Impacts of an urban flood control infrastructure on the limnology and ichthyofauna of a basaltic Cuesta stream (southeast Brazil).

Strategies for flood control associated to extreme precipitation events in urban areas are urgent, in order to prevent not only material damages but also to avoid human losses. The construction of flood contention reservoirs ("piscinões") has become a common engineering intervention in urban and peri-urban areas. However, there is a lack of studies focused on the evaluation of environmental impacts of this type of construction. This study intended to verify the ecological effects of a retention reservoir built directly on the course of the Cascata stream, Botucatu (SP). Three sampling sites were selected, located upstream the reservoir, in the reservoir and downstream. Samplings were carried out in July (winter - dry) and November (late spring - rainy) 2020. In situ measurements were obtained through a multiparameter probe (temperature, pH, electrical conductivity, dissolved oxygen, total dissolved solids, and oxidation-reduction potential) and water samples were collected for laboratory determinations (nitrogen, total phosphorus, thermotolerant coliforms, and chlorophyll-a). For fish sampling, manual trawls, sieves and hand nets were used, with a sampling effort of 10 throws per artefact and site. Despite the small distance between the sampling points (~1,300 m) considerable changes in the limnological conditions and fish community structure were observed. The studied environment is originally a small river surrounded by riparian forest, but this characteristic was abruptly changed in the reservoir stretch, with the direct exposition of a much larger water surface to intense solar radiation and atmosphere exchanges. Consequently, as evidenced by the PCA analysis, there was a considerable (stream-reservoir increase) of temperature, dissolved oxygen and chlorophyll. However, this spatial trend was partially disturbed by an accidental sewage-pipe rupture (posteriorly fixed) adjacent to the first sampling point, due to a previous event of extreme precipitation, which resulted in increased values of nutrients, chlorophyll, conductivity and thermotolerant coliforms. Eleven fish species were collected (two non-native), belonging to seven families and five orders. The upstream reference point (despite not be pristine), was characterized by the predominance of native species, while the reservoir condition favored the development of large populations of the non-native species. Despite the urgency of effective actions to prevent floods in urban areas, construction of contention reservoirs directly on stream courses should be avoided, due to their negative ecological impacts.

Microbial contamination of resin composites inside their dispensers: An increased risk of cross-infection?

OBJECTIVES: To evaluate the effects of microorganisms' contamination inside the dispensing syringes of different types of resin-based composites (RBCs). METHODS: This study encompassed two sections. First, an anonymous electronic survey was submitted via Google forms to Italian dentists to acquire information about composite handling during clinical procedures. Then, a bench test was performed on nanohybrid RBCs differing in matrix chemistry and fillers [FiltekTM Supreme XTE (3MTM); Venus Pearl (Kulzer GmbH); Admira Fusion x-tra (Voco)] to evaluate the microbial viability on their surfaces with/out photocuring. Uncured RBCs were exposed to standardized inocula of Streptococcus Mutans, Candida Albicans, Lactobacillus Rhamnosus, or mixt plaque in an in vitro model reproducing clinical restorative procedures. Half of the RBC specimens were cured after exposure. Microbial viability was assessed using an MTT-based test. Statistical analysis included three-way ANOVA and Tukey's tests (p<0.05). RESULTS: Among 300 dentists completing the survey, the majority declared to use the spatula to carry the RBCs from the syringe to the dental cavity (50% same spatula; 35% two spatulas). However, 80% of respondents had personal feelings that using one spatula could be a source of cross-contamination. In vitro results using one spatula showed microbial contamination of all RBCs after one hour of storage. The contamination levels depended on the used strain and RBC type (p<0.0001), but photocuring did not reduce contamination (p = 0.2992). CONCLUSIONS: Microbial species' viability on uncured RBCs and after photocuring shows the existence of a considerable risk of cross-infection. Clinical procedures in Restorative Dentistry need to acknowledge and to reduce such risk during RBCs handling. CLINICAL SIGNIFICANCE: Dentists must be aware of the possibility of cross-infection during restorative procedures, especially when the same spatula is repeatedly used for placing RBC in the cavity.

A new urinary catheter design reduces in-vitro biofilm formation by influencing hydrodynamics.

AIM: To evaluate the performance of a new catheter design based on different hydrodynamics aiming to reduce the development of biofilm, and compare it with a conventional Foley catheter (FC). METHODS: The new proposed design (NPD) catheter is a modification of the FC, based on asymmetric positioning of the balloon and additional drainage holes allowing continuous urine drainage and complete voiding of the bladder. A first experiment was undertaken to assess drainage capability, and a second experiment was performed using a bioreactor with a set-up simulating the bladder and using the test catheter as a flow-through system. The biofilm formation of five bacterial species associated with catheter-associated urinary tract infection (CAUTI) was determined after 24 h of incubation using an MTT assay. Morphological evaluation was performed using scanning electron microscopy. In-vitro determination of residual fluid, and quantitative and morphological data on biofilm formation on the intravesical and intraluminal parts of the tested catheters were assessed. RESULTS: Residual fluid was significantly higher in the FC (5.60 ± 0.43 mL) compared with the NPD catheter (0.2 ± 0.03 mL). The NPD catheter showed significantly less biofilm formation (P<0.0001) than the FC. Catheter design had a variable effect on biofilm formation depending on the bacterial strain tested. There was significantly less intraluminal biomass compared with intravesical biomass in both catheters (P<0.0001). Multi-layered biofilms that covered the FC surfaces completely were seen for all tested strains, while the NPD catheter surfaces showed reduced biofilm formation. CONCLUSIONS: Modifications of the hydrodynamic characteristics of a catheter can significantly reduce bacterial colonization. Integrated design approaches combining chemical, mechanical and topographical elements can help to reduce the occurrence of CAUTI.

Antibacterial and antibiofilm effects of radioactive thermal water.

OBJECTIVE: Most of the infections of the upper respiratory tract are caused by biofilm-forming microorganisms belonging to the Pseudomonas, Streptococcus, Staphylococcus, and Enterobacter genus. Many of these microorganisms also show antibiotic resistance, partly related to biofilm formation. The treatment of these affections may include inhalation of radioactive thermal water (RTW). The present study aimed to evaluate the in vitro antibiofilm effect of RTW collected from Merano springs, Italy. MATERIALS AND METHODS: A series of experiments were performed evaluating the effect of RTW against planktonic cultures (1 h exposure) and on biofilms (10 min and 1 h exposure) formed by Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Viable biomass was assessed using a colorimetric assay. A model based on the infection by the same strains of a reconstituted human respiratory epithelium (RHRE) was used to morphologically evaluate the antibiofilm effect of RTW. RESULTS: RTW decreased the viability of S. aureus and S. pneumoniae planktonic cultures by about 20%. RTW also decreased biofilm viability by all strains except for E. coli at both time points. In the RHRE model, bacterial adherence and colonization occurred in all specimens, showing a particular affinity for the epithelium's cilia. Bacterial infections caused significant alterations in the epithelium structure, showing enlargement of the intercellular spaces, and damage to the cell structure. Specimens infected with S. aureus showed slightly lower colonization levels after RTW treatment. CONCLUSIONS: Results of this in vitro study showed a significant effect of RTW against Gram-positive planktonic bacterial cells as well as a significant antibiofilm activity.

Can Pseudomonas aeruginosa growth be modulated by natural compounds?

Pseudomonas aeruginosa is an opportunistic human pathogen that frequently induces antibiotic resistance, as it mainly tends to form biofilms. Iron chelation may be an intriguing strategy to contrast bacterial growth. Lactoferrin is a natural compound able to chelate iron. A new multi-component medical device also contains lactoferrin. This study analyzed this compound investigating the in vitro capacity to inhibit Pseudomonas aeruginosa growth. In conclusion, this study demonstrated that a multicomponent medical device (Saflovir), also containing lactoferrin, could inhibit the in vitro growth of P. aeruginosa. This activity could be positively used in the prevention of respiratory nasal infections.

Efficient parametric generation in a nonlinear photonic crystal pumped by a dual beam.

