Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade

There is limited knowledge about the metabolic reprogramming induced by cancer therapies, and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation. Consistent with this, we observed significantly increased lipid droplets, with subsequent mobilization to mitochondria. These changes were abrogated in cells deficient for the essential autophagy gene, ATG5. Accordingly, inhibition of PLA2 significantly decreased lipid droplets, decreased oxidative phosphorylation and increased apoptosis. Together, these results describe how treatment-induced autophagy provides nutrients for cancer cell survival and identifies novel co-treatment strategies to override this survival advantage

Interactivity Improves Usability of Geographic Maps for Visually Impaired People

International audienceTactile relief maps are used by visually impaired people to acquire mental representation of space, but they retain important limitations (limited amount of information, braille text, etc.). Interactive maps may overcome these limitations. However, usability of these two types of maps had never been compared. It is then unknown whether interactive maps are equivalent or even better solutions than traditional raised-line maps. This study presents a comparison of usability of a classical raised-line map vs. an interactive map composed by a multi-touch screen, a raised-line overlay and audio output. Both maps were tested by 24 blind participants. We measured usability as efficiency, effectiveness and satisfaction. Our results show that replacing braille with simple audio-tactile interaction significantly improved efficiency and user satisfaction. Effectiveness was not related to the map type but depended on users' characteristics as well as the category of assessed spatial knowledge. Long-term evaluation of acquired spatial information revealed that maps, whether interactive or not, are useful to build robust survey-type mental representations in blind users. Altogether, these results are encouraging as they show that interactive maps are a good solution for improving map exploration and cognitive mapping in visually impaired people

Motor-evoked potential gain is a helpful test for the detection of corticospinal tract dysfunction in amyotrophic lateral sclerosis

International audienceh i g h l i g h t s Motor-evoked potential (MEP) gain is decreased in patients with amyotrophic lateral sclerosis (ALS). MEP gain may allow the early detection of upper motor neuron dysfunction in patients and improve the diagnosis of ALS. The diagnostic utility of MEP gain is equivalent to the triple stimulation technique (TST) and better than diffusion tensor imaging (DTI). a b s t r a c t Objective: The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amy-otrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background elec-tromyographic activity) represents an efficient alternative to assess UMN dysfunction. Methods: MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). Results: MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. Conclusion: MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. Significance: MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction

Acceptation du recours à l'interruption volontaire de grossesse chez les Français de 18–24 ans en 2021

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Active targeting with Y-90 radiolabelled octreotate functionalized AGuIX ultra-small nano particles

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[(11)C]Ascorbic and [(11)C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography.

Here we report the radiosynthesis of an endogenous redox pair, [(11)C]ascorbic acid ([(11)C]VitC) and [(11)C]dehydroascorbic acid ([(11)C]DHA), the reduced and oxidized forms of vitamin C, and their application to ROS sensing. These results provide the basis for in vivo detection of ROS using positron emission tomography (PET)

The Medical Assistive and Transactional Technologies (MATT): A case study of co-conception design

IntroductionThe development of Assistive Technology (AT) is an answer for disabled persons if it meets their needs. Even when technological barriers are overcomed, users often abandon their devices. Many studies show high abandonment rate of AT. The reasons are: misunderstanding of AT, unfitting devices to the personal needs of very demanding users, low adaptive performances of AT to worsening disabilities.Therefore, we wanted an end-user of the MATT (a Locked-in patient with partial functional abilities of one left hand finger) to participate actively in co-design and assess this AT.Co-design approachMATT is an interactive system of environment control and communications, connected to bedroom objects — lights, roller shutter, TV, radio station, nurse warning —, all in one, designed for people with motor and sensory impairments. Firstly, the needs — communication, environment control, Internet applications, audio message, etc. — were identified by the patient, her husband and the occupational therapist team. Secondly, an efficient prototype of the MATT virtual interface was quickly designed by the SOftware KEYboard Toolkit [1] which also allows choosing several parameters: type of interaction–pointing or scanning–and its settings–scanning frequency, command mode, etc. Thirdly, MATT was experimented by the patient. From this observation phase, a new cycle of iteration–requirement defined by the user feedback together with her occupational therapist, prototyping and test–is set up, and so on.DiscussionThis case study has demonstrated that co-design is an appropriate method to design adapted and adaptable AT for severe disabled patients. Specific requirements such as text input function, serious game, repetition command facility, timeout to avoid involuntary command were easily added. Currently, the patient enjoys the use of MATT and is requiring for new developments in her daily living activities. The next step is to assess the use of MATT with qualitative and quantitative criteria and its contributions for rehabilitation