Abdominal obesity‐related disturbance of insulin sensitivity is associated with cd8+ emra cells in the elderly

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross‐sectional study, we aimed to investigate the potential mediating role of T‐EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA‐IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower‐weight subgroups. Linear regression analysis revealed that an elevated HOMA‐IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist‐to‐hip ratio on HOMA‐IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Magneto-mechanical treatment of human glioblastoma cells with engineered iron oxide powder microparticles for triggering apoptosis

International audienceIn nanomedicine, treatments based on physical mechanisms are more and more investigated and are promising alternatives for challenging tumor therapy. One of these approaches, called magneto-mechanical treatment, consists in triggering cell death via the vibration of anisotropic magnetic particles, under a low frequency magnetic field. In this work, we introduce a new type of easily accessible magnetic microparticles (MMPs) and study the influence of their surface functionalization on their ability to induce such an effect, and its mechanism. We prepared anisotropic magnetite microparticles by liquid-phase ball milling of a magnetite powder. These particles are completely different from the often-used SPIONs: they are micron-size, ferromagnetic, with a closed-flux magnetic structure reminiscent of that of vortex particles. The magnetic particles were covered with a silica shell, and grafted with PEGylated ligands with various physicochemical properties. We investigated both bare and coated particles' in vitro cytotoxicity, and compared their efficiency to induce U87-MG human glioblastoma cell apoptosis under a low frequency rotating magnetic field (RMF). Our results indicated that (1) the magneto-mechanical treatment with bare MMPs induces a rapid decrease in cell viability whereas the effect is slower with PEGylated particles; (2) the number of apoptotic cells after magneto-mechanical treatment is higher with PEGylated particles; (3) a lower frequency of RMF (down to 2 Hz) favors the apoptosis. These results highlight a difference in the cell death mechanism according to the properties of particles used – the rapid cell death observed with the bare MMPs indicates a death pathway via necrosis, while PEGylated particles seem to favor apoptosis

Abdominal Obesity-Related Disturbance of Insulin Sensitivity Is Associated with CD8+ EMRA Cells in the Elderly

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross-sectional study, we aimed to investigate the potential mediating role of T-EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA-IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower-weight subgroups. Linear regression analysis revealed that an elevated HOMA-IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist-to-hip ratio on HOMA-IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes

Autonomy, Heteronomy, and Bioethics in BioShock

Abstract The digital game BioShock addresses questions about human enhancement, unbounded biomedical research and unregulated technology. Our analysis is situated in an interdisciplinary field between media studies, the history of ideas, and bioethics. We focus on the processes of generating meaning and knowledge while playing a game, and therefore on the context in which the game is played and how it may be understood by different audiences. What marks this medium as potentially more powerful than movies or novels is that the player interacts with the game and participates in both the narrative and the ludic experience. In this chapter, we explore how the theme of autonomy/heteronomy is addressed in ludic terms in the game and give two examples of narrative elements that address autonomy within the context of bioethics and medical ethics. We show that in BioShock the medium of computer games has been used as a thought experiment, examining the consequences of unregulated medical research and practice