Relevance of a mobile internet platform for capturing inter- and intrasubject variabilities in circadian coordination during daily routine : pilot study

Background: Experimental and epidemiologic studies have shown that circadian clocks disruption can play an important role in the development of cancer and metabolic diseases. The cellular clocks outside the brain are effectively coordinated by the body temperature rhythm. We hypothesized that concurrent measurements of body temperature and rest-activity rhythms would assess circadian clocks coordination in individual patients, thus enabling the integration of biological rhythms into precision medicine. Objective The objective was to evaluate the circadian clocks’ coordination in healthy subjects and patients through simultaneous measurements of rest-activity and body temperature rhythms. Methods Non-invasive real-time measurements of rest-activity and chest temperature rhythms were recorded during the subject’s daily life, using a dedicated new mobile e-health platform (PiCADo). It involved a chest sensor that jointly measured accelerations, 3D-orientation and skin surface temperature every 1-5 min, and relayed them out to a mobile gateway via Bluetooth-Low-Energy. The gateway tele-transmitted all stored data to a server via GPRS every 24 h. The technical capabilities of PiCADo were validated in 55 healthy subjects and 12 cancer patients, whose rhythms were e-monitored during their daily routine for 3-30 days. Spectral analyses enabled to compute rhythm parameters values, with their 90% confidence limits, and their dynamics in each subject. Results All the individuals displayed a dominant circadian rhythm in activity with maxima occurring from 12:09 to 20:25. This was not the case for the dominant temperature period, which clustered around 24 h for 51 out of 67 subjects (76%), and around 12 h for 13 others (19%). Statistically significant sex- and age- related differences in circadian coordination were identified in the non-cancerous subjects, based upon the range of variations in temperature rhythm amplitudes, maxima (acrophases), and phase relations with rest-activity. The circadian acrophase of chest temperature was located at night for the majority of people, but it occurred at daytime for 26% (14/55) of the non-cancerous people and 33% (4/12) of the cancer patients, hence supporting important inter-subject differences in circadian coordination. Sex, age and cancer significantly impacted on the circadian coordination of both rhythms, based on their phase relationships. Conclusions Complementing rest-activity with chest temperature circadian e-monitoring revealed striking inter-subject differences regarding human circadian clocks coordination and timing during daily routine. To further delineate the clinical importance of such finding, the PiCADo platform is currently applied for both the assessment of health effects resulting from atypical work schedules, and the identification of the key determinants of circadian disruption in cancer patients

La plateforme PiCADo : premier pilote de Domomédecine

International audienc

La plateforme PiCADo : premier pilote de Domomédecine

International audienc

Innovative Project for Domomedicine Deployment: The PiCADo Pilot Project

International audienc

Projet Innovant pour le Changement d’Ampleur de la Domomédecine (PiCADo)

International audienc

Projet Innovant pour le Changement d’Ampleur de la Domomédecine (PiCADo)

International audienc

Projet Innovant pour le Changement d’Ampleur de la Domomédecine (PiCADo)

International audienc

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field