Engagement civique des électeurs au seuil de l’âge adulte en région parisienne

Pour favoriser la participation des jeunes à la vie civique, il nous faut comprendre les facteurs individuels et contextuels qui déterminent leur engagement dans les domaines civique et politique. Cette étude illustre les rapports entre les caractéristiques personnelles des jeunes, le contexte proximal et national dans lequel ils évoluent et leur participation à la vie politique. L’article, qui utilise les données extraites d’une enquête effectuée auprès de 632 élèves de quatre lycées à forte diversité ethnique de la région parisienne, se fonde essentiellement sur celles provenant des 245 participants en âge de voter. Nous y examinons les facteurs relevant du contexte individuel, proximal et national susceptible d’influencer l’engagement des jeunes en utilisant trois indices de participation politique et civique : l’engagement dans des activités politiques, la participation à des mouvements sociaux et la participation non conventionnelle. Il ressort des résultats que les jeunes qui possèdent de plus grandes connaissances dans le domaine politique ont plus de chances de participer à des activités politiques conventionnelles. Les variations dans deux des trois indices s’expliquent aussi par le genre et l’appartenance ethnique. Le rapport étroit révélé entre les contextes de l’école et des pairs et chaque type d’engagement souligne l’importance de l’éducation civique, de l’efficacité collective à l’école et d’un climat de classe ouvert favorisant la discussion dans la promotion de la participation politique des jeunes adultes.To encourage youth’s involvement in civic life, we need to understand the individual and contextual factors that shape their involvement with civic and political issues. This study illustrates how youths’ individual characteristics and their interactions with proximal and national contexts relate to their participation in political life. Using survey data collected from 632 students from four ethnically diverse high schools in the Paris region, this paper focuses on data from 245 participants who were of voting age. We examine individual, proximal, and national context factors that may affect youth’s involvement using three indices of political and civic engagement: Commitment to Political Activities, Social Movement Participation, and Unconventional Participation. Results showed that youth with greater political knowledge were more likely to engage in Conventional Political Activities. Gender and race/ethnicity also explained some variation in two of the three indices. School and peer contexts were strongly related to each type of engagement, underscoring the importance of citizenship education, collective school efficacy, and open classroom climate for discussion in promoting young adults’ political participation

Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer

Purpose Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors. Materials and Methods We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1-mouse model for in vivo experiments to confirm our findings. Results In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3 beta serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion. Conclusion Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken together, our results support further clinical development of DDR-targeting strategies for PC.

Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer

Purpose Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. Materials and Methods In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models. Results AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy. Conclusion Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Relationship of the Duration and Timing of Exercise with Sleep Quality in Community-Dwelling Adults

Background and Objective We aimed to compare the differences in the subjective and objective sleep quality, and quality of life (QOL) according to the duration and timing of exercise in community-dwelling adults, and to compare these between the exercise group (EG) and non-exercise group (non-EG) in insomnia patients. Methods We recruited 223 volunteers (EG: n = 119, age: 60.8 ± 12.8 years; non-EG: n = 104, age 61.6 ± 13.3 years), who visited to 3 Public Health Centers in a rural area of South Korea. The Pittsburgh Sleep Quality Index (PSQI), Korean version of Epworth Sleepiness Scale (KESS), and Short Form-12 Health Survey Questionnaire (SF-12) were administered for each subject. Actigraphy (Actiwatch-2, Philips Respironics Co.) recording was done for 7 days at home, and we included the data of 183 subjects in our analysis. We compared the scores of questionnaires and objective sleep parameters according to the duration and timing of exercise, and compared these between the EG and non-EG in insomnia patients. Results Physical component summary (PCS) scores in SF-12 were higher in the EG for more than 60 minutes per day. In the subjects with outdoor exercise, the afternoon EG had lower PSQI scores and higher KESS scores. In insomnia patients, PCS scores in the EG was higher than those of the non-EG. Conclusions Community-dwelling adults who exercised for more than one hour showed higher physical QOL compared to those for less than one hour. Insomnia patients who exercised also showed higher physical QOL. In outdoor exercise, afternoon exercise would be beneficial for subjective sleep quality than morning exercise

