Fusobacterium Detected in Barrett's Esophagus and Esophageal Adenocarcinoma Tissues.

We examined Fusobacterium nucreatum (F. nucleatum) and whole Fusobacterium species (Pan-fusobacterium) in non-neoplastic Barrett's esophagus (BE) from patients without cancer (n = 67; N group), with esophageal adenocarcinoma (EAC) (n = 27) and EAC tissue (n = 22). F. nucleatum was only detectable in 22.7% of EAC tissue. Pan-fusobacterium was enriched in EAC tissue and associated with aggressive clinicopathological features. Amount of Pan-fusobacterium in non-neoplastic BE was correlated with presence of hital hernia and telomere shortening. The result suggested potential association of Fusobacterium species in EAC and BE, featuring clinicpathological and molecular features.

Repeated Stimulation of Toll-Like Receptor 2 and Dectin-1 Induces Chronic Pancreatitis in Mice Through the Participation of Acquired Immunity.

BACKGROUND: Stimulation of Toll-like receptor 3 (TLR3) induces autoimmune-mediated pancreatitis in susceptible mice, whereas stimulation of TLR4 causes nonautoimmune-mediated pancreatitis. However, the effects of TLR2 stimulation on the pancreas are unknown. AIMS: We investigated the role of TLR2 stimulation on pancreatic damage by repeatedly stimulating mice with TLR2 ligands. METHODS: Wild-type (WT) and interleukin 10-deficient (IL-10-knockout (KO)) mice were administered zymosan and lipoteichoic acid (LTA) intraperitoneally at various doses twice weekly for 4 weeks. Syngeneic T-cell-deficient mice, B-cell-deficient mice, recombination activating gene 2-deficient (RAG2-KO) mice and RAG2-KO mice that had been reconstituted with CD4+ or CD8+ T cells isolated from WT mice were treated with zymosan similarly. Mice were killed, the severity of pancreatitis was graded histologically, and serum cytokine levels were measured. RESULTS: Repeated administration of zymosan induced pancreatitis dose dependently in both WT and IL-10-KO mice. Administration of LTA induced pancreatitis only in IL-10-KO mice. Adoptive transfer of splenocytes obtained from IL-10-KO mice with pancreatitis did not cause pancreatitis in recipient RAG2-KO mice. Pancreatitis was scarcely observed in RAG2-KO mice and was attenuated in T-cell-deficient and B-cell-deficient mice compared with WT mice. A single administration of zymosan significantly increased the serum level of monocyte chemoattractant protein 1 (MCP-1) in WT mice. CONCLUSIONS: Repeated stimulation of TLR2 and dectin-1 induced nonautoimmune-mediated pancreatitis in mice. Participation of acquired immunity seems to play an important role in the pathogenesis of pancreatitis in association with the increase in serum MCP-1 level.

Inhibition of the dephosphorylation of eukaryotic initiation factor 2α ameliorates murine experimental pancreatitis.

BACKGROUND: Endoplasmic reticulum (ER) stress in the pancreas is closely associated with the development of acute pancreatitis. However, the role of the protein kinase RNA-like ER kinase (PERK) in this disease is not fully understood. We investigated whether an inhibitor of the dephosphorylation of eukaryotic initiation factor 2α, salubrinal, could improve murine experimental pancreatitis through the amelioration of ER stress. METHODS: Acute pancreatitis was induced by the intraperitoneal administration of cerulein (50 µg/kg) six times at 1-h intervals followed by lipopolysaccharide (10 mg/kg). Salubrinal was administered intraperitoneally immediately after lipopolysaccharide injection and 3 h later. Mice were sacrificed 24 h after the first injection of cerulein, and serum amylase and proinflammatory cytokines were measured. The severity of pancreatitis was evaluated histologically using a scoring system. The expression levels of ER stress-related proteins were evaluated by Western blotting. RESULTS: The administration of salubrinal significantly attenuated the increase in serum amylase levels and improved histologically assessed pancreatitis. The serum levels of proinflammatory cytokines were significantly suppressed in salubrinal-treated mice, as was the expression of glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, and cleaved caspase-3. CONCLUSIONS: The amelioration of ER stress through augmentation of the PERK-signaling pathway may be a therapeutic target for the treatment of acute pancreatitis.

Effectiveness of Nonvitamin K Antagonist Oral Anticoagulants and Warfarin for Preventing Further Cerebral Microbleeds in Acute Ischemic Stroke Patients with Nonvalvular Atrial Fibrillation and At Least One Microbleed: CMB-NOW Multisite Pilot Trial.