We investigate parametric down-conversion in a hexagonally poled nonlinear photonic crystal, pumped by a dual pump with a transverse modulation that matches the periodicity of the χ (2) nonlinear grating. A peculiar feature of this resonant configuration is that the two pumps simultaneously generate photon pairs over an entire branch of modes, via quasi-phase matching with both fundamental vectors of the reciprocal lattice of the nonlinearity. The parametric gain of these modes depends thus coherently on the sum of the two pump amplitudes and can be controlled by varying their relative intensities and phases. We find that a significant enhancement of the source conversion efficiency, comparable to that of one-dimensionally poled crystals, can be achieved by a dual symmetric pump. We also show how the four-mode coupling arising among shared modes at resonance can be tailored by changing the dual pump parameters.

Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer

Purpose: Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. Methods and patients: 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations. METex14 mutations, MET copy number alterations and the levels of MET protein were determined by Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry, respectively. Concurrent alterations of other important cancer genes and immunostaining of the downstream effector, phopho-S6, were also determined. Results: METex14 mutations and MET amplification were detected in seven tumors. MET genetic alterations were found predominantly in the lung adenocarcinoma (ADC) and PSC histopathologies. High levels of MET protein were found in most MET-amplified tumors, but not in all METex14-mutated tumors. Strong phopho-S6 staining was observed in about half of the MET-activated tumors. One tumor with METex14 exhibited concurrent ERBB2 amplification. Conclusions: MET activation, by either METex14 mutations or amplification, is characteristic of a subset of early stage NSCLCs and may coexist with ERBB2 amplification. This may have potential therapeutic implications. The presence of METex14 mutations was associated with low levels of MET protein, which may limit the use of total MET immunostaining as a marker for preselecting patients for MET-targeted therapies

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A contribution for the limnological knowledge of basaltic knickzones / Uma contribuição para o conhecimento limnológico dos pedrais basálticos

Abstract The knickzones are defined as locally steep riverbed segments, such as a convex reach in a concave-up longitudinal profile. They are worldwide distributed and geologically well studied, but despite their distinctiveness as a particular kind of macrohabitat there is a notorious lack of ecological knowledge. In this context, this research proposal aims to provide a physical description, in terms of kind of habitats, and a limnological characterization of a basaltic knickzone. Information is based on a case study carried out in the Sapucaí-Mirim River, Southeast Brazil. Samplings were performed in three different habitats well represented in the knickzone (runs, riffles and pools) during rainy and dry conditions. A clear discrimination in terms of habitat type and seasonality was demonstrated through a principal component analysis. Pools exhibited higher amplitude of variation for most limnological parameters when compared to runs and riffles, probably due to a great influence of the internal metabolism (photosynthetic production and community respiration). Despite of their geological ancient formation and the little understanding of their ecological role, the knickzones are in imminent threat in several regions of the world by hydropower dams implementation. The lack of ecological information on knickzones is probably due to inherent access difficulties and how to compare the distinct kinds of habitats. Thereby, further studies should be encouraged.

Resumo Os pedrais são definidos como segmentos de rio com leito localmente íngreme, tais como um alcance convexo em um perfil longitudinal côncavo. Eles são mundialmente distribuídos e geologicamente bem estudados, mas apesar de sua distinção como um tipo particular de macrohabitat há uma notória falta de conhecimento ecológico. Neste contexto, a proposta desta pesquisa é fornecer uma descrição física, em termos de tipo de habitats, e uma caracterização limnológica de um pedral basáltico. A informação é baseada em um estudo de caso realizado no rio Sapucaí-Mirim, no Sudeste do Brasil. As amostragens foram realizadas em três diferentes habitats bem representados na zona de pedral (rápidos, corredeiras e poças) durante as condições chuvosa e seca. Uma clara discriminação em termos de tipo de habitat e sazonalidade foi demonstrada através de uma análise de componentes principais. As poças apresentaram maior amplitude de variação para a maioria dos parâmetros limnológicos quando comparadas aos rápidos e corredeiras, provavelmente devido a grande influência do metabolismo interno (produção fotossintética e respiração das comunidades). Apesar de sua formação geológica antiga e da pouca compreensão de seu papel ecológico, os pedrais estão em ameaça iminente em várias regiões do mundo pela implementação de barragens hidrelétricas. A falta de informações ecológicas sobre os pedrais é provavelmente devido às dificuldades inerentes de acesso e como comparar os tipos distintos de habitats. Assim, devem ser encorajados novos estudos.

