria, a strong link between CepI/CepR-based QS and HMAQs is proposed, as we have previously reported an increased production of C8-HSL in HMAQ-negative mutants. Here, we report the identification of all AHLs produced by the clinical B. ambifaria strain HSJ1, namely C6-HSL, C8-HSL, C10-HSL, 3OHC8-HSL, 3OHC10-HSL, and 3OHC12-HSL. Production of significant levels of hydroxylated AHLs prompted the identification of a second complete LuxI/LuxR-type QS system relying on 3OHC10-HSL and 3OHC12-HSL, that we have named CepI2/CepR2. The connection between these two QS systems and the hmqABCDEFG operon, responsible for HMAQs biosynthesis, was investigated. The CepI/CepR system strongly induced the operon, while the second system appears moderately involved. On the other hand, a HMAQ-negative mutant overproduces AHLs from both QS systems. Even if HMAQs are not classical QS signals, their effect on AHL-based QS system still gives them a part to play in the QS circuitry in B. ambifaria and thus, on regulation of various phenotypes

Burkholderia pseudomallei, B. thailandensis, and B. ambifaria Produce 4-Hydroxy-2-Alkylquinoline Analogues with a Methyl Group at the 3 Position That Is Required for Quorum-Sensing Regulation ▿

4-Hydroxy-2-alkylquinolines (HAQs), especially 3,4-dihydroxy-2-heptylquinoline (Pseudomonas quinolone signal) and its precursor, 4-hydroxy-2-heptylquinoline, are attracting much attention, mainly because of their role as signaling molecules in Pseudomonas aeruginosa. The pqsABCDE operon is centrally involved in their biosynthesis. The presence of a homologous operon in Burkholderia pseudomallei and B. thailandensis was recently reported. Thus, we have investigated the abilities of 11 Burkholderia species to produce HAQ-like molecules by liquid chromatography/mass spectrometry. We have identified 29 different HAQ derivatives produced by the only three Burkholderia species where a pqsABCDE homologue was found among available sequenced Burkholderia species genomes, including B. ambifaria, a member of the Burkholderia cepacia complex. In contrast with those of P. aeruginosa, Burkholderia HAQs typically bear a methyl group, hence their designation as 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs). We identified three families of HMAQs with a saturated or unsaturated alkyl chain at the 2′ position, in contrast with the 1′ position of P. aeruginosa, including one with an N-oxide group. Furthermore, the operon in these species contains two more genes downstream of the pqsE homologue, resulting in the hmqABCDEFG operon. While the inactivation of hmqA inhibits the production of HMAQs, the methylation of the quinoline ring requires a putative methyltransferase encoded by hmqG. Interestingly, hmqA or hmqG mutations increase the production of acyl homoserine lactones and, consequently, phenotypes under the control of quorum sensing in B. ambifaria: antifungal activity, siderophore production, and proteolytic activity. These results indicate that only HAQs bearing a methyl group (HMAQs) are involved in quorum-sensing regulation

The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids.

International audienceGroups of pathogenic bacteria use diffusible signals to regulate their virulence in a concerted manner. Pseudomonas aeruginosa uses 4-hydroxy-2-alkylquinolines (HAQs), including 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), as unique signals. We demonstrate that octanoic acid is directly incorporated into HHQ. This finding rules out the long-standing hypothesis that 3-ketofatty acids are the precursors of HAQs. We found that HAQ biosynthesis, which requires the PqsABCD enzymes, proceeds by a two-step pathway: (1) PqsD mediates the synthesis of 2-aminobenzoylacetate (2-ABA) from anthraniloyl-coenzyme A (CoA) and malonyl-CoA, then (2) the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC produces HHQ, the direct precursor of PQS. PqsB is tightly associated with PqsC and required for the second step. This finding uncovers promising targets for the development of specific antivirulence drugs to combat this opportunistic pathogen