Meat-Borne-Parasite: A Nanopore-Based Meta-Barcoding Work-Flow for Parasitic Microbiodiversity Assessment in the Wild Fauna of French Guiana.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there has been limited data available on the description of parasites circulating in this area, especially on protozoan belonging to the phylum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on the Oxford Nanopore Technologies sequencing platform using the 18S gene of 14 Apicomplexa positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify 10 samples out of 14 as Apicomplexa positive and reveal the presence of co-carriages. The same samples were also sequenced with the Illumina platform for validation purposes. For samples identified as Apicomplexa positive by both platforms, a strong positive correlation at up to the genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detection, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Trace elements fractionation in anaerobic digestates: Recommendation for using diffusive gradients in thin films passive samplers.

This study proposes an evaluation of the Diffusive Gradients in Thin films (DGT) technique to assess the labile fraction of trace metals and metalloids in anaerobic digestates. Experiments were performed in presence and absence of air to determine whether maintaining anaerobic conditions is mandatory during DGT deployments. A theoretically expected linear accumulation profile was observed for Fe, Mn, Ni, Mo, and As(III) in a manure-derived digestate and for Mn in distillery waste-derived digestate, whereas Al and Cu were detected without a consistent trend over time. The DGT technique can thus be used to evaluate the labile fraction of some trace elements in these digestates. The labile fraction of some elements was shown to evolve over 72 h when deployments were performed in the presence of air. We thus strongly recommend to systematically perform time-series deployments to identify and consider only the elements with a linear accumulation trend and to maintain anaerobic conditions.

Embolization before Gamma Knife radiosurgery for cerebral arteriovenous malformations does not negatively impact its obliteration rate: a series of 190 patients.

PURPOSE: Embolization of arteriovenous malformations (AVMs) before radiosurgery has been reported to negatively impact the obliteration rate. This study aims to assess treatment outcomes in a series of 190 patients treated by Gamma Knife radiosurgery (GKRS) for previously embolized AVMs. METHODS: The institutional database of AVMs was retrospectively reviewed between January 2004 and March 2018. The clinical and radiological data of patients treated with GKRS for previously embolized AVMs were analyzed. Predicting factors of obliteration and hemorrhage following GKRS were assessed with univariate and multivariate regression analyses. RESULTS: The mean AVM size was significantly reduced after embolization (p < 0.001). The obliteration rate was 78.4%. Multivariate analyses showed that a lower Spetzler-Martin grade (p = 0.035) and a higher marginal dose (p = 0.007) were associated with obliteration. Post-GKRS hemorrhages occurred in 14 patients (7.4%). A longer time between diagnosis and GKRS was the only factor associated with post-GKRS hemorrhages in multivariate analysis (p = 0.022). Complications related to the combined treatment were responsible for a new permanent neurological disability in 20 patients (10.5%), and a case of death (0.5%). CONCLUSIONS: This study shows that the embolization of AVMs does not have a negative impact on the obliteration rate after radiosurgery. Embolization reduces the AVM size to a treatable volume by GKRS. However, the combined treatment results in an increased complication rate related to the addition of the risks of each treatment modality.

Intraoperative electron radiotherapy in early invasive ductal breast cancer: 6-year median follow-up results of a prospective monocentric registry.

BACKGROUND: Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial. METHODS: At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical). RESULTS: Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan-Meier estimate of local recurrence was 2.7%. CONCLUSIONS: The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

Validation of Swab Sampling and SYBR Green-Based Real-Time PCR for the Diagnosis of Cutaneous Leishmaniasis in French Guiana.

Recent studies have highlighted the interest in noninvasive sampling procedures coupled with real-time PCR methods for the detection of Leishmania species in South America. In French Guiana, the sampling method still relied on skin biopsies. Noninvasive protocols should be tested on a large annual cohort to improve routine laboratory diagnosis of cutaneous leishmaniasis. Therefore, we evaluated the performance of a new Leishmania detection and species identification protocol involving cotton swabs and SYBR green-based real-time PCR of the Hsp70 gene, coupled with Sanger sequencing. Between May 2017 and May 2018, 145 patients with ulcerated lesions compatible with cutaneous leishmaniasis were included in the study at the Cayenne Hospital and its remote health centers. Each patient underwent scrapings for a smear, skin biopsies for parasite culture and PCR-restriction fragment length polymorphism (RFLP) (RNA polymerase II), and sampling with a cotton swab for SYBR green-based PCR. The most accurate diagnostic test was the SYBR green-based PCR on swab samples, showing 98% sensitivity. The mean PCR cycle threshold (CT ) was 24.4 (minimum CT , 17; maximum CT , 36) and was <35 in 97.6% of samples. All samples positive by SYBR green-based real-time PCR were successfully identified at the species level by DNA sequencing. This new method should be considered for routine diagnosis of cutaneous leishmaniasis in South America and especially for remote areas, since noninvasive collection tools are easier to use and require fewer precautions for transportation.

Lead sorption by biochar produced from digestates: Consequences of chemical modification and washing.

The main objectives of this work are to investigate the consequences of different chemical treatments (i.e. potassium hydroxide (KOH) and hydrogen peroxide (H2O2)) and the effect of biochar washing on the Pb sorption capacity. Biochars derived from sewage sludge digestate and the organic fraction of municipal solid waste digestate were separately modified with 2 M KOH or 10% H2O2 followed by semi-continuous or continuous washing with ultrapure water using batch or a column reactor, respectively. The results showed that the Pb adsorption capacity could be enhanced by chemical treatment of sludge-based biochar. Indeed, for municipal solid waste biochar, the Pb maximum sorption capacity was improved from 73 mg g-1 for unmodified biochar to 90 mg g-1 and 106 mg g-1 after H2O2 and KOH treatment, respectively. In the case of sewage sludge biochar, it increased from 6.5 mg g-1 (unmodified biochar) to 25 mg g-1 for H2O2 treatment. The sorption capacity was not determined after KOH treatment, since the Langmuir model did not fit the experimental data. The study also highlights that insufficient washing after KOH treatment can strongly hinder Pb sorption due to the release of organic matter from the modified biochar. This organic matter may interact in solution with Pb, resulting in an inhibition of its sorption onto the biochar surface. Continuous column-washing of modified biochars was able to correct this issue, highlighting the importance of implementing a proper treated biochar washing procedure.

Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants: Involvement of Sost/Sclerostin.

The muscle segment homeogenes Msx1 and Msx2 play a major role in tooth and bone formation. Periodontal osteoclast impairment also occurs in Msx2 null mutant mice, which is restored by overexpression of the receptor activator of NF-κB targeted in osteoclast lineage. Here, we investigated the role of Msx2 in dentinogenesis. Experiments were performed on Msx2(-/-) mice and the MDPC-23 odontoblastic cell line. After Msx2 gene silencing, real-time quantitative RT-PCR data showed significant overexpression of Runx2, Bglap, Dspp, and Alpl. Of three inhibitors of Wnt/ß-catenin signaling (Dkk1, SostDc1, and Sost/Sclerostin), only Sost was expressed in postnatal teeth and overexpressed in Msx2(-/-) tooth samples. Initial crown dentin formation-primary dentinogenesis-occurred fairly normally in Msx2(-/-) teeth, albeit with distorted cusp patterns. Later stages of tooth development were characterized by a deviation from secondary toward tertiary dentinogenesis with osteodentin formation and impaired dentin deposition leading to limited root elongation. In Msx2(-/-)/receptor activator of NF-κB-transgenic double mutants, the dentin phenotype, notably in the roots, was rescued and sclerostin levels were normalized. These data suggest that Msx2 may act indirectly on dentinogenesis by controlling osteoclast activity and the signaling network related to eruption, supporting and further extending the concept that Msx2 controls formation of mineralized tissues by inhibition of the Wnt/ß-catenin pathway; Sost in dentin and Dkk1 in bone, as previously demonstrated.

Interactions between Gastrointestinal Nematodes and Malaria in a Cohort of Children in an Amazonian Village.

INTRODUCTION: Most studies on nematode-malaria interactions were conducted outside of the Americas. The objective of the present study was thus to study the relation between malaria and nematodes in a cohort of children in an Amazonian village. METHODS: Odds ratios for intestinal nematode infections as an explanatory variable to malaria resistant vs. malaria sensitive were computed. RESULTS: Ascaris lumbricoides was significantly more frequent in the 'resistant' malaria group than in the 'sensitive' one. CONCLUSIONS: Despite its low statistical power, the present results find that Ascaris was associated with less malaria, as observed by a number of studies.

Plithotaxis, a collective cell migration, regulates the sliding of proliferating pulp cells located in the apical niche.

Using the proliferating cell nuclear antigen (PCNA) immunostaining, we previously identified, after pulp exposure, three zones of proliferating cells in the rat molar pulp. Zones I and II were in the crown near the pulp. Zone III was near the apex revealing a recruitment of mitotic cells at distance from the lesion. To gain further insight into the spatio-temporal evolution of proliferating pulp cells of zone III, we performed a longitudinal study of PCNA staining in rat molar mesial root at 3, 8, and 15 d after pulp exposure associated to implantation of unloaded or amelogenin loaded agarose beads. At day 3 after implantation, PCNA-positive cells were located in the central part of the radicular pulp. At day 8, PCNA-labeled cells were aligned in the lateral part of the pulp beneath the odontoblast/sub-odontoblast layer. At day 15, PCNA labeling became undetectable in the root and was located in the coronal pulp. These results suggest that after pulp exposure, PCNA-positive cells may migrate from the central part of the radicular pulp to the sub-odontoblast cell layer and then from the apical root to the crown. Electron microscopy and immunostaining analysis showed that pulpal cells were linked by desmosome-like and gap-junctions. Extracellular matrix was composed of thin collagen fibrils associated with glycosaminoglycans favoring cell mobility. These data suggest that the syncytium-like structure formed by pulp radicular cells may be a pre-request for plithotaxis, a collective cell migration process. This emergent mechanism may govern pulp healing and regeneration after dental lesion.

Intraoperative electron beam intercomparison of 6 sites using mailed thermoluminescence dosimetry: Absolute dose and energy.

PURPOSE: In 2018, the Netherlands Commission on Radiation Dosimetry subcommittee on IORT initiated a limited intercomparison of electron IORT (IOERT) in Belgium and The Netherlands. The participating institutions have enough variability in age, type of equipment, and in dose calibration protocols. METHODS: In this study, three types of IOERT-dedicated mobile accelerators were represented: Mobetron 2000, LIAC HWL and LIAC. Mobetron produces electron beams with energies of 6, 9 and 12 MeV, while LIAC HWL and LIAC can deliver 6, 8, 10 and 12 MeV electron beams. For all energies, the reference beam (10 cm diameter, 0° incidence) and 5 cm diameter beams were measured, as these smaller beams are used more frequently in clinic. The mailed TLD service from the Radiation Dosimetry Services (RDS, Houston, USA) has been used. Following RDS' standard procedures, each beam was irradiated to 300 cGy at dmax with TLDs around dmax and around depth of 50 % dose (R50). Absolute dose at 100 % and beam energy, expressed as R50, could be verified in this way. RESULTS: All absolute doses and energies under reference conditions were well within RDS-stated uncertainties: dose deviations were <5 % and deviations in R50 were <5 mm. For the small 5 cm beams, all results were also within acceptance levels except one absolute dose value. Deviations were not significantly dependent on manufacturer, energy, diameter and calibration protocol. CONCLUSIONS: All absolute dose values, except one of a non-reference beam, and all energy values were well within the measurement accuracy of RDS TLDs.

Adsorption of As(III), As(V) and dimethylarsinic acid onto synthesized lepidocrocite.

