Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells.

Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized by the replacement of myocardium by fibro-fatty infiltration and cardiomyocyte loss. ACM predisposes to a high risk for ventricular arrhythmias. ACM has initially been defined as a desmosomal disease because most of the known variants causing the disease concern genes encoding desmosomal proteins. Studying this pathology is complex, in particular because human samples are rare and, when available, reflect the most advanced stages of the disease. Usual cellular and animal models cannot reproduce all the hallmarks of human pathology. In the last decade, human-induced pluripotent stem cells (hiPSC) have been proposed as an innovative human cellular model. The differentiation of hiPSCs into cardiomyocytes (hiPSC-CM) is now well-controlled and widely used in many laboratories. This hiPSC-CM model recapitulates critical features of the pathology and enables a cardiomyocyte-centered comprehensive approach to the disease and the screening of anti-arrhythmic drugs (AAD) prescribed sometimes empirically to the patient. In this regard, this model provides unique opportunities to explore and develop new therapeutic approaches. The use of hiPSC-CMs will undoubtedly help the development of precision medicine to better cure patients suffering from ACM. This review aims to summarize the recent advances allowing the use of hiPSCs in the ACM context.

Ablating Ion Velocity Distributions in Short-Pulse-Heated Solids via X-Ray Doppler Shifts.

Solids ablate under laser irradiation, but experiments have not previously characterized the initiation of this process at ultrarelativistic laser intensities. We present first measurements of bulk ion velocity distributions as ablation begins, captured as a function of depth via Doppler-shifted x-ray line emission from two viewing angles. Bayesian analysis indicates that bulk ions are either nearly stationary or flowing outward at the plasma sound speed. The measurements quantitatively constrain the laser-plasma ablation mechanism, suggesting that a steplike electrostatic potential structure drives solid disassembly.

Resonant dielectric multilayer with controlled absorption for enhanced total internal reflection fluorescence microscopy.

Total internal reflection fluorescence microscopy (TIRF-M) is widely used in biological imaging. Evanescent waves, generated at the glass-sample interface, theoretically strongly improve the axial resolution down to a hundred of nanometers. However, objective based TIRF-M suffers from different limitations such as interference fringes and uneven illumination, mixing both propagating and evanescent waves, which degrade the image quality. In principle, uneven illumination could be avoided by increasing the excitation angle, but this results in a drastic loss of excitation power. We designed dedicated 1D photonic crystals in order to circumvent this power loss by directly acting on the intensity of the evanescent field at controlled incident angles. In this framework, we used dedicated resonant multi-dielectric stacks, supporting Bloch surface waves and resulting in large field enhancement when illuminated under the conditions of total internal reflection. Here, we present a numerical optimization of such resonant stacks by adapting the resulting resonance to the angular illumination conditions in TIRF-M and to the fluorescence collection constraints. We thus propose a dedicated resonant structure with a control of the absorption during thin film deposition. A first experimental demonstration illustrates the concept with a 3-fold fluorescence enhancement in agreement with the numerical predictions.

Vacuum laser acceleration of super-ponderomotive electrons using relativistic transparency injection.

Intense lasers can accelerate electrons to very high energy over a short distance. Such compact accelerators have several potential applications including fast ignition, high energy physics, and radiography. Among the various schemes of laser-based electron acceleration, vacuum laser acceleration has the merits of super-high acceleration gradient and great simplicity. Yet its realization has been difficult because injecting free electrons into the fast-oscillating laser field is not trivial. Here we demonstrate free-electron injection and subsequent vacuum laser acceleration of electrons up to 20 MeV using the relativistic transparency effect. When a high-contrast intense laser drives a thin solid foil, electrons from the dense opaque plasma are first accelerated to near-light speed by the standing laser wave in front of the solid foil and subsequently injected into the transmitted laser field as the opaque plasma becomes relativistically transparent. It is possible to further optimize the electron injection/acceleration by manipulating the laser polarization, incident angle, and temporal pulse shaping. Our result also sheds light on the fundamental relativistic transparency process, crucial for producing secondary particle and light sources.

[Clinical impact of small bowell capsule endoscopy in obscure gastrointestinal bleeding : retrospective single-center study]. / Impact clinique de la vidéocapsule endoscopique du grêle dans les saignements digestifs inexpliqués. Etude rétrospective monocentrique.

INTRODUCTION: The small-bowel capsule endoscopy (VCE) has been validated in the investigation of obscure gastrointestinal bleeding (OGIB). The aim of this study was to evaluate the clinical impact of VCE for OGIB in routine practice, in terms of subsequent management and the risk of rebleeding. METHODS: Our retrospective study analyzed the VCE at the CHU of Liège from March 2016 to December 2019 (cohort of 110 patients with OGIB). RESULTS: We found a diagnostic yield of 58 %, a change in therapeutic attitude in 39 % of patients and a recurrence rate of 22.5 % (out of 102 patients followed at 2 years). The rate of rebleeding was particularly low in patients with normal VCE and in those for whom a therapeutic modification was made. Finally, about 45 % of patients did not have any change in therapeutic attitude nor recurrence. CONCLUSION: VCE leads to a therapeutic modification in about 40 % of patients with a low risk of relapse. However, VCE could be avoided in some patients as evidenced by a subgroup representing 45 % of patients for whom there was no therapeutic modification nor recurrence.

introduction et but : La vidéocapsule endoscopique grêle (VCE) est validée dans l'exploration des saignements digestifs inexpliqués (OGIB). Le but de notre travail a été d'évaluer l'impact clinique de la réalisation d'une VCE pour OGIB en pratique courante, en termes de prise en charge ultérieure et de risque de récidive du saignement. Méthodes : Notre étude rétrospective a analysé les VCE réalisées au CHU de Liège de mars 2016 à décembre 2019. Résultats : Les VCE de 110 patients ont été rétrospectivement analysées. Nous avons observé un pouvoir diagnostique de 58 % et une modification d'attitude thérapeutique chez 39 % des patients. Le taux de récidive (pour les 102 patients dont le suivi était disponible à maximum 2 ans) était de 22,5 %. Le taux de récidive de saignement était particulièrement faible chez les patients avec VCE normale et chez ceux pour lesquels une modification thérapeutique a été faite. Enfin, environ 45 % des patients n'ont pas eu de modification de l'attitude thérapeutique ni de récidive. Conclusions : La VCE débouche sur une modification thérapeutique chez environ 40 % des patients avec, dans la foulée, un faible risque de récidive. Par contre, la VCE pourrait être évitée chez certains patients comme en témoigne un sous-groupe représentant 45 % des patients pour lesquels il n'y a eu ni modification thérapeutique ni rechute.

Solid-Density Ion Temperature from Redshifted and Double-Peaked Stark Line Shapes.

Heß spectral line shapes are important for diagnosing temperature and density in many dense plasmas. This work presents Heß line shapes measured with high spectral resolution from solid-density plasmas with minimized gradients. The line shapes show hallmark features of Stark broadening, including quantifiable redshifts and double-peaked structure with a significant dip between the peaks; these features are compared to models through a Markov chain Monte Carlo framework. Line shape theory using the dipole approximation can fit the width and peak separation of measured line shapes, but it cannot resolve an ambiguity between electron density n_{e} and ion temperature T_{i}, since both parameters influence the strength of quasistatic ion microfields. Here a line shape model employing a full Coulomb interaction for the electron broadening computes self-consistent line widths and redshifts through the monopole term; redshifts have different dependence on plasma parameters and thus resolve the n_{e}-T_{i} ambiguity. The measured line shapes indicate densities that are 80-100% of solid, identifying a regime of highly ionized but well-tamped plasma. This analysis also provides the first strong evidence that dense ions and electrons are not in thermal equilibrium, despite equilibration times much shorter than the duration of x-ray emission; cooler ions may arise from nonclassical thermalization rates or anomalous energy transport. The experimental platform and diagnostic technique constitute a promising new approach for studying ion-electron equilibration in dense plasmas.

Comparing plasma conditions in short-pulse-heated foils via fine-structure x-ray emission.

Fine-structure x-ray spectra have been measured from foils with embedded tracer layers at two laser facilities. A suite of layered foils with thin Ti tracers under varied tamper layers was studied at both the Titan and the ALEPH 400 nm laser facilities, where Ti Heα emission was recorded using a high-resolution Bragg crystal spectrometer. Several indicators of plasma parameters are examined in the spectra, including temperature- and density-dependent line ratios and line broadening from Stark and opacity effects. Spectra indicate that (1) the plasma density at ALEPH is significantly higher than at Titan and (2) the electron temperature is high for near-surface layers at both facilities but drops more quickly with depth at ALEPH. These inferences of plasma conditions are consistent with differing levels of temporal contrast at each laser facility.

