L'image du mois. Sous le pont myocardique coule la coronaire.

Peer reviewe

DYNAMIC EMPLOYEE EMISSIONS MANAGEMENT CONTROLLER

Efforts to reduce greenhouse gas emissions from the transport industry are critical in addressing global emissions. Employee commuting contributes significantly to emissions in the transportation industry (Scope 3 emissions). To overcome this issue, proposed herein is Dynamic Employee Emissions Management (DEEM), a system and method for dynamic urban mobility management in transportation networks, calculating emissions from employee commuting (under Scope 3, Category 7)

Exploring with [18F]UCB-H the in vivo cariations in SV2A expression through the kainic acid rat model of temporal lobe epilepsy

Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [F-18]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [F-18]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [F-18]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [F-18]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease

Radiation recall dermatitis after oral cyclophosphamide

peer reviewedRadiation recall dermatitis is an inflammatory skin reaction occurring in a previously irradiated field following the delivery of a promoting agent. It has been described after a number of antineoplastic agents such as gemcitabine, taxanes, anthracyclines. We report the case of a 50-year-old man with metastatic prostate cancer who developed two consecutive radiation recall dermatitis episodes triggered by oral cyclophosphamide. They occurred 4 to 5 weeks after palliative radiotherapy on bone metastasis. Spontaneous resolution was observed within 6 weeks after discontinuation of cyclophosphamide and with local supportive care. To our knowledge this is the first reported case of radiation recall dermatitis after oral cyclophosphamide

Incidence, risk factors, and CT characteristics of radiation recall pneumonitis induced by immune checkpoint inhibitor in lung cancer.

BACKGROUND AND PURPOSE: Radiation recall pneumonitis (RRP) is a delayed radiation-induced lung toxicity triggered by systemic agents, typically anticancer drugs. Immune checkpoint inhibitors (ICIs) have recently been identified as potential causal agents of RRP but its real incidence and potential risk factors remain unknown. MATERIALS AND METHODS: Medical records and CTs of patients treated with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors for advanced lung cancer between 2014 and 2019 at our tertiary center, and who had a previous history of lung irradiation were retrospectively analyzed. We identified RRP as lung CT modifications occurring in the irradiation field >6 months after conventionally fractionated radiotherapy completion and >1 year after stereotactic body radiation therapy. Clinical and dosimetric data were analyzed to identify potential risk factors for RRP. RESULTS: Among 348 patients treated with ICIs, data from 80 eligible patients were analyzed (median age, 69 years [interquartile range, 11]; 45 men). Fifteen patients (18.8%) presented with RRP. Median time between end of radiotherapy and RRP was 450 days (range, 231-1859). No risk factor was significantly associated with RRP. ICI-related pneumonitis was associated with RRP in 33.3% of cases (p = 0.0021), developing either concomitantly or after RRP. Incidence of grade ≥ 3 pneumonitis in the RRP population was 13.3 %. CONCLUSION: We demonstrated a high incidence of RRP (18.8%) in our population of previously irradiated patients treated with ICIs for lung cancer. We identified no risk factors for RRP, but an association was noted between RRP and ICI-related pneumonitis.Peer reviewe

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically-modified animal models, together with biochemical and pharmacological approaches, we provide a high resolution expression map and a detailed functional characterization of A2AR-CB1R heteromers in the dorsal striatum. Specifically, our data unveil that the A2AR-CB1R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington’s disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases

Identification of CT radiomic features robust to acquisition and segmentation variations for improved prediction of radiotherapy-treated lung cancer patient recurrence.

peer reviewedThe primary objective of the present study was to identify a subset of radiomic features extracted from primary tumor imaged by computed tomography of early-stage non-small cell lung cancer patients, which remain unaffected by variations in segmentation quality and in computed tomography image acquisition protocol. The robustness of these features to segmentation variations was assessed by analyzing the correlation of feature values extracted from lesion volumes delineated by two annotators. The robustness to variations in acquisition protocol was evaluated by examining the correlation of features extracted from high-dose and low-dose computed tomography scans, both of which were acquired for each patient as part of the stereotactic body radiotherapy planning process. Among 106 radiomic features considered, 21 were identified as robust. An analysis including univariate and multivariate assessments was subsequently conducted to estimate the predictive performance of these robust features on the outcome of early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy. The univariate predictive analysis revealed that robust features demonstrated superior predictive potential compared to non-robust features. The multivariate analysis indicated that linear regression models built with robust features displayed greater generalization capabilities by outperforming other models in predicting the outcomes of an external validation dataset

When Cytokinin, a Plant Hormone, Meets the Adenosine A2A Receptor: A Novel Neuroprotectant and Lead for Treating Neurodegenerative Disorders?

