[Antimicrobial peptides: A new alternative for the treatment of aspergillosis]. / Peptides antimicrobiens : une nouvelle alternative pour le traitement des aspergilloses.

Aspergillus fumigatus is the predominant fungal species causing pulmonary aspergillosis. The present-day anti-aspergillosis arsenal is limited, with a number of molecules occasioning severe side effects (amphotericin B) or provoking significant drug interactions (azole derivatives). Moreover, the recent emergence of azole-resistant A. fumigatus strains is a cause for concern. In this context, antimicrobial peptides (AMPs) are emerging as a promising therapeutic approach and alternative or complement to conventional antifungals.

Machine learning to improve the interpretation of intercalating dye-based quantitative PCR results.

This study aimed to evaluate the contribution of Machine Learning (ML) approach in the interpretation of intercalating dye-based quantitative PCR (IDqPCR) signals applied to the diagnosis of mucormycosis. The ML-based classification approach was applied to 734 results of IDqPCR categorized as positive (n = 74) or negative (n = 660) for mucormycosis after combining "visual reading" of the amplification and denaturation curves with clinical, radiological and microbiological criteria. Fourteen features were calculated to characterize the curves and injected in several pipelines including four ML-algorithms. An initial subset (n = 345) was used for the conception of classifiers. The classifier predictions were combined with majority voting to estimate performances of 48 meta-classifiers on an external dataset (n = 389). The visual reading returned 57 (7.7%), 568 (77.4%) and 109 (14.8%) positive, negative and doubtful results respectively. The Kappa coefficients of all the meta-classifiers were greater than 0.83 for the classification of IDqPCR results on the external dataset. Among these meta-classifiers, 6 exhibited Kappa coefficients at 1. The proposed ML-based approach allows a rigorous interpretation of IDqPCR curves, making the diagnosis of mucormycosis available for non-specialists in molecular diagnosis. A free online application was developed to classify IDqPCR from the raw data of the thermal cycler output ( http://gepamy-sat.asso.st/ ).

Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant Aspergillus Section Fumigati Clinical Isolates.

Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus, more suitable techniques for routine testing are needed. The gradient concentration strip (GCS) method has been favorably evaluated for yeast testing. The aim of this study was to compare the CGS test with EUCAST broth microdilution for amphotericin B (AMB), posaconazole (PCZ), itraconazole (ITZ), voriconazole (VRZ), and isavuconazole (ISA). A total of 121 Aspergillus section Fumigati strains were collected, including 24 A. fumigatus sensu stricto strains that were resistant to at least one azole drug. MICs were determined using GCS and EUCAST methods. Essential agreement between the 2 methods was considered when MICs fell within ±1 dilution or ±2 dilutions of the 2-fold dilution scale. Categorical agreement was defined as the percentage of strains classified in the same category (susceptible, intermediate, or resistant) with both methods. Essential agreements with ±1 dilution and ±2 dilutions were 96.7, 93.4, 90.0, 89.3, and 95% and 100, 99.2, 100, 97.5, and 100% for AMB, PCZ, ITZ, VRZ, and ISA, respectively. Categorical agreements were 94.3, 86.1, 89.3, and 88.5% for AMB, PCZ, ITZ, and VRZ, respectively. Detection of resistance was missed with the GCS for one strain (4.1%) for PCZ and for 2 strains (8.3%) for ISA. Determination of ITZ MICs using the GCS allowed the detection of 91.7% of azole-resistant strains. The GCS test appears to be a valuable method for screening azole-resistant A. fumigatus clinical isolates.

In Vitro Susceptibility of Fusarium to Isavuconazole.

To evaluate the in vitro susceptibility of Fusarium to isavuconazole, 75 clinical isolates were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and then tested with a broth microdilution method (EUCAST) and the gradient concentration strip (GCS) technique. The activity of isavuconazole overall was shown to be limited, with an MIC50 of >16 µg/ml, without significant differences between the species complexes. The categorical agreement between GCS and EUCAST was 97.4% to 100%, making the GCS as a valuable alternative.

