Genotoxic risk of ethyl-paraben could be related to telomere shortening.

The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.

[Experimentation of an e-platform to detect situations at risk of cardiac impairment (platform E-care) in an internal medicine unit]. / Expérimentation d'une plateforme de détection automatisée des situations à risque de décompensation cardiaque (plateforme E-care) dans une unité de médecine interne.

INTRODUCTION: Monitoring patients with heart failure by telemedicine systems is a potential means susceptible to optimize the management of these patients and avoid life-threatening emergencies. In this context, we experimented in internal medicine unit an e-platform E-care dedicated to automated, intelligent detection of situations at risk of heart failure. METHODS: The E-care platform based on medical sensors (blood pressure, heart rate, O2, weight), communicating (Bluetooth), to go up, in real time, to an intelligent physiological information and an analysis of the ontology medical, leading ultimately to the generation of alerts. After a development phase (proof of concept), the E-care platform has been deployed and tested by health professionals and patients in an internal medicine unit with 20 beds, opened on emergencies to the Strasbourg University Hospitals. RESULTS: One hundred and eighty patients were included and 1500 measurements were obtained. The patient profile included in this experiment was an elderly patient, with comorbidity in 90% of cases, with a loss of autonomy in 25%. Health professionals were using E-care platform every day to their great satisfaction. This experiment made it possible to validate the technology choices, to consolidate the system, and to test the robustness of the platform E-care. The collection continuously allowed us to have the critical number of patients for more detailed analysis of the relevance of alerts related to heart impairment. A preliminary analysis showed the relevance of the generated alerts. CONCLUSION: Preliminary results following the deployment of E-care platform in hospitals appear to show the relevance of technological choices, tools and solutions developed and adopted. This telemedicine system allows automatic, non-intrusive, generate alerts related to the detection of situations at risk for heart failure. Ultimately, E-care was capable of preventing hospitalization. A home deployment is currently underway.

Telomere shortening: a new prognostic factor for cardiovascular disease post-radiation exposure.

Telomere length has been proposed as a marker of mitotic cell age and as a general index of human organism aging. Telomere shortening in peripheral blood lymphocytes has been linked to cardiovascular-related morbidity and mortality. The authors investigated the potential correlation of conventional risk factors, radiation dose and telomere shortening with the development of coronary artery disease (CAD) following radiation therapy in a large cohort of Hodgkin lymphoma (HL) patients. Multivariate analysis demonstrated that hypertension and telomere length were the only independent risk factors. This is the first study in a large cohort of patients that demonstrates significant telomere shortening in patients treated by radiation therapy who developed cardiovascular disease. Telomere length appears to be an independent prognostic factor that could help determine patients at high risk of developing CAD after exposure in order to implement early detection and prevention.

QRS detection using S-Transform and Shannon energy.

This paper presents a novel method for QRS detection in electrocardiograms (ECG). It is based on the S-Transform, a new time frequency representation (TFR). The S-Transform provides frequency-dependent resolution while maintaining a direct relationship with the Fourier spectrum. We exploit the advantages of the S-Transform to isolate the QRS complexes in the time-frequency domain. Shannon energy of each obtained local spectrum is then computed in order to localize the R waves in the time domain. Significant performance enhancement is confirmed when the proposed approach is tested with the MIT-BIH arrhythmia database (MITDB). The obtained results show a sensitivity of 99.84%, a positive predictivity of 99.91% and an error rate of 0.25%. Furthermore, to be more convincing, the authors illustrated the detection parameters in the case of certain ECG segments with complicated patterns.

Fast 4D Microscopy.

Many cellular processes involve fast movements of weakly labeled cellular structures in all directions, which should be recorded in 3D time-lapse microscopy (4D microscopy). This chapter introduces fast 4D imaging, which is used for sampling the cell's volume by collecting focal planes in time-lapse mode as rapidly as possible, without perturbing the sample by strong illumination. The final images should contain sufficient contrast allowing for the isolation of structures of interest by segmentation and the analysis of their intracellular movements by tracking. Because they are the most sensitive, systems using wide-field microscopy and deconvolution techniques are discussed in greater depth. We discuss important points to consider, including system components and multifunctionality, spatial resolution and sampling conditions, and mechanical and optical stability and how to test for it. We consider image formation using high numerical aperture optics and discuss the influence of optical blur and noise on image formation of living cells. Spherical aberrations, their consequences for axial image quality, and their impact on the success of deconvolution of low intensity image stacks are explained in detail. Simple protocols for acquiring and treating point spread functions (PSFs) and live cells are provided. A compromise for counteracting spherical aberration involving the use of a kit of immersion oils for PSF and cell acquisition is illustrated. Recommendations for evaluating acquisition conditions and deconvolution parameters are given. Finally, we discuss future developments based on the use of adaptive optics which will push back many of today's limits.

Multiple-objective microscopy with three-dimensional resolution near 100 nm and a long working distance.

The resolution of microscopes is limited by the sizes of their point-spread functions. The invention of confocal, theta, and 4Pi microscopes has permitted the classic Abbe limit to be exceeded. We propose the use of a combination of 4Pi and theta microscopy to decrease resolution by using four illumination objectives and two detection objectives. Using middle numerical aperture, long-working-distance objectives yielded a resolution near 100 nm in the three dimensions, which opens the possibility of exploring large volumes with a high resolution.

Influence of S9788, a new modulator of multidrug resistance, on the cellular accumulation and subcellular distribution of daunorubicin in P-glycoprotein-expressing MCF7 human breast adenocarcinoma cells.

A triazinoaminopiperidine derivative synthesized as a modulator of multidrug resistance, S9788, was investigated in the human breast adenocarcinoma MCF7DXR cell line expressing P-glycoprotein. In addition to being less sensitive to daunorubicin, the resistant cell line showed dramatic alterations in the subcellular distribution of daunorubicin, as observed via fluorescence microscopy and quantified via tritiated daunorubicin nuclear distribution analysis. Compared to verapamil and cyclosporin A at 2 and 5 mumol/liter, S9788 proved to be more potent in restoring the cellular accumulation and the subcellular distribution of daunorubicin in the resistant cells. Significant activity of S9788 was observed at 2 mumol/liter, which is clinically achievable, and S9788 restored the nuclear distribution of the drug to the level observed in the parental sensitive cell line. Consequently, the restoration of the cytotoxicity of daunorubicin by S9788 was nearly complete (> 90%) at 2 mumol/liter, wheras cyclosporin A reached this level of activity at 5 mumol/liter, and verapamil was always less active at both concentrations. These results suggest that the modulation of multidrug resistance by S9788 is not only related to the enhancement of the cellular accumulation but also especially by the restoration of the subcellular distribution of the drugs to their nuclear sites of action.