Current knowledge and practice of Candida auris screening in France: A nationwide survey from the French Society of Medical Mycology (SFMM).

Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission.

Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart.

The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers. Cardiomyocytes undergo post-mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53-dependent pathway in stress-induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin-treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell-type specific senescence in age-associated cardiac diseases.

Multicentric Analysis of the Species Distribution and Antifungal Susceptibility of Clinical Isolates from Aspergillus Section Circumdati.

The clinical involvement and antifungal susceptibility of Aspergillus section Circumdati are poorly known. We analyzed 52 isolates, including 48 clinical isolates, belonging to 9 species inside the section Circumdati. The whole section exhibited, by the EUCAST reference method, a poor susceptibility to amphotericin B, but species/series-specific patterns were observed for azole drugs. This underlines the interest in getting an accurate identification inside the section Circumdati to guide the choice of antifungal treatment in clinical practice.

Antifungal susceptibility testing practices in mycology laboratories in France, 2018.

A survey of mycology laboratories for antifungal susceptibility testing (AFST) was undertaken in France in 2018, to better understand the difference in practices between the participating centers and to identify the difficulties they may encounter as well as eventual gaps with published standards and guidelines. The survey captured information from 45 mycology laboratories in France on how they perform AFST (number of strains tested, preferred method, technical and quality aspects, interpretation of the MIC values, reading and interpretation difficulties). Results indicated that 86% of respondents used Etest as AFST method, with a combination of one to seven antifungal agents tested. Most of the participating laboratories used similar technical parameters to perform their AFST method and a large majority used, as recommended, internal and external quality assessments. Almost all the participating mycology laboratories (98%) reported difficulties to interpret the MIC values, especially when no clinical breakpoints are available. The survey highlighted that the current AFST practices in France need homogenization, particularly for MIC reading and interpretation.

Performance of semiconductor sequencing platform for non-invasive prenatal genetic screening for fetal aneuploidy: results from a multicenter prospective cohort study in a clinical setting.

OBJECTIVE: To validate and evaluate the performance metrics of the high-throughput semiconductor sequencing platform, Ion Proton®, in non-invasive prenatal genetic screening (NIPS) for common fetal aneuploidies in a clinical setting. METHODS: This prospective cohort study included 2505 pregnant women from eight academic genetics laboratories (695 high risk for trisomy 21 (risk ≥ 1/250) pregnancies in a validation study, and 1810 such pregnancies, without ultrasound anomalies, in a real-life NIPS clinical setting). Outcome was available for all cases in the validation cohort and for 521 in the clinical cohort. Cell-free DNA from plasma samples was sequenced using the Ion Proton sequencer, and sequencing data were analyzed using the open-access software, WISECONDOR. Performance metrics for detection of trisomies 21, 18 and 13 were calculated based on either fetal karyotype result or clinical data collected at birth. We also evaluated the failure rate and compared three methods of fetal fraction quantification (RASSF1A assay, and DEFRAG and SANEFALCON software). RESULTS: Results from both cohorts were consistent and their gestational age was not significantly different so their data were combined to increase the sample size for analysis. Sensitivities and specificities, respectively, were as follows: for trisomy 21, 98.3% (95% CI, 93.5-99.7%) and 99.9% (95% CI, 99.4-100%); for trisomy 18, 96.7% (95% CI, 80.9-99.8%) and 100% (95% CI, 99.6-100%); and for trisomy 13, 94.1% (95% CI, 69.2-99.7%) and 100% (95% CI, 99.6-100%). Our failure rate was 1.2% initially and as low as 0.6% after retesting some of the failed samples. Fetal fraction estimation by the RASSF1A assay was consistent with DEFRAG results, and both were adequate for routine diagnosis. CONCLUSIONS: We describe one of the largest studies evaluating Ion Proton-based NIPS and the first clinical study reporting pregnancy outcome in a large series of patients. This platform is highly efficient in detecting the three most common trisomies. Our protocol is robust and can be implemented easily in any medical genetics laboratory. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Use of a Visual Aid in addition to a Collector Bag to Evaluate Postpartum Blood loss: A Prospective Simulation Study.

Postpartum hemorrhage (PPH) is one of the most common causes of mortality in obstetrics worldwide. The accuracy of estimated blood loss is a priority in determining appropriate treatment. Will the additional use of a visual aid improve physicians' accuracy in estimating blood loss compared to the use of a collector bag and baby scale alone? Simulation training sessions created three vaginal delivery scenarios for participants to estimate volumes of blood loss: firstly, using only a collector bag and a baby weight scale and secondly, adding a visual aid depicting known volumes of blood. The primary endpoint was to determine if participants could accurately evaluate blood loss within a 20% error margin. The addition of the visual estimator resulted in overestimation of blood loss. The rates of participants' estimations were significantly more accurate when using the collector bag with the baby weight scale without the addition of the visual aid; 85.5% versus 33.3% (p < 0.01) for 350 mL, 88.4% versus 50.7% (p < 0.01) for 1100 mL and 88.4% versus 78.3% (p < 0.01) for 2500 mL, respectively. Additional use of a visual aid with a collector bag does not seem to be useful in improving the accuracy in the estimation of blood loss.

[For a targeted use of aspirin]. / Pour une prescription ciblée de l'aspirine.

The use of low-dose aspirin in pregnancy should remain a highly targeted indication since its long-term safety has not been established and should be restricted to women at high risk of vascular complications. Indications for which the benefit of aspirin has been shown are women with a history of preeclampsia responsible for a premature birth before 34 weeks, those having at least two history of preeclampsia, those with an antiphospholipid syndrome and those with lupus associated with positive antiphospholipid antibodies or renal failure. In all other cases, the level of evidence of the benefit of aspirin is insufficient to recommend its routine prescription.

INTERNATIONAL STANDARDS ON FOOD AND ENVIRONMENTAL RADIOACTIVITY MEASUREMENT FOR RADIOLOGICAL PROTECTION: STATUS AND PERSPECTIVES.

Radiological protection is a matter of concern for members of the public and thus national authorities are more likely to trust the quality of radioactivity data provided by accredited laboratories using common standards. Normative approach based on international standards aims to ensure the accuracy or validity of the test result through calibrations and measurements traceable to the International System of Units. This approach guarantees that radioactivity test results on the same types of samples are comparable over time and space as well as between different testing laboratories. Today, testing laboratories involved in radioactivity measurement have a set of more than 150 international standards to help them perform their work. Most of them are published by the International Standardization Organization (ISO) and the International Electrotechnical Commission (IEC). This paper reviews the most essential ISO standards that give guidance to testing laboratories at different stages from sampling planning to the transmission of the test report to their customers, summarizes recent activities and achievements and present the perspectives on new standards under development by the ISO Working Groups dealing with radioactivity measurement in connection with radiological protection.

[Prevention of spontaneous preterm birth (excluding preterm premature rupture of membranes): Guidelines for clinical practice - Text of the Guidelines (short text)]. / Recommandations pour la pratique clinique : prévention de la prématurité spontanée et de ses conséquences (hors rupture des membranes) ­ Texte des recommandations (texte court).

OBJECTIVES: To determine the measures to prevent spontaneous preterm birth (excluding preterm premature rupture of membranes)and its consequences. MATERIALS AND METHODS: The PubMed database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: In France, premature birth concerns 60,000 neonates every year (7.4 %), half of them are delivered after spontaneous onset of labor. Among preventable risk factors of spontaneous prematurity, only cessation of smoking is associated to a decrease of prematurity (level of evidence [LE] 1). This is therefore recommended (grade A). Routine screening and treatment of vaginal bacteriosis in general population is not recommended (grade A). Asymptomatic women with single pregnancy without history of preterm delivery and a short cervix between 16 and 24 weeks is the only population in which vaginal progesterone is recommended (grade B). A history-indicated cerclage is not recommended in case of only past history of conisation (grade C), uterine malformation (Professional consensus), isolated history of pretem delivery (grade B) or twin pregnancies in primary (grade B) or secondary (grade C) prevention of preterm birth. A history-indicated cerclage is recommended for single pregnancy with a history of at least 3 late miscarriages or preterm deliveries (grade A).). In case of past history of a single pregnancy delivery before 34 weeks gestation (WG), ultrasound cervical length screening is recommended between 16 and 22 WG in order to propose a cerclage in case of length<25mm before 24 WG (grade C). Cervical pessary is not recommended for the prevention of preterm birth in a general population of asymptomatic women with a twin pregnancy (grade A) and in populations of asymptomatic women with a short cervix (Professional consensus). Although the implementation of a universal transvaginal cervical length screening at 18-24 weeks of gestation in women with a singleton gestation and no history of preterm birth can be considered by individual practitioners, this screening cannot be universally recommended. In case of preterm labor, (i) it is not possible to recommend one of the methods over another (ultrasound of the cervical length, vaginal examination, fetal fibronectin) to predict preterm birth (grade B); (ii) routine antibiotic therapy is not recommended (grade A); (iii) prolonged hospitalization (grade B) and bed rest (grade C) is not recommended. Compared with placebo, tocolytics are not associated with a reduction in neonatal mortality or morbidity (LE2) and maternal severe adverse effects may occur with all tocolytics (LE4). Atosiban and nifedipine (grade B), contrary to betamimetics (grade C), can be used for tocolysis in spontaneous preterm labour without preterm premature rupture of membranes. Maintenance tocolysis is not recomended (grade B). Antenatal corticosteroid administration is recommended to every woman at risk of preterm delivery before 34 weeks of gestation (grade A). After 34 weeks, evidences are not consistent enough to recommend systematic antenatal corticosteroid treatment (grade B), however, a course might be indicated in the clinical situations associated with the higher risk of severe respiratory distress syndrome, mainly in case of planned cesarean delivery (grade C). Repeated courses of antenatal corticosteroids are not recommended (grade A). Rescue courses are not recommended (Professional consensus). Magnesium sulfate administration is recommended to women at high risk of imminent preterm birth before 32WG (grade A). Cesarean is not recommended in case of vertex presentation (Professional consensus). Both planned vaginal or elective cesarean delivery is possible in case of breech presentation (Professional consensus). A delayed cord clamping may be considered if the neonatal or maternal state so permits (Professional consensus). CONCLUSION: Except for antenatal corticosteroid and magnesium sulfate administration, diagnostic tools or prenatal pharmacological treatments implemented since 30 years to prevent preterm birth and its consequences have not matched expectations of caregivers and families.

[Cervical pessary and spontaneous preterm birth]. / Pessaire et prématurité spontanée.

OBJECTIVES: To determine the efficacy of the cervical pessary for the prevention of preterm delivery and to propose recommendations. MATERIALS AND METHOD: We searched the MedLine and the Cochrane Library and checked the international guidelines: ACOG and SOGC. RESULTS: The data concerning the efficacy of the cervical pessary for the prevention of preterm birth in a population of asymptomatic women with a singleton pregnancy with a short cervix≤25mm between 20 and 24 weeks 6 days of gestation and in a population of asymptomatic women with a twin pregnancy at high risk of preterm delivery defined by a short cervix are contradictory. More studies are necessary to recommend its use in these indications (Professional consensus). A cervical pessary placed before 22 weeks of gestation does not reduce the risk of preterm birth in the general population of asymptomatic women with a twin pregnancy (EL1). It is therefore not recommended to use the cervical pessary in order to prevent preterm delivery in the general population of asymptomatic women with a twin pregnancy (grade A). CONCLUSION: More studies are necessary to recommend the use of the cervical pesssary in singleton and in twin pregnancies with a short cervix.

Chronic inflammatory demyelinating polyradiculoneuropathy: A new animal model for new therapeutic targets.

Animal models are fundamental to advance knowledge of disease pathogenesis and to test/develop new therapeutic strategies. Most of the current knowledge about the pathogenic mechanisms underpinning autoimmune demyelination processes implicating autoantigens has been obtained using the Experimental Autoimmune Neuritis (EAN) animal model. The most widely used EAN model is obtained by active immunization of Lewis rats using a peptide, P0 (180-199), issuing from the major peripheral nervous system myelin protein. But this model mimics only the classical monophasic acute form of demyelinating polyradiculoneuropathy, i.e. Guillain-Barré syndrome (GBS). We developed a new model by immunizing Lewis rats using the same immunodominant neuritogenic peptide P0 (180-199) but this time with its S-palmitoyl derivative, S-palm P0 (180-199). All of the animals immunized with the S-palm P0 (180-199) peptide developed a chronic relapsing-remitting form of the disease corresponding to the electrophysiological criteria of demyelination (slow sensory nerve conduction velocity, prolonged motor nerve latency, partial motor nerve conduction blocks) with axon degeneration. These findings were confirmed by immunohistopathology study and thus, appear to mimic human chronic inflammatory demyelinating polyradiculopathy (CIDP). This new model opens up new avenues of research for testing new anti-inflammatory and neuroprotective therapeutic strategies.

Aspergillus PCR in serum for the diagnosis, follow-up and prognosis of invasive aspergillosis in neutropenic and nonneutropenic patients.

We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan (GM), PCR and mycologic analysis of pulmonary samples in both neutropenic and nonneutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value, while the GM index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the European Organization for Research and Treatment of Cancer (EORTC) and the Mycosis Study Group (MSG) mycologic criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased the sensitivity to 71.7%. Combining the GM index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative in 16 patients with noninvasive forms of aspergillosis (namely aspergilloma and chronic aspergillosis). Remaining PCR positive after a period of 14 to 20 days of treatment was related to poor outcome at 30 and 90 days. Our results also indicate that, unlike the determination of the GM index, the initial fungus load as determined by PCR was highly predictive of 90-day mortality, with the rate of the latter being 15.8% for patients with <150 copies/mL vs. 73.2% for patients at or above that cutoff (p <0.0001). Therefore, PCR appears to be a powerful and interesting tool for the identification of patients with invasive aspergillosis who might benefit from more intense care.

[Visceral leishmaniasis without splenomegaly. A pediatric case report]. / Leishmaniose viscérale sans splénomégalie. À propos d'un cas chez un nourrisson.

Pediatric visceral leishmaniasis is caused by Leishmania infantum, a dog parasite transmitted to humans by the bite of the female phlebotomine sand fly. The well-known clinical triad is fever, pallor, and splenomegaly. A secondary macrophage activation syndrome (MAS) can complicate this infection, which is lethal when not treated. When MAS is observed without any explanation, a visceral leishmaniasis is highly recommended. We report a case of visceral leishmaniasis in a 21-month-old child complicated by a macrophage activation syndrome without splenomegaly. No immunodeficiency was diagnosed that could explain this unusual clinical condition. To our knowledge, this is the first case of visceral leishmaniasis without splenomegaly reported to date.

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.

Role of boundary conditions in helicoidal flow collimation: Consequences for the von Kármán sodium dynamo experiment.

We present hydrodynamic and magnetohydrodynamic (MHD) simulations of liquid sodium flow with the PLUTO compressible MHD code to investigate influence of magnetic boundary conditions on the collimation of helicoidal motions. We use a simplified cartesian geometry to represent the flow dynamics in the vicinity of one cavity of a multiblades impeller inspired by those used in the Von-Kármán-sodium (VKS) experiment. We show that the impinging of the large-scale flow upon the impeller generates a coherent helicoidal vortex inside the blades, located at a distance from the upstream blade piloted by the incident angle of the flow. This vortex collimates any existing magnetic field lines leading to an enhancement of the radial magnetic field that is stronger for ferromagnetic than for conducting blades. The induced magnetic field modifies locally the velocity fluctuations, resulting in an enhanced helicity. This process possibly explains why dynamo action is more easily triggered in the VKS experiment when using soft iron impellers.

Dirac model of electronic transport in graphene antidot barriers.

In order to use graphene for semiconductor applications, such as transistors with high on/off ratios, a band gap must be introduced into this otherwise semimetallic material. A promising method of achieving a band gap is by introducing nanoscale perforations (antidots) in a periodic pattern, known as a graphene antidot lattice (GAL). A graphene antidot barrier (GAB) can be made by introducing a 1D GAL strip in an otherwise pristine sheet of graphene. In this paper, we will use the Dirac equation (DE) with a spatially varying mass term to calculate the electronic transport through such structures. Our approach is much more general than previous attempts to use the Dirac equation to calculate scattering of Dirac electrons on antidots. The advantage of using the DE is that the computational time is scale invariant and our method may therefore be used to calculate properties of arbitrarily large structures. We show that the results of our Dirac model are in quantitative agreement with tight-binding for hexagonal antidots with armchair edges. Furthermore, for a wide range of structures, we verify that a relatively narrow GAB, with only a few antidots in the unit cell, is sufficient to give rise to a transport gap.

Electronic and optical properties of graphene antidot lattices: comparison of Dirac and tight-binding models.

The electronic properties of graphene may be changed from semimetallic to semiconducting by introducing perforations (antidots) in a periodic pattern. The properties of such graphene antidot lattices (GALs) have previously been studied using atomistic models, which are very time consuming for large structures. We present a continuum model that uses the Dirac equation (DE) to describe the electronic and optical properties of GALs. The advantages of the Dirac model are that the calculation time does not depend on the size of the structures and that the results are scalable. In addition, an approximation of the band gap using the DE is presented. The Dirac model is compared with nearest-neighbour tight-binding (TB) in order to assess its accuracy. Extended zigzag regions give rise to localized edge states, whereas armchair edges do not. We find that the Dirac model is in quantitative agreement with TB for GALs without edge states, but deviates for antidots with large zigzag regions.

hCG in screening for aneuploidy: a possible role for its glycoforms?

Fetal trisomy 21 is associated with elevated maternal serum hCG and its free beta-subunit (hCG-beta) in vivo, and abnormal placental hCG production and glycosylation in vitro. Other maternal serum markers may also be disrupted in major aneuploidies (T21, T18, T13). We evaluated our aneuploidy screening practices, focusing on hCG-beta and hCG glycoforms, and retrospectively analyzed 55 aneuploidy cases diagnosed over a 2 year period, determining maternal serum hCG glycoforms profiles using 2D-electrophoresis. Screening efficiency reached 96.7%. T21 was associated with elevated hCG-beta while T18 presented with diminished serum markers. hCG glycoforms tended to be basic in aneuploidy (mainly T13).