Electrochemical preparation of peroxodisulfuric acid using boron doped diamond thin film electrodes

We have investigated the electrochemical oxidation of sulfuric acid on boron-doped synthetic diamond electrodes (BDD) obtained by HF CVD on p-Si. The results have shown that high current efficiency for sulfuric acid oxidation to peroxodisulfuric acid can be achieved in concentrated H2SO4 (>2 M) at moderate temperatures (8–10 °C). The main side reaction is oxygen evolution. Small amounts of peroxomonosulfuric acid (Caro's acid) have also been detected. A reaction mechanism involving hydroxyl radicals, HSO4− and undissociated H2SO4 has been proposed. According to this mechanism electrogenerated hydroxyl radicals at the BDD anode react with HSO4− and H2SO4 giving peroxodisulfate

MyD88-adaptor protein acts as a preventive mechanism for memory deficits in a mouse model of Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with brain innate immune activation mainly mediated by microglia. These cells are known to be activated in the brain of AD patients and to produce inflammatory cytokines and neurotoxic molecules in response to Amyloid beta (Aβ). Activation of microglia can also promote Aβ clearance via Toll-like receptors (TLRs). Myeloid differentiation factor 88 (MyD88) is the adaptor molecule for most of these innate immune receptors, transducing the intracellular signal from TLRs to nucleus.</p> <p>Results</p> <p>Here, we report that more than 50% reduction in MyD88 expression in a mouse model of AD accelerated spatial learning and memory deficits. Brain of APP_swe/PS1-MyD88^+/-mice was characterized by a delay in accumulation of Aβ plaques and increased soluble levels of Aβ oligomers. Furthermore, inflammatory monocyte subset and brain IL-1β gene expression were significantly reduced in APP_swe/PS1 mice with impaired MyD88 signaling.</p> <p>Conclusions</p> <p>These data indicate that activation of MyD88 intracellular signaling pathway, likely by TLRs, acts as a natural innate immune mechanism to restrict disease progression of APP_swe/PS1 mice.</p

Integrative analysis of RUNX1 downstream pathways and target genes

Background: The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results: Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBF[Beta], and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBF[Beta]. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion: This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications

Consensus guidelines for the detection of immunogenic cell death

none82siApoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.Kepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong-Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean-Ehrland; Riganti, Chiara; Rovere-Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei-Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, LorenzoKepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G; Cirone, Mara; Colombo, Maria I; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G; Faggioni, Alberto; Formenti, Silvia C; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong Min; Huang, Xing; Illidge, Tim M; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V; Loi, Sherene; Lowenstein, Pedro R; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean Ehrland; Riganti, Chiara; Rovere Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T; Yang, Haining; Zong, Wei Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenz

Le stridor chez l'enfant (revue de la littérature et étude de 89 dossiers)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Surgery of insular and paralimbic diffuse low-grade gliomas: technical considerations

International audienceOnce considered a "no man's land" especially when invaded by a diffuse low grade glioma (DLGG), the insula remains to this day a surgical challenge. Surgery for insular DLGG involves consideration of its hidden location under the potentially eloquent operculae, the proximity to vascular tree and high density of functions not only in the insular cortex but also in the white fiber pathways passing under the insular lobe. The natural history of DLGG and the potential benefits and consequences of the surgical approach also need a close look. In the last decade, a better knowledge of the functional anatomy and connectivity of this region, as well as an improvement in surgical techniques as direct stimulation mapping, combined with an increasing literature showing a favorable impact of maximal resection for DLGG, were deciding factors in the paradigmatic shift from expectative treatment to early surgical management. Here, our goal is to discuss the structural and functional aspects of the insula, the specificities of insular and paralimbic DLGG by emphasizing the technical considerations of surgery in this region, as well as its oncological and functional outcomes. In summary, this new strategy based upon early maximal safe surgical resection showed both oncological benefit and preservation of quality of life-or even an improvement thanks to epilepsy relief

