Les écrans chez les enfants d'âge préscolaire et leurs habiletés socioémotionnelles : exploration de différents types d'utilisation des écrans et du rôle modérateur de la médiation parentale

L'utilisation des appareils numériques par les jeunes est un sujet qui a pris beaucoup d'ampleur dans les dernières années. On ne connaît pas précisément l'impact qu'ils peuvent avoir sur le développement de ceux-ci. Ce mémoire s'intéresse à l'association entre l'utilisation des écrans par les enfants et leurs habiletés socioémotionnelles, en explorant le rôle modérateur de la médiation parentale dans ces relations. Une enquête en ligne a permis de constituer un échantillon de 116 parents francophones d'enfants âgées de 3 à 5 ans habitant au Québec. Trois outils de collecte de données ont été utilisés, soit : 1) un calendrier hebdomadaire pour évaluer le temps d'écran actif et passif; 2) la version francophone du Social Skills Improvement System Rating Scales (SSIS-RS) et 3) une traduction du questionnaire sur la médiation parentale des écrans auprès des enfants de 0 à 7 ans. Afin de comprendre l'association du temps d'écran actif ou passif avec les habiletés socioémotionnelles, trois régressions linéaires ont été réalisées. Dans le but de vérifier si les différents types de médiation parentale modèrent le lien entre le temps d'écran et les habiletés socioémotionnelles, des régressions linéaires multiples ont été effectuées en utilisant le modèle 1 du PROCESS de Hayes (2018). Aucun lien n'a été trouvé entre le temps d'écran et les habiletés socioémotionnelles. La supervision ressort comme un modérateur significatif de la relation. Des liens directs ont été trouvés entre les habiletés socioémotionnelles et les deux types de médiation parentale suivants, soit la supervision et les restrictions techniques. Explorer différents types de temps d'écran et de médiation parentale représente une avenue pertinente pour les recherches futures. Un apport de ce projet est qu'un outil d'évaluation a été créé pour évaluer le temps d'écran passif et le temps d'écran actif sur une semaine complète

Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation

Although defects in intestinal barrier function are discussed as a key pathogenic factor in patients with inflammatory bowel diseases (IBD), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we performed a novel approach to characterize the transcriptome of IECs from IBD patients using a genome wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBD where Rho-A activation was suppressed due to reduced expression of the Rho-A prenylation enzyme GGTase-I. The functional relevance of this pathway was highlighted by studies in mice with conditional gene targeting in which deletion of RhoA or GGTase-I in IECs caused spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4+ T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBD. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-I deficient IECs, our findings open new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients

PARSEC: stellar tracks and isochrones with the PAdova and TRieste Stellar Evolution Code

We present the updated version of the code used to compute stellar evolutionary tracks in Padova. It is the result of a thorough revision of the major input physics, together with the inclusion of the pre-main sequence phase, not present in our previous releases of stellar models. Another innovative aspect is the possibility of promptly generating accurate opacity tables fully consistent with any selected initial chemical composition, by coupling the OPAL opacity data at high temperatures to the molecular opacities computed with our AESOPUS code (Marigo & Aringer 2009). In this work we present extended sets of stellar evolutionary models for various initial chemical compositions, while other sets with different metallicities and/or different distributions of heavy elements are being computed. For the present release of models we adopt the solar distribution of heavy elements from the recent revision by Caffau et al. (2011), corresponding to a Sun's metallicity Z=0.0152. From all computed sets of stellar tracks, we also derive isochrones in several photometric systems. The aim is to provide the community with the basic tools to model star clusters and galaxies by means of population synthesis techniques.Comment: To appear on MNRAS. While the full database is still being prepared, the first isochrones can be retrieved via http://stev.oapd.inaf.it/cm

Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer.

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m-2: 1.24, 95% confidence interval (CI): 1.18-1.31), with more than twofold increased risk for survivors treated with ≥200 mg m-2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200-299 mg m-2, HR: 2.33 for 300-399 mg m-2 and HR: 2.78 for ≥400 mg m-2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59-6.63). For patients treated with or without chest irradiation, HRs per 100 mg m-2 of doxorubicin were 1.11 (95% CI: 1.02-1.21) and 1.26 (95% CI: 1.17-1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m-2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols

Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort.

PURPOSE The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age. PARTICIPANTS The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis. FINDINGS TO DATE This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts' follow-up started 1951-1981 and ended 2013-2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0-32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5-11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0-40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively. FUTURE PLANS The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future

Acquisition of Chemoresistance in Gliomas Is Associated with Increased Mitochondrial Coupling and Decreased ROS Production

Temozolomide (TMZ) is an alkylating agent used for treating gliomas. Chemoresistance is a severe limitation to TMZ therapy; there is a critical need to understand the underlying mechanisms that determine tumor response to TMZ. We recently reported that chemoresistance to TMZ is related to a remodeling of the entire electron transport chain, with significant increases in the activity of complexes II/III and cytochrome c oxidase (CcO). Moreover, pharmacologic and genetic manipulation of CcO reverses chemoresistance. Therefore, to test the hypothesis that TMZ-resistance arises from tighter mitochondrial coupling and decreased production of reactive oxygen species (ROS), we have assessed mitochondrial function in TMZ-sensitive and -resistant glioma cells, and in TMZ-resistant glioblastoma multiform (GBM) xenograft lines (xenolines). Maximum ADP-stimulated (state 3) rates of mitochondrial oxygen consumption were greater in TMZ-resistant cells and xenolines, and basal respiration (state 2), proton leak (state 4), and mitochondrial ROS production were significantly lower in TMZ-resistant cells. Furthermore, TMZ-resistant cells consumed less glucose and produced less lactic acid. Chemoresistant cells were insensitive to the oxidative stress induced by TMZ and hydrogen peroxide challenges, but treatment with the oxidant L-buthionine-S,R-sulfoximine increased TMZ-dependent ROS generation and reversed chemoresistance. Importantly, treatment with the antioxidant N-acetyl-cysteine inhibited TMZ-dependent ROS generation in chemosensitive cells, preventing TMZ toxicity. Finally, we found that mitochondrial DNA-depleted cells (ρ°) were resistant to TMZ and had lower intracellular ROS levels after TMZ exposure compared with parental cells. Repopulation of ρ° cells with mitochondria restored ROS production and sensitivity to TMZ. Taken together, our results indicate that chemoresistance to TMZ is linked to tighter mitochondrial coupling and low ROS production, and suggest a novel mitochondrial ROS-dependent mechanism underlying TMZ-chemoresistance in glioma. Thus, perturbation of mitochondrial functions and changes in redox status might constitute a novel strategy for sensitizing glioma cells to therapeutic approaches

CD133 Is a Marker of Bioenergetic Stress in Human Glioma

Mitochondria dysfunction and hypoxic microenvironment are hallmarks of cancer cell biology. Recently, many studies have focused on isolation of brain cancer stem cells using CD133 expression. In this study, we investigated whether CD133 expression is regulated by bioenergetic stresses affecting mitochondrial functions in human glioma cells. First, we determined that hypoxia induced a reversible up-regulation of CD133 expression. Second, mitochondrial dysfunction through pharmacological inhibition of the Electron Transport Chain (ETC) produced an up-regulation of CD133 expression that was inversely correlated with changes in mitochondrial membrane potential. Third, generation of stable glioma cells depleted of mitochondrial DNA showed significant and stable increases in CD133 expression. These glioma cells, termed rho0 or ρ0, are characterized by an exaggerated, uncoupled glycolytic phenotype and by constitutive and stable up-regulation of CD133 through many cell passages. Moreover, these ρ0 cells display the ability to form “tumor spheroids” in serumless medium and are positive for CD133 and the neural progenitor cell marker, nestin. Under differentiating conditions, ρ0 cells expressed multi-lineage properties. Reversibility of CD133 expression was demonstrated by transfering parental mitochondria to ρ0 cells resulting in stable trans-mitochondrial “cybrid” clones. This study provides a novel mechanistic insight about the regulation of CD133 by environmental conditions (hypoxia) and mitochondrial dysfunction (genetic and chemical). Considering these new findings, the concept that CD133 is a marker of brain tumor stem cells may need to be revised

Breaking Functional Connectivity into Components: A Novel Approach Using an Individual-Based Model, and First Outcomes

Landscape connectivity is a key factor determining the viability of populations in fragmented landscapes. Predicting ‘functional connectivity’, namely whether a patch or a landscape functions as connected from the perspective of a focal species, poses various challenges. First, empirical data on the movement behaviour of species is often scarce. Second, animal-landscape interactions are bound to yield complex patterns. Lastly, functional connectivity involves various components that are rarely assessed separately. We introduce the spatially explicit, individual-based model FunCon as means to distinguish between components of functional connectivity and to assess how each of them affects the sensitivity of species and communities to landscape structures. We then present the results of exploratory simulations over six landscapes of different fragmentation levels and across a range of hypothetical bird species that differ in their response to habitat edges. i) Our results demonstrate that estimations of functional connectivity depend not only on the response of species to edges (avoidance versus penetration into the matrix), the movement mode investigated (home range movements versus dispersal), and the way in which the matrix is being crossed (random walk versus gap crossing), but also on the choice of connectivity measure (in this case, the model output examined). ii) We further show a strong effect of the mortality scenario applied, indicating that movement decisions that do not fully match the mortality risks are likely to reduce connectivity and enhance sensitivity to fragmentation. iii) Despite these complexities, some consistent patterns emerged. For instance, the ranking order of landscapes in terms of functional connectivity was mostly consistent across the entire range of hypothetical species, indicating that simple landscape indices can potentially serve as valuable surrogates for functional connectivity. Yet such simplifications must be carefully evaluated in terms of the components of functional connectivity they actually predict

Alien Registration- Turcotte, Claudia (Sidney, Kennebec County)

https://digitalmaine.com/alien_docs/16432/thumbnail.jp