Epigenetic fields for cancerization are involved in development of human cancers, especially those associated with inflammation and multiple occurrences. However, it is still unclear when such field ...defects are formed and what component of inflammation is involved in induction of aberrant DNA methylation. Here, in a mouse colitis model induced by dextran sulfate sodium (DSS), we identified three CpG islands specifically methylated in colonic epithelial cells exposed to colitis. Their methylation levels started to increase as early as 8 weeks after DSS treatment and continued to increase until colon cancers developed at 15 weeks. In contrast to the temporal profile of DNA methylation levels, infiltration of inflammatory cells spiked immediately after the DSS treatment and then gradually decreased. Exposure of cultured colonic epithelial cells to DSS did not induce DNA methylation and it was indicated that inflammation triggered by the DSS treatment was responsible for methylation induction. To clarify components of inflammation involved, severe combined immunodeficiency (SCID) mice that lack functional T- and B-cells were similarly treated. Even in SCID mice, DNA methylation, along with colon tumors, were induced at the same levels as in their background strain of mice (C.B17). Comparative analysis of inflammation-related genes showed that Ifng, Il1b and Nos2 had expression concordant with methylation induction whereas Il2, Il6, Il10, Tnf did not. These results showed that an epigenetic field defect is formed at early stages of colitis-associated carcinogenesis and that functional T and B cells are non-essential for the formation.
T1-weighted pointwise encoding time reduction with radial acquisition (PETRA) sequences require limited gradient activity and allow quiet scanning. We aimed to assess the usefulness of PETRA in ...pediatric brain imaging.
We included consecutive pediatric patients who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios between WM and GM were compared in the cerebellar WM, internal capsule, and corpus callosum. The degree of myelination was rated by using 4-point scales at each of these locations plus the subcortical WM in the anterior frontal, anterior temporal, and posterior occipital lobes. Two radiologists made all assessments, and the intra- and interrater agreement was calculated by using intraclass correlation coefficients. Acoustic noise on MPRAGE and PETRA was measured.
We included 56 patients 5 days to 14 years of age (mean age, 36.6 months) who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios for PETRA were significantly higher than those for MPRAGE (P < .05), excluding the signal ratio for cerebellar WM. Excellent intra- and interrater agreement were obtained for myelination at all locations except the cerebellar WM. The acoustic noise on PETRA (58.2 dBA) was much lower than that on MPRAGE (87.4 dBA).
PETRA generally showed better objective imaging quality without a difference in subjective image-quality evaluation and produced much less acoustic noise compared with MPRAGE. We conclude that PETRA can substitute for MPRAGE in pediatric brain imaging.
We propose a highly scalable switch architecture suitable for client-side cross-connect switches in reconfigurable optical add/drop multiplexers and optical switching in data centers. It consists of ...cascaded cyclic arrayed waveguide gratings (AWGs). We develop a 270 × 270 prototype switch consisting of an assembly of arrayed small switches and couplers and AWGs that are fabricated on planar lightwave circuit chips. Transmission experiments verify its technical feasibility.
The purpose of this study was to determine if the apparent diffusion coefficient (ADC) on diffusion-weighted MRI could predict the response of patients with advanced pancreatic cancer to ...chemotherapy. Diffusion-weighted MRI was performed in 63 consecutive patients with advanced pancreatic cancer who were subsequently treated with chemotherapy. The ADC values of the primary tumour with a middle b-value (400 s mm(-2)) and a high b-value (1000 s mm(-2)) were determined; cystic or necrotic components were avoided. The patients were classified into two groups: (i) those with progressive disease and (ii) those who were stable 3 months and 6 months after initial treatment. The groups were compared with respect to the ADC and clinical factors, including gender, age, Union International Contre le Cancer (UICC ) stage, initial tumour size and chemotherapy agents used. Local tumour progression rates were evaluated using the Kaplan-Meier method. The middle b-value ADC of the pancreatic cancers ranged from 0.93-2.42 x10(-3) mm(2) s(-1) (mean, 1.50 x10(-3) mm(2) s(-1)), and the high b-value ADC ranged from 0.72-1.88 x10(-3) mm(2) s(-1) (mean, 1.20 x10(-3) mm(2) s(-1)). The high b-value ADC was significantly different between the progressive and stable groups at 3 months' and 6 months' follow-up (p = 0.03 and p = 0.04, respectively). The rate of tumour progression was significantly higher in those with a lower high b-value ADC than in those with a higher b-value ADC (median progression time, 140 days vs 182 days; p = 0.01). In conclusion, a lower high b-value ADC in patients with advanced pancreatic cancer may be predictive of early progression in chemotherapy-treated patients.
Abstract
PUB, Singapore's National Water Agency, has been using polymeric UF membrane in drinking water plants to produce high quality water whilst requiring a smaller footprint. Submerged polymeric ...hollow-fiber membrane has been used since 2003 in Chestnut Avenue Water Works (CAWW). PUB decided to use submerged-type ceramic membranes for enhancement of production capacity at CAWW. The flat-sheet ceramic membrane system was retrofitted into two spare, empty tanks with a combined design capacity of 36,400 m3/d. The system has been successfully put into operation, running at a net flux of 160 L/m2-h (LMH) since June 2017. Membrane integrity testing is automatically carried out once a week to ensure the membranes' integrity. Stable filtrate quality has been achieved with a low turbidity of 0.018 NTU on average. Pretreatment for seawater desalination is another application in which a ceramic membrane system can be operated at higher flux compared to that for polymeric membranes. A pilot scale system was installed at PUB R&D facility in Tuas to investigate sustainable operating flux and permeate quality. FeCl3 was used as a coagulant before ceramic filtration, with a dosage of 4–6 mg/L. It was shown that sustainable flux can be 181–249 LMH in seawater treatment system with flat sheet ceramic membranes. The silt density index and turbidity of permeate were 1.6–2.2 and 0.04–0.10 NTU, respectively, which indicates that the system can produce high quality water for feed of reverse osmosis systems.
We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG).
A questionnaire was administered and serum anti-H. pylori IgG ...antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers.
The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P=0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the high-intake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data.
Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.
Background: The process of bone remodelling is disturbed in the development of osteoporosis. Objective: To investigate if proteins in osteoporotic bone are modified by advanced glycation end products ...(AGEs), and whether these alterations are related to measures of bone remodelling based on histomorphometric findings. Methods: Bone specimens taken from the iliac crest by bone biopsy of eight osteoporotic patients were investigated by histomorphometry and by immunohistochemical staining with the AGEs imidazolone and Nε-carboxymethyllysine. Results: Both AGEs were found in all bone specimens. The intensity of staining correlated with patient age. The percentage of bone surface covered with osteoblasts showed a significantly negative correlation with the staining intensity of both AGEs. Conclusions: It is known that AGEs can regulate proliferation and differentiation of osteoblastic cells and that AGE-specific binding sites are present in cultured osteoblast-like cells. Moreover, AGE induced biological effects in these cells might be mediated by RAGE (receptor of AGE) or by other AGE receptors in different stages of osteoblast development. The inverse relation between AGE staining intensity and the percentage of bone surface covered with osteoblasts in the trabecular bone may provide evidence that AGE modification of bone proteins disturbs bone remodelling.
High serum uric acid (UA) levels are believed to be an independent risk factor for the development of diabetes. We aimed to investigate the relationship between serum UA concentrations and ...early-phase insulin secretion following a 75 g oral glucose tolerance test (OGTT) in nondiabetic subjects. We enrolled 570 Japanese subjects (354 males and 216 females, aged 50.5 ± 8.9 years and 52.6 ± 7.3 years, respectively), who underwent the 75 g OGTT during their annual health examination. The OGTT confirmed their nondiabetic status. Insulin secretion was estimated by the disposition index (DI) (Δ insulin/Δ glucose (0-30 min) × (1/HOMA-IR), which is an adjusted measure of β-cell function relative to variations in insulin sensitivity. Simple linear regression analysis showed negative correlations between serum UA levels and DI, when examined in the whole study population and female subjects only (r = -0.209, p < 0.001 and r = -0.232, p < 0.001, respectively). However, in male subjects, UA levels did not correlate with DI. In females, multivariate linear regression analysis revealed that serum UA levels were the major predictors of DI, explaining 16.4% of its variation (p < 0.001). Serum UA levels significantly correlate with early-phase insulin secretion in nondiabetic Japanese women. It may be an independent risk factor for predicting β-cell function in women.
Aims. We examined the physical properties of molecular clouds (morphology, column density, number density, mass) to investigate the mechanism of triggered star formation by UV radiation from a ...massive star. Methods. We made extensive, high-resolution maps of molecular clouds associated and interacting with the W5-East H ii region using the 45-m telescope at the Nobeyama Radio Observatory (HPBW = 15$\farcs$6) in 13CO $(J = 1{-}0)$ and C18O $(J = 1{-}0)$ to reveal details in the high-density regions of the molecular clouds. In addition, to investigate the spatial distributions of young stellar objects (YSOs) in the W5-East H ii region, we mapped the spatial distributions of Class I and II candidates. Results. We identified eight 13CO molecular clouds (three of them are known bright-rimmed clouds) and nine 18O clumps. The masses of the clouds and clumps range from 460 to 36 000 $M_{\odot}$ and from 55 to 740 $M_{\odot}$, respectively. The peak 13CO column densities of the clouds facing the H ii region are twice as large as the others. They have steep density gradients toward the H ii region, indicating interactions with the H ii region. We selected 55 Class I candidates and 778 Class II candidates associated with the W5-East H ii region from the previous Spitzer IRAC/MIPS survey. Most Class I candidates are located around integrated intensity peaks of 13CO, whereas most Class II candidates are distributed along the front sides of the BRC arcs close to the exciting star. Conclusions. The alignments of the YSO candidates and the molecular clouds in order of age indicate that triggered star formation occurs in the W5-East H ii region as a result of gas compression by strong UV radiation. Based on the column densities of 13CO and the spatial distribution of YSO candidates, we identified a new bright-rimmed cloud candidate on the west side of the W5-East H ii region.
A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line ...treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile.
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