The landscape of postsurgical recurrence patterns in diffuse low-grade gliomas

International audienceEarly and maximal safe surgical resection optionally followed by adjuvant treatment is currently recommended in diffuse low-grade glioma (DLGG). Although this management delays malignant transformation (MT), recurrence will most often occur. Because this relapse usually arises locally, reoperation can be considered, with possible further chemotherapy/radiotherapy. However, due to a prolonged overall survival, a large spectrum of unusual recurrence patterns begins to emerge during long-term follow-up, beyond the classical slow and local tumor re-growth. We review various atypical patterns of DLGG relapse, we discuss their pathophysiological mechanisms and how to adapt the treatment(s). Those patterns include very diffuse, ipsi- or bilateral gliomatosis-like progression, multicentric recurrence with emergence of remote low-grade or high-grade glioma, leptomeningeal dissemination, acute (early or delayed) local MT or bulky relapse into the operating cavity. This landscape of recurrence patterns may allow physicians to elaborate new tailored therapeutic strategies and scientists to develop original hypotheses for basic research

Le Web 2.0 pour soutenir le réseautage en santé mentale au Québec

Pour soutenir l’accès et l’implantation des meilleures pratiques de réadaptation en santé mentale au Québec, le Centre d’études sur la réadaptation, le rétablissement et l’insertion sociale (www.cerrisweb.com) a mis sur pied une communauté de pratique et organisé des activités Web 2.0 accessibles à distance. Dans cet article, les auteures présentent cette communauté de pratique et les résultats d’une expérience de trois années (2010-2013) concernant l’appréciation de ses membres de deux activités Web 2.0 de dissémination et d’échange de connaissances : la conférence en ligne et le débat-blogue. L’utilisation d’outils Web 2.0 semble une avenue intéressante pour faciliter l’accès aux connaissances et favoriser les échanges entre acteurs du réseau de la santé mentale du Québec.Objectives: To support knowledge application of evidence-based practices in mental health rehabilitation in Quebec, the Centre for Studies on Rehabilitation, Recovery and Social Inclusion (CÉRRIS – www.cerrisweb.com) has set up a community of practice and has organized online activities. In this article, the authors present the community of practice (457 members to date) and the results of a three-year experience aimed at evaluating their appreciation with two online activities of dissemination and knowledge exchange: Web conference and debate blog. Methods: The methodology used in this publication is part of a process of program evaluation. More specifically, a research mixed method was used (concurrent triangulation design). Qualitative data (from qualitative questionnaires) and quantitative data (from Google analytics –participation and attendance data) were collected in parallel and incorporated into analysis step. Forty qualitative questionnaires were completed to identify the benefits, barriers, challenges and facilitators encountered during their participation in the activity. The participants are members of the community of practice of the CÉRRIS and are people with mental illness, family members, practitioners, researchers, students, managers and policy makers in the field of mental health rehabilitation and come from different regions of Quebec, Canada and French speaking areas of Europe. Quantitative data on participation and attendance were collected and analyzed throughout the first three years of implementation of the CÉRRIS. Qualitative data from the questionnaires were analyzed following a content analysis process. Quantitative data were analyzed using Excel. Results: Since September 2010, 14,061 unique visitors navigated on the CÉRRIS website (23,391 visits) and 2,278 people visited the blog (10,393 visits). Ninety-nine members of the community of practice attended at least one of the 13 Web conferences. Web conference allows a) access to evidence-based practices, b) networking and contact between individuals of different areas and c) access to continuing education remotely. A total of 62 members of the community of practice have actively taken part in one of the 5 debates on the blog. The activity of debate blog a) promotes egalitarian exchanges between different actors in mental health sector, b) encourages diversity of viewpoints and c) create a forum for dialogue and reduce stigma towards people with mental illnesses. For both types of Web activities, technological barriers (network security, outdated computer equipment, etc.) restrained the full participation of the participants. However, the assistance received from organizations and their openness towards new technologies has facilitated the experience of participants in both activities. Conclusion: Online activities as Web conference and debate blog are interesting avenues to facilitate access to knowledge and support exchanges between clinical, academic, community-based communities, people who use mental health services and their families