Ion Microscopy: A New Approach for Subcellular Localization of Labelled Molecules

Secondary ion mass spectroscopy (SIMS) was used to obtain images representing the intracellular distribution of molecules labelled with carbon 14. Deoxyadenosine labelled with carbon 14 was added to a cultured human fibroblast cell medium, and the intracellular distribution of this molecule was studied using three different SIMS instruments: the CAMECA IMS 3F and SMI 300 ion microscopes and the UC-HRL scanning ion microprobe. Carbon 14 distribution images obtained by this method show that deoxyadenosine U-C14 is present in the cytoplasm as well as the nucleus, with a higher concentration in\u27 the nucleoli. Our study clearly demonstrates that ion microscopy is well suited for carbon 14 detection and localization at the subcellular level, permitting a wide variety of microanalytical tracer experiments

Classroom active breaks to increase children’s physical activity: A cross-sectional study in the province of Naples, Italy

Background: Classroom Active Breaks (CABs), short active sessions integrated in the school time, have been recognized as a promising tool to reduce sedentary behavior and increase Physical Activity (PA) levels in children. “AulAttiva” is a six-month CABs-based program implemented in primary schools of the province of Naples. The aim of this study was to evaluate its effectiveness by comparing PA and sedentary time of participating pupils respect to a control group, considering also their weight status. Methods: Four third-grade classes, each from 4 schools out of 32 participating in AulAttiva, and 4 third-grade classes, each from 4 schools out of 74 that did not take part, were randomly selected. Finally, 58 children composed the intervention group and 57 the control group. Age, gender, weight and height were registered for each participant. Weight status was classified as non-overweight and overweight/obesity. Sedentary time and PA were assessed through accelerometers along a school day. Results: Light PA was 4 min higher in the AulAttiva group with respect to controls (p = 0.046). Within the non-overweight children, the AulAttiva group spent less time in sedentary behavior and more time in light and total PA than controls. No significant differences were found between the overweight/obese subgroups. Conclusions: The results support the effectiveness of CABs in increasing PA during the school day. Greater effects were registered among normal weight pupils, suggesting the possible influence of weight status on children’s participation to the intervention. Further studies are needed to improve the compliance of overweight/obese children to this intervention

Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease

Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD

Modelling constraints on the emission inventory and on vertical dispersion for CO and SO2 in the Mexico City Metropolitan Area using Solar FTIR and zenith sky UV spectroscopy

Emissions of air pollutants in and around urban areas lead to negative health impacts on the population. To estimate these impacts, it is important to know the sources and transport mechanisms of the pollutants accurately. Mexico City has a large urban fleet in a topographically constrained basin leading to high levels of carbon monoxide ( CO). Large point sources of sulfur dioxide (SO2) surrounding the basin lead to episodes with high concentrations. An Eulerian grid model (CAMx) and a particle trajectory model ( FLEXPART) are used to evaluate the estimates of CO and SO2 in the current emission inventory using mesoscale meteorological simulations from MM5. Vertical column measurements of CO are used to constrain the total amount of emitted CO in the model and to identify the most appropriate vertical dispersion scheme. Zenith sky UV spectroscopy is used to estimate the emissions of SO2 from a large power plant and the Popocatepetl volcano. Results suggest that the models are able to identify correctly large point sources and that both the power plant and the volcano impact the MCMA. Modelled concentrations of CO based on the current emission inventory match observations suggesting that the current total emissions estimate is correct. Possible adjustments to the spatial and temporal distribution can be inferred from model results. Accurate source and dispersion modelling provides feedback for development of the emission inventory, verification of transport processes in air quality models and guidance for policy decisions

Modelling constraints on the emission inventory and on vertical dispersion for CO and SO₂ in the Mexico City Metropolitan Area using Solar FTIR and zenith sky UV spectroscopy

International audienceEmissions of air pollutants in and around urban areas lead to negative health impacts on the population. To estimate these impacts, it is important to know the sources and transport mechanisms of the pollutants accurately. Mexico City has a large urban fleet in a topographically constrained basin leading to high levels of carbon monoxide (CO). Large point sources of sulfur dioxide (SO2) surrounding the basin lead to episodes with high concentrations. An Eulerian grid model (CAMx) and a particle trajectory model (FLEXPART) are used to evaluate the estimates of CO and SO2 in the current emission inventory using mesoscale meteorological simulations from MM5. Vertical column measurements of CO are used to constrain the total amount of emitted CO in the model and to identify the most appropriate vertical dispersion scheme. Zenith sky UV spectroscopy is used to estimate the emissions of SO2 from a large power plant and the Popocatépetl volcano. Results suggest that the models are able to identify correctly large point sources and that both the power plant and the volcano impact the MCMA. Modelled concentrations of CO based on the current emission inventory match observations suggesting that the current total emissions estimate is correct. Possible adjustments to the spatial and temporal distribution can be inferred from model results. Accurate source and dispersion modelling provides feedback for development of the emission inventory, verification of transport processes in air quality models and guidance for policy decisions

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years). Methods: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP) and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). Results: A total of 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866) and ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. Conclusions: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with elevated AFP, irrespective of age, including ≥75 years

ramucirumab in advanced hepatocellular carcinoma and elevated alpha fetoprotein following sorafenib outcomes by prior transarterial chemoembolisation from two randomised double blind placebo controlled phase 3 studies reach 2 and reach

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