Targeted nuclear irradiation with a proton microbeam induces oxidative DNA base damage and triggers the recruitment of DNA glycosylases OGG1 and NTH1.

DNA is the major target of radiation therapy of malignant tumors. Ionizing radiation (IR) induces a variety of DNA lesions, including chemically modified bases and strand breaks. The use of proton beam therapy for cancer treatment is ramping up, as it is expected to reduce normal tissue damage. Thus, it is important to understand the molecular mechanisms of recognition, signaling, and repair of DNA damage induced by protons in the perspective of assessing not only the risk associated with human exposure to IR but also the possibility to improve the efficacy of therapy. Here, we used targeted irradiation of nuclear regions of living cells with controlled number of protons at a high spatio-temporal resolution to detect the induced base lesions and characterize the recruitment kinetics of the specific DNA glycosylases to DNA damage sites. We show that localized irradiation with 4 MeV protons induces, in addition to DNA double strand breaks (DSBs), the oxidized bases 7,8-dihydro-8-oxoguanine (8-oxoG) and thymine glycol (TG) at the site of irradiation. Consistently, the DNA glycosylases OGG1 and NTH1, capable of excising 8-oxoG and TG, respectively, and initiating the base excision repair (BER) pathway, are recruited to the site of damage. To our knowledge, this is the first direct evidence indicating that proton microbeams induce oxidative base damage, and thus implicating BER in the repair of DNA lesions induced by protons.

Targeted Central Nervous System Irradiation with Proton Microbeam Induces Mitochondrial Changes in Caenorhabditis elegans.

Fifty percent of all patients with cancer worldwide require radiotherapy. In the case of brain tumors, despite the improvement in the precision of radiation delivery with proton therapy, studies have shown structural and functional changes in the brains of treated patients with protons. The molecular pathways involved in generating these effects are not completely understood. In this context, we analyzed the impact of proton exposure in the central nervous system area of Caenorhabditis elegans with a focus on mitochondrial function, which is potentially implicated in the occurrence of radiation-induced damage. To achieve this objective, the nematode C. elegans were micro-irradiated with 220 Gy of protons (4 MeV) in the nerve ring (head region) using the proton microbeam, MIRCOM. Our results show that protons induce mitochondrial dysfunction, characterized by an immediate dose-dependent loss of the mitochondrial membrane potential (ΔΨm) associated with oxidative stress 24 h after irradiation, which is itself characterized by the induction of the antioxidant proteins in the targeted region, observed using SOD-1::GFP and SOD-3::GFP strains. Moreover, we demonstrated a two-fold increase in the mtDNA copy number in the targeted region 24 h after irradiation. In addition, using the GFP::LGG-1 strain, an induction of autophagy in the irradiated region was observed 6 h following the irradiation, which is associated with the up-regulation of the gene expression of pink-1 (PTEN-induced kinase) and pdr-1 (C. elegans parkin homolog). Furthermore, our data showed that micro-irradiation of the nerve ring region did not impact the whole-body oxygen consumption 24 h following the irradiation. These results indicate a global mitochondrial dysfunction in the irradiated region following proton exposure. This provides a better understanding of the molecular pathways involved in radiation-induced side effects and may help in finding new therapies.

Accuracy and precision of simpler and lower-cost technologies to measure the initial lean angle, step length and step velocity for forward lean releases.

Current technologies to measure the maximum forward lean angle, step length and velocity in a clinical setting are neither simple nor cheap. Therefore, the purpose of this study was to determine the accuracy and precision of four live and one post-processing measurement methods compared to the 3D motion analysis gold standard. Twelve healthy younger adults recovered balance, after being released from six randomly ordered forward initial lean angles, using four different live measurement methods: LabVIEW, load cell, inclinometer and protractor. The initial lean angle, step length and velocity were also calculated in post-processing using 2D video analysis and 3D motion analysis. The LabVIEW method was the most accurate and precise, followed by the protractor, inclinometer and load cell methods. The load cell method was the most complex, followed by the LabVIEW, inclinometer and protractor methods. The LabVIEW method was the most expensive, followed by the load cell, inclinometer and protractor methods. Video analysis was sufficiently accurate and precise, equal in complexity and much less expensive than the gold standard. Simpler and lower-cost technologies to measure the initial lean angle, step length and velocity are sufficiently accurate and precise (live: protractor, post-processing: video analysis) to potentially use in a clinical setting.

[Lifestyle Redesign® (Remodeler sa vie): First Pilot Study Among Older French-Canadians]. / Remodeler sa vie® (Lifestyle Redesign) : première étude pilote auprès d'aînés franco-canadiens.

DESCRIPTION.: Recently translated and adapted to the French-Canadian context, the program Remodeler sa vie (Lifestyle Redesign) aims to develop meaningful and healthy lifestyle. The influence of this newly adapted program on older French-Canadians was, however, unknown. OBJECTIVE.: The aim of this study was to describe the influence of the Remodeler sa vie on older French-Canadians' life balance, engagement in meaningful activities, self-compassion and gratitude. METHOD.: A mixed-method design (preexperimental and qualitative clinical) was used in a pilot study with 16 participants distributed in two groups (with and without disabilities). Pre- and post-intervention questionnaires as well as semi-structured interviews were completed. RESULTS.: An increase of life-balance in all participants (p = .03) and of engagement in meaningful activities in older adults without disability (p = .02) was observed. The participants also reported improvements for all outcomes. CONCLUSION.: Remodeler sa vie is a culturally promising program to promote health among older French-Canadians.

DESCRIPTION.: Récemment traduit et adapté au contexte franco-canadien, le programme Remodeler sa vie (Lifestyle Redesign) vise le développement de modes de vie sains et porteurs de sens. On connaît toutefois peu l'influence de ce programme chez les aînés francophones. BUT.: Décrire l'influence du programme Remodeler sa vie sur l'équilibre de vie, l'engagement dans les activités signifiantes, la compassion et la gratitude d'aînés franco-canadiens. MÉTHODOLOGIE.: Une étude pilote mixte (préexpérimental et qualitatif clinique) a été réalisée auprès de 16 aînés répartis en deux groupes (avec et sans incapacités). Des questionnaires pré et post-intervention ainsi que des entretiens semi-dirigés ont été complétés. RÉSULTATS.: Une augmentation de l'équilibre de vie de l'ensemble participants (p = 0,03) et de l'engagement dans des activités signifiantes des aînés sans incapacité (p = 0,02) a été observée. Les participants rapportaient des améliorations pour l'ensemble des résultantes. CONSÉQUENCES.: Remodeler sa vie est un programme prometteur pour promouvoir la santé des aînés franco-canadiens.