The trapping of arsenic by zero valent iron is strongly dependant on iron by-products. Among these, lepidocrite has been scarcely studied. In this work, we studied the adsorption of two inorganic (As(III), As(V)) and one organic (dimethylarsinic acid, DMA) arsenic species onto lepidocrocite. pH influence was considered in the range 5 to 9, which corresponds to natural water pH. Langmuir model was used to simulate As adsorption isotherms. Our results showed that lepidocrocite offers high adsorption capacities: up to 0,25, 0,41 and 1 mol for As(V), DMA and As(III) could be respectively trapped per kilogram of zero-valent iron. pH influence varied from one arsenic species to another: increasing pH improve As(III) and DMA sorption whereas it has a very low effect on As(V) sorption.

Validation of the French version of the ICHOM adult oral health standard set.

INTRODUCTION: The ICHOM Adult Oral Health Standard Set (AOHSS) recently developed by the ICHOM Oral Adult Health Working Group is a standard set of outcomes designed for its collection in clinical practice in dental health. The outcome standard set is made up of clinical-reported outcome measures (CROMs) and patient-reported outcome measures (PROMs). The purpose of this study was to translate and cross-culturally adapt the PROM section of the Standard Set in French for France to enable comprehensive evaluation of the patients' oral health quality of life in a French population. METHODS: The questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcome Research (ISPOR). We included patients consulting in a dentistry clinic (n = 127) and seeking dental care. The PROM and CROM data were collected from all patients. Both reliability and the internal consistency were evaluated. RESULTS: The ICHOM AOHSS was successfully translated into French. We sampled and surveyed 126 patients in a dentistry clinic in France using the French translation of the ICHOM AOHSS. Cronbach's α was calculated to measure the internal consistency. The resulting Cronbach's α was 0.8, indicating acceptable homogeneity. CONCLUSIONS: The French version of the ICHOM AOHSS shows acceptable psychometric properties in terms of reliability and internal consistency. This translation is suitable for its implementation in a French-speaking patient population.

Interest of a new large diffusive gradients in thin films (L-DGT) for organic compounds monitoring: On-field comparison with conventional passive samplers.

In this work, the performances of a Large Diffusive Gradients in Thin films (L-DGT, i.e., a DGT based on a Chemcatcher® holder with a 5-fold larger sampling area) were compared on-field with the conventional DGT and the Polar Organic Chemical Integrative Sampler (POCIS) for the monitoring of a wide range of organic contaminants (i.e., 65 pesticides and metabolites, 53 pharmaceuticals and 12 hormones). These three passive samplers were simultaneously deployed in four rivers during 14 days. Their performances were then evaluated according to their detection and quantification capacities and their physical robustness. The results obtained confirm the advantages of the L-DGT over the conventional DGT regarding its sensitivity but also its robustness during field deployment. The POCIS provides the higher sensitivity, allowing the detection of more organic compounds compared to the DGT and, to a lesser extent, the L-DGT. However, both L-DGT and DGT reduces the uncertainty on the determination of the time-weighted average concentrations (CW), mainly due to the narrow range of variation of their calibration parameters. Indeed, for a given compound, CW can vary up to only a 3-fold factor with DGT and L-DGT compared to a 2 to 10-fold factor (up to 50) with POCIS. Thus, the L-DGT appears to be more suitable than DGT in low-contaminated contexts, which require higher sensitivity, or than POCIS when a CW determination is needed. For a qualitative evaluation however, the POCIS remains the most suitable passive sampler.

Correction: Krayem et al. The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma. Cancers 2019, 11, 1093.

In the original article [...].

Surface properties and intracellular speciation revealed an original adaptive mechanism to arsenic in the acid mine drainage bio-indicator Euglena mutabilis.

Euglena mutabilis is a protist ubiquitously found in extreme environments such as acid mine drainages which are often rich in arsenic. The response of E. mutabilis to this metalloid was compared to that of Euglena gracilis, a protist not found in such environments. Membrane fatty acid composition, cell surface properties, arsenic accumulation kinetics, and intracellular arsenic speciation were determined. The results revealed a modification in fatty acid composition leading to an increased membrane fluidity in both Euglena species under sublethal arsenic concentrations exposure. This increased membrane fluidity correlated to an induced gliding motility observed in E. mutabilis in the presence of this metalloid but did not affect the flagellar dependent motility of E. gracilis. Moreover, when compared to E. gracilis, E. mutabilis showed highly hydrophobic cell surface properties and a higher tolerance to water-soluble arsenical compounds but not to hydrophobic ones. Finally, E. mutabilis showed a lower accumulation of total arsenic in the intracellular compartment and an absence of arsenic methylated species in contrast to E. gracilis. Taken together, our results revealed the existence of a specific arsenical response of E. mutabilis that may play a role in its hypertolerance to this toxic metalloid.

Histoplasma capsulatum in Cayenne, French Guiana.

We carried out a soil sampling survey in September 2008 in central Cayenne, French Guiana, using molecular methods to assess the presence of the dimorphic fungus Histoplasma capsulatum. Four of the 31 samples collected (12.9 %) tested positive by PCR, with confirmation of the result by DNA sequencing. H. capsulatum is therefore present in urban environments in French Guiana. These results provide additional support for the primary prophylaxis of AIDS-related histoplasmosis in French Guiana.

Leishmaniasis epidemiology in endemic areas of metropolitan France and its overseas territories from 1998 to 2020.

BACKGROUND: In France, leishmaniasis is endemic in the Mediterranean region, in French Guiana and to a lesser extent, in the French West Indies. This study wanted to provide an updated picture of leishmaniasis epidemiology in metropolitan France and in its overseas territories. METHODOLOGY/PRINCIPAL FINDINGS: Leishmaniasis cases were collected by passive notification to the French National Reference Centre for Leishmaniases (NRCL) in Montpellier from 1998 to 2020 and at the associated Centre in Cayenne (French Guiana) from 2003 to 2020. In metropolitan France, 517 autochthonous leishmaniasis cases, mostly visceral forms due to Leishmania infantum (79%), and 1725 imported cases (French Guiana excluded), mainly cutaneous leishmaniasis from Maghreb, were recorded. A slight decrease of autochthonous cases was observed during the survey period, from 0.48 cases/100,000 inhabitants per year in 1999 (highest value) to 0.1 cases/100,000 inhabitants per year in 2017 (lowest value). Conversely, imported cases increased over time (from 59.7 in the 2000s to 94.5 in the 2010s). In French Guiana, 4126 cutaneous and mucocutaneous leishmaniasis cases were reported from 2003 to 2020. The mean incidence was 103.3 cases per 100,000 inhabitants/year but varied in function of the year (from 198 in 2004 to 54 in 2006). In Guadeloupe and Martinique (French West Indies), only sporadic cases were reported. CONCLUSIONS/SIGNIFICANCE: Because of concerns about disease expansion and outbreaks in other Southern Europe countries, and leishmaniasis monitoring by the NRCL should be continued and associated with a more active surveillance.

Enamel protein regulation and dental and periodontal physiopathology in MSX2 mutant mice.

Signaling pathways that underlie postnatal dental and periodontal physiopathology are less studied than those of early tooth development. Members of the muscle segment homeobox gene (Msx) family encode homeoproteins that show functional redundancy during development and are known to be involved in epithelial-mesenchymal interactions that lead to crown morphogenesis and ameloblast cell differentiation. This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult. The analysis focused on enamel and periodontal defects and enamel proteins in Msx2-null mutant mice. In the epithelial lifecycle, the levels of MSX2 expression and enamel protein secretion were inversely related. Msx2+/- mice showed increased amelogenin expression, enamel thickness, and rod size. Msx2-/- mice displayed compound phenotypic characteristics of enamel defects, related to both enamel-specific gene mutations (amelogenin and enamelin) in isolated amelogenesis imperfecta, and cell-cell junction elements (laminin 5 and cytokeratin 5) in other syndromes. These effects were also related to ameloblast disappearance, which differed between incisors and molars. In Msx2-/- roots, Malassez cells formed giant islands that overexpressed amelogenin and ameloblastin that grew over months. Aberrant expression of enamel proteins is proposed to underlie the regional osteopetrosis and hyperproduction of cellular cementum. These enamel and periodontal phenotypes of Msx2 mutants constitute the first case report of structural and signaling defects associated with enamel protein overexpression in a postnatal context.