[Systemic Rosai-Dorfman-Destombes disease associated with a myelodysplastic syndrome. Efficacy of hematologic treatment]. / Maladie de Rosai-Dorfman-Destombes (RDD) multifocale réfractaire associée à un syndrome myélodysplasique. Efficacité du traitement hématologique.

INTRODUCTION: We report an original observation of multifocal refractory Destombes-Rosai-Dorfman disease associated with a myelodysplastic syndrome. The treatment of myelodysplasia allowed a good and prolonged response of both pathologies. CASE REPORT: A 35-year-old patient was investigated for bilateral exophthalmia, histologically related to Destombes-Rosai-Dorfman disease. The extension workup showed sinus, kidney and lymph node involvement. It was treated unsuccessfully with corticosteroids, colchicine, methotrexate, infliximab, cladribine and tociluzimab. The secondary appearance of myelodysplasia (AREB IPSS score intermediate-2) led to induction treatment with aracytin and idarubicin, and maintenance with azacytidine for 2 years. With 5 years of follow-up, the patient is in remission both of the myelodysplastic syndrome and Destombes-Rosai-Dorfman disease. CONCLUSION: Our observation discusses the interest of the treatment of myelodysplastic syndrome for the management of associated extra-hematological manifestations.

High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19.

BACKGROUND: Systemic reactivation of herpesviruses may occur in intensive care unit (ICU) patients and is associated with morbidity and mortality. Data on severe Coronavirus disease-19 (COVID-19) and concomitant reactivation of herpesviruses are lacking. METHODS: We selected patients admitted to ICU for confirmed COVID-19 who underwent systematic testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human-herpes virus-6 (HHV-6) DNAemia while in the ICU. We retrospectively analysed frequency, timing, duration and co-occurrence of viral DNAemia. RESULTS: Thirty-four patients were included. Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively. EBV reactivation occurred early after ICU admission and was associated with longer ICU length-of-stay. CONCLUSIONS: While in the ICU, critically ill patients with COVID-19 are prone to develop reactivations due to various types of herpesviruses.

Speech outcome after intravelar veloplasty.

OBJECTIVE: Cleft lip and palate is the main craniofacial malformation in France. Many surgical techniques had been described to restore cleft palate. In this study, we evaluate phonation in a homogeneous series of patient with isolated unilateral non-syndromic cleft lip and palate before (and after) alveolar cleft closure, operated according to our surgical protocol. METHODS: We included retrospectively 71 patients with isolated non-syndromic unilateral cleft lip and palate (UCLP), operated in our department from 2009 to 2013. All patients underwent the same surgical protocol: modified Millard cheilorhinoplasty (from 5 to 9-month-old); direct hard palatal closure (from 12 to 20-month-old); alveolar cleft closure with cancellous iliac bone graft (from 4 to 6-year-old). The phonation and clinical statute were evaluated before and after alveolar cleft closure. Fistula rate and speech evaluation were recorded. RESULTS: The rate of oronasal fistula was 12.7%. About phonation, 76% and 86% of patients were competent or borderline competent respectively before and after gingivoperiostoplasty. CONCLUSION: This surgical protocol provided speech results in patients with isolated unilateral non-syndromic cleft lip and palate. The gingivoperiostoplasty improved the speech intelligibility.

Direct application of an ECG-based sleep staging algorithm on reflective photoplethysmography data decreases performance.

OBJECTIVE: The maturation of neural network-based techniques in combination with the availability of large sleep datasets has increased the interest in alternative methods of sleep monitoring. For unobtrusive sleep staging, the most promising algorithms are based on heart rate variability computed from inter-beat intervals (IBIs) derived from ECG-data. The practical application of these algorithms is even more promising when alternative ways of obtaining IBIs, such as wrist-worn photoplethysmography (PPG) can be used. However, studies validating sleep staging algorithms directly on PPG-based data are limited. RESULTS: We applied an automatic sleep staging algorithm trained and validated on ECG-data directly on inter-beat intervals derived from a wrist-worn PPG sensor, in 389 polysomnographic recordings of patients with a variety of sleep disorders. While the algorithm reached moderate agreement with gold standard polysomnography, the performance was significantly lower when applied on PPG- versus ECG-derived heart rate variability data (kappa 0.56 versus 0.60, p < 0.001; accuracy 73.0% versus 75.9% p < 0.001). These results show that direct application of an algorithm on a different source of data may negatively affect performance. Algorithms need to be validated using each data source and re-training should be considered whenever possible.

Vascularization of the maxilla by a branch of the submandibular artery.

Vascular variations are common. A cervicofacial anatomical dissection carried out at the anatomy laboratory allowed us to document a rare vascular variation. The facial artery did not give rise to branches that led to the submandibular gland; an artery arising directly from the external carotid artery vascularized the submandibular gland and gave rise to the ascending palatine artery that led to the maxilla. We did not find cases in the literature where an artery emanated directly from the external carotid artery to vascularize the submandibular gland and that gave rise to an ascending palatine artery leading to the maxilla. Knowledge of the variations of the arterial vascularisation of the submandibular gland is important for submandibulectomies and transfers of the gland.

Edge-emitting polariton laser and amplifier based on a ZnO waveguide.

We demonstrate edge-emitting exciton-polariton (polariton) laser operation from 5 to 300 K and polariton amplifiers based on polariton modes within ZnO waveguides. The guided mode dispersion below and above the lasing threshold is directly measured using gratings placed on top of the sample, fully demonstrating the polaritonic nature of the lasing modes. The threshold is found to be smaller than that expected for radiative polaritons in planar ZnO microcavities below 150 K and comparable above. These results open up broad perspectives for guided polaritonics by enabling easier and more straightforward implementation of polariton integrated circuits that exploit fast propagating polaritons, and, possibly, topological protection.

Severe atypical pneumonia in critically ill patients: a retrospective multicenter study.

BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia.

Matched coordinates in the framework of polynomial modal methods for complex metasurface modeling.

The polynomial modal method (PMM) is one of the most powerful methods for modeling diffraction from lamellar gratings. In the present work, we show that applying it to the so-called matched coordinates leads to important improvement of convergence for crossed lamellar gratings with patterns that are not parallel to the coordinates' axes. After giving the new formulation of the PMM under matched coordinates in the general framework of biperiodic structures, we provide numerical examples to demonstrate the effectiveness of the proposed approach.

Anterior pedicle temporalis muscle flap interposition in the treatment of TMJ disorders.

Temporomandibular joint (TMJ) disorders are a common reason for consultation. Failure of medical treatments sometimes leads to the need for one of many surgical alternatives. Our purpose was to evaluate the results of anterior pedicle temporalis muscle flap interposition in the treatment of TMJ disorders. MATERIAL AND METHODS: For this prospective study, we selected 18 patients who underwent TMJ surgery involving the interposition of a temporalis muscle flap according to a standardized technique, between January 1, 2009 and August 31, 2014. CT imaging was performed on all patients prior to surgery. We documented the etiology of TMJ dysfunction, pre and postoperative pain using a visual analogue scale (VAS), pre and postoperative (last consultation) mouth opening, and complications. We used the Wilcoxon test for our statistical analysis. RESULTS: We observed a significant variation in preoperative and postoperative pain and mouth opening, with an average decrease in VAS values of 4.9/10 and an average increase of mouth opening of 11.1mm. No major complications were observed. DISCUSSION: The interposition of an anterior pedicle temporalis muscle flap in the treatment of temporomandibular joint disorder is a simple and effective technique.

Galectin-1 is required for the regulatory function of B cells.

Galectin-1 (Gal-1) is required for the development of B cells in the bone marrow (BM), however very little is known about the contribution of Gal-1 to the development of B cell regulatory function. Here, we report an important role for Gal-1 in the induction of B cells regulatory function. Mice deficient of Gal-1 (Gal-1-/-) showed significant loss of Transitional-2 (T2) B cells, previously reported to include IL-10+ regulatory B cells. Gal-1-/- B cells stimulated in vitro via CD40 molecules have impaired IL-10 and Tim-1 expression, the latter reported to be required for IL-10 production in regulatory B cells, and increased TNF-α expression compared to wild type (WT) B cells. Unlike their WT counterparts, T2 and T1 Gal-1-/- B cells did not suppress TNF-α expression by CD4+ T cells activated in vitro with allogenic DCs (allo-DCs), nor were they suppressive in vivo, being unable to delay MHC-class I mismatched skin allograft rejection following adoptive transfer. Moreover, T cells stimulated with allo-DCs show an increase in their survival when co-cultured with Gal-1-/- T2 and MZ B cells compared to WT T2 and MZ B cells. Collectively, these data suggest that Gal-1 contributes to the induction of B cells regulatory function.