Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.

Micromechanically-based formulation of the cooperative model for the yield behavior of starch-based nano-biocomposites.

The tensile yield stress of plasticized starch filled with montmorillonite has been studied as a function of the temperature and the strain rate and has been compared to the yield behavior of the original matrix. Aggregated/intercalated and exfoliated nano-biocomposites, obtained from different nanofillers, have been produced and tested under uniaxial tension (tensile test). To model the nanocomposite tensile yield stress behavior, a preexisting micro-mechanically based cooperative model, which describes properly the yield of semi-crystalline polymers has been modified. According to our development, the yield behavior of nano-biocomposites is strongly dependant on the clay concentration and exfoliation ratio. Based on the thermodynamics properties, an effective activation volume and effective activation energy are computed through the Takayanagi homogenization model. The predicted results for the yield stress at low strain rates and at different temperatures are in agreement with our experimental results.

The study of the pseudo-polyrotaxane architecture as a route for mild surface functionalization by click chemistry of poly(ε-caprolactone)-based electrospun fibers.

Polycaprolactone (PCL) electrospun fibers are widely developed for biomedical applications. However, their hydrophobicity and passivity towards cell growth is an important limitation. An original method to functionalize PCL nanofibers, making them reactive for bioconjugation of proteins or other molecules of interest in water under mild conditions, is reported here. This method involves the preparation of pseudo-polyrotaxanes (pPRs) of cyclodextrin (CD) and PCL. Core:shell PCL:pPR fibers were then prepared by coaxial electrospinning in order to bring available reactive hydroxyl groups from the CD to the fiber surface. Different pPR architectures (star, miktoarm and block-copolymer-like) were synthesized to study the effect of the pPR structure on fiber morphology and surface reactivity by grafting fluorescein isothiocyanate (FITC). Finally, bicyclononyne groups were grafted onto the star-pPR based fibers allowing the conjugation of a fluorescent dye by click chemistry in water without any copper catalyst proving the potential of the method for the biofunctionalization of PCL-based fibers.

Sepiolite as a promising nanoclay for nano-biocomposites based on starch and biodegradable polyester.

The effects of sepiolite addition (0, 1, 3 and 5wt%) were evaluated on dynamic-mechanical behaviour, water uptake, thermal and optical properties of thermoplastic starch (TPS)/poly (butylene adipate-co-terephthalate) (PBAT) nano-biocomposites, with different TPS/PBAT (w/w) ratios and nanofiller contents. The results highlighted the improvement of the dynamic-mechanical behaviour with the addition of sepiolite, producing high performance materials. An increase of 25°C in the Tg of TPS was recorded by DMTA analysis at sepiolite content of 5wt%. The sepiolite influenced the crystallisation of nano-biocomposites, without causing interference in the crystal organisation, evidenced by DSC analysis. The addition of sepiolite nanoclay decreased the water adsorption rate and water adsorption capacity of the corresponding nano-biocomposites. For such multiphase systems, the successful use of natural sepiolite brought a clear benefit, without the need of any modifications or additional processes to produce advanced nano-biocomposites.

Fungal Fermentation of Lignocellulosic Biomass for Itaconic and Fumaric Acid Production.

The production of high-value chemicals from natural resources as an alternative for petroleum-based products is currently expanding in parallel with biorefinery. The use of lignocellulosic biomass as raw material is promising to achieve economic and environmental sustainability. Filamentous fungi, particularly Aspergillus species, are already used industrially to produce organic acid as well as many enzymes. The production of lignocellulose-degrading enzymes opens the possibility for direct fungal fermentation towards organic acids such as itaconic acid (IA) and fumaric acid (FA). These acids have wide-range applications and potentially addressable markets as platform chemicals. However, current technologies for the production of these compounds are mostly based on submerged fermentation. This work showed the capacity of two Aspergillus species (A. terreus and A. oryzae) to yield both acids by solid-state fermentation and simultaneous saccharification and fermentation. FA was optimally produced at by A. oryzae in simultaneous saccharification and fermentation (0.54 mg/g wheat bran). The yield of 0.11 mg IA/g biomass by A. oryzae is the highest reported in the literature for simultaneous solid-state fermentation without sugar supplements.

Distribution, location, and transcriptional profile of Peyer's patch conventional DC subsets at steady state and under TLR7 ligand stimulation.

The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b+ conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b+ cDCs belong to a unique SIRPα+ cDC subset. At steady state, cDCs and TIM-4+ macrophages are mainly located in T-cell zones, i.e., interfollicular regions, whereas a majority of subepithelial phagocytes are monocyte-derived cells, namely, LysoDCs and TIM-4- macrophages. Finally, oral administration of a Toll-like receptor 7 ligand induces at least three TNF-dependent events: (i) migration of dome-associated villus cDCs in interfollicular regions, (ii) increase of CD8α+ interfollicular cDC number, and (iii) activation of both CD11b+ and CD8α+ interfollicular cDCs. The latter is marked by a genetic reprograming leading to the upregulation of type I interferon-stimulated and of both immuno-stimulatory and -inhibitory gene expression.

Tissue-specific differentiation of colonic macrophages requires TGFß receptor-mediated signaling.

Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. Here we have used global transcriptomic analysis to identify a unique homeostatic signature of mature colonic mφ that is acquired as they differentiate in the mucosa. By comparing the analogous monocyte differentiation process found in the dermis, we identify TGFß as an indispensable part of monocyte differentiation in the intestine and show that it enables mφ to adapt precisely to the requirements of their environment. Importantly, TGFßR signaling on mφ has a crucial role in regulating the accumulation of monocytes in the mucosa, via mechanisms that are distinct from those used by IL10.

Elaboration, morphology and properties of starch/polyester nano-biocomposites based on sepiolite clay.

The incorporation of nano-sized sepiolite clays into thermoplastic starch/poly(butylene adipate-co-terephthalate) (TPS/PBAT) blends has been investigated with the goal of improving the matrix properties. TPS/PBAT nano-biocomposites were elaborated with two different proportions of the polymeric phases. The influence of the sepiolite nanoclays on the mechanical, thermal and structural properties of the corresponding blends was evaluated. SEM images confirmed the good dispersion of the sepiolite clay, with a low occurrence of small aggregates in the polymeric matrix. Wide-angle X-ray diffraction showed no significant alteration of the crystalline structures of PBAT and starch induced by the sepiolite clay. The addition of sepiolite slightly affected the thermal degradation of the nano-biocomposites; however, the mechanical tests revealed an increase in some mechanical properties, demonstrating that sepiolite is a promising nanofiller for TPS-based materials.

[Diagnostic and prognostic value of continuous Doppler in pulmonary embolism]. / Intérêt diagnostique et pronostique du Doppler continu dans l'embolie pulmonaire.

A prospective study of 18 patients admitted to hospital for acute pulmonary embolism confirmed the reliability of continuous wave cardiac doppler as a non-invasive method of evaluating systolic pulmonary artery pressures. These pressures were calculated by applying the simplified Bernoulli equation to the maximal velocity of regurgitant tricuspid flow and compared with the results of cardiac catheterisation and angiography, the percentage of vascular obstruction being assessed using Miller's index. The correlations between the two methods were good, r = 0.96; p less than 0.001, with a standard error of +/- 5.2 mmHg. The correlations between the velocity of tricuspid flow and the percentage of obstruction were less significant (r = 0.65; p less than 0.005) but improved when patients with pre-existing cardiopulmonary disease were excluded. This technique of non-invasive assessment of haemodynamic parameters also helps in evaluating the underlying pathology; tricuspid regurgitation with velocities greater than 3.5 m/s is associated with pre-existing chronic cor pulmonale, information of prognostic interest which would guide therapeutic management.

[Validation of a method for measuring the area of aortic stenosis using only continuous Doppler. Value for the surveillance of transluminal aortic valvuloplasties]. / Validation d'une méthode de mesure de la surface des sténoses aortiques utilisant uniquement le doppler continu. Intérêt pour la surveillance des valvuloplasties aortiques transluminales.

Forty patients with aortic valve stenosis underwent continuous wave doppler-echocardiographic exploration followed by catheterization within 24 hours on average. Three methods of aortic functional area calculation, based on the continuity equation principle, were tried and compared with the haemodynamic data. The results of the reference equation (continuity through the whole systole) gave a correlation coefficient r = 0.77 with a standard error (SE) of 0.17 cm2. The continuity equation using only maximum velocity values was less satisfactory: r = 0.69; SE = 0.19 cm2. The simplified equation with an arbitrary 2 cm subaortic diameter and a subaortic velocity obtained by continuous wave doppler recording yielded results that were very similar to those of the reference equation: r = 0.78; SE = 0.16 cm2. It is suggested that this third equation should be used in the follow-up of transluminal aortic valvuloplasties, since its calculation is based only on aortic velocity, which reflects the degree of stenosis, and subaortic velocity, which indirectly reflects left ventricular function.

[Spontaneous pneumopericardium. Review of the literature apropos of 2 cases in the young adult]. / Les pneumopéricardes spontanés--revue de la littérature. A propos de deux observations chez l'adulte jeune.

Pneumopericardium is defined as the presence of air in the pericardial cavity. It is a rare condition in adults, usually due to trauma; it is commoner in the more exposed neonate and usually iatrogenic. The clinical presentation of chest pain and shortness of breath is associated with the pathognomonic auscultatory sign described by Bricheteau: a water-mill bruit. The diagnosis is confirmed by chest X-ray which shows the air-gap sign surrounding the cardiac silhouette. The principal differential diagnosis is a pneumomediastinum. The prognosis of pneumopericardium depends on the cause and complications of which tamponade and infection are the most serious and potentially life-threatening. The treatment of pneumopericardium is bed rest and surveillance when uncomplicated: evacuation of the air becomes necessary when complications set in.

[Acute dysfunction of mitral bioprosthesis: Doppler expression of a musical holosystolic murmur. Apropos of 2 cases]. / Dysfonctionnement aigu de bioprothèse mitrale: traduction doppler d'un souffle musical holosystolique. A propos de 2 observations.

Two women who had been fitted with a porcine mitral valve seven years previously suddenly developed acute dysfunction of the bioprosthesis with regurgitation. In both patients physical examination revealed an intense, vibrating, musical holosystolic murmur sounding like a "goose cry" and located at the apex. Pulsed doppler showed major, jet-like, central orothetic mitral regurgitation. A harmonic graph was recorded when the doppler window was positioned upstream of the porcine valve leaflets. The finding of such a doppler signal in this clinical context suggests tearing or perforation of one cuspid and rules out the possibility of bioprosthesis degeneration.

[Postoperative hemopericardium compressing the left atrium. Apropos of a case]. / Hémopéricarde postopératoire comprimant l'oreillete gauche. A propos d'un cas.

We report a case of tamponade due to an effusion of blood which had occurred two weeks after an aorto-coronary bypass and was unusually located behind the left atrium. The effusion, with severe clinical symptoms, was diagnosed by echocardiography and computerized tomography of the chest. These examinations provided an accurate anatomical diagnosis on which the approach route of the emergency operation was based.

[Fifty-two cases of postoperative endophthalmitis treated with one protocol: anatomical and functional results]. / 52 cas d'endophtalmie post-opératoire traités par un protocole thérapeutique unique: résultats anatomiques et fonctionnels.

PURPOSE: To evaluate our management of postoperative endophthalmitis and compare our protocol to the Endophthalmitis Vitrectomy Study's (EVS) recommended protocol. PATIENTS AND METHODS: This study comprises 52 patients with postoperative endophthalmitis treated with the same protocol in 1996 and 1997. Patients were given an intravitreal injection of antibiotics (vancomycin-amikacin) and steroids (dexamethasone), systemic antibiotics (pefloxacin-piperracillin), and systemic steroids in bolus. Vitrectomy was not systematic. So as not to delay the treatment, cultures were obtained only from an anterior chamber paracentesis. RESULTS: Visual acuity was measurable in 86.5% of the patients, with 20/100 in 63.4% and 20/40 in 44.2%. Our results are similar to those of the EVS even when initial visual acuity was Light Perception. CONCLUSION: Our protocol is simple and easy to perform in all ophthalmology centers. It is based on intravitreal injection, which must be performed as quickly as possible.

[Iatrogenic arteriovenous fistula between the internal mammary artery and the innominate venous trunk. Contribution of digital arteriography in the positive and anatomic diagnosis]. / Fistule artérioveineuse iatrogène entre artère mammaire interne et tronc veineux innominé. Apport de l'artériographie digitalisée dans le diagnostic positif et anatomique.

The authors report the case of an arterio-venous fistula between the internal mammary artery and the trunk of the innominate vein following puncture of the internal jugular. The clinical signs of this unusual complication led the authors to list the differential diagnoses which should be considered and to draw attention to the importance of digitalized angiography in anatomical diagnosis.

[Natural course of type III traumatic chronic dissection in a patient with Marfan's syndrome]. / Evolution naturelle d'une dissection chronique traumatique de type III chez une malade atteinte d'un syndrome de Marfan.

Description of a traumatic dissection of the descending thoracic aorta, occurring in a female patient with Marfan's syndrome, the chronic course of which over more than three years was complicated by retrograde extension to the ascending thoracic aorta, resulting in death by massive aortic insufficiency and pleuro-pericardial effusion. Advantages of clinical and sonocardiographic monitoring of chronic dissections.

[Differential analysis of mitral and tricuspid regurgitation by continuous Doppler]. / Analyse différentielle des fuites mitrales et tricuspides par le Doppler continu.

The following parameters have been measured by continuous Doppler in 40 patients with both mitral failure (MF) and tricuspid failure (TF): effusion time (ET), peak time (PT), maximum effusion speed (S. max), maximum anterograde speed (S. ant), taking into account the cardiac rate and the ejection fraction. Only the S. max. and the S. ant. are significantly different and enable the determination of the effusion origin with a percentage error of about 4%. When a straight line is drawn to joint 3.7 m/s on the ordinate (S. ant) and 5 m/s on the abcissa (S. max), the TF lie below the line and the MF above it. The selection of the sub-groups with low ejection fraction (less or equal to 30%) or with arterial pulmonary hypertension (S. max MF higher or equal to 3 m/s) does not modify the precision of the discrimination. The graph suggested seems therefore to be a rapid and reliable means of characterizing TF in order to assess the arterial pulmonary hypertension of dilated hypokinetic cardiomyopathies.

[Comparative study of pulsed and continuous Doppler in the quantification of aortic insufficiency]. / Etude comparative des Dopplers pulsé et continu dans la quantification des insuffisances aortiques.

31 patients whose mean age was 61 +/- 29 yrs. presenting with aortic regurgitation (AR) benefited from cardiac catheterization which was preceded by Doppler ultrasound examination in a prospective study to compare the diagnostic contributions made by continuous vs pulsed wave techniques respectively in the quantitative assessment of AR, with reference to semi-quantitative angiographic evaluation. Pulsed Doppler analysis involves mapping of the left ventricle in two projections as well as the investigation of blood flow in the aortic isthmus using a suprasternal approach. Collection of continuous wave signals from the cardiac apex makes it possible to measure circulatory deceleration and the half-time of decrease in signal velocity and the protodiastolic pressure gradient. Our results corroborate the reliability of data obtained using continuous-wave Doppler technique in finding significant correlations for each parameter respectively: r' = 0.88 (p less than 0.001); r' = -0.81 (p less than 0.001); r' = -0.75 (p less than 0.001). Values determined by pulsed wave Doppler mapping of the left ventricle appear to be less satisfactory but are significant: r' = 0.68 (p less than 0.001) while measurement of end-diastolic blood flow recorded in the isthmus of the aorta is more highly correlated: r' = 0.84 (p less than 0.01), with the main disadvantage being its limited applicability to a small number of our patients (48%). We thus concluded that continuous-wave Doppler ultrasound is a better technique in the quantitative evaluation of AR, while recalling the essential additional value of pulsed-wave Doppler technique to localize the leakage and of ultrasound to assess its impact on the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

[Floating thrombus of the right atrium in acute pulmonary embolism. Clinical, echocardiographic aspects and therapeutic sequelae]. / Thrombus flottant de l'oreillette droite dans l'embolie pulmonaire aiguë. Aspects cliniques, échocardiographiques et incidences thérapeutiques.

The performance of a systematic sonocardiography in all our patients hospitalized since January 1985 for pulmonary embolism, has enabled to discover five cases of floating thrombus of the right atrium. Three patients presented an abnormal auscultation, with one of them presenting a tricuspid wedge syndrome. On the sonogram, the aspect of the thrombus, "coil or ball-shaped", floating in the atrial cavity, sometimes prolapsed through the tricuspid valve, associated with the signs of a pulmonary heart, enables to rule out other right intraatrial masses. Pulmonary angiography seems contra-indicated because of the risk of embolus of this thrombus, the migration of which may be fatal. Embolectomy, under extra-corporeal circulation (heart-lung pump) with examination of the right cavities appears to be the treatment of choice.

[Comparative study of cibenzoline and flecainide administered via an intravenous route in reducing auricular arrhythmia]. / Etude comparative de la cibenzoline et du flécaïnide par voie intraveineuse dans la réduction des troubles du rythme auriculaire.

The efficacy of intravenous flecainide and cibenzoline acetate in the reduction of atrial rhythm disorders was compared in two groups of 30 patients. These arrhythmias are divided in 31 atrial fibrillation, 11 tachy-systoles, 18 atrial flutters. Parenteral administration of the anti-arrhythmic drug over a 24 hour-period is preceded by a bolus injection of 1.5 mg/kg of flecainide acetate for group I, and a bolus of 1 mg/kg of cibenzoline for group II. The overall efficacy of the two molecules is comparable (53%) as well as the reduction of the atrial fibrillations (65% vs 57%). Flecainide acetate seems more effective in treating effectively atrial tachycardias (66.6% vs 40%), and cibenzoline is more effective in the treatment of atrial flutters (54% vs 14%). The functional, electrical and haemodynamic tolerance has always been good in both group, except in 2 patients, because of the indirect pro-arrhythmic effect of cibenzoline. We are concluding that the efficacy of both molecules is satisfactory and we advocate their use, as first intention, in recent and idiopathic atrial fibrillation; it seems that cibenzoline is more effective on ischemic cardiopathies and flecainide acetate is more effective on valvular cardiopathies. Nevertheless, the possible indirect pro-arrhythmic effect, sometimes poorly tolerated in the first minutes following administration of the bolus, only on organized atrial rhythm disorder, leads us to advocate the prescription of these two drugs when attempts of transesophageal or endocardiac atrial stimulation have failed.