BACKGROUND: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months. METHODS: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups. RESULTS: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs. DISCUSSION: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out.

Characteristic phase distribution in the white matter of infants on phase difference enhanced imaging.

BACKGROUND AND PURPOSE: The infantile brain is continuously undergoing development. Non-invasive methods to assess the neurological development of infants are important for the early detection of abnormalities. Some microstructures in the brain have been demonstrated via phase difference-enhanced imaging (PADRE), which may reflect myelin-related microstructures. We aimed to assess the white matter (WM) signal distribution in infants using PADRE and compared it with that using T1-weighted images (T1WI) and diffusion tensor imaging (DTI) on magnetic resonance imaging (MRI). MATERIALS AND METHOD: This study included 18 infants (postmenstrual age at MRI, 37-40 weeks) without abnormal findings on MRI. Signal distribution using T1WI, a fractional anisotropy (FA) map and PADRE was assessed regarding the following intraparenchymal structures: the optic radiation (OR), internal capsule (IC), corpus callosum, corticospinal tract (CST), semiovale center and subcortical regions. RESULTS: We found that the signal distribution was significantly different (P<0.001) with a relatively large signal change found at the IC and CST across the three imaging methods. Signal changes were also greater at the OR and rolandic subcortical WM on PADRE, whereas these were smaller on T1WI and FA. CONCLUSION: PADRE demonstrated a characteristic phase shift distribution in infantile WM, which was different from that observed on T1WI and FA maps, and may demonstrate the developing myelin-related structures. PADRE can be a unique indicator of infantile brain development.

Improved image quality of helical computed tomography of the head in children by iterative reconstruction.

BACKGROUND AND PURPOSE: Iterative reconstruction (IR) offers noise reduction and improved image quality of computed tomography (CT). Our aim was to assess the imaging quality of non-contrast helical CT of the head in children using IR. MATERIALS AND METHODS: This study recruited 78 consecutive children aged ≤5 years (range: from 3 months to 5 years; mean: 1.7 years) who underwent an emergent non-enhanced helical CT of the head with no abnormal findings. The acquired data were reconstructed using filtered back projection (FBP) and sinogram-affirmed IR (SAFIRE) with strength levels of 2 (IR2) and 4 (IR4). The imaging quality of FBP, IR2 and IR4 was scored by two experienced neuroradiologists in terms of the contrast between the gray-white matter junction and artifacts from the skull at the level of the semioval center, basal ganglia and fourth ventricle. FBP, IR2 and IR4 scores were compared at each slice level. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for FBP, IR2 and IR4 and were compared among the three reconstruction algorithms. RESULTS: The score of IR2 and IR4 was significantly higher than that of FBP in terms of both the contrast between the gray-white matter junction and artifacts from the skull at each slice level (P<0.001). SNR and CNR on IR4 were the highest followed by those on IR2 and FBP (P<0.001). CONCLUSIONS: IR may improve the image quality of helical CT of the head in children.

Phosphorylation of Smad2/3 at specific linker threonine indicates slow-cycling intestinal stem-like cells before reentry to cell cycle.

BACKGROUND: Quiescent (slow-cycling) and active (rapid-cycling) stem cells are demonstrated in small intestines. We have identified significant expression of Smad2/3, phosphorylated at specific linker threonine residues (pSmad2/3L-Thr), in murine stomach, and suggested these cells are epithelial stem cells. AIM: Here, we explore whether pSmad2/3L-Thr could serve as a biomarker for small intestine and colon stem cells. METHODS: We examined small intestines and colons from C57BL/6 mice and colons with dextran sulfate sodium (DSS)-induced colitis. We performed double-immunofluorescent staining of pSmad2/3L-Thr with Ki67, cytokeratin 8, chromogranin A, CDK4, DCAMKL1, and Musashi-1. Small intestines and colons from Lgr5-EGFP knock-in mice were examined by pSmad2/3L-Thr immunofluorescent staining. To examine BrdU label retention of pSmad2/3L-Thr immunostaining-positive cells, we collected specimens after BrdU administration and observed double-immunofluorescent staining of pSmad2/3L-Thr with BrdU. RESULTS: In small intestines and colons, pSmad2/3L-Thr immunostaining-strongly positive cells were detected around crypt bases. Immunohistochemical co-localization of pSmad2/3L-Thr with Ki67 was not observed. pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with cytokeratin 8, CDK4, and Musashi-1 and different localization from chromogranin A and DCAMKL1 immunostaining-positive cells. Under a light microscope, pSmad2/3L-Thr immunostaining-strongly positive cells were morphologically undifferentiated. In Lgr5-EGFP knock-in mice, some but not all pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with Lgr5. pSmad2/3L-Thr immunostaining-strongly positive cells showed co-localization with BrdU at 5, 10, and 15 days after administration. In DSS-induced colitis, pSmad2/3L-Thr and Ki67 immunostaining-positive cells increased in the regeneration phase and decreased in the injury phase. CONCLUSION: In murine small intestines and colons, we suggest pSmad2/3L-Thr immunostaining-strongly positive cells are epithelial stem-like cells just before reentry to the cell cycle.

Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial.

RATIONALE: Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs). AIMS: This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. DESIGN: We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(∗)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke.

Inhibition of the dephosphorylation of eukaryotic initiation factor 2α ameliorates murine experimental colitis.

BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress in the intestine is closely associated with the development of inflammatory bowel disease (IBD). However, the role of the protein kinase RNA-like ER kinase in this disease is not fully known. We studied whether an inhibitor of the dephosphorylation of eukaryotic initiation factor 2α, salubrinal, improves murine experimental colitis through the amelioration of ER stress. METHODS: Colitis was induced by the administration of 3% dextran sulfate sodium (DSS) for 5 days. Mice were injected salubrinal intraperitoneally from the commencement of DSS treatment and were sacrificed on day 10. The severity of colitis was evaluated histologically using a scoring system.Myeloperoxidase activity and the expression of proinflammatory cytokine genes in the colon were analyzed. The expression levels of ER stress-related proteins were evaluated by Western blotting. RESULTS: The administration of salubrinal significantly attenuated body weight loss and improved colitis, as assessed histologically. The elevation of myeloperoxidase activity and the expression of proinflammatory cytokine genes were suppressed in salubrinal-treated mice. The expression of glucose-regulated protein 78, activating translation factor 4, and heat-shock protein 70 was elevated in mice treated with salubrinal. CONCLUSION: The amelioration of ER stress may be a therapeutic target for the treatment of IBD.

Successful treatment of a patient with Budd-Chiari syndrome with main hepatic vein obstruction with percutaneous transluminal angioplasty and stent placement.

A woman in her 40s presented at our department with abdominal fullness. Abdominal computed tomography showed hepatomegaly and ascites, and gastrointestinal endoscopy showed esophageal varices. A diagnosis of Budd-Chiari syndrome (BCS) was confirmed by percutaneous hepatic venography, which detected obstruction of the main hepatic vein. It was treated using percutaneous transluminal angioplasty and metallic stent placement. Rupture of the esophageal varices occurred 5 months later because of the occlusion of the stent lumen; however, she was successfully retreated with further stent placement.

Turbo spin-echo-based enhanced acceleration-selective arterial spin labeling without electrocardiography or peripheral pulse unit triggering and contrast enhancement for lower extremity MRA.

PURPOSE: Lower extremity magnetic resonance angiography (MRA) without electrocardiography (ECG) or peripheral pulse unit (PPU) triggering and contrast enhancement is beneficial for diagnosing peripheral arterial disease (PAD) while avoiding synchronization failure and nephrogenic systemic fibrosis. This study aimed to compare the diagnostic performance of turbo spin-echo-based enhanced acceleration-selective arterial spin labeling (eAccASL) (TSE-Acc) of the lower extremities with that of turbo field-echo-based eAccASL (TFE-Acc) and triggered angiography non-contrast enhanced (TRANCE). METHODS: Nine healthy volunteers and a patient with PAD were examined on a 3.0 Tesla magnetic resonance imaging (MRI) system. The artery-to-muscle signal intensity ratio (SIR) and contrast-to-noise ratio (CNR) were calculated. The arterial visibility (1: poor, 4: excellent) and artifact contamination (1: severe, 4: no) were independently assessed by two radiologists. Phase-contrast MRI and digital subtraction angiography were referenced in a patient with PAD. Friedman's test and a post-hoc test according to the Bonferroni-adjusted Wilcoxon signed-rank test were used for the SIR, CNR, and visual assessment. p < 0.05 was considered statistically significant. RESULTS: No significant differences in nearly all the SIRs were observed among the three MRA methods. Higher CNRs were observed with TSE-Acc than those with TFE-Acc (anterior tibial artery, p = 0.014; peroneal artery, p = 0.029; and posterior tibial artery, p = 0.014) in distal arterial segments; however, no significant differences were observed upon comparison with TRANCE (all p > 0.05). The arterial visibility scores exhibited similar trends as the CNRs. The artifact contamination scores with TSE-Acc were significantly lower (but within an acceptable level) compared to those with TFE-Acc. In the patient with PAD, the sluggish peripheral arteries were better visualized using TSE-Acc than those using TFE-Acc, and the collateral and stenosis arteries were better visualized using TSE-Acc than those using TRANCE. CONCLUSION: Peripheral arterial visualization was better with TSE-Acc than that with TFE-Acc in lower extremity MRA without ECG or PPU triggering and contrast enhancement, which was comparable with TRANCE as the reference standard. Furthermore, TSE-Acc may propose satisfactory diagnostic performance for diagnosing PAD in patients with arrhythmia and chronic kidney disease.

