Evaluation et prise en charge de l’envahissement mandibulaire dans les carcinomes epidermoïdes de la cavite orale et de l’oropharynx

Objectif : Le but de notre étude est l’évaluation de l’atteinte mandibulaire dans les carcinomes épidermoïdes de la cavité orale et de l’oropharynx. Matériel et méthodes : Il s’agit d’une étude rétrospective à propos de 34 patients colligés sur 6 ans (1999-2004) et ayant un carcinome épidermoïde de la cavité orale et/ou de l’oropharynx avec envahissement mandibulaire confirmé à l’anatomopathologie. L’atteinte mandibulaire a été évaluée par l’examen clinique,  l’orthopantomographie, la tomodensitométrie, et par les constatations peropératoires du chirurgien. Tous les patients ont eu un évidement ganglionnaire, une exérèse tumorale associée à une mandibulectomie segmentaire interruptrice ou conservatrice. Résultats : L’envahissement mandibulaire a été suspecté cliniquement chez 70,5% des patients devant l’adhérence de la tumeur à l’os. Après examen clinique et imagerie, cette atteinte a été diagnostiquée chez 88,2% des patients. Dans 11,8% des cas, l’atteinte n’a été suspectée qu’en peropératoire. L’examen histologique a confirmé l’atteinte osseuse chez tous les patients. La mandibulectomie segmentaire a été pratiquée chez 17 patients devant l’atteinte du canal mandibulaire. Vingt-huit patients ont eu une radiothérapie postopératoire à la dose moyenne de 64 Gy. Les taux de récidive, de métastase et de décès étaient respectivement de 11,7%, 17,6% et 17,6% pour les patients qui ont eu une mandibulectomie segmentaire, et de 23,5%, 17,6% et 23,5% pour ceux qui ont eu une mandibulectomie conservatrice. Par ailleurs, 76,5% et 29,5% des patients ayant eu respectivement une mandibulectomie segmentaire et une mandibulectomie conservatrice avaient une gêne fonctionnelle importante lors de l’alimentation. Conclusion : L’examen clinique, l’imagerie et l’examen peropératoire sont d’un apport capital dans l’évaluation de l’atteinte mandibulaire. Une atteinte épargnant le canal mandibulaire justifie une mandibulectomie conservatrice permettant d’avoir de meilleurs résultats esthétiques et fonctionnels tout en assurant un contrôle carcinologiquement satisfaisant.Mots clés : envahissement mandibulaire, carcinome épidermoïde, cavité orale, oropharynx, mandibulectomie segmentaire, mandibulectomie conservatric

Tumor suppression in mice lacking GABARAP, an Atg8/LC3 family member implicated in autophagy, is associated with alterations in cytokine secretion and cell death

GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized. Here, we report that the ablation of murine GABARAP, a member of the Atg8/LC3 family that is central to autophagosome formation, suppresses the incidence of tumor formation mediated by the carcinogen DMBA and results in an enhancement of the immune response through increased secretion of IL-1β, IL-6, IL-2 and IFN-γ from stimulated macrophages and lymphocytes. In contrast, TGF-β1 was significantly reduced in the serum of these knockout mice. Further, DMBA treatment of these GABARAP knockout mice reduced the cellularity of the spleen and the growth of mammary glands through the induction of apoptosis. Gene expression profiling of mammary glands revealed significantly elevated levels of Xaf1, an apoptotic inducer and tumor-suppressor gene, in knockout mice. Furthermore, DMBA treatment triggered the upregulation of pro-apoptotic (Bid, Apaf1, Bax), cell death (Tnfrsf10b, Ripk1) and cell cycle inhibitor (Cdkn1a, Cdkn2c) genes in the mammary glands. Finally, tumor growth of B16 melanoma cells after subcutaneous inoculation was inhibited in GABARAP-deficient mice. Together, these data provide strong evidence for the involvement of GABARAP in tumorigenesis in vivo by delaying cell death and its associated immune-related response

Evapotranspiration and evaporation/transpiration partitioning with dual source energy balance models in agricultural lands

EvapoTranspiration (ET) is an important component of the water cycle, especially in semi-arid lands. Its quantification is crucial for a sustainable management of scarce water resources. A way to quantify ET is to exploit the available surface temperature data from remote sensing as a signature of the surface energy balance, including the latent heat flux. Remotely sensed energy balance models enable to estimate stress levels and, in turn, the water status of most continental surfaces. The evaporation and transpiration components of ET are also just as important in agricultural water management and ecosystem health monitoring. Single temperatures can be used with dual source energy balance models but rely on specific assumptions on raw levels of plant water stress to get both components out of a single source of information. Additional information from remote sensing data are thus required, either something specifically related to evaporation (such as surface water content) or transpiration (such as PRI or fluorescence). This works evaluates the SPARSE dual source energy balance model ability to compute not only total ET, but also water stress and transpiration/evaporation components. First, the theoretical limits of the ET component retrieval are assessed through a simulation experiment using both retrieval and prescribed modes of SPARSE with the sole surface temperature. A similar work is performed with an additional constraint, the topsoil surface soil moisture level, showing the significant improvement on the retrieval. Then, a flux dataset acquired over rainfed wheat is used to check the robustness of both stress levels and ET retrievals. In particular, retrieval of the evaporation and transpiration components is assessed in both conditions (forcing by the sole temperature or the combination of temperature and soil moisture). In our example, there is no significant difference in the performance of the total ET retrieval, since the evaporation rate retrieved from the sole surface temperature is already fairly close to the one we can reconstruct from observed surface soil moisture time series, but current work is underway to test it over other plots.</p

Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a candidate gene

Vitamin D receptor (VDR) polymorphisms are associated with an increased asthma incidence in human populations; however, observations in Vdr knockout mice are unclear. The aim of our study was to determine the influence of the genetic variation in Vdr among inbred strains on lung resistance (i.e., dynamic and airway resistance). In an intercross between the strains C57BL/6J (B6) and KK/HlJ (KK), we identified that a significant QTL for dynamic resistance on Chr X was interacting with a QTL on Chr 15. The Chr 15 QTL peak was located in close proximity to the Vdr locus. We further examined if phenotypes of several inbred strains with varying Vdr genotypes differed. Strains with a B6-like genotype on the Vdr locus had significantly lower airway resistance than strains with a KK-like genotype. Vdr knockout mice were examined for dynamic resistance and showed significantly higher resistance than mice with one (i.e., heterozygous) or both copies (i.e., wild-type) of the Vdr. In comparison to B6, the strain A/J is more resistant but carries the same genotype at the Vdr locus. Dietary vitamin D manipulation in the strain A/J did not rescue the high airway resistance phenotype. Finally, we observed that serum vitamin D does not correlate significantly with lung resistance parameters in a survey of 18 strains. Conclusively, Vdr contributes to the phenotypic variation of lung resistance in inbred mice but other molecules in the Vdr pathway and extended network [i.e., Chr X gene(s)] may contribute as well

Study of Heparin in Intestinal Ischemia and Reperfusion in Rats: Morphologic and Functional Evaluation

To study whether treatment with heparin (HEP) attenuates intestinal dysfunction caused by ischemia (I) and reperfusion (R), rats were treated with HEP (100 U/kg intravenously) or saline solution (SS) before I (60 min), which was produced by occlusion of the superior mesenteric artery, and R (120 min). After I or I/R, we mounted 2-cm jejunal segment in an organ bath to study neurogenic contractions stimulated by electrical pulses or KCl, using a digital recording system. Thin jejunal slices were stained with hematoxylin and eosin for optical microscopy. Compared with the sham group, jejunal contractions were similar in the I + HEP and the I/R + HEP groups, but reduced in the I + SS and the I/R + SS groups. the jejunal enteric nerves were damaged in the I + SS and the I/R + SS, but not in the I + HEP and the I/R + HEP cohorts. These results suggested that HEP attenuated intestinal dysfunction caused by I and I/R.Universidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol, BR-04023900 São Paulo, BrazilFed Univ Great Dourados, Sch Med, Dourados, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Surg, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol, BR-04023900 São Paulo, BrazilWeb of Scienc

Particulate air pollution and chronic ischemic heart disease in the eastern United States: a county level ecological study using satellite aerosol data

<p>Abstract</p> <p>Background</p> <p>There are several known factors that cause ischemic heart disease. However, the part played by air pollution still remains something of a mystery. Recent attention has focused on the chronic effect of particulate matter on heart disease. Satellite-derived aerosol optical depth (AOD) was found to be correlated with <it>PM</it>_2.5in the eastern US. The objective of this study was to examine if there is an association between aerosol air pollution as indicated by AOD and chronic ischemic heart disease (CIHD) in the eastern US.</p> <p>Methods</p> <p>An ecological geographic study method was employed. Race and age standardized mortality rate (SMR) of CIHD was computed for each of the 2306 counties for the time period 2003–2004. A mean AOD raster grid for the same period was derived from Moderate Resolution Imaging Spectrometer (MODIS) aerosol data and the average AOD was calculated for each county. A bivariate Moran's I scatter plot, a map of local indicator of spatial association (LISA) clusters, and three regression models (ordinary least square, spatial lag, and spatial error) were used to analyze the relationship between AOD and CIHD SMR.</p> <p>Results</p> <p>The global Moran's I value is 0.2673 (<it>p </it>= 0.001), indicating an overall positive spatial correlation of CIHD SMR and AOD. The entire study area is dominated by spatial clusters of AOD against SMR (high AOD and high SMR in the east, and low AOD and low SMR in the west) (permutations = 999, <it>p </it>= 0.05). Of the three regression models, the spatial error model achieved the best fit (R²= 0.28). The effect of AOD is positive and significant (beta = 0.7774, p = 0.01).</p> <p>Conclusion</p> <p>Aerosol particle pollution has adverse effect on CIHD mortality risk in the eastern US. High risk of CIHD mortality was found in areas with elevated levels of outdoor aerosol air pollution as indicated by satellite derived AOD. The evidence of the association would support targeting of policy interventions on such areas to reduce air pollution levels. Remote sensing AOD data could be used as an alternative health-related indictor of air quality.</p

Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure

IMPECCABLE: Integrated Modeling PipelinE for COVID Cure by Assessing Better LEads

The drug discovery process currently employed in the pharmaceutical industry typically requires about 10 years and $2–3 billion to deliver one new drug. This is both too expensive and too slow, especially in emergencies like the COVID-19 pandemic. In silico methodologies need to be improved both to select better lead compounds, so as to improve the efficiency of later stages in the drug discovery protocol, and to identify those lead compounds more quickly. No known methodological approach can deliver this combination of higher quality and speed. Here, we describe an Integrated Modeling PipEline for COVID Cure by Assessing Better LEads (IMPECCABLE) that employs multiple methodological innovations to overcome this fundamental limitation. We also describe the computational framework that we have developed to support these innovations at scale, and characterize the performance of this framework in terms of throughput, peak performance, and scientific results. We show that individual workflow components deliver 100 × to 1000 × improvement over traditional methods, and that the integration of methods, supported by scalable infrastructure, speeds up drug discovery by orders of magnitudes. IMPECCABLE has screened ∼ 1011 ligands and has been used to discover a promising drug candidate. These capabilities have been used by the US DOE National Virtual Biotechnology Laboratory and the EU Centre of Excellence in Computational Biomedicine