10 research outputs found
Ivabradine in Septic Shock: A Narrative Review
No full textIn patients with septic shock, compensatory tachycardia initially serves to maintain ade- quate cardiac output and tissue oxygenation but may persist despite appropriate fluid and vasopressor resuscitation. This sustained elevation in heart rate and altered heart rate variability, indicative of autonomic dysfunction, is a well-established independent predictor of adverse outcomes in critical illness. Elevated heart rate exacerbates myocardial oxygen demand, reduces ventricular filling time, compromises coronary perfusion during diastole, and impairs the isovolumetric relaxation phase of the cardiac cycle, contributing to ventricular-arterial decoupling. This also leads to increased ventric- ular and atrial filling pressures, with a heightened risk of arrhythmias. Ivabradine, a highly selective inhibitor of the sinoatrial node’s pacemaker current (If or “funny” current), mitigates heart rate by modulating diastolic depolarization slope without affecting contractility. By exerting a selective chronotropic effect devoid of negative inotropic properties, ivabradine shows potential for improving hemodynamics in septic shock patients with cardiac dysfunction. This review evaluates the plausible mechanisms and existing evidence regarding the utility of ivabradine in managing patients with septic shock
Non-coding RNAs in tumor progression and resistance
No full textLes ARN non codants, tels que les miARNs et les lncARNs, sont des régulateurs de l’expression des gènes et peuvent participer à la communication intercellulaire en étant encapsulés dans des petites vésicules extracellulaires. Cependant, leur chargement dans ces vésicules circulantes ainsi que leur rôle dans l’échappement immunitaire et la résistance à la radiothérapie, restent peu connus. Nos travaux montrent que les vésicules extracellulaires de mélanome sont internalisées par des lymphocytes T CD8+ et que leur contenu en miARNs diminue leurs capacités cytotoxiques participant ainsi à l’immunosuppression. Nous avons aussi montré que les cellules de mélanome mutées TP53 sécrètent des vésicules extracellulaires avec un contenu spécifique en miARNs et en lncARNs. Nos résultats suggèrent aussi que la protéine Sam68, dont l’expression est associée aux mutations TP53, contrôle l’expression et l’export de ces ARN non codants dans ces vésicules extracellulaires. Enfin, dans le cancer de la prostate, nous avons montré que l’expression des miARNs est dérégulée dans les cellules tumorales et dans leurs vésicules extracellulaires lors de l’acquisition de la radiorésistance. L’expression du miR-200c-3p est notamment drastiquement diminuée, et sa réexpression resensibilise les cellules radiorésistantes à l’irradiation. En conclusion, ces travaux soulignent le rôle crucial des ARN non codants dans la progression tumorale, l’échappement immunitaire et la résistance à la radiothérapie. Ces résultats pourraient conduire au développement de nouvelles thérapies et/ou de nouveaux biomarqueurs circulants pronostic de la réponse au traitement.Non-coding RNAs, such as miRNAs and lncRNAs, are important regulators of gene expression and can participate in intercellular communication by being encapsulated in small extracellular vesicles. However, little is known about their loading into these vesicles neither in their role in immune escape and resistance to radiotherapy. We found that melanoma extracellular vesicles are internalized by CD8+ T cells, and that their miRNA content reduces their cytotoxic activity to participate in immune suppression. Furthermore, we showed that TP53-mutant melanoma cells secrete extracellular vesicles with a specific miRNA and lncRNA cargo. Our results also suggest that the Sam68 protein, whose expression is associated with TP53mutations, controls the expression and the loading of these non-coding RNAs in melanoma extracellular vesicles. Finally, we showed that miRNA expression is deregulated in prostate cancer cells and their extracellular vesicles during radioresistance acquisition. In particular, miR-200c-3p expression is highly decreased, and its reexpression resensitizes radioresistant cells to irradiation. Altogether, this work highlights the critical role of non-coding RNAs in tumor progression, immune escape and resistance to radiotherapy. These results could lead to the development of new therapies and prognostic biomarkers