Photodistributed Telangiectasia Induced by Amlodipine

Calcium channel blockers are widely used antihypertensive drugs, which are uncommonly associated with cutaneous reactions, such as pruritus, urticaria, or alopecia. Photosensitivity presenting with telangiectasia has rarely been described. We present here a case of photodistributed telangiectasia induced clinically by amlodipine and histologically by enlarged capillaries in the upper dermis without signs of vasculitis

Effect of few-walled carbon nanotube crystallinity on electron field emission property

We discuss the influence of few-walled carbon nanotubes (FWCNTs) treated with nitric acid and/or sulfuric acid on field emission characteristics. FWCNTs/tetraethyl orthosilicate (TEOS) thin film field emitters were fabricated by a spray method using FWCNTs/TEOS sol one-component solution onto indium tin oxide (ITO) glass. After thermal curing, they were found tightly adhered to the ITO glass, and after an activation process by a taping method, numerous FWCNTs were aligned preferentially in the vertical direction. Pristine FWCNT/ TEOS-based field emitters revealed higher current density, lower turn-on field, and a higher field enhancement factor than the oxidized FWCNTs-based field emitters. However, the unstable dispersion of pristine FWCNT in TEOS/N,N-dimethylformamide solution was not applicable to the field emitter fabrication using a spray method. Although the field emitter of nitric acid-treated FWCNT showed slightly lower field emission characteristics, this could be improved by the introduction of metal nanoparticles or resistive layer coating. Thus, we can conclude that our spray method using nitric acid-treated FWCNT could be useful for fabricating a field emitter and offers several advantages compared to previously reported techniques such as chemical vapor deposition and screen printing.ope

A Case of Cicatricial Alopecia Associated with Erlotinib

Erlotinib is a small-molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). Erlotinib has been used primarily to treat non-small cell lung cancer. In addition to its role in tumor cells, EGFR is also an important regulator of growth and differentiation in the skin and hair. Therefore, EGFR-TKIs have been associated with a number of cutaneous side effects including follicular acneiform eruptions, cutaneous xerosis, chronic paronychia, desquamation, seborrheic dermatitis, and hair texture changes. Herein, we report a rare case of a 61-year-old woman who was treated with erlotinib and experienced cicatricial alopecia

TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy

The aim of this study was to elucidate the carryover effect of olaparib to subsequent chemotherapy and its underlying mechanisms. We generated olaparib-resistant SNU-484, SNU-601, SNU-668, and KATO-III gastric cancer cell lines and confirmed their resistance by cell viability and colony forming assays. Notably, olaparib-resistant cell lines displayed cross-resistance to cisplatin except for KATO-III. Inversely, olaparib-resistant SNU-484, SNU-668, and KATO-III were more sensitive to irinotecan than their parental cells. However, sensitivity to paclitaxel remained unaltered. There were compensatory changes in the ATM/ATR axis and p-Chk1/2 protein expression. ERCC1 was also induced in olaparib-resistant SNU-484, SNU-601, and SNU-668, which showed cross-resistance to cisplatin. Olaparib-resistant cells showed tyrosyl-DNA phosphodiesterase 1 (TDP1) downregulation with higher topoisomerase 1 (TOP1) activity, which is a target of irinotecan. These changes of TOP1 and TDP1 in olaparib-resistant cells was confirmed as the underlying mechanism for increased irinotecan sensitivity through manipulated gene expression of TOP1 and TDP1 by specific plasmid transfection and siRNA. The patient-derived xenograft model established from the patient who acquired resistance to olaparib with BRCA2 mutation showed increased sensitivity in irinotecan. In conclusion, the carryover effects of olaparib to improve antitumor effect of subsequent irinotecan were demonstrated. These effects should be considered when determining the subsequent therapy with olaparib.

Inhibitory Effect of Inflexinol on Nitric Oxide Generation and iNOS Expression via Inhibition of NF-κB Activation

Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae) have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 μM) suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-κB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases