Conception d’un modèle interprofessionnel d’interventions de soutien à l’adhésion au traitement par corset chez les adolescents atteints de scoliose idiopathique

Le port d’un corset orthopédique de 20 à 23 heures par jour est reconnu comme efficace pour prévenir la progression de la courbe chez les adolescents atteints de scoliose idiopathique, mais il engendre des conséquences biopsychosociales importantes qui perturbent leur quotidien et qui contribuent à un problème de non-adhésion au corset généralisé. En effet, le temps de port réel observé est d’environ 12 heures par jour. Il n’existe aucune intervention dans la littérature qui vise à améliorer l’adhésion au corset pour cette population spécifique. Le but de ce mémoire était de concevoir un modèle interprofessionnel d’interventions de soutien à l’adhésion au traitement par corset chez les patients atteints de scoliose idiopathique. Pour répondre à ce but, nous avons effectué des entrevues individuelles auprès de neuf professionnels d’expertises variées afin de comprendre leurs perspectives et leurs stratégies potentielles pour soutenir les patients vers une meilleure adhésion au corset. Les entrevues ont été enregistrées, transcrites et codées. Nous avons procédé à l’analyse thématique des verbatim et conçu le modèle d’intervention résultant. Lors des entrevues, les participants ont relevé des barrières à l’adhésion au corset et au soutien professionnel ainsi que des stratégies fonctionnelles, éducatives, motivationnelles, psychologiques et interprofessionnelles pour répondre à ces barrières. Le modèle a été validé par un panel d’experts cliniques. Le modèle d’intervention Interprofessionnel en Soutien à l’Adhésion (IPSA) au traitement par corset est structuré en trois paliers (préparation au corset, ateliers de groupe et consultation individuelle) et nous estimons qu’il a un grand potentiel d’implantation en clinique de scoliose.Wearing a spinal brace between 20 to 23 hours a day is recognized as effective to prevent curve progression in adolescents with idiopathic scoliosis, but it generates important biopsychosocial consequences that disturb patients’ daily activities and that contribute to the generalized problem of brace nonadherence. Indeed, the observed time spent in-brace is approximately 12 hours a day. A thorough review of the literature could not yield any intervention to enhance brace adherence for this specific population. The purpose of this master’s thesis is to develop an interprofessional support intervention model to enhance brace adherence in adolescents with idiopathic scoliosis. To fulfill this purpose, we have conducted individual interviews with 9 professionals of various expertise in order to understand their perspectives and their potential strategies to support patients towards better brace adherence. The interviews were audiotaped, transcribed and coded. We proceeded to a thematic analysis of the interview transcripts, which resulted in the intervention model. During the interviews, participants mentioned adherence barriers to brace treatment and professional support barriers as well as functional, educational, motivational, psychological and interprofessional teamwork strategies for answering these issues. The model was reviewed by an expert panel of clinicians. The Interprofessional Adherence Support intervention model (IPAS) to brace treatment is three-tiered to provide different levels of intensity of support to patients (brace preparation, group workshops and one-on-one consultations) and has great potential for implementation in clinical practice

Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting

Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300-600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane.status: Published onlin

Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting

Peroxisomes have the intrinsic ability to produce and scavenge hydrogen peroxide (H2O2), a diffusible second messenger that controls diverse cellular processes by modulating protein activity through cysteine oxidation. Current evidence indicates that H2O2, a molecule whose physicochemical properties are similar to those of water, traverses cellular membranes through specific aquaporin channels, called peroxiporins. Until now, no peroxiporin-like proteins have been identified in the peroxisomal membrane, and it is widely assumed that small molecules such as H2O2 can freely permeate this membrane through PXMP2, a non-selective pore-forming protein with an upper molecular size limit of 300–600 Da. By employing the CRISPR-Cas9 technology in combination with a Flp-In T-REx 293 cell line that can be used to selectively generate H2O2 inside peroxisomes in a controlled manner, we provide evidence that PXMP2 is not essential for H2O2 permeation across the peroxisomal membrane, neither in control cells nor in cells lacking PEX11B, a peroxisomal membrane-shaping protein whose yeast homologue facilitates the permeation of molecules up to 400 Da. During the course of this study, we unexpectedly noted that inactivation of PEX11B leads to partial localization of both peroxisomal membrane and matrix proteins to mitochondria and a decrease in peroxisome density. These findings are discussed in terms of the formation of a functional peroxisomal matrix protein import machinery in the outer mitochondrial membrane

Stem cell therapy targeting the right ventricle in pulmonary arterial hypertension: is it a potential avenue of therapy?