A contribution for the limnological knowledge of basaltic knickzones.

The knickzones are defined as locally steep riverbed segments, such as a convex reach in a concave-up longitudinal profile. They are worldwide distributed and geologically well studied, but despite their distinctiveness as a particular kind of macrohabitat there is a notorious lack of ecological knowledge. In this context, this research proposal aims to provide a physical description, in terms of kind of habitats, and a limnological characterization of a basaltic knickzone. Information is based on a case study carried out in the Sapucaí-Mirim River, Southeast Brazil. Samplings were performed in three different habitats well represented in the knickzone (runs, riffles and pools) during rainy and dry conditions. A clear discrimination in terms of habitat type and seasonality was demonstrated through a principal component analysis. Pools exhibited higher amplitude of variation for most limnological parameters when compared to runs and riffles, probably due to a great influence of the internal metabolism (photosynthetic production and community respiration). Despite of their geological ancient formation and the little understanding of their ecological role, the knickzones are in imminent threat in several regions of the world by hydropower dams implementation. The lack of ecological information on knickzones is probably due to inherent access difficulties and how to compare the distinct kinds of habitats. Thereby, further studies should be encouraged.

Genetic screening and molecular characterization of MET alterations in non-small cell lung cancer.

PURPOSE: Aberrant activation of MET as a result of exon 14-skipping (METex14) mutations or gene amplification is an oncogenic mechanism in non-small cell lung carcinoma (NSCLC) and a potential therapeutic target. The purpose of this study was to characterize MET alterations in a cohort of NSCLC patients treated with surgery. METHODS AND PATIENTS: 157 NSCLCs of various histopathologies, including pulmonary sarcomatoid carcinomas (PSC), were tested for MET alterations. METex14 mutations, MET copy number alterations and the levels of MET protein were determined by Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry, respectively. Concurrent alterations of other important cancer genes and immunostaining of the downstream effector, phopho-S6, were also determined. RESULTS: METex14 mutations and MET amplification were detected in seven tumors. MET genetic alterations were found predominantly in the lung adenocarcinoma (ADC) and PSC histopathologies. High levels of MET protein were found in most MET-amplified tumors, but not in all METex14-mutated tumors. Strong phopho-S6 staining was observed in about half of the MET-activated tumors. One tumor with METex14 exhibited concurrent ERBB2 amplification. CONCLUSIONS: MET activation, by either METex14 mutations or amplification, is characteristic of a subset of early stage NSCLCs and may coexist with ERBB2 amplification. This may have potential therapeutic implications. The presence of METex14 mutations was associated with low levels of MET protein, which may limit the use of total MET immunostaining as a marker for preselecting patients for MET-targeted therapies.

PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.

Background: The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Patients and methods: Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results: Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. Conclusions: PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.

A contribution for the limnological knowledge of basaltic knickzones

Abstract The knickzones are defined as locally steep riverbed segments, such as a convex reach in a concave-up longitudinal profile. They are worldwide distributed and geologically well studied, but despite their distinctiveness as a particular kind of macrohabitat there is a notorious lack of ecological knowledge. In this context, this research proposal aims to provide a physical description, in terms of kind of habitats, and a limnological characterization of a basaltic knickzone. Information is based on a case study carried out in the Sapucaí-Mirim River, Southeast Brazil. Samplings were performed in three different habitats well represented in the knickzone (runs, riffles and pools) during rainy and dry conditions. A clear discrimination in terms of habitat type and seasonality was demonstrated through a principal component analysis. Pools exhibited higher amplitude of variation for most limnological parameters when compared to runs and riffles, probably due to a great influence of the internal metabolism (photosynthetic production and community respiration). Despite of their geological ancient formation and the little understanding of their ecological role, the knickzones are in imminent threat in several regions of the world by hydropower dams implementation. The lack of ecological information on knickzones is probably due to inherent access difficulties and how to compare the distinct kinds of habitats. Thereby, further studies should be encouraged.

Resumo Os pedrais são definidos como segmentos de rio com leito localmente íngreme, tais como um alcance convexo em um perfil longitudinal côncavo. Eles são mundialmente distribuídos e geologicamente bem estudados, mas apesar de sua distinção como um tipo particular de macrohabitat há uma notória falta de conhecimento ecológico. Neste contexto, a proposta desta pesquisa é fornecer uma descrição física, em termos de tipo de habitats, e uma caracterização limnológica de um pedral basáltico. A informação é baseada em um estudo de caso realizado no rio Sapucaí-Mirim, no Sudeste do Brasil. As amostragens foram realizadas em três diferentes habitats bem representados na zona de pedral (rápidos, corredeiras e poças) durante as condições chuvosa e seca. Uma clara discriminação em termos de tipo de habitat e sazonalidade foi demonstrada através de uma análise de componentes principais. As poças apresentaram maior amplitude de variação para a maioria dos parâmetros limnológicos quando comparadas aos rápidos e corredeiras, provavelmente devido a grande influência do metabolismo interno (produção fotossintética e respiração das comunidades). Apesar de sua formação geológica antiga e da pouca compreensão de seu papel ecológico, os pedrais estão em ameaça iminente em várias regiões do mundo pela implementação de barragens hidrelétricas. A falta de informações ecológicas sobre os pedrais é provavelmente devido às dificuldades inerentes de acesso e como comparar os tipos distintos de habitats. Assim, devem ser encorajados novos estudos.

Lung adenocarcinomas: correlation of computed tomography and pathology findings.

Adenocarcinoma is the most common histologic type of lung cancer. Recent lung adenocarcinoma classifications from the International Association for the Study of Lung cancer, the American Thoracic Society and the European Respiratory Society (IASLC/ETS/ERS, 2011) and World Health Organization (WHO, 2015) define a wide range of adenocarcinoma types and subtypes featuring different prognosis and management. This spectrum of lesions translates into various CT presentations and features, which generally show good correlation with histopathology, stressing the key role of the radiologist in the diagnosis and management of those patients. This review aims at helping radiologists to understand the basics of the up-to-date adenocarcinoma pathological classifications, radio-pathological correlations and how to use them in the clinical setting, as well as other imaging-related correlations (radiogenomics, quantitative analysis, PET-CT).

Influence of Light-curing Parameters on Biofilm Development and Flexural Strength of a Silorane-based Composite.

OBJECTIVES: The aim of this study was to evaluate the differences in biological and mechanical performances of a silorane-based and a methacrylate-based composite. Another aim was to assess the influence of light-curing time and light-curing intensity on in vitro biofilm formation and flexural strength of the two tested composites. METHODS: Experiment 1: 432 specimens obtained from a silorane-based composite and from a standard methacrylate-based composite were divided into six groups and light-cured for 10, 20, 30, 40, 60, or 80 seconds, using one of two light-curing intensities, 400 mW/cm(2) or 800 mW/cm(2). At 24 hours, a monospecific Streptococcus mutans biofilm adherent to the surfaces of the samples was obtained. Then, a colorimetric technique (MTT assay) was used to evaluate the adherent viable biomass. Two samples per group were observed using confocal laser scanning microscopy. Analysis of variance (ANOVA) and Tukey tests were used to analyze the results (p<0.05). Experiment 2: 192 bar-shaped specimens were obtained and light-cured as in the previous experiment. A three-point bend test using a universal testing machine was performed to obtain flexural strength values. ANOVA and Tukey tests were used to analyze the results (p<0.05). RESULTS: In experiment 1, a highly significant difference (p<0.0001) in biofilm development was shown between silorane-based and methacrylate-based composites. In fact, the silorane-based composite exhibited better biological performance. Significant differences were also found between the two light-curing intensities (p<0.018) and for curing times (p<0.0001): silorane-based composite light-cured for 80 seconds at 800 mW/cm(2) light-curing intensity showed the lowest biofilm development. In experiment 2, a significant difference in flexural strength (p<0.0318) was only found between the different composites. Nevertheless, both resin composites showed flexural strength values in accordance with International Organization for Standardization guidelines even after 10 seconds of light-curing time. CONCLUSIONS: Silorane-based composite was less prone to biofilm development compared with a methacrylate-based composite. Acceptable flexural strength values for both composites were obtained after 10 seconds of light-curing time.