It is well known that cytokinins are a class of phytohormones that promote cell division in plant roots and shoots. However, their targets, biological functions, and implications in mammalian systems have rarely been examined. In this study, we show that one cytokinin, zeatin riboside, can prevent pheochromocytoma (PC12) cells from serum deprivation-induced apoptosis by acting on the adenosine A2A receptor (A2A-R), which was blocked by an A2A-R antagonist and a protein kinase A (PKA) inhibitor, demonstrating the functional ability of zeatin riboside by mediating through A2A-R signaling event. Since the A2A-R was implicated as a therapeutic target in treating Huntington’s disease (HD), a cellular model of HD was applied by transfecting mutant huntingtin in PC12 cells. By using filter retardation assay and confocal microscopy we found that zeatin riboside reversed mutant huntingtin (Htt)-induced protein aggregations and proteasome deactivation through A2A-R signaling. PKA inhibitor blocked zeatin riboside-induced suppression of mutant Htt aggregations. In addition, PKA activated proteasome activity and reduced mutant Htt protein aggregations. However, a proteasome inhibitor blocked both zeatin riboside-and PKA activator-mediated suppression of mutant Htt aggregations, confirming mediation of the A2A-R/PKA/proteasome pathway. Taken together, zeatin riboside might have therapeutic potential as a novel neuroprotectant and a lead for treating neurodegenerative disorders

Synthèse, caractérisation et photoréactivité d'oligomères hyperbranchés

Depuis une dizaine d'années, les polymères hyperbranchés sont apparus dans la littérature. Ils possèdent un grand nombre de branchements ainsi qu'un grand nombre de groupes terminaux. La structure globulaire des polymères hyperbranchés les empêche de former des enchevêtrements. Il en résulte un avantage décisif pour leur application sous forme de revêtement de surface: les polymères hyperbranchés ont une viscosité plus faible à l'état fondu que les polymères linéaires. Cela permet aisément de les étaler sous forme de films minces sans utiliser de solvant. De plus, les polymères hyperbranchés possèdent un grand nombre de groupes terminaux qui peuvent être fonctionnalisés avec des monomères photoréticulables.Le but du travail de thèse est d'obtenir de nouveaux revêtements de surface, à partir de polymères hyperbranchés ou de polymères fortement branchés, qui trouveront leur application dans l'industrie chimique.La thèse s'articule autour de trois chapitres de synthèse suivis d'un chapitre traitant de la photoréactivité des oligomères linéaires, fortement branchés, et hyperbranchés.La première approche de synthèse envisagée est la copolymérisation alternante radicalaire. Divers maléimides ont été engagés dans des copolymérisations radicalaires avec des allyléthers sans succès. Lorsque ces derniers sont remplacés par des vinyls éthers, une copolymérisation alternante est observée. Néanmoins, une importante irreproductibilité est constatée, certains batchs donnant lieu à une gélification.La seconde voie de synthèse étudiée est l'approche classique de polycondensation de monomères de type AB2 .Le monomère AB2 est obtenu par addition de Michael de la diéthanolamine sur l'acrylate de méthyle. La polycondensation est concomitante avec l'acrylation des fonctions alcools. La compétition entre ces deux réactions limite les masses molaires accessibles bien que les réactions de transestérification soient catalysées par des dérivés du Zr et que la stoechiométrie ait été variée.La troisième voie de synthèse se base aussi sur la réaction de Michael. Des oligomères fortement branchés sont obtenus à partir de 1,6-hexanedioldiacrylate et d'éthylènediamine. Leurs analogues linéaires sont synthétisés en remplaçant l'éthylènediamine par la propylamine. Lors de ces synthèses, il est apparu que les oligomères fortement branchés ont une viscosité supérieure à celle des oligomères linéaires!Les oligomères hyperbranchés et acrylés, les oligomères linéaires et leurs analogues fortement branchés ont été étudiés du point de vue de leur photoréticulation sous rayonnement UV. Contrairement à ce qui était attendu, ils se sont montrés moins réactifs que les produits les plus performants de Cytec-Surface Specialties. Lors de cette étude, l'effet bénéfique des mines tertiaires sur l'inhibition par l'oxygène est apparu plus complexe que décrit dans la littérature.Doctorat en sciences appliquéesinfo:eu-repo/semantics/nonPublishe