Spin Flips versus Spin Transport in Nonthermal Electrons Excited by Ultrashort Optical Pulses in Transition Metals.

A joint theoretical and experimental investigation is performed to understand the underlying physics of laser-induced demagnetization in Ni and Co films with varying thicknesses excited by 10 fs optical pulses. Experimentally, the dynamics of spins is studied by determining the time-dependent amplitude of the Voigt vector, retrieved from a full set of magnetic and nonmagnetic quantities performed on both sides of films, with absolute time reference. Theoretically, ab initio calculations are performed using time-dependent density functional theory. Overall, we demonstrate that spin-orbit induced spin flips are the most significant contributors with superdiffusive spin transport, which assumes only that the transport of majority spins without spin flips induced by scattering does not apply in Ni. In Co it plays a significant role during the first ∼20 fs only. Our study highlights the material dependent nature of the demagnetization during the process of thermalization of nonequilibrium spins.

Transcriptomic Signature of the CD24hi CD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients.

The role of B cells after transplant regarding allograft rejection or tolerance has become a topic of major interest. Recently, in renal transplant recipients, a B cell signature characterized by the overexpression of CD19+ CD38hi CD24hi transitional B cells has been observed in operationally tolerant patients and in belatacept-treated patients with significantly lower incidence of donor-specific antibodies. The phenotypic and functional characterization of these transitional B cells is far from exhaustive. We present the first transcriptomic and phenotypic analysis associated with this cell phenotype. Three populations were studied and compared: (i) transitional CD24hi CD38hi , (ii) CD24+ CD38- , and (iii) CD24int CD38int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24hi CD38hi population. Phenotypic analysis showed that CD24hi CD38hi transitional B cells also expressed CD9, CD10, CD1b and inducible T cell costimulator ligand (ICOS-L) markers. In addition, we found enrichment of IL-10+ cells among CD24hi CD38hi cells expressing ICOS-L and CD1b, the latter showing regulatory properties. Renal transplant recipients treated with belatacept exhibited significant expression of CD1b. Our results show that transitional CD24hi CD38hi B cells exhibit a distinct and specific profile, and this could be helpful for understanding of immune-regulatory mechanisms and immune monitoring in the field of organ transplant and autoimmune disease.

Deep infiltrating endometriosis: Should rectal and vaginal opacification be systematically used in MR imaging?

OBJECTIVES: To evaluate the interest of rectal and vaginal filling in vaginal and recto-sigmoid endometriosis with MR imaging. To compare the results between a senior and a junior radiologist review. METHODS: Sixty-seven patients with clinically suspected deep infiltrating endometriosis were included in our MRI protocol consisting of repeated T2-weigthed sequences (axial and sagittal) before and after rectal and vaginal marking with ultrasonography gel. Vaginal and recto-sigmoid endometriosis lesions were analyzed before and after opacification. The inter-reader agreement between senior and junior scores was studied. RESULTS: Concerning vaginal and muscularis and beyond colonic involvement, no significant difference (P=0.32) was observed and the inter-reader agreement was excellent (K=0.96 and 0.97 respectively). Concerning serosa colonic lesions, a significant difference was observed (P=0.01) and the inter-reader agreement was poor (K=0). CONCLUSIONS: Rectal and vaginal filling in endometriosis staging with MRI is not necessary no matter the reader experiment.

Directly probing spin dynamics in a molecular magnet with femtosecond time-resolution.

We show that a vanadium-chromium Prussian blue analogue, which is a room-temperature molecule-based magnet, displays a fast magnetic response on a femtosecond timescale that is attributed to the super-exchange interaction between the metal ions. These dynamics are obtained from femtosecond Faraday magneto-optical (MO) measurements, performed at 50 and 300 K. Exciting at the ligand-to-metal charge-transfer (LMCT) band results in the formation of the 2E excited state on the Cr ion via intersystem crossing (ISC) from the 4LMCT state in less than 250 fs. Subsequent vibrational relaxation in the 2E state occurs on a 0.78 ± 0.05 ps timescale at 50 K and 1.1 ± 0.1 ps at 300 K. The MO measurements can detect the formation of the 2E state on the Cr ion from the change in the super-exchange interaction taking place as a result of the corresponding spin flip associated with the formation of the 2E state. These results open up a new avenue to study molecular magnets using a powerful method that is capable of directly probing spin dynamics on a sub-picosecond timescale in thin film environments.

The contribution of fetal MR imaging to the assessment of oesophageal atresia.

OBJECTIVE: Present challenges are to improve the diagnosis rate of oesophageal atresia (OA) and evaluate as completely as possible a fetus affected by OA, specifically the type of OA and the length of the gap. Our aim was to evaluate the accuracy of fetal MR imaging (fMRI) for diagnosis of OA. METHODS: We reviewed fMRI performed because of sonographic suspicion of an OA. The signs reviewed included stomach size, "pouch sign", bowing of the trachea and visualization of the lower oesophageal lumen. The fetuses were assigned by consensus as having or not having EA, as well as having a tracheaoesophageal fistula (TOF). All findings were correlated with postnatal data. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Se, Sp, PPV and NPV of the technique were respectively 91%, 100%, 100% and 88%. The presence of the pouch sign yielded corresponding values of 82%, 100%, 100% and 78%. Mid-tracheal bowing was correlated positively with EA. The type of atresia was correctly evaluated in 90% of patients. CONCLUSION: fMRI is useful for the diagnosis of EA through the visualization of the oesophageal pouch or through associated signs such as tracheal bowing. Visualization of the lower oesophageal lumen seems to be a good sign of TEF. KEY POINTS: • Challenges are to improve the prenatal diagnosis of EA and associated malformations. • fMRI is able to diagnose EA through demonstration of the pouch sign. • Tracheal bowing is a promising indirect sign of EA. • Tracheoesophageal fistula can also be suspected thanks to fMRI. • Obstetrical US, fMRI and fetal CT are complementary for assessing associated malformations.

How to improve the preoperative staging of presumed early-stage endometrioid endometrial cancer?

PURPOSE OF INVESTIGATION: Accurate preoperative staging of early-stage endometrioid endometrial cancer (EEC) is necessary to avoid under or over surgical treatment. The objective is to determine the rate of understaging and to evaluate the accuracy of different methods: hysteroscopy-curettage versus endometrial biopsy in predicting the final stage. MATERIALS AND METHODS: This retrospective single-centre study led from 2000 to 2010, included women with EEC preoperatively assessed at low- or intermediate-risk. Understaging was defined as a postoperative FIGO Stage > 1 or a determination of high risk after the final histopathologic diagnosis. RESULTS: The study included 101 women (75 low-risk and 26 intermediate-risk). Final diagnosis was upstaged for 26 of them, more frequently in the presumed intermediate-risk group (57.7% vs 14.7%, p < 0.001). The rate of preoperative understaging was higher in the women with endometrial biopsies than those with curettage (34.5% vs 15.2%, p = 0.04). CONCLUSIONS: Hysteroscopy-curettage combined with magnetic resonance imaging (MRI) may improve preoperative staging of early-stage EEC, especially for presumed intermediate-risk disease.

Ultrafast Optical Properties of Dense Electron Gas in Silicon Nanostructures.

We investigate the ultrafast dynamics of carriers in a silicon nanostructure by performing spectrally resolved femtosecond spectroscopy measurements with a supercontinuum probe. The nanostructure consists of a 158-nm-thick crystalline Si layer on top of which a SiO2 passivation layer leads to a very high quality of the Si surface. In addition, a dielectric function approach, including contributions from a Drude part and interband transitions, combined with the Transition Matrix Approximation is used to model the photogenerated carrier dynamics. The spectrotemporal reflectivity reveals two mechanisms. First, an electron-hole plasma is created by the pump pulse and lasts for a few picoseconds. Importantly, its spectral signature is either a positive or a negative change of reflectivity, depending on the probe wavelength. This is complementary to the already reported results obtained with degenerate frequency measurements. The second mechanism is a thermal diffusion of carriers which occurs during several hundreds of picoseconds. The overall dynamics at short and long delays in the whole visible spectrum is well explained with our model which shows that the main contribution to the reflectivity dynamics is due to the Drude dielectric function. The observation of this predominance of free carriers requires both a long lived high density of carriers as well as a little influence of surface scattering as provided by our thin crystalline Si layer with passivated Si/SiO2 interface.

Does a combination of ultrasound, MRI, and biochemical amniotic fluid analysis improve prenatal diagnosis of esophageal atresia?

OBJECTIVE: Prenatal diagnosis of esophageal atresia (EA) remains a challenge. Our objective was to evaluate the combination of sonography, magnetic resonance imaging (MRI), and amniotic fluid biochemical markers in prenatal diagnosis of EA. STUDY DESIGN: A retrospective study of all cases with prenatal suspicion of EA from January 2008 to May 2013 in our regional reference center was carried out. Patients were included if all the three tests were performed. For each test, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) were evaluated. Each test was compared using Fisher's exact test. RESULTS: Fifteen patients were referred at a median gestational age of 28(+5) weeks (24-36) for suspicion of EA on the basis of small or non-visualized fetal stomach bubble and/or polyhydramnios. Se, Sp, PPV, and NPV for sonographic pouch sign/MRI/biochemical amniotic fluid were respectively 40/100/100/45.5%, 80/100/100/71.4%, and 90/60/81.8/75%. MRI was the best predictive test (p = 0.007). CONCLUSION: In case of ultrasound prenatal suspicion of EA (with or without visualization of the pouch sign), an MRI at 30-32 weeks using fast imaging employing steady-state acquisition should be proposed. Biochemical amniotic fluid may be helpful and should be evaluated in a larger study.

Kidney transplant recipients treated with belatacept exhibit increased naïve and transitional B cells.

Phase III clinical studies have shown that kidney transplant (KT) recipients treated with the costimulation blocker belatacept exhibited a better renal allograft function and lower donor-specific anti-HLA immunization when compared to recipients treated with calcineurin inhibitors (CNI). We analyzed B cell phenotype in KT recipients treated with belatacept and stable renal function (N = 13). Results were compared to those observed in stable patients treated with CNI (N = 12), or with chronic antibody-mediated rejection (N = 5). Both transcriptional profile and phenotypic characterization of peripheral B cells were performed by real-time polymerase chain reaction and flow cytometry, respectively. In belatacept group, the frequency and absolute number of transitional B cells as defined by both phenotypes: CD19(+) CD24(hi) CD38(hi) and CD19(+) IgD(hi) CD38(hi) CD27(-) , as well as naïve B cells were significantly higher compared with CNI group. B cell activating factor (BAFF) and BAFF receptor mRNA levels were significantly lower in belatacept group than in CNI group. These results show for the first time that belatacept influences B cell compartment by favoring the occurrence of transitional B cells with potential regulatory properties, as described in operational tolerant patients. This role may explain the lower alloimmunization rate observed in belatacept-treated patients.

[Placenta accreta: can prenatal diagnosis be performed? Ultrasound and MRI interests. About 27 cases]. / Placenta accreta : peut-on faire le diagnostic en anténatal ? Apport de l'échographie et de l'IRM. À propos de 27 cas.

OBJECTIVES: To list ultrasonography signs identified when a placenta accreta is suspected. Secondary objectives are to analyze the relevance of diagnosis with ultrasonography and magnetic resonance imaging, and to know diagnosis circumstances in order to identify main risk factors. PATIENTS AND METHODS: We present a monocentric retrospective study. All the cases of placentas accreta, observed from 2005 to 2010 at Lille University Hospital (France), have been included. RESULTS: Twenty-seven patients had a placenta accreta during this period. There was an antenatal suspicion for 22 cases and 21 were confirmed after delivery. Six cases were discovered per-partum. Diagnosis was suspected after metrorrhagia for 41% of women. In case of antenatal diagnosis, 100% of the patients had an anterior placenta praevia and an uterine scare. Fifty percent of the placentas accreta diagnosed per-partum were posterior. The most frequently ultrasonography signs are "intra-placental lacuna" (85.7%), "abnormal vascularization" (71.4%), "loss of normal hypoechoic retroplacental myometrial zone" (66.7%), "irregularity of the vesical wall" (66.7%). Sensibility of ultrasonography screening is 78%. Twenty-one magnetic resonance imaging examinations executed secondarily confirmed the diagnosis in 66.7% of the cases. DISCUSSION AND CONCLUSION: Ultrasonography is a relevant exam for the diagnosis of placenta accreta. Posterior placenta should not be forsaken. Anterior placenta praevia in multiparous patients with a uterine scare should be a warning.

[Esophageal atresia: prevalence, prenatal diagnosis and prognosis]. / Atrésie de l'œsophage : prévalence, diagnostic anténatal et pronostic.

Esophageal atresia (EA) is a rare congenital malformation (1 in 2,500 to 3,500 births). Prenatal diagnosis (PN) is particularly interesting allowing search for associated malformations related to worse prognosis forms (reference ultrasound, MRI and amniocentesis) and planning the birth in an adapted medico-surgical center. Diagnosis of EA is usually suspected because of indirect and non-specific signs: association of polyhydramnios and absent or small stomach bubble. The visualization in ultrasound or MRI of cervical or thoracic fluid image corresponding to the expansion of the bottom of upper esophageal ("pouch sign") increases the specificity of diagnosis. However, prenatal diagnosis remains difficult and less than 50 % of EA are diagnosed prenatally. Biochemical analysis could improve these results. If EA is confirmed at birth, surgical management consists in a primary end-to-end anastomosis in first days of life, or in two-steps surgery if the defect is too large. Although current prognosis of EA is good, frequency of surgical complications and esophageal lesions secondary to gastroesophageal reflux justify a systematic and multidisciplinary extended follow-up.

Exciton diffusion in near-infrared absorbing solution-processed organic thin films.

We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.

[Prenatal analysis of primary sulci by ultrasonography and MRI]. / Analyse anténatale des sillons primaires en échographie et en IRM.

Gyration abnormalities often reflect severe neurological diseases. Their diagnosis is impeded by our limited knowledge about normal sulci anatomy throughout fetal brain development. Primary sulci appears in a specific chronology which is unchanged among all fetuses. We think it is interesting to remind of sulci anatomy and then to depict sulci MRI and ultrasonography appearance at 22, 27 and 32 weeks of gestation. We pay particular attention to the lateral sulcus, also called Sylvian fissure.

Congenital high scapula (Sprengel's deformity): four cases.

We report a series of four cases of congenital high scapula (or Sprengel's deformity) diagnosed and followed in our establishment. The main feature of this very rare congenital malformation of the pectoral girdle is an abnormally high, more or less dysmorphic scapula. A congenitally high scapula is often discovered in young children, when consequences for aesthetics, and sometimes functional difficulties, are brought to light. When surgical treatment is envisaged, imaging is recommended to diagnose a supernumerary structure, ossified (an omovertebral bone) or not (a fibrous and/or cartilaginous connection), extending from the scapula to the cervical spine. This needs to be resected. A CT scan is essential for detecting an omovertebral bone and the vertebral bone abnormalities that are often associated with it. MRI and ultrasound are very useful for assessing any fibrous and/or cartilaginous components. An ultrasound examination has the undeniable advantage of being quick and easy in these young children.

Progressive anterior vertebral fusion: a report of three cases.

We report a series of three cases of progressive anterior vertebral fusion diagnosed and monitored in our establishment. This very rare condition was discovered in young children while exploring a spinal deformity. With X-rays of the thoracolumbar spine it was possible to make a positive diagnosis and ensure follow-up. The radiographic semeiotics are characteristic and combine anterior pinching of the disc, well-delimited erosion of the anterior vertebral corners and anterior then posterior intervertebral ankylosis. MRI is very useful for assessing the extent of the intervertebral ankylosis and the condition of the residual discs, without irradiation. The condition develops over several months or years. Conservative treatment is usually sufficient.