Silver-polysaccharide antimicrobial nanocomposite coating for methacrylic surfaces reduces Streptococcus mutans biofilm formation in vitro.

OBJECTIVES: The aim of this study was to determine the in vitro microbiological performances of a lactose-modified chitosan (Chitlac) coating inside which silver nanoparticles were embedded (Chitlac-nAg) for BisGMA/TEGDMA methacrylic specimens. METHODS: Different concentrations of nAg inside Chitlac coating were tested (1 mM, 2 mM, 5 mM). Specimen surface was analyzed by means of field-emission scanning electron microscopy (FEISEM) and energy-dispersive X-ray spectroscopy (EDS). A 48 h monospecific Streptococcus mutans biofilm was developed over the specimen surfaces using a modified drip-flow bioreactor; adherent viable biomass was assessed by MTT test and biofilm was imaged by confocal laser-scanning microscopy (CLSM). RESULTS: The presence of finely dispersed nanoparticles inside the Chitlac coating was confirmed by FEISEM and EDS analysis. All nanoparticles were embedded in the Chitlac coating layer. Chitlac-nAg coatings were able to significantly decrease biofilm formation depending on the nAg concentration, reaching a -80% viable biomass decrease when the 5 mM nAg-Chitlac group was confronted to non-coated control specimens. CLSM analysis did not provide evidence of a contact-killing activity, however the antibacterial Chitlac-nAg coating was able to alter biofilm morphology preventing the development of mature biofilm structures. CONCLUSIONS: The microbiological model applied in this study helped in assessing the antibacterial properties of a coating designed for methacrylate surfaces. CLINICAL SIGNIFICANCE: A microbiological model based on a bioreactor-grown biofilm is useful for preliminary in vitro tests of dental materials. In translational terms, an antibacterial nanocomposite coating based on Chitlac-nAg and designed to be applied to methacrylic surfaces may be a promising way to obtain dental materials able to actively prevent secondary caries.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

An in vitro and in vivo comparison of the effect of Stevia rebaudiana extracts on different caries-related variables: a randomized controlled trial pilot study.

The effect of Stevia extracts on in vitro Streptococcus mutans biofilm formation and in vivo plaque pH was evaluated in this paper. Three 10% solutions containing stevioside, rebaudioside A or sucrose were prepared. MTT assay was used to evaluate microbiological counts in vitro. Twenty volunteers rinsed for 1 min with each solutions, and plaque pH was measured at 7 time points after each rinse. Higher in vitro S. mutans biofilm formation was observed in sucrose solution (p < 0.01). After 5, 10, 15 and 30 min, the sucrose in vivo rinse produced a statistically significantly lower pH value compared to the Stevia extracts (F = 99.45, p < 0.01).Stevia extracts can be considered nonacidogenic.

p14(ARF) inhibits the growth of lung adenocarcinoma cells harbouring an EGFR L858R mutation by activating a STAT3-dependent pro-apoptotic signalling pathway.

Epidermal growth factor receptor (EGFR) stimulates proliferative and survival signals. Activating mutations of EGFR are involved in the aetiology and maintenance of the malignant phenotype of lung tumours. We previously described the frequent association of these mutations with the decreased expression of the p14(ARF) tumour suppressor, another common feature of lung cancer. Based on these data, we postulated that p14(ARF) could protect cells against untimely or excessive mitotic signals induced by mutant EGFR. In this study, we demonstrate that p14(ARF) promotes apoptosis in lung tumour cells harbouring the EGFR L858R mutation through the accumulation of phosphorylated signal transducer and activator of transcription 3 (STAT3) on Tyr 705 residue, which leads to Bcl-2 downregulation. Using siRNA against PTP-RT, the phosphatase that specifically targets Tyr 705 residue, we show that accumulation of pSTAT3-Tyr705 promotes EGFR L858R mutant cell death, thereby confirming the existence of a STAT3-dependent pro-apoptotic pathway in these cells. Finally, we show that the expression of the EGFR L858R mutant represses p14(ARF) expression and inhibits STAT3/Bcl-2 signalling. These results identify a novel link between the p14(ARF) and EGFR pathways and suggest that EGFR L858R counteracts the pro-apoptotic function of p14(ARF) by downregulating its expression to promote carcinogenesis.