To prospectively evaluate multiobserver diagnostic performance and reader agreement for colorectal polyp detection in a well-characterized cohort of patients with increased number of polyps, compared ...with an average-risk patient, with colonoscopy as the reference standard.
A cohort of 70 patients suspected of having polyps was examined with spiral computed tomographic (CT) colonography, with colonoscopy performed the same day. After air insufflation per rectum, supine and prone images were obtained with single-detector row CT (5-mm collimation, 8-mm table increment, 2-mm reconstruction interval). Images were analyzed independently by four experienced abdominal radiologists using two-dimensional multiplanar reformation followed by selective use of three-dimensional endoscopic volume-rendered images. Data were analyzed both per polyp and per patient.
Analysis per polyp demonstrated a pooled sensitivity of 0.68 for lesions 10 mm or larger (n = 40), with 75% agreement among the four readers. Analysis per patient demonstrated improved detection and agreement, with a pooled sensitivity of 0.88 for patients with polyps or cancers 10 mm or larger (n = 28), with 94% agreement. When sensitivity and receiver operating characteristic analyses were analyzed per polyp size threshold, results among readers converged and peaked at polyp diameters of approximately 10 mm.
In this patient cohort, diagnostic performance and interobserver agreement with single-detector row CT colonography was sufficient for detection of patients with lesions 10 mm or larger, with more variable results for smaller polyps.
The associations between residential outdoor and ambient particle mass, fine particle absorbance, particle number (PN) concentrations, and residential and traffic determinants were investigated in ...four European urban areas (Helsinki, Athens, Amsterdam, and Birmingham). A total of 152 nonsmoking participants with respiratory diseases, not exposed to occupational pollution, were included in the study, which comprised a 7-day intensive exposure monitoring period of both indoor and home outdoor particle mass and number concentrations. The same pollutants were also continuously measured at ambient fixed sites centrally located to the studied areas (fixed ambient sites). Relationships between concentrations measured directly outside the homes (residential outdoor) and at the fixed ambient sites were pollutant-specific, with substantial variations among the urban areas. Differences were more pronounced for coarse particles due to resuspension of road dust and PN, which is strongly related to traffic emissions. Less significant outdoor-to-fixed variation for particle mass was observed for Amsterdam and Birmingham, predominantly due to regional secondary aerosol. On the contrary, a strong spatial variation was observed for Athens and to a lesser extent for Helsinki. This was attributed to the overwhelming and time-varied inputs from traffic and other local sources. The location of the residence and traffic volume and distance to street and traffic light were important determinants of residential outdoor particle concentrations. On average, particle mass levels in suburban areas were less than 30% of those measured for residences located in the city center. Residences located less than 10 m from a street experienced 133% higher PN concentrations than residences located further away. Overall, the findings of this multi-city study, indicated that (1) spatial variation was larger for PN than for fine particulate matter (PM) mass and varied between the cities, (2) vehicular emissions in the residential street and location in the center of the city were significant predictors of spatial variation, and (3) the impact of traffic and location in the city was much larger for PN than for fine particle mass.
Soil represents an important environmental compartment that can be regarded as a final sink for metal nanoparticles including silver particles (Ag-NPs). Assessing realistic exposure scenarios, ...including the bioavailability of Ag-NPs for soil organisms, requires taking into account that Ag-NPs can undergo physico-chemical transformations, such as sulphidisation, before interacting with organisms. However, differentiating between uptake of true metal NPs and that of released ions is essential to assess the actual role of these two metal forms in toxicity over time. The present study quantified the toxicokinetic rate constants of particulate and ionic Ag in
Eisenia fetida
exposed to soil treated with pristine Ag-NPs (50 nm), Ag
2
S-NPs (20 nm) as an environmentally relevant form, and AgNO
3
as an ionic control. Results showed that the uptake and elimination rate constants of Ag in earthworms exposed to Ag-NPs and AgNO
3
were not significantly different from each other, whereas the uptake of Ag
2
S-NPs was significantly lower. Interestingly, the biogenic formation of particulate Ag (∼10% of the total Ag accumulated over time) in earthworms exposed to AgNO
3
led to a kinetic pattern of particulate Ag similar to that of pristine Ag-NPs. SEM-EDX analysis confirmed the presence of particulate Ag in earthworms exposed to both Ag-NPs and AgNO
3
, showing that these particles were different from those to which earthworms were exposed. We demonstrated that around 85% of the Ag accumulated in the worms after exposure to Ag-NPs and AgNO
3
was present as ions or as particles with size <20 nm. Additionally, the low accumulation of the non-soluble, sulphidised form of nano-Ag, reflecting aged particles in the environment, confirms the importance of ionic uptake of Ag. This study clearly shows that the main form of Ag taken up in earthworms is the ionic species, which stresses the fundamental need to use environmentally relevant forms of metal NPs in performing ecotoxicological tests, because pristine NPs may behave completely differently.
Discrimination between nano (≥20 nm) and ionic Ag in earthworms exposed to Ag-NPs, Ag
2
S-NPs and AgNO
3
reveals that accumulated silver is mainly present as ions.
Estimation of the terms in the upper-ocean heat budget from a moored array in the central Arabian Sea shows periods when a rough balance between the temperature trend and the horizontal advection of ...heat exists. Altimetry and sea-surface temperature imagery are used to demonstrate that these episodes of strong horizontal advection are associated with mesoscale features. During the wintertime Northeast (NE) Monsoon these are capped-off mesoscale eddy features generated during the previous summertime Southwest (SW) Monsoon and have little horizontal transport of heat within the mixed layer. During the SW Monsoon the major contribution is strong offshore export of coastally upwelled water in a filament with a strong surface presence. Temperature and salinity properties from the moored array and a SeaSoar survey during the formation of the coastal filament confirm the offshore transport of the upwelled water mass to the site of the moored array, more than 600
km offshore. Estimates of the filament section heat flux are several percent of the total estimated heat flux due to upwelling along the Arabian Peninsula, and remote sensing data show that similar mesoscale variability along the coast is enhanced during the SW Monsoon. This points to the importance of mesoscale-modulated transports in not only the observed heat budget at the moored array, but in the overall upper-ocean heat budget in the Arabian Sea.
Atg16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with inflammatory bowel disease. Here we find ...that Atg16L1 deficiency leads to an exacerbated graft-versus-host disease (GVHD) in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Atg16L1-deficient allo-HSCT recipients with GVHD displayed increased T cell proliferation due to increased dendritic cell (DC) numbers and costimulatory molecule expression. Reduced autophagy within DCs was associated with lysosomal abnormalities and decreased amounts of A20, a negative regulator of DC activation. These results broaden the function of Atg16L1 and the autophagy pathway to include a role in limiting a DC-mediated response during inflammatory disease, such as GVHD.
PD 108635 (
1) was identified as a potent dopamine D
4 ligand and we wanted to replace the benzylic alcohol with a metabolically more stable moiety. Investigations led to the discovery of a series of ...isoindolinones having D
4 affinity.
PD 108635 (
1) was identified as a potent dopamine D
4 ligand and we wanted to replace the benzylic alcohol with a metabolically more stable moiety. Our investigations led to the discovery of a series of isoindolinones (
5) with D
4 affinity.
Objective and Design: Ultraviolet (UV) exposure induces local immunosuppression and inflammation in human skin. Cytokines are, in part, responsible for these responses. To investigate the effects of ...UV-induced gene expression at the molecular level we established a sensitive in vivo/ex vivo method for a comparative quantification of cytokines and receptors involved in the local skin immune reactions.Material and Methods: Specific mRNA levels of human UV-irradiated skin were determined by real time quantification (TaqMan super(TM) RT-PCR). Highly efficient PCR-reaction conditions were obtained by designing very short PCR-templates (72-87bp). The most sensitive PCR-conditions were obtained by optimisation of primer and Mn(OAc) sub(2)-concentrations, which led to significant PCR signals (C sub(T)-value) of less than 36 cycles. A strong correlation between PCR efficiency of the internal control (GAPDH) compared to targets (IL-1 beta , IL-10, IL-10r, TNF alpha , IL-7) allowed the use of delta delta C sub(T)-method to quantify comparable mRNA levels.Results: Interleukin-1 beta (IL-1 beta ), Interleukin-10 (IL-10), and tumour necrosis factor alpha (TNF alpha ) mRNA levels were increased in a time- and dose-dependent manner. Interleukin-1 beta induction reached a maximum (approx. 44-fold) 6 h after a UV-dose equivalent to 3 times the minimal erythemal doses just perceptible (MED sub(jp)). Maximal TNF alpha mRNA expression (approx. 14-fold) was also detected 6 h after UV exposure. Interleukin-10 mRNA induction reached a maximum of approximately 14-fold 24 h after UV-irradiation of 3 MED sub(jp). Time- and dose-dependent changes in Interleukin-7 and Interleukin-10 receptor mRNA levels did not occur after UV-irradiation.Conclusions: Time-distinct gene induction of IL-1 beta , TNF alpha and IL-10 is involved in UV-induced immune reactions, but no considerable changes were found for IL-10r or IL-7.
Titanocene complexes TiCp
2(Cl)R, TiCp
2(Cl)SR, TiCp
2(SR)
2 with benzothienyl and dibenzothienyl containing ligands were synthesized and studied. Crystal structure determinations of complexes with ...dibenzothienyl ligands revealed planar heteroaromatic rings. HeLa and COLO 320M tumor cell lines were used in preliminary experiments to examine cell growth inhibition displayed by the compounds.
The titanocene complexes TiCp
2(Cl)R (
1), TiCp
2(Cl)SR (
2), TiCp
2(SR)
2 (
3) with R
=
benzothienyl (BT)
A and dibenzothienyl (DBT)
B, were synthesized and the molecular structures of TiCp
2(Cl)DBT (
1B) and TiCp
2(Cl)SDBT (
2B) confirmed by single crystal X-ray diffraction studies. The dibenzothiophene rings are planar and for
1B in the plane of the titanium and chloro ligand. The chloro ligand is in a
trans position to the sulfur atom with respect to the titanium–carbon bond. The complexes were studied for their electronic and structural features and preliminary tests were conducted for their tumor inhibiting properties against HeLa and COLO 320M tumor cell lines. These antitumor activities were compared against those observed for titanocene dichloride (
S-01) under similar conditions and the highest antitumor activity was recorded for
2B.
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