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The splitting of carbon dioxide was investigated for a coaxial dielectric barrier discharge, which was operated with nanosecond high-voltage pulses of 500 ns and amplitudes up to 20 kV at ambient temperature and atmospheric pressure. A non-thermal plasma could be established across a gap distance of 4 mm and a length of 90 mm for gas flows of 30–210 sccm of pure CO2 and with admixtures of Argon. The application of high-voltage pulses of either positive or negative polarity resulted in distinct differences in effective conversion and CO production. The highest observed conversion of 6.6%, corresponding to a CO production of 7%, was achieved for positive high-voltage pulses of 20 kV that were applied with a repetition rate of 3 kHz for a ratio of CO2:Ar of 1:2 at a flow rate of 30 sccm. Conversely, an operation with negative high-voltage pulses, for otherwise the same operating parameters, resulted in an effective conversion of only 5.3% and CO production of 5.4%. The corresponding conversion rates for specific energy input (SEI), concerning different operating parameters, could be related to reaction enthalpies that were calculated from thermodynamic functions. The differences in polarity were associated with discharge characteristics, i.e., plasmas appeared more filamentary for positive high-voltage pulses. In this case, a visible plasma could also be established for much lower pulse amplitudes. Graphical Abstract

Resumen Las perdidas de sustancia (PDS) de la region craneocervical pueden definirse como amplias o complejas cuando sus extensiones sobrepasan las localizaciones clasicas, presentan dimensiones poco comunes y/o se inscriben en condiciones etiologicas o patologicas particulares. En su tratamiento se emplea una combinacion metodica y planificada de tecnicas de cirugia reconstructiva convencionales a las que se anaden especificidades que permiten superar el marco habitual impuesto por estas PDS. El cirujano debe tener en cuenta muchos factores, poseer conocimientos avanzados de los procedimientos de reconstruccion clasicos y saber adaptarse a la singularidad de cada caso. En este articulo, se presentan los principios fundamentales del tratamiento de estos casos complejos y las bases indispensables para un tratamiento adecuado.

Microsurgery (MS) is a discipline addressed by many specialties and it is our interest to be able to carry out a pedagogical assessment of the Master Degree in Reconstructive Microsurgery (MRM) as a training program in MS.The MRM is a hybrid, blended program (virtual and face-to-face), developed in 12 modules, over a 2-year duration, which completes 2625 hours. This program is directed by recognized professors in the discipline from different parts of the World and enrolls 35 students per edition.The program reserves 35% of the places for students from emerging countries. Once each of the modules has been received and the exams passed, the students will undergo a period of clinical immersion in the reference centers around the world and after defending the research project they will be able to receive the distinction of the Master granted by the Autonomous University of Barcelona (UAB).There have been 11 editions of MRM since 2009 without interruption, with an enrollment of 400 students, 83% received the MRM degree. 65% work as Microsurgeons. 60% were Men and 40%, Women. 32% have become MS leaders in each region.We consider that the MRM is a solid, reproducible and adaptable program that guarantees each one of the pedagogical aspects. The program is unique and brings together all the qualities so that students have the necessary tools and thus make a safe start in MS.

The potential of electrical impedance spectroscopy (EIS) was demonstrated for the investigation of microstructural properties of osseous tissue. Therefore, a deep neural network (DNN) was implemented for a sensitive assessment of different structural features that were derived on the basis of dielectric parameters, especially relative permittivities, recorded over a frequency range from 40 Hz to 5 MHz. The advantages of the developed method over conventional approaches, including equivalent circuit models (ECMs), linear regression and effective medium approximation (EMA), is the comprehensive quantification of bone morphologies by several microstructural parameters simultaneously, such as bone volume fraction (BV/TV), bone surface-volume-ratio (BS/BV), structure model index (SMI), trabecular number (Tb.N) and trabecular thickness (Tb.Th). The comparison of predictions of the DNN with an analysis of µCT-images confirmed a high accuracy for different microstructural parameters, which was indicated by corresponding Pearson correlation coefficients, especially for Tb.Th (r = 0.89) and BS/BV (r = 0.80). Concurrently, the approach was able to unambiguously discriminate anatomically similar bone regions (femoral head, greater trochanter and femoral neck) and therefore was capable to determine the morphological status of osseous tissue in detail. The classification was more discriminative than one based on classical linear discriminant analysis (LDA), due to the distinguishing features extracted by the DNN model. Accordingly, the method and model can serve as a potential tool for evaluating bone quality and bone status.

International audience; Background: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival.Patients and methods: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015.Results: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (p = 0.004), diabetes (p = 0.02) and advanced stage (p = 0.03) were found to have a significant negative impact on OS. Diabetes (p = 0.001), alcohol consumption (p = 0.003) and advanced stage (p = 0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (p = 0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (p = 0.00005) and DFS (p = 0.0005). Postoperative radiotherapy had no impact in multivariate analysis.Conclusion: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.

Reconstruction of the auricle is challenging to surgeons as a result of its complex anatomy. Defects including the conchal bowl and the external auditory canal (EAC) do not accept imperfection as functional consequences may add to aesthetic ones. Local flaps that are relying mainly on posteriorly based auricle flaps do not represent ideal solutions. This study aims to report the perforator modification of an anteriorly based pre-auricular flap that matches all requires goals of reconstruction.From 2015 to 2019, three capillary perforator-based island flaps (c-PBIF), with the Superficial Temporal Artery (STA) as source pedicle, were performed to reconstruct a combined Conchal Bowl-External Auditory Canal (CB-EAC) defect, secondary to basal cell carcinoma resection. Free margins were obtained via the Tubigen micrographic approach. All three flaps were raised on the perforator originating from the superficial temporal pedicle. In 2 of the cases, the perforator was found at the level of the tragus while in the last case, it was found 1cm more distal. Capillary perforators were isolated and dissected down to their origin from the STA thereby increasing their arc of rotation and pliability. The median follow-up time was 4 years.All flaps survived. Aesthetic results were excellent leaving no distortion of the external ear and the hollow aspect of the conchal was well supported. The tragus mount was preserved, EAC lining was secured, and good audition was restored with no bulging of the flap into the canal in all the cases.Harvesting pre-auricular flaps as c-PBIFs are safe and acts as an excellent solution for the reconstruction of the challenging combined CB-EAC defect. It allows a one-stage reconstruction that does not need a secondary revision, it also gives excellent correction and functional results. We would recommend it as a useful option for the reconstruction of the conchal-EAC defects.

Medicinal mushrooms contain highly valuable substances with proven positive effects on human health. To extract these components, different methods are available. Most of them suffer from individual disadvantages, therefore making them economically unviable. Pulsed electric fields (PEFs) could provide an opportunity to improve these processes. PEFs cause pore formation of cell membranes, facilitating substance transport out of cells. Thus, the influence of this technique on the extraction yield of medicinal mushrooms was studied for the first time. Lentinus edodes was used as model case and PEF treatment was compared with standard Soxhlet extraction alone. A square pulse generator (Electro Square Porator™ ECM 830) with a voltage of 3 kV and pulse length of 100 μs was used for PEF treatment. Extraction was studied for fresh and dried fruiting bodies, and dichloromethane and hot water extracts were analyzed. Extracts were quantified gravimetrically, and carbohydrate yields were also determined qualitatively with GC-MS and quantitatively with anthrone method. PEFs could increase in particular the yield of water-soluble compounds of fresh mushroom material. However, the lipid fraction was not affected by PEF in neither fresh nor dried material.

Elevated serum homocysteine, an intermediate of cellular one-carbon metabolism, is an independent risk factor for cardiovascular disease (CVD). Folate deficiency increases serum homocysteine and may contribute to CVD progression. Vascular smooth muscle cells (VSMCs) regulate vascular contractility, but also contribute to repair processes in response to vascular injury. Nutritional deficiencies, like folate deficiency, are thought to impact on this phenotypic plasticity, possibly by epigenetic mechanisms. We have investigated the effect of folate deficiency on VSMCs in two cell culture systems representing early and late stages of smooth muscle cells differentiation. We find that folate deficiency promotes differentiation towards a more contractile phenotype as indicated by increased expression of respective marker genes. However, microarray analysis identified markers of striated muscle as the predominant gene expression change elicited by folate deficiency. These changes are not merely a reflection of cell cycle arrest, as foetal calf serum restriction or iron deficiency do not replicate the gene expression changes observed in response to folate deficiency. Folate deficiency only has a marginal effect on global DNA methylation. DNA methylation of CpG islands associated with genes regulated by folate deficiency remains unaffected. This supports our earlier findings in a mouse model system which also did not show any changes in global DNA methylation in response to folate and vitamin B6/B12 deficiency. These data suggest that folate deficiency enhances the expression of smooth muscle marker gene expression, promotes a shift towards a skeletal muscle phenotype, and does not regulate gene expression via DNA methylation.

Electroactive hydrogels can be used to influence cell response and maturation by electrical stimulation. However, hydrogel formulations which are 3D printable, electroactive, cytocompatible, and allow cell adhesion, remain a challenge in the design of such stimuli‐responsive biomaterials for tissue engineering. Here, a combination of pyrrole with a high gelatin‐content oxidized alginate‐gelatin (ADA‐GEL) hydrogel is reported, offering 3D‐printability of hydrogel precursors to prepare cytocompatible and electrically conductive hydrogel scaffolds. By oxidation of pyrrole, electroactive polypyrrole:polystyrenesulfonate (PPy:PSS) is synthesized inside the ADA‐GEL matrix. The hydrogels are assessed regarding their electrical/mechanical properties, 3D‐printability, and cytocompatibility. It is possible to prepare open‐porous scaffolds via bioplotting which are electrically conductive and have a higher cell seeding efficiency in scaffold depth in comparison to flat 2D hydrogels, which is confirmed via multiphoton fluorescence microscopy. The formation of an interpenetrating polypyrrole matrix in the hydrogel matrix increases the conductivity and stiffness of the hydrogels, maintaining the capacity of the gels to promote cell adhesion and proliferation. The results demonstrate that a 3D‐printable ADA‐GEL can be rendered conductive (ADA‐GEL‐PPy:PSS), and that such hydrogel formulations have promise for cell therapies, in vitro cell culture, and electrical‐stimulation assisted tissue engineering.

Resume Introduction Le cancer du sein et sa prise en charge restent un probleme majeur de sante publique chez la femme. L’epidemiologie des complications liee a la radiotherapie apres une reconstruction mammaire immediate prothetique (RMIP) reste insuffisante et ses consequences esthetiques mal definies. L’objectif de ce travail etait de comparer les taux de complications et les resultats esthetiques des reconstructions mammaires immediates (RMI) par prothese avec et sans radiotherapie, afin de determiner les facteurs de risques de complications et de mauvais resultats esthetiques. Materiel et methode Une etude retrospective a ete conduite entre janvier 2014 et decembre 2016 portant sur des patientes atteintes d’un cancer du sein et devant beneficier d’une mastectomie totale sous cutanee (MTSC) avec une RMIP. Le critere d’evaluation etait le taux d’echec de reconstruction et le rendu esthetique global, les criteres secondaires evaluaient le taux de complications precoces et tardives. Il fut realise une analyse multivariee pour deceler des facteurs de risques predictifs de complication. Resultats Trois cent trente-trois patientes ont ete incluses : 157 dans le bras radiotherapie et 176 pour le groupe sans radiotherapie. Les caracteristiques preoperatoires etaient comparables. Le suivi moyen etait de 1 a 3 ans sans perdu de vue. Le resultat sur le critere de jugement principal montrait que les patientes qui avaient beneficie d’une radiotherapie avaient le meme risque d’echec de reconstruction que les patientes non irradiees. L’analyse en sous-groupe ne revelait aucune difference significative : 12,7 % d’echec de reconstruction pour le bras irradie versus 12,5 %. Concernant l’evaluation de l’alteration des resultats esthetiques, il fut constate comme difference un meilleur taux de patientes avec d’« excellents » resultats dans le bras sans radiotherapie (35 % vs 8,2 %). Les resultats sur les criteres secondaires etaient comparables. Conclusion La radiotherapie chez les patientes beneficiant d’une RMIP n’augmente pas le risque d’echec de reconstruction et de mauvais resultats esthetiques comparativement aux patientes non irradiees. Il est donc licite de proposer pour toutes patientes devant beneficier d’une MTSC suivie d’une radiotherapie, une RMIP et ainsi de leur eviter une reconstruction secondaire, plus impactante sur le plan psychologique.

New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9&ndash, 1.0 kV/cm and 100-&mu, s pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation, however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment.

Low-temperature plasma with reactive species including the hydroxyl radical is found very effective for the degradation of many pharmaceuticals and macromolecular organic matter in wastewater. The most efficient way is to excite plasma directly in the wastewater using high-voltage sub-microsecond pulses which prevents the corona discharges developing into arc discharges. Recently, plasma generated with high-voltage pulses of only several hundred nanosecond durations has been found to be especially efficient. Therefore, an all solid-state sub-microsecond pulse generator prototype based on the Marx concept is constructed, with MOSFET power semiconductor devices. This pulse generator is able to generate rectangular pulses with adjustable durations in impedance-varying wastewater. The sub-microsecond signals are generated by field-programmable gate array, and simulations of the driving circuits are carried out to optimize the driving signals so as to trigger the switches synchronously in a few nanoseconds. First, experiments show that sub-microsecond pulses with amplitudes over 7 kV and a minimum pulse duration of about 100 ns can be generated. Both rise time and fall time are about 22 ns. Pulse frequency up to 30 kHz is achieved. Besides, most of these parameters can be adjusted. The pulse generator itself is compact and portable.

Objective We analyzed the outcomes for patients with a retropharyngeal internal carotid artery (ICA) who underwent a transoral robotic surgery (TORS) procedure involving a cervical-transoral robotic oropharyngectomy course with free flap reconstruction. Methods Patients were included in the prospective multicentric trial NCT02517125. These patients were scheduled to undergo surgery for an oropharyngeal localization. By pre-operative CT scan and MRI it was determined that they had a retropharyngeal internal carotid artery. Results Three patients had a retropharyngeal ICA: a patient with a 35 mm synovial sarcoma of the tonsillar fossa, a patient with a T2N2b squamous-cell carcinoma (SCC) of the glossotonsillar sulcus, and a patient with a T3N0 SCC of the tonsillar fossa in a previously irradiated field. These patients encountered neither preoperative nor postoperative complications. Conclusions In our experience, TORS for oropharyngeal cancers appears to be feasible in patients with a retropharyngeal ICA, provided that the procedure has been adapted for complex situations. Level of evidence 4.

Pulsed electrical discharges in water were used for nanostructuration of the polysilane-silicon quantum dots (SiQDs) composite dispersed in a cellulose acetate matrix. For this purpose, the polysilane-SiQDs composite was synthesized by chain scission of a poly[diphenyl-co-methyl(H)] oligomer in the presence of molten sodium and catalytic amounts of methyl(H) dichlorosilane. The resulting solid was utilized to prepare free standing thin films using the cellulose acetate matrix as support. Samples of these films were exposed to nanosecond pulsed electrical discharges in water. Through this approach, chemo-mechanical nanostructuration of specific silicon-based structures occurred by removing the excess of polysilane and by oxidative action. Fluorescence measurements of the plasma treated samples showed a higher intensity compared to the untreated ones. The elemental composition and the morphology of the film surface were investigated by TEM, XPS, UHR-SEM and AFM analysis. Such a technique represents a new approach toward a selective processing of the polysilane-SiQDs composite to obtain patterns with different optoelectronic properties on various supports.

Archaeological and geomorphological investigations of Little Bluff (47Tr32), in Trempealeau, Wisconsin, reveal how and, possibly, why this loess-capped sandstone ridge spur was anthropogenically altered in the mid-eleventh century A.D. Project excavation units and trenches dug in 2010–2011 revealed the timing, rate of completion, structure, symmetry, and orientation of the construction. In addition to delineating construction details and associated archaeological features, our research suggests that Cahokians, by sculpting and rebuilding this ridge spur, were actively positioning themselves vis-a-vis the wider Mississippi Valley landscape, if not the cosmos generally.

Nanosecond pulsed electric fields (nsPEFs) applied to cells can induce different biological effects depending on pulse duration and field strength. One known process is the induction of apoptosis whereby nsPEFs are currently investigated as a novel cancer therapy. Another and probably related change is the breakdown of the cytoskeleton. We investigated the elasticity of rat liver epithelial cells WB-F344 in a monolayer using atomic force microscopy (AFM) with respect to the potential of cells to undergo malignant transformation or to develop a potential to metastasize. We found that the elastic modulus of the cells decreased significantly within the first 8 min after treatment with 20 pulses of 100 ns and with a field strength of 20 kV/cm but was still higher than the elasticity of their tumorigenic counterpart WB-ras. AFM measurements and immunofluorescent staining showed that the cellular actin cytoskeleton became reorganized within 5 min. However, both a colony formation assay and a cell migration assay revealed no significant changes after nsPEF treatment, implying that cells seem not to adopt malignant characteristics associated with metastasis formation despite the induced transient changes to elasticity and cytoskeleton that can be observed for up to 1 h.

This study presents a cost-efficient single-step-method to synthesize nanographite from isopropanol by bipolar pulsed electric discharges. The influence of pulse width within the nanosecond range, repetition frequency within the kilohertz range and processing time on the product was systematically investigated by Raman spectroscopy, high-resolution transmission electron microscopy and gas chromatography - mass spectrometry. It was found that long pulses in the microsecond range promote the creation of amorphous and oxidic carbon structures. Although, hydrocarbon cracking and subsequent graphitization do occur, these process conditions are not suitable to drive intermediate reduction processes. In contrast, applying short pulses in the nanosecond regime ensures fast reduction processes and formation of graphene-related nanostructures. The number of observed nanographite layers lies in the range of 3–13 with an average interlayer spacing of 3.4(0.3) A and an average distance between defects of 11.5(6.0) nm meaning that the produced nanographite is in the area of small defect density. Furthermore, no significant influence of process times on the product properties over a period up to 15 min was observed, indicating good process homogeneity.

Obesity is the abnormal accumulation of fat in the body. It is an increasing global health challenge with health, social, and economic costs. Health risks associated with obesity include diabetes, hypertension, cardiovascular diseases, stroke, osteoarthritis, sleep apnea, and some types of cancer. The treatment/management of obesity has involved the use of dietary intervention alongside a few synthetic drugs, currently on the market, which is reported to have unpleasant side effects. For this reason, it is paramount to search for antiobesity drugs from synthetic and natural sources aimed at existing and/or new therapeutic targets. This chapter highlights a number of antiobesity lead compounds discovered from various classes of phytochemicals acting on identified therapeutic targets, which have been evaluated through preclinical and clinical studies in an attempt to develop them into antiobesity drugs, although most of them are yet to make it into the commercial market.

Pulsed electrical discharges generated at atmospheric pressure in liquids have become one of the most interesting techniques for the functionalization of polymers. The generation of plasmas in liquids with short high voltage pulses for material modification is very new, but the approach offers the potential to be highly flexible with regard to their range of applications. When water is subjected to a high electric field, a high amount of excited species, such as hydrogen, oxygen, nitrogen, and hydroxyl radicals, are produced, which may efficiently interact with molecules and bulk-materials, inducing structural modifications. The material surface tailoring with different functionalities is possible, due to a wide range of functional groups that can be generated in liquid plasma by using anionic or cationic solutions. Polymer nanocomposites may be synthesized in a one-step process, nanomaterials being generated in plasma discharge and incorporated into the polymer matrix which is also placed in the plasma reactor during this process. Different reactions set in motion are determined by the way the electrical energy that is provided is dissipated in different mechanisms. Our experiments have shown that structural modifications of polymers and nanocomposite obtained when using nanosecond voltage pulses differ significantly from treatments with plasmas in liquids that have been generated with longer (microsecond) pulse duration. Therefore, pulse electrical discharges in liquids may be used for a controlled and efficient structural modification of polymers.

International audience; BACKGROUND:Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established.MATERIAL & METHODS:Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed.RESULTS:In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor.CONCLUSION:Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

Water is a scarce resource that is continuously threatened by pollution, growing population and strain on available reservoirs due to fast developing economies. A problem of considerable concern is posed by anthropogenic pollutants, foremost artificial organic compounds. Especially pharmaceutical residues with their intended stability are found in increasing concentrations in potable water in regions such as Chennai. Despite high standards and blanket coverage of water purification technologies for water, currently available methods most likely fail to remove many of the accumulating pharmaceuticals sufficiently. This shortcoming includes advanced oxidation technologies that are currently investigated, such as UV exposures, ozonation, hydrogen peroxide admixture and combinations of these approaches. The objective of this paper is the development of a novel and flexible technology for water purification. The immediate target is the removal of pharmaceutical residues in drinking water but other pollutants and also wastewaters will be addressed as well. Using non-thermal plasma, the closed process does not require chemical supplies or direct manual processes control. Therefore, the technology is appropriate in conditions where it is difficult to maintain a supply infrastructure. The method is only relying on electrical energy and can be adopted according to pollution levels and also operated as batch process by a discontinued power supply. With this approach, methods based on electrical power only are intended as a corner stone of a smart water treatment management that can be implemented at different locations along the supply chain on different scale. Accordingly, it is specifically anticipated a suitable enabler of smart grids.

Improved health span and lifespan extension in a wide phylogenetic range of species is associated with the induction of the environmental cell stress response through a signalling pathway regulated by the transcription factor Nrf2. Phytochemicals which stimulate this response may form part of therapeutic interventions which stimulate endogenous cytoprotective mechanisms, thereby delaying the onset of age-related diseases and promoting healthy ageing in humans. In order to identify compounds that activate the Nrf2 pathway, a cell-based reporter system was established in HepG2 cells using a luciferase reporter gene under the control of the Nqo1 promoter. Sulforaphane, an isothiocyanate derived from cruciferous vegetables and a known activator of the Nrf2 pathway, was used to validate the reporter system. The transfected cell line HepG2 C1 was subsequently used to screen natural product libraries. Five compounds were identified as activating the bioluminescent reporter by greater than 5-fold. The two most potent compounds, MBC20 and MBC37, were further characterised and shown to stimulate endogenous cytoprotective gene and protein expression. The bioluminescent reporter system will allow rapid, in vitro identification of novel compounds that have the potential to improve health span through activation of the environmental stress response.

Breast cancer and its treatment remains a public health problem. There is still a lack of epidemiological data concerning complications and aesthetic results bound to radiotherapy after an immediate breast reconstruction. The objective of this study was to compare outcomes of immediate breast reconstruction regardless to the use of radiotherapy (history of radiotherapy or adjuvant radiation therapy), in order to determine risk factor of complications and bad aesthetic results.We conducted a retrospective study between January 2014 and December 2016 at the hospital "Gustave Roussy" in Paris, concerning breast cancer patients who needed immediate breast reconstruction after total mastectomy. The primary endpoint was to assess the failure rate of reconstruction and the aesthetic result, the secondary endpoint assessed the early and late rate of complications. We realized a multivariate analysis in order to identify risks factors that may predict complications.Three hundred and thirty three patients have been included: 157 in the "radiotherapy group" compared to 176 in the "no radiotherapy group". Preoperative characteristics were comparable. Average follow-up was between 1 and 3years without missing. Patients who benefited from radiotherapy had an equal risk failure of reconstruction. The subgroup analysis revealed non-significant differences: 12.7% failure rate reconstruction in the "radiotherapy group" vs. 12.5%. We could notify a better rate of "excellent results" in the "no radiotherapy group": 35% vs. 8.2%. Secondary outcomes were comparable.Radiotherapy related to immediate breast reconstruction didn't increase the failure rate of reconstruction or aesthetic results, comparatively to non-irradiated patients. It is therefore permissible to suggest an immediate breast reconstruction to any patients which would benefit from a total mastectomy followed by radiotherapy; in order to prevent them from a secondary breast reconstruction, who could be physically and psychologically more impactful.