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 [...].

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.

Monte Carlo as quality control tool of stereotactic body radiation therapy treatment plans.

PURPOSE/OBJECTIVE: The objective of this study was to verify the accuracy of treatment plans of stereotactic body radiation therapy (SBRT) and to verify the feasibility of the use of Monte Carlo (MC) as quality control (QC) on a daily basis. MATERIAL/METHODS: Using EGSnrc, a MC model of Agility™ linear accelerator was created. Various measurements (Percentage depth dose (PDD), Profiles and Output factors) were done for different fields sizes from 1x1 up to 40x40 (cm2). An iterative model optimization was performed to achieve adequate parameters of MC simulation. 40 SBRT patient's dosimetry plans were calculated by Monaco™ 3.1.1. CT images, RT-STRUCT and RT-PLAN files from Monaco™ being used as input for Moderato MC code. Finally, dose volume histogram (DVH) and paired t-tests for each contour were used for dosimetry comparison of the Monaco™ and MC. RESULTS: Validation of MC model was successful, as <2% difference comparing to measurements for all field's sizes. The main energy of electron source incident on the target was 5.8 MeV, and the full width at half maximum (FWHM) of Gaussian electron source were 0.09 and 0.2 (cm) in X and Y directions, respectively. For 40 treatment plan comparisons, the minimum absolute difference of mean dose of planning treatment planning (PTV) was 0.1% while the maximum was 6.3%. The minimum absolute difference of Max dose of PTV was 0.2% while the maximum was 8.1%. CONCLUSION: SBRT treatment plans of Monaco agreed with MC results. It possible to use MC for treatment plans verifications as independent QC tool.

Cadmium Selenide Formation Influences the Production and Characteristics of Extracellular Polymeric Substances of Anaerobic Granular Sludge.

Feeding cadmium (II) and selenium (IV) simultaneously to anaerobic granular sludge with the aim of synthesizing cadmium selenide (CdSe) nanoparticles induces compositional changes in the extracellular polymeric substances (EPS) matrix of this sludge. A methanogenic anaerobic granular sludge was repeatedly exposed to Cd(II) (10-50 mg L-1) and selenite (79 mg L-1) for 300 days at pH 7.3 and 30 °C in a fed-batch feeding regime for enrichment of Se-reducing bacteria and synthesis of CdSe nanoparticles. EPS fingerprints of the granular sludge, obtained by size exclusion chromatography coupled to a fluorescence detector, showed a significant increase in the intensity of protein-like substances with > 100 kDa apparent molecular weight (aMW) upon repeated exposure to Cd(II) and Se(VI). This was accompanied by a prominent decrease in protein-like substances of aMW < 10 kDa. The fingerprint of the humic-like substances showed emergence of a new peak with aMW of 13 to 300 kDa in the EPS extracted from the Cd/Se fed granular sludge. Experiments on metal(loid)-EPS interactions showed that the CdSe nanoparticles interact mainly with loosely bound EPS (LB-EPS). This study showed that the formation of Se(0) and CdSe nanoparticles occurs in the LB-EPS fraction of the granular sludge and repeated exposure to Cd and Se induces compositional changes in the EPS matrix.

American cutaneous leishmaniasis in French Guiana: an epidemiological update and study of environmental risk factors.

BACKGROUND: American cutaneous leishmaniasis (ACL) is endemic in French Guiana. Its epidemiology is evolving, notably because of immigration, anthropization of natural areas, and new microbiological methods. Our first objective was to update epidemiological data. Our second objective was to look for risk factors of ACL. METHODS: This multicentric study was conducted from October 2017 to June 2018 in French Guiana. Patients with suspicion of mucocutaneous leishmaniasis were included in case of positive smear, culture, or PCR-RFLP on skin biopsy. RESULTS: One hundred and twenty-three patients met the inclusion criteria. Among those patients, 59.3% were Brazilian, mostly gold miners. Most of them (58%) were between 16 and 40 years old, and 69% were male. A large proportion of patients lived in traditional wooden houses (51%). Patients living in coastal towns were usually infected during trips to the primary forest (60%) and had a shorter time to diagnosis than workers of the hinterland. Among environmental risk factors, the presence of a water spring (40%) and dogs around houses (40%) were frequently reported. Leishmania guyanensis represented 80% of cases, followed by Leishmania braziliensis (6%), Leishmania naiffi (2%), and Leishmania amazonensis (1%). CONCLUSIONS: Gold mining and trips to the primary forest represent high-risk situations for ACL in French Guiana, where the population of infected patients is dominated by Brazilian immigrants. Possible environmental risk factors such as the presence of dogs, water sources, and traditional wooden houses require further investigation.

The Benefit of Reactivating p53 under MAPK Inhibition on the Efficacy of Radiotherapy in Melanoma.

Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1Met) significantly enhanced the radiosensitivity of BRAF-mutant melanoma cells. This was accompanied by an increase in both p53 expression and activity. Of note, we found that radiation alone markedly promoted both ERK and AKT phosphorylation, thus contributing to radioresistance. The combination of vemurafenib and PRIMA-1Met caused the inactivation of both MAPK kinase and PI3K/AKT pathways. Furthermore, when combined with radiotherapy, it was able to significantly enhance melanoma cell radiosensitivity. Interestingly, in nude mice bearing melanoma xenografts, the latter triple combination had not only a synergistic effect on tumor growth inhibition, but also a potent control on tumor regrowth in all animals after finishing the triple combination therapy. RT alone had only a weak effect. In conclusion, we provide a basis for a strategy that may overcome the radioresistance of BRAF-mutated melanoma cells to radiotherapy. Whether this will translate into a rational to use radiotherapy in the curative setting in BRAF-mutated melanoma patients deserves consideration.

Utility of PCR in Patients with Strongyloides stercoralis and HTLV-1 Coinfection in French Guiana.

Strongyloides stercoralis and human T-lymphotropic virus 1 (HTLV-1) coinfections have been extensively reported in the literature, but the diagnosis and treatment of strongyloidiasis remains a challenge, particularly in HTLV-1 carriers. Our objectives were to evaluate the efficacy of a new PCR method for the detection of S. stercoralis in HTLV-1-positive patients. Stools were collected over a 1-year period across the endemic region of French Guiana, including remote forest areas. Two systems of real-time PCR were then used comparatively, with small subunit and specific repeat as respective targets, and compared with the results of microscopic examinations. One-hundred and twelve stool samples were included. Twenty-seven patients (24.1%) presented a positive HTLV-1 serology. The overall prevalence of strongyloidiasis among the 112 patients was 30% with small-subunit PCR and 11.6% with microscopic examinations. In the seropositive population, all tested stools were negative, whereas 51.2% were positive using small-subunit PCR. Thus, PCR allowed a much-improved sensitivity, particularly in HTLV-1 carriers. Among the two systems investigated, small subunit yielded better results than specific repeat PCR, with prevalence rates in HTLV-1 carriers of 51.2% and 22.2%, respectively. Therefore, PCR should be considered as a useful tool for the diagnosis of strongyloidiasis, particularly in HTLV-1 carriers who often present a light parasitic load due to erratic administration of anthelmintic drugs.

3D Monte Carlo dosimetry of intraoperative electron radiation therapy (IOERT).

PURPOSE: This paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient's CT images. METHODS: The IOERT treatment planning was performed using the following successive steps: I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out. RESULTS: The tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS). CONCLUSIONS: The method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.

Shielding disk position in intra-operative electron radiotherapy (IOERT): A Monte Carlo study.

PURPOSE: In IOERT breast treatments, a shielding disk is frequently used to protect the underlying healthy structures. The disk is usually composed of two materials, a low-Z material intended to be oriented towards the beam and a high-Z material. As tissues are repositioned around the shield before treatment, the disk is no longer visible and its correct alignment with respect to the beam is guaranteed. This paper studies the dosimetric characteristics of four possible clinical positioning scenarios of the shielding disk. A new alignment method for the shielding disk in the beam is introduced. Finally, it suggests a new design for the shielding disk. METHODS: As the first step, the IOERT machine "Mobetron 1000" was modeled by using Monte Carlo simulation, tuning the MC model until an excellent match with the measured PDDs and profiles was achieved. Four possible shielding disk positioning scenarios were considered, determining the dosimetric impact. Furthermore, in our center, to prevent beam misalignment, we have developed a shielding disk equipped with guiding rods. Having ascertained a correct alignment between the disk and the beam, we can propose a new internal design of the shielding disk that can improve the dose distribution with a better coverage of the treated area. RESULTS: All MC simulations were performed with a 12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip applicator, this applicator being the most clinically used. The simulations were compared with measurements performed in a water phantom and showed good results within 2.2% of root mean square difference (RMSD). The misplacement positions of the shielding disk have dosimetric impacts in the treatment volume and a small translation could have a significant influence on healthy tissues. The D-scenario is the worst which could happens when the shielding disk is flipped upside down, giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk. A new shielding design used, together with our alignment tool, is able to give a more homogeneous dose in the target area. CONCLUSIONS: The accuracy of shielding disk position can still be problematic in IOERT dosimetry. Any method that can ascertain the good alignment between the shielding disk and the beam is beneficial for the dose distribution and is a prerequisite for an optimized shield internal design that could improve the coverage of the treated area and the protection of healthy tissues.

Position paper for the evaluation and management of oral status in patients with valvular disease: Groupe de Travail Valvulopathies de la Société Française de Cardiologie, Société Française de Chirurgie Orale, Société Française de Parodontologie et d'Implantologie Orale, Société Française d'Endodontie et Société de Pathologie Infectieuse de Langue Française.

Oral health is of particular importance in patients with heart valve diseases because of the risk of infective endocarditis. Recommendations for antibiotic prophylaxis before dental procedures have been restricted, but the modalities of oral evaluation and dental care are not detailed in guidelines. Therefore, a multidisciplinary working group reviewed the literature to propose detailed approaches for the evaluation and management of buccodental status in patients with valvular disease. Simple questions asked by a non-dental specialist may draw attention to buccodental diseases. Besides clinical examination, recent imaging techniques are highly sensitive for the detection of inflammatory bone destruction directly related to oral or dental infection foci. The management of buccodental disease before cardiac valvular surgery should be adapted to the timing of the intervention. Simple therapeutic principles can be applied even before urgent intervention. Restorative dentistry and endodontic and periodontal therapy can be performed before elective valvular intervention and during the follow-up of patients at high risk of endocarditis. The detection and treatment of buccodental foci of infection should follow specific rules in patients who present with acute endocarditis. Implant placement is no longer contraindicated in patients at intermediate risk of endocarditis, and can also be performed in selected high-risk patients. The decision for implant placement should follow an analysis of general and local factors increasing the risk of implant failure. The surgical and prosthetic procedures should be performed in optimal safety conditions. It is therefore now possible to safely decrease the number of contraindicated dental procedures in patients at risk of endocarditis.

Pulp Inflammation Diagnosis from Clinical to Inflammatory Mediators: A Systematic Review.

INTRODUCTION: Similar to other tissues, the dental pulp mounts an inflammatory reaction as a way to eliminate pathogens and stimulate repair. Pulp inflammation is prerequisite for dentin pulp complex repair and regeneration; otherwise, chronic disease or pulp necrosis occurs. Evaluation of pulp inflammation severity is necessary to predict the clinical success of maintaining pulp vitality. Clinical limitations to evaluating in situ inflammatory status are well-described. A molecular approach that aids clinical distinction between reversible and irreversible pulpitis could improve the success rate of vital pulp therapy. The aim of this article is to review inflammatory mediator expression in the context of clinical diagnosis. METHODS: We searched PubMed and Cochrane databases for articles published between 1970 and December 2016. Only published studies of inflammatory mediator expression related to clinical diagnosis were eligible for inclusion and analysis. RESULTS: Thirty-two articles were analyzed. Two molecular approaches were described by study methods, protein expression analysis and gene expression analysis. Our review indicates that interleukin-8, matrix metalloproteinase 9, tumor necrosis factor-α, and receptor for advanced glycation end products expression increase at both the gene and protein levels during inflammation. CONCLUSIONS: Clinical irreversible pulpitis is related to specific levels of inflammatory mediator expression. The difference in expression between reversible and irreversible disease is both quantitative and qualitative. On the basis of our analysis, in situ quantification of inflammatory mediators may aid in the clinical distinction between reversible and irreversible pulpitis.

Neotropical echinococcosis caused by Echinococcus vogeli in a 6-year-old child: the second case report in humans in French Guiana.

Human polycystic echinococcosis is a parasitic infection caused by the larval stage of Echinococcus vogeli which occurs in rural areas of Central and South America. Abdominal echinococcosis caused by E. vogeli is reported for the first time in a child, a 6-year-old boy in French Guiana. The diagnosis was made by histological and molecular techniques. In tropical regions, this neglected disease must be considered even in children.

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.

Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study.

BACKGROUND: Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain. The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in AIDS patients in the French West Indies and Guiana. METHODOLOGY/PRINCIPAL FINDINGS: Adult patients with HIV and suspicion of toxoplasmic encephalitis with start of specific antitoxoplasmic therapy were included in this study during 40 months. The real-time PCR assay targeting the 529 bp repeat region of T. gondii was performed in two different centers for all blood samples. A Neighbor-Joining tree was reconstructed from microsatellite data to examine the relationships between strains from human cases of toxoplasmosis in South America and the Caribbean. A total of 44 cases were validated by a committee of experts, including 36 cases with toxoplasmic encephalitis. The specificity of the PCR assay in blood samples was 100% but the sensitivity was only 25% with moderate agreement between the two centers. Altered level of consciousness and being born in the French West Indies and Guiana were the only two variables that were associated with significantly decreased risk of false negative results with the PCR assay. CONCLUSION/SIGNIFICANCE: Our results showed that PCR sensitivity in blood samples increased with severity of toxoplasmic encephalitis in AIDS patients. Geographic origin of patients was likely to influence PCR sensitivity but there was little evidence that it was caused by differences in T. gondii strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803621.

Comparative Physicochemical Analysis of Pulp Stone and Dentin.

INTRODUCTION: Odontoblasts are responsible for the synthesis of dentin throughout the life of the tooth. Tooth pulp tissue may undergo a pathologic process of mineralization, resulting in formation of pulp stones. Although the prevalence of pulp stones in dental caries is significant, their development and histopathology are poorly understood, and their precise composition has never been established. The aim of the present study was to investigate the physicochemical properties of the mineralized tissues of teeth to elucidate the pathologic origin of pulp stones. METHODS: Areas of carious and healthy dentin of 8 decayed teeth intended for extraction were analyzed and compared. In addition, 6 pulp stones were recovered from 5 teeth requiring root canal treatment. The samples were embedded in resin, sectioned, and observed by scanning electron microscopy and energy-dispersive spectroscopy. X-ray diffraction was performed to identify phases and crystallinity. X-ray fluorescence provided information on the elemental composition of the samples. RESULTS: Pulp stones showed heterogeneous structure and chemical composition. X-ray diffraction revealed partially carbonated apatite. X-ray fluorescence identified P, Ca, Cu, Zn, and Sr within dentin and pulp stones. Zn and Cu concentrations were higher in pulp stones and carious dentin compared with healthy dentin. CONCLUSIONS: Pulpal cells produce unstructured apatitic mineralizations containing abnormally high Zn and Cu levels.

Biodentine induces immortalized murine pulp cell differentiation into odontoblast-like cells and stimulates biomineralization.

INTRODUCTION: Biodentine (Septodont, Saint Maur des Faussés, France), a new tricalcium silicate-based cement, has recently been commercialized and advertised as a bioactive material. Its clinical application and physical properties have been widely described, but, so far, its bioactivity and biological effect on pulp cells have not been clearly shown. Thus, the aim of this study was to evaluate the biological effect of Biodentine on immortalized murine pulp cells (OD-21). METHODS: OD-21 cells were cultured with or without Biodentine. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) colorimetric assay after 2, 3, and 5 days of stimulation. The expression of several biomolecular markers was analyzed to screen differentiation pathways, both on a gene level with Real-time reverse transcription polymerase chain reaction and on a protein level by measuring alkaline phosphatase activity. Alizarin red staining was used to assess and quantify biomineralization. RESULTS: The expression patterns of several genes confirmed the differentiation of OD-21 cells into odontoblasts during the period of cell culture. Our results suggest that Biodentine is bioactive because it increased OD-21 cell proliferation and biomineralization in comparison with controls. CONCLUSIONS: Because of its bioactivity, Biodentine can be considered as a suitable material for clinical indications of dentin-pulp complex regeneration, such as direct pulp capping.

AsIII oxidation by Thiomonas arsenivorans in up-flow fixed-bed reactors coupled to As sequestration onto zero-valent iron-coated sand.

The combined processes of biological As(III) oxidation and removal of As(III) and As(V) by zero-valent iron were investigated with synthetic water containing high As(III) concentration (10 mg L(-1)). Two up-flow fixed-bed reactors (R1 and R2) were filled with 2 L of sieved sand (d = 3 ± 1 mm) while zero-valent iron powder (d = 76 µm; 1% (w/w) of sand) was mixed evenly with sand in R2. Thiomonas arsenivorans was inoculated in the two reactors. The pilot unit was studied for 33 days, with HRT of 4 and 1 h. The maximal As(III) oxidation rate was 8.36 mg h(-1) L(-1) in R1 and about 45% of total As was removed in R2 for an HRT of 1 h. A first order model fitted well with the As(III) concentration evolution at the different levels in R1. At the end of the pilot monitoring, batch tests were conducted with support collected at different levels in R1. They showed that bacterial As(III) oxidation rate was correlated with the axial length of reactor, which could be explained by biomass distribution in reactor or by bacterial activity. In opposition, As(III) oxidation rate was not stable in R2 due to the simultaneous bacterial As(III) oxidation and chemical removal by zero-valent iron and its oxidant products. However, a durable removal of total As was realized and zero-valent iron was not saturated by As over 33 days in R2. Furthermore, the influence of zero-valent iron and its oxidant corrosion products on the evolution of As(III)-oxidizing bacteria diversity was highlighted by the molecular fingerprinting method of PCR-DGGE using aoxB gene as a functional marker of aerobic As(III) oxidizers.

The MAP kinase pathway is involved in odontoblast stimulation via p38 phosphorylation.

INTRODUCTION: We have previously shown that the p38 gene is highly expressed in odontoblasts during active primary dentinogenesis, but is drastically down-regulated as cells become quiescent in secondary dentinogenesis. Based on these observations, we hypothesized that p38 expression might be upregulated, and the protein activated by phosphorylation, when odontoblasts are stimulated such as during tertiary reactionary dentinogenesis. METHODS: We stimulated immortalized, odontoblast-like MDPC-23 cells, alone or in combination, with heat-inactivated Streptococcus mutans, EDTA-extracted dentine matrix proteins (DMPs), or growth factors, including transforming growth factor (TGF)-beta1, tumor necrosis factor-alpha (TNF-alpha), and adrenomedullin (ADM). We used ELISA to measure the resulting phosphorylation of the p38 protein, as well as its degree of nuclear translocation. RESULTS: Our results suggest that the p38-MAPKinase pathway is activated during odontoblast stimulation in tertiary dentinogenesis by both p38 phosphorylation and enhanced nuclear translocation. CONCLUSIONS: Data indicate that odontoblast behaviour therefore potentially recapitulates that during active primary dentinogenesis.