Thrombotic risk in patients admitted to the intensive care unit for sepsis : characterization, stratification and therapeutic strategies
No full textObjectifs Les patients hospitalisés en réanimation pour un sepsis sont à haut risque d’accidents thrombotiques (AT) intéressant l’ensemble des circulations (grande, coronaire, petite). Nous souhaitons étudier ce risque thrombotique lors du sepsis (i) au sein de la grande circulation chez les patients présentant une fibrillation atriale de novo (FAN), (ii) au sein de la circulation coronaire chez les patients présentant un infarctus du myocarde (IDM) et (iii) au sein de la petite circulation chez les patients COVID-19 sévère. Par ailleurs, si le risque d’AT pose la question de l’intérêt de la thromboprophylaxie à dose croissante, l’évaluation du risque hémorragique en regard devra être systématique afin d’établir la balance bénéfice/risque d’un tel traitement. Méthodes Nous avons investigué le risque d’événements cardio-vasculaires majeurs (caractérisation et stratification) incluant les ATs, les hémorragies sévères, et le décès au sein de trois populations de patients septiques présentant une FAN, un IDM, ou une COVID-19 sévère par l’étude (i) de marqueurs tels que la dysfonction de l’auricule gauche à l’échocardiographie trans-oesophagienne (ETO) et la troponine cardiaque, et (ii) des scores de risque thrombotique et hémorragique utilisés chez les patients de cardiologie. Nous avons mené une enquête de pratique sur la gestion du risque thrombotique chez les patients ayant une FA lors d’un sepsis. Enfin nous avons effectué deux essais thérapeutiques : l’essai CAFS (Control Atrial Fibrillation Sepsis) de supériorité multicentrique randomisé, contrôlé comparant trois stratégies usuelles de prévention du risque hémodynamique chez les patients en choc septique présentant une FAN (en cours d’inclusion), et l’essai ANTICOVID (ANTIcoagulation in patients with hypoxemic COVID-19 pneumonia) comparant trois stratégies de traitement anticoagulant avec escalade de dose chez des patients présentant une pneumonie hypoxémiante COVID-19. Résultats Le risque d’évènements cardio-vasculaires majeures est élevé au cours d’un sepsis. Chez les patients en FAN, les approches cardiologiques de stratification des risques thrombotiques (anomalies ETO, score CHA2DS2-VASc) et hémorragiques (score HAS-BLED) semblent limitées. Une approche individualisée basée sur l’ETO et le score CHA2DS2-VASc pourrait néanmoins être intéressante. Ce travail a également mieux caractérisé le risque de formation d’un thrombus intra-cardiaque (absence de thrombus dans les 48 h suivant le début de la FA, prévalence rare de la sidération post cardioversion de l’auricule gauche). Enfin, nous avons confirmé l’hétérogénéité de prise en charge des risques hémodynamiques et thrombotiques justifiant la réalisation d’essais thérapeutiques. Chez les patients ayant un IDM au cours d’un sepsis, les approches cardiologiques usuelles de stratification des risques thrombotiques (scores GRACE et TIMI) semblent également limitées. En pratique usuelle, une stratégie invasive avec revascularisation coronaire précoce est très rarement effectuée. Chez les patients explorés par angiographie coronaire, l’incidence d’une coronaropathie obstructive est importante. Chez les patients présentant une pneumonie hypoxémiante COVID-19, le traitement anticoagulant préventif à dose forte, comparé au traitement anticoagulant préventif à dose standard, a été associé à un meilleur bénéfice clinique net, en raison d’une diminution du risque de thrombose et d'un faible risque hémorragique. Le traitement anticoagulant curatif n'a pas apporté de bénéfice supplémentaire. Conclusions Sur une base physiopathologique pro-thrombotique inhérente au sepsis, ce travail a permis (i) de mieux caractériser certaines situations à haut risque thrombotique (FAN, IDM, COVID sévère), (ii) élaborer des stratégies individuelles thérapeutiques de prévention du risque thrombotique (COVID-19), et (iii) poser les bases de futurs essais au sein de populations spécifiques à très haut risque thrombotique.Objectives Patients admitted to intensive care units with sepsis are at high risk of thrombotic events (TEs) throughout the circulatory systems (systemic, coronary, and pulmonary). We aimed to investigate the thrombotic risk during sepsis (i) within the systemic circulation in patients with new-onset atrial fibrillation (NOAF), (ii) within the coronary circulation in patients with acute myocardial infarction (MI), and (iii) within the pulmonary circulation in patients with severe COVID-19. Furthermore, while the risk of TE raises the question of whether thromboprophylaxis doses should be escalated, assessment of associated bleeding risk should be systematic in order to establish the benefit/risk balance of such treatment. Methods We investigated the risk of major cardiovascular events (risk characterization and stratification), including AT, major bleeding and death in three populations of septic patients with NOAF, MI or severe COVID-19 by studying (i) markers such as left atrial dysfunction on transesophageal echocardiography (TEE) and cardiac troponin, and (ii) thrombotic and hemorrhagic risk scores used in cardiology patients. We conducted a practice survey on thrombotic risk management in patients with de NOAF during sepsis. Finally, we carried out two therapeutic trials: the CAFS (Control Atrial Fibrillation Sepsis) multicenter, randomized, controlled superiority trial comparing three usual strategies to prevent hemodynamic risk with NOAF during septic shock (currently being included), and the ANTICOVID (ANTIcoagulation in patients with hypoxemic COVID-19 pneumonia) multicenter, randomized, controlled superiority trial comparing three anticoagulation strategies with dose escalation in patients with hypoxemic COVID-19 pneumonia Results Our work confirmed the high risk of major cardiovascular events during sepsis. In patients with NOAF, cardiological approaches to thrombotic (TEE abnormalities, CHA2DS2-VASc score) and hemorrhagic (HAS-BLED score) risk stratification seem limited. An individualized approach with TEE based on the CHA2DS2-VASc score could nevertheless be of interest. This work also better characterized the risk of intra-cardiac thrombus formation (absence of thrombus within 48 h of AF onset, low prevalence of post-cardioversion left atrial stunning). Finally, we confirmed the heterogeneity of hemodynamic and thrombotic risks management, calling for randomized trials. In patients with MI during sepsis, cardiological approaches to thrombotic risk stratification (GRACE and TIMI scores) also appear limited. In usual practice, an invasive strategy involving early coronary revascularization is very uncommon. In patients investigated using coronary angiography, the incidence of obstructive coronary artery disease is high. In patients with hypoxemic COVID-19 pneumonia, high-dose prophylactic anticoagulation, provided a better net clinical benefit driven by a 4-fold reduction in de novo thrombosis rate with no increase in major bleeding compared with standard-dose prophylactic anticoagulation. Also, therapeutic anticoagulation did not provide additional benefit in comparison with high-dose prophylactic anticoagulation. Conclusions On the basis of the common pro-thrombotic pathophysiology described in septic conditions, our work has made it possible to (i) better characterize clinical situations at particularly high thrombotic risk (NOAF, MI, severe COVID-19 infection), (ii) develop individual therapeutic strategies for thrombotic risk prevention (COVID-19), and (iii) establish the basis for subsequent trials in specific intensive care populations at very high thrombotic risk
The importance of being earnest (and average)
No full textWhen the aim of a study is comparing and contrasting texts of the same genre and achieving a good arrangement for a text clustering, we often resort to lexical-based approaches and appropriate measures of similarity/distance (Burrows, 2002; Juola, 2008; Rudman, 1998, Stamatatos, 2009; Labbé and Labbé, 2001; Tuzzi, 2010) between texts, e.g. cosine similarity, Burrows's Delta, Labbé's intertextual distance, etc. Given the properties and the formula of a distance, we obtain a square matrix that includes n×n cells and n(n-1)/2 positive non-zero non-redundant values that can be exploited for an automatic classification of the n available texts. This distance matrix might be read from an alternative perspective, i.e. as a ranking system: for each text we can sort all the other n-1 texts from the closest to the furthest. The distribution of these ranks among texts represents an interesting object of research (Alvo and Yu, 2014) when we consider the whole corpus and also when we observe groups of texts that share some properties (e.g. they belong to the same author).
A preliminary experiment involved a large corpus of contemporary Italian novels and showed that we can indentify some novels that systematically top positions in all rankings and prove to be close to most of the available texts; on the contrary, we have novels that do not show strong similarities in any list and systematically lie in the furthest positions. This study compared results achieved through different measures and formulated some hypothesis to understand when in text clustering it is worth either to distinguish "average" and "eccentric" novels or disregard them in in-depth investigations
Dynamic Electrochemiluminescence Imaging of Single Giant Liposome Opening at Polarized Electrodes
No full textIn this work, the characterization
of release events from liposomes
has been addressed quantitatively by an electrochemiluminescence (ECL)
imaging strategy. First, ECL reagents ([Ru(bpy)3]2+ and tripropylamine) were encapsulated in sealed giant asymmetrical
liposomes (100 μm in diameter) made of DOPG/DOPC phospholipids.
After sedimentation on an indium tin oxide electrode material, the
opening of liposomes was triggered by polarization of the surface.
Under these conditions, amperometry, epifluorescence imaging, and
ECL imaging were combined and synchronized to monitor and image the
rupture of giant liposomes during the release and subsequent ECL emission
of their redox content. Amperometry allowed the quantification of
the content released from single liposomes. The location and status
of liposomes (closed or opened) were assessed by epifluorescence imaging.
ECL provided the image of the efflux of matter after liposome opening.
This original ECL imaging approach favorably compares with strictly
photoluminescent or electrochemical techniques and appears to be adapted
for the investigation of membrane rupture/permeation events
Dynamic Electrochemiluminescence Imaging of Single Giant Liposome Opening at Polarized Electrodes
No full textIn this work, the characterization
of release events from liposomes
has been addressed quantitatively by an electrochemiluminescence (ECL)
imaging strategy. First, ECL reagents ([Ru(bpy)3]2+ and tripropylamine) were encapsulated in sealed giant asymmetrical
liposomes (100 μm in diameter) made of DOPG/DOPC phospholipids.
After sedimentation on an indium tin oxide electrode material, the
opening of liposomes was triggered by polarization of the surface.
Under these conditions, amperometry, epifluorescence imaging, and
ECL imaging were combined and synchronized to monitor and image the
rupture of giant liposomes during the release and subsequent ECL emission
of their redox content. Amperometry allowed the quantification of
the content released from single liposomes. The location and status
of liposomes (closed or opened) were assessed by epifluorescence imaging.
ECL provided the image of the efflux of matter after liposome opening.
This original ECL imaging approach favorably compares with strictly
photoluminescent or electrochemical techniques and appears to be adapted
for the investigation of membrane rupture/permeation events
Effect of the Supporting Electrolyte Anion on the Thickness of PSS/PAH Multilayer Films and on Their Permeability to an Electroactive Probe
No full textQuartz crystal microbalance and cyclic voltammetry are used to investigate the influence of the supporting salt of polyelectrolyte solutions on the buildup and the structure of PSS/PAH polyelectrolyte multilayers (PSS: poly(4-styrene sulfonate); PAH: poly(allylamine hydrochloride)). This film constitutes a model polyelectrolyte multilayer system. The supporting electrolytes were sodium salts where the nature of the anion was changed by following the Hofmeister series from cosmotropic to chaotropic anions (F−, Cl−, NO3−, ClO4−). For all the investigated anions, the film thickness increases linearly with the number of deposition steps. We find that chaotropic anions lead to larger thickness increments per bilayer during the film buildup than cosmotropic ones, confirming results found on PSS/PDADMA multilayers (PDADMA: poly(diallyldimethylammonium)). Films constituted by more than nine PSS/PAH bilayers are still permeable to hexacyanoferrate(II) ions, Fe(CN)64−, whatever the nature of the supporting salt anion. On the other hand, these films are impermeable to ruthenium(II) hexamine ions, Ru(NH3)62+, after the third PAH layer in the presence of NaF, NaCl, or NaNO3. These results are explained by the presence of an excess of positive charges in the film, which leads to a positive Donnan potential. We find that this potential is more positive when more chaotropic anions are used during the film buildup. We also find that a film constructed in the presence of chaotropic anions swells and becomes more permeable to Fe(CN)64− ions when the film is brought into contact with a solution containing more cosmotropic anions. All our experimental findings can be explained by a strong interaction between chaotropic anions with the NH3+ groups of PAH that is equivalent, as far as the multilayer buildup and electrochemical response is concerned, to a deprotonation of PAH as it is observed when the film is constructed at a higher pH. We thus arrive to a coherent explanation of the effect of the nature of the anions of the supporting electrolyte on the polyelectrolyte multilayer. We also find that great care must be taken when investigating polyelectrolyte multilayer films by electrochemical probing because electrochemical reactions involving the probes can appreciably modify the multilayer structure
Dynamic Electrochemiluminescence Imaging of Single Giant Liposome Opening at Polarized Electrodes
No full textIn this work, the characterization
of release events from liposomes
has been addressed quantitatively by an electrochemiluminescence (ECL)
imaging strategy. First, ECL reagents ([Ru(bpy)3]2+ and tripropylamine) were encapsulated in sealed giant asymmetrical
liposomes (100 μm in diameter) made of DOPG/DOPC phospholipids.
After sedimentation on an indium tin oxide electrode material, the
opening of liposomes was triggered by polarization of the surface.
Under these conditions, amperometry, epifluorescence imaging, and
ECL imaging were combined and synchronized to monitor and image the
rupture of giant liposomes during the release and subsequent ECL emission
of their redox content. Amperometry allowed the quantification of
the content released from single liposomes. The location and status
of liposomes (closed or opened) were assessed by epifluorescence imaging.
ECL provided the image of the efflux of matter after liposome opening.
This original ECL imaging approach favorably compares with strictly
photoluminescent or electrochemical techniques and appears to be adapted
for the investigation of membrane rupture/permeation events
Multianalytical Study of the Binding between a Small Chiral Molecule and a DNA Aptamer: Evidence for Asymmetric Steric Effect upon 3′- versus 5′-End Sequence Modification
No full textInternational audienc
Product uniformity control - A research collaboration of European steel industries to non-destructive evaluation of microstructure and mechanical properties
No full textIn steel manufacturing, the conventional method to determine the mechanical properties and microstructure is by offline, destructive (lab-)characterisation of sample material that is typically taken from the head or the tail of the coil. Since coils can be up to 7 km long, the samples are not always representative for the main coil body. Also, the time delay (typically a few days) between the actual production and the availability of the characterisation results implies that these results cannot be exploited for real-time adaptation of the process settings. Information about the microstructure and material properties can also be obtained from electromagnetic (EM) and ultrasonic (US) parameters, which can be measured in real-time, non-destructively, and over the full length of the steel strip product. With the aim to improve the consistency in product quality by use of inline EM and US measurements, a European project called "Product Uniformity Control" (PUC) has been set up as a broad collaboration between 4 major European Steel Manufacturers and 10 Universities / Research institutes. Using both numerical simulations and experimental characterisations, we study the inline measured EM and US parameters in regard of the microstructural and mechanical properties. In this way, we aim to establish an improved understanding of their mutual relationships, and to apply this knowledge in existing and new nondestructive evaluation techniques. In this paper, the concerted approach of modelling and experimental validation will be addressed, and results of this work will be shown in combination with inline measured data.com</p