Fanny Loisel and Bastien Provost : Equal contributors.International audiencePulmonary arterial hypertension (PAH) is an incurable disease characterized by an increase in pulmonary arterial pressure due to pathological changes to the pulmonary vascular bed. As a result, the right ventricle (RV) is subject to an increased afterload and undergoes multiple changes, including a decrease in capillary density. All of these dysfunctions lead to RV failure. A number of studies have shown that RV function is one of the main prognostic factors for PAH patients. Many stem cell therapies targeting the left ventricle are currently undergoing development. The promising results observed in animal models have led to clinical trials that have shown an improvement of cardiac function. In contrast to left heart disease, stem cell therapy applied to the RV has remained poorly studied, even though it too may provide a therapeutic benefit. In this review, we discuss stem cell therapy as a treatment for RV failure in PAH. We provide an overview of the results of preclinical and clinical studies for RV cell therapies. Although a large number of studies have targeted the pulmonary circulation rather than the RV directly, there are nonetheless encouraging results in the literature that indicate that cell therapies may have a direct beneficial effect on RV function. This cell therapy strategy may therefore hold great promise and warrants further studies in PAH patients

Validation of a Short Version of the Maternal Behavior Q-set Applied to a Brief Video Record of Mother–infant Interaction

A 25 item version of the maternal behavior Q-set (MBQS) was validated with 40 adolescent mother–infant dyads. Observations were made from 10 min play interactions when infants were 10 months old. Results show that the short MBQS is reliable (ri = .94), is related to assessments using the full MBQS at 6 months (r = .35), to cognitive development at 10 and 15 months (r = .48), and attachment security at 15 months (r = .34), indicating appropriate psychometric characteristics

Autologous endothelial progenitor cell therapy improves right ventricular function in a model of chronic thromboembolic pulmonary hypertension.

International audienceBACKGROUND:Right ventricular (RV) failure is the main prognostic factor in pulmonary hypertension, and ventricular capillary density (CD) has been reported to be a marker of RV maladaptive remodeling and failure. Our aim was to determine whether right intracoronary endothelial progenitor cell (EPC) infusion can improve RV function and CD in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH).METHODS:We compared 3 groups: sham (n = 5), CTEPH (n = 6), and CTEPH with EPC infusion (CTEPH+EPC; n = 5). After EPC isolation from CTEPH+EPC piglet peripheral blood samples at 3 weeks, the CTEPH and sham groups underwent right intracoronary infusion of saline, and the CTEPH+EPC group received EPCs at 6 weeks. RV function, pulmonary hemodynamics, and myocardial morphometry were investigated in the animals at 10 weeks.RESULTS:After EPC administration, the RV fractional area change increased from 32.75% (interquartile range [IQR], 29.5%-36.5%) to 39% (IQR, 37.25%-46.50%; P = .030). The CTEPH+EPC piglets had reduced cardiomyocyte surface areas (from 298.3 μm2 [IQR, 277.4-335.3 μm2] to 234.6 μm2 (IQR, 211.1-264.7 μm2; P = .017), and increased CD31 expression (from 3.12 [IQR, 1.27-5.09] to 7.14 [IQR, 5.56-8.41; P = .017). EPCs were found in the RV free wall at 4 and 24 hours after injection but not 4 weeks later.CONCLUSIONS:Intracoronary infusion of EPC improved RV function and CD in a piglet model of CTEPH. This novel cell-based therapy might represent a promising RV-targeted treatment in patients with pulmonary hypertension

Magnetic Resonance Imaging or Computed Tomography Before Treatment in Acute Ischemic Stroke: Effect on Workflow and Functional Outcome

International audienceS ince the benefits of recanalization are highly time-dependent in acute ischemic stroke, 1-4 minimizing the workflow duration is crucial. Computed tomography (CT) is the most widely used diagnostic tool because of its availability and rapid acquisition time. However, magnetic resonance imaging (MRI) has advantages over CT. Diffusion-weighted imaging (DWI) best detects acute ischemia, 5 stroke-like events 6-8 and is the reference for infarct core extent measurement, which is crucial in selecting patients for endovascular treatment in the later time window. 9,10 In patients with unknown onset time, MRI identifies strokes that occurred approximately within the previous 4.5 hours and could benefit from thrombolysis. 11 MRI drawbacks theoretically include screening time for contraindications, limited access, additional time needed to clear the MRI scan and place the patient on the table, and longer scan duration. The recent trials showing the efficacy of endovascular therapy in acute ischemic stroke used primarily CT-based Background and Purpose-The acute management of stroke patients requires a fast and efficient screening imaging modality. We compared workflow and functional outcome in acute ischemic stroke patients screened by magnetic resonance imaging (MRI) or computed tomography (CT) before treatment in the THRACE trial (Thrombectomie des Artères Cérébrales), with the emphasis on the duration of the imaging step. Methods-The THRACE randomized trial (June 2010 to February 2015) evaluated the efficacy of mechanical thrombectomy after intravenous tPA (tissue-type plasminogen activator) in ischemic stroke patients with proximal occlusion. The choice of screening imaging modality was left to each enrolling center. Differences between MRI and CT groups were assessed using univariable analysis and the impact of imaging modality on favorable 3-month functional outcome (modified Rankin Scale score of ≤2) was tested using multivariable logistic regression. Results-Four hundred one patients were included (25 centers), comprising 299 MRI-selected and 102 CT-selected patients. Median baseline National Institutes of Health Stroke Scale score was 18 in both groups. MRI scan duration (median [interquartile range]) was longer than CT (MRI: 13 minutes [10-16]; CT: 9 minutes [7-12]; P<0.001). Stroke-onset-toimaging time (MRI: median 114 minutes [interquartile range, 89-138]; CT: 107 minutes [88-139]; P=0.19), onset-tointravenous tPA time (MRI: 150 minutes [124-179]; CT: 150 minutes [123-180]; P=0.38) and onset-to-angiographysuite time (MRI: 200 minutes [170-250]; CT: 213 minutes [180-246]; P=0.57) did not differ between groups. Imaging modality was not significantly associated with functional outcome in the multivariable analysis. Conclusions-Although MRI scan duration is slightly longer than CT, MRI-based selection for acute ischemic stroke patients is accomplished within a timeframe similar to CT-based selection, without delaying treatment or impacting functional outcome. This should help to promote wider use of MRI, which has inherent imaging advantages over CT

Velocity Gradient Separation Reveals a New Extracellular Vesicle Population Enriched in miR-155 and Mitochondrial DNA

Extracellular vesicles (EVs) and their contents (proteins, lipids, messenger RNA, microRNA, and DNA) are viewed as intercellular signals, cell-transforming agents, and shelters for viruses that allow both diagnostic and therapeutic interventions. EVs circulating in the blood of individuals infected with human immunodeficiency virus (HIV-1) may provide insights into pathogenesis, inflammation, and disease progression. However, distinguishing plasma membrane EVs from exosomes, exomeres, apoptotic bodies, virions, and contaminating proteins remains challenging. We aimed at comparing sucrose and iodixanol density and velocity gradients along with commercial kits as a means of separating EVs from HIV particles and contaminating protein like calprotectin; and thereby evaluating the suitability of current plasma EVs analysis techniques for identifying new biomarkers of HIV-1 immune activation. Multiple analysis have been performed on HIV-1 infected cell lines, plasma from HIV-1 patients, or plasma from HIV-negative individuals spiked with HIV-1. Commercial kits, the differential centrifugation and density or velocity gradients to precipitate and separate HIV, EVs, and proteins such as calprotectin, have been used. EVs, virions, and contaminating proteins were characterized using Western blot, ELISA, RT-PCR, hydrodynamic size measurement, and enzymatic assay. Conversely to iodixanol density or velocity gradient, protein and virions co-sedimented in the same fractions of the sucrose density gradient than AChE-positive EVs. Iodixanol velocity gradient provided the optimal separation of EVs from viruses and free proteins in culture supernatants and plasma samples from a person living with HIV (PLWH) or a control and revealed a new population of large EVs enriched in microRNA miR-155 and mitochondrial DNA. Although EVs and their contents provide helpful information about several key events in HIV-1 pathogenesis, their purification and extensive characterization by velocity gradient must be investigated thoroughly before further use as biomarkers. By revealing a new population of EVs enriched in miR-155 and mitochondrial DNA, this study paves a way to increase our understanding of HIV-1 pathogenesis