Bifeo3 Harmonic Nanoparticle (Bfo-Hnps) Use for the Stem Cell Tracking: Labeling Investigation by Non Linear Microscopy and X-Ray Fluorescence

Duchenne Muscular Dystrophy is the most common form of degenerative muscle disease; currently, there is no effective treatment. In 2011, our group showed that an adult stem cell population (MuStem) isolated from healthy dog skeletal muscle induces long-term muscle repair and striking clinical efficacy after its systemic delivery in clinically relevant dystrophic dog. During last years, our group isolated the human counterparts (hMuStem) [1]. To achieve the full therapeutic potential of the hMuStem cells, their homing process, survival and engraftment post-transplantation must be clearly understood. BiFeO3 harmonic nanoparticles (BFO-HNPs) were used as probes for the hMuStem cell tracking [2]. We demonstrate the possibility of identifying <100 nm BFO-HNPs in depth of muscle tissue at more than 1 mm from the surface by multiphoton microscopy. Based on this successful assessment, we monitor over 14 days any modification on proliferation and morphology features of the hMuStem cells upon exposure to BFO-HNPs revealing their high biocompatibility. To complete these studies, the stability of BFO-HNPs was followed in the labeled hMuStem cells by investigation of Bi and Fe X-ray fluorescence mapping on both Nanoscopium (Soleil, Gif-sur-Yvette, France) and ID16B (ESRF, Grenoble, France) beamlines. In this work, correlation between non-linear microscopy and X-Ray fluorescence was done. Bi and Fe X-Ray fluorescence allowed us to localize with high resolution the BFO-HNPs in the labeled hMuStem cells and the variation of Bi/Fe ratio was analyzed to detect possible dissociation of the nanoparticles in the labeled cells

The Behavioural Response of Australian Fur Seals to Motor Boat Noise

Australian fur seals breed on thirteen islands located in the Bass Strait, Australia. Land access to these islands is restricted, minimising human presence but boat access is still permissible with limitations on approach distances. Thirty-two controlled noise exposure experiments were conducted on breeding Australian fur seals to determine their behavioural response to controlled in-air motor boat noise on Kanowna Island (39°10′S, 146°18′E). Our results show there were significant differences in the seals' behaviour at low (64–70 dB) versus high (75–85 dB) sound levels, with seals orientating themselves towards or physically moving away from the louder boat noise at three different sound levels. Furthermore, seals responded more aggressively with one another and were more alert when they heard louder boat noise. Australian fur seals demonstrated plasticity in their vocal responses to boat noise with calls being significantly different between the various sound intensities and barks tending to get faster as the boat noise got louder. These results suggest that Australian fur seals on Kanowna Island show behavioural disturbance to high level boat noise. Consequently, it is recommended that an appropriate level of received boat sound emissions at breeding fur seal colonies be below 74 dB and that these findings be taken into account when evaluating appropriate approach distances and speed limits for boats

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Human muscle-derived stem cells "MuStem" : immunomodulatory properties and regenerative potential

Les dystrophies musculaires (MD) sont un groupe de maladies qui restent sans traitement malgré des avancées récentes probantes en médecine régénérative. Si l’identification des cellules souches adultes (ASC) et de leur potentiel myogénique ont permis d’établir de nouvelles propositions thérapeutiques, les démonstrations de potentialités de réparation des candidats humains dans des contextes applicables en clinique sont cependant peu nombreuses. De plus, l’interaction des ASC avec le système immunitaire qui est un acteur clé de la physiopathologie des MD est peu renseignée. L’UMR a isolé dans le muscle une population d’ASC nommées MuStem et démontré l’efficacité de son administration locale et systémique en contexte allogénique dans un modèle canin de MD. Les cellules MuStem ont été récemment caractérisées chez l’Homme (hMuStem) et décrites pour leur contribution efficace à la formation de fibres après injection dans un muscle lésé de souris immunodéficiente. Mon travail de thèse a consisté à approfondir la caractérisation de la population hMuStem en terme de propriétés immunomodulatrices et de potentiel régénératif. In vitro, une modulation de la réponse immune par les cellules hMuStem a été montrée avec l’inhibition de la prolifération des lymphocytes T (LT), la suppression de la cytotoxicité des LT CD8+ et la genèse de cellules régulatrices. Par ailleurs, une participation à la régénération musculaire a été établie chez le primate non humain dans un contexte de transplantation locale cliniquement pertinent. Collectivement, ces résultats renseignent les modalités d’action des cellules MuStem et renforcent leur positionnement comme candidat pour le traitement des MD.Muscular dystrophies (MD) are a group of disorders that today remain without effective treatment despite recent and conclusive advances in regenerative medicine. While the identification of adult stem cells (ASC) and their myogenic potential have led to new therapeutic proposals, there are however few demonstrations of the repair potential for human candidates in clinically applicable contexts. In addition, little is known about the interaction of ASC with the immune system,a key player in the pathophysiology of MD. The UMR has isolated a population of ASCs called MuStem in muscle and demonstrated the efficacy of its local and systemic administration in an allogeneic context in a canine model of MD. MuStem cells have recently been characterized in humans (hMuStem) and described for their effective contribution to fiber formation after injection into injured muscle of immunodeficient mice. The aim of my PhD was to further characterize population of hMuStem cells in terms of immunomodulatory properties and regenerative potential. In vitro, modulation of the immune response by hMuStem cells was demonstrated with inhibition of Tlymphocyte (TL) proliferation, suppression of CD8+ TL cytotoxicity and production of regulatory cells. In addition, participation in muscle regeneration has been established in the non-human primate in a clinically relevant local transplantation context. Collectively, these results highlight the modalities of action of MuStem cells and reinforce their positioning as a candidate for the treatment of MD

Inventaire numérique de la correspondance de Mme du Deffand

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Éditer une correspondance du XVIIIe siècle à l’ère du numérique : Mme du Deffand

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Isolation and Characterization of MuStem cell-derived extracellular vesicles: potential roles in regenerative medicine?

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Isolement et caractérisation des vésicules extracellulaires sécrétées par les cellules souches humaines MuStem : rôle potentiel en médecine régénératrice ?

Isolement et caractérisation des vésicules extracellulaires sécrétées par les cellules souches humaines MuStem : rôle potentiel en médecine régénératrice ?. XXXème congrès de l'AFH: les nouveaux mondes de l'histologi

Strategies used by emergency care professionals to handle interpersonal difficulties with patients: a qualitative study

Objectives Identify the strategies implemented by emergency care professionals when facing tension and interpersonal violence from patients and their friends and family.Design Descriptive qualitative study based on 38 semidirective interviews.Participants Doctors, nurses, nursing assistants and administrative staff.Setting Four emergency departments (EDs) from three French university hospitals.Results According to the medical professionals interviewed, the difficulties that they encounter with patients or their accompanying family members can be explained by a lack of understanding of the functioning of EDs, by a general increase in individualistic behaviours leading to a lack of civility or by deviant behaviours (related to toxic substance abuse or mental illness). While managing deviant behaviours may sometimes require a collective intervention, ED staff also implement what are essentially individual communication strategies (with the use of rational explanation, seduction and empathy), confrontation or flight to deal with interpersonal difficulties.Conclusions Strategies used by staff members tend to be individualised for the most part, and some, such as confrontational or escape strategies, may not be adapted to all situations. In the face of difficulties between staff and patients, mediators, specialised in resolving conflict, could entrust some cases to professionals.Trial registration number ClinicalTrials.gov Registry (NCT03139110)