Injury to the Muscle Layer and Risk of Non-cardiac Chest Pain after Endoscopic Submucosal Dissection for Esophageal Cancer.

BACKGROUND AND AIMS: Non-cardiac chest pain (NCCP) is a frequent complication of endoscopic submucosal dissection (ESD) for early-stage esophageal cancer. However, little is known about relationships between ESD findings and NCCP. This study aims to evaluate the risk factors for NCCP, including ESD findings related to injury to the muscle layer. METHODS: We enrolled a total of 296 lesions from 270 patients with esophageal squamous cell carcinoma (ESCC), who underwent ESD in our center. The grade of injury to the muscle layer caused by ESD was categorized as follows: grade 0: no exposure of muscularis propria; grade 1: muscularis propria exposure and/or whitish color change by the electrocoagulation; grade 2: torn muscularis propria with whitish color change by the electrocoagulation; and grade 3, esophageal perforation. The risk factors for NCCP, including ESD findings, were analyzed by univariate and multivariate analyses. RESULTS: NCCP occurred in 89 patients (33.0%) after esophageal ESD. Multivariate analysis demonstrated that younger age [odds ratio (OR) 0.95, 95% confidence interval (95%CI) 0.92-0.98, p=0.003), postoperative fever (>= 38°C) (OR=25.9, 95%CI: 2.89-232.10, p=0.004), ESD findings (grade 1: OR=3.99, 95%CI: 1.63-9.75, p=0.003 and grade 2: OR=3.18, 95%CI: 1.54-6.57, p=0.002) were independently associated with the incidence of post ESD NCCP. CONCLUSIONS: ESD findings relate to slight Injury to the muscle layer, such as muscularis propria exposure and whitish color change by the electrocoagulation were identified as risk factor for post ESD NCCP. We should therefore perform esophageal ESD carefully to avoid injuring the muscle layers.

Surface functionalization of a polymeric lipid bilayer for coupling a model biological membrane with molecules, cells, and microstructures.

We describe a stable and functional model biological membrane based on a polymerized lipid bilayer with a chemically modified surface. A polymerized lipid bilayer was formed from a mixture of two diacetylene-containing phospholipids, 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DiynePC) and 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphoethanolamine (DiynePE). DiynePC formed a stable bilayer structure, whereas the ethanolamine headgroup of DiynePE enabled functional molecules to be grafted onto the membrane surface. Copolymerization of DiynePC and DiynePE resulted in a robust bilayer. Functionalization of the polymeric bilayer provided a route to a robust and biomimetic surface that can be linked with biomolecules, cells, and three-dimensional (3D) microstructures. Biotin and peptides were grafted onto the polymeric bilayer for attaching streptavidin and cultured mammalian cells by molecular recognition, respectively. Nonspecific adsorption of proteins and cells on polymeric bilayers was minimum. DiynePE was also used to attach a microstructure made of an elastomer (polydimethylsiloxan: PDMS) onto the membrane, forming a confined aqueous solution between the two surfaces. The microcompartment enabled us to assay the activity of a membrane-bound enzyme (cyochrome P450). Natural (fluid) lipid bilayers were incorporated together with membrane-bound proteins by lithographically polymerizing DiynePC/DiynePE bilayers. The hybrid membrane of functionalized polymeric bilayers and fluid bilayers offers a novel platform for a wide range of biomedical applications including biosensor, bioassay, cell culture, and cell-based assay.

Changes in extractive components and bacterial flora in live mussels Mytilus galloprovincialis during storage at different temperatures.

To estimate the quality of mussels during storage, the mortality, succinate dehydrogenase (SDH) activity, extractive components, viable bacterial count (VBC), and bacterial flora of live mussels were investigated. The hierarchical cluster analysis, based on extractive components and VBC, taste active value (TAV), and equivalent umami concentration (EUC), suggested that metabolite composition, bacterial, and taste changing patterns of samples stored at 5 and 10°C differed from those stored at 0°C. The mortality of mussels stored at 5 and 10°C was lower than those at 0°C. The gills of live mussels stored at 0°C for more than 7 days exhibited significantly lower SDH activity than those stored at 5 and 10°C. There was no significant difference in EUC among the samples stored at different temperatures, but a significantly higher TAV of Ala and succinic acid was observed in live mussels after 12 days of storage at 5 and 10°C than in those stored at 0°C. Next-generation sequencing analysis showed that samples stored at 5 and 10°C lost bacterial diversity, and their bacterial flora changed compared to that before storage. Considering these results, the most suitable storage condition to maintain high quality for live mussels is 5°C for less than 7 days.

Automatic detection of punctate white matter lesions in infants using deep learning of composite images from two cases.

Punctate white matter lesions (PWMLs) in infants may be related to neurodevelopmental outcomes based on the location or number of lesions. This study aimed to assess the automatic detectability of PWMLs in infants on deep learning using composite images created from several cases. To create the initial composite images, magnetic resonance (MR) images of two infants with the most PWMLs were used; their PWMLs were extracted and pasted onto MR images of infants without abnormality, creating many composite PWML images. Deep learning models based on a convolutional neural network, You Only Look Once v3 (YOLOv3), were constructed using the training set of 600, 1200, 2400, and 3600 composite images. As a result, a threshold of detection probability of 20% and 30% for all deep learning model sets yielded a relatively high sensitivity for automatic PWML detection (0.908-0.957). Although relatively high false-positive detections occurred with the lower threshold of detection probability, primarily, in the partial volume of the cerebral cortex (≥ 85.8%), those can be easily distinguished from the white matter lesions. Relatively highly sensitive automatic detection of PWMLs was achieved by creating composite images from two cases using deep learning.

Usefulness of texture and color enhancement imaging (TXI) in early gastric cancer found after Helicobacter pylori eradication.

Early-stage gastric cancer (EGC) found after Helicobacter pylori (Hp) eradication is often difficult to diagnose using conventional white light (WL) endoscopy. We aimed to evaluate whether Texture and Color Enhancement Imaging (TXI), a new image-enhanced endoscopy enhances the EGC lesions after Hp eradication. We also compared diagnostic accuracy and lesion detection time between WL and TXI in trainee endoscopists. 58 EGC lesions after successful Hp eradication were enrolled. Using endoscopic images in WLI, TXI mode 1 (TXI1), and TXI mode 2 (TXI2), visibility of EGC was assessed by six expert endoscopists using a subjective score. Mean color differences (ΔE) of four matched adjacent and intra-tumoral points were examined. Using randomly allocated images, diagnostic accuracy and lesion detection time were evaluated in three trainee endoscopists. Visibility score was unchanged (Score 0) in 20.7% (12/58) and 45.6% (26/57), slightly improved (Score 1) in 60.3% (35/58) and 52.6% (30/57), obviously improved (Score 2) in 45.6% (26/58) and 1.8% (1/57), in TXI1 and TXI2 compared to WL, respectively. Mean ΔE ± SEM in TXI1 (22.90 ± 0.96), and TXI2 (15.32 ± 0.71) were higher than that in WL (1.88 ± 0.26, both P < 0.0001). TXI1 presented higher diagnostic accuracy compared to WL, in two of three trainees (94.8% vs. 74.1%, 100% vs. 89.7%, P = 0.003; < 0.005, respectively). Lesion detection time was shorter in TXI1 in two of three trainees (P = 0.006, 0.004, respectively) compared to WL. TXI improves visibility of EGC after Hp eradication that may contribute to correct diagnosis.

Microarchitectures of Barrett's esophagus associated with DNA methylation status.

Aim: DNA methylation is involved in esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE). Microarchitectures of on-neoplastic BE associated with DNA methylation status were examined using magnifying narrow-band imaging (NBI) endoscopy. Patients and methods: Using biopsies from non-neoplastic BE without cancer (n = 66; N group), with EAC (n = 27; ADJ group) and EAC tissue (n = 22; T group), methylation of N33, DPYS, SLC16A12, miR124a3 and miR34bc genes were quantified. Magnifying NBI features of non-neoplastic BE were classified according to their morphologies. Results: The ADJ and T groups presented higher DNA methylation compared with the N group. Magnifying NBI endoscopic features of non-neoplastic BE also correlated with DNA methylation as an independent factor. Conclusion: Microarchitectures of BE visualized by magnifying NBI endoscopy correlated with DNA methylation.

Binding of islet amyloid polypeptide to supported lipid bilayers and amyloid aggregation at the membranes.

Amyloid deposition of human islet amyloid polypeptide (hIAPP) in the islets of Langerhans is closely associated with the pathogenesis of type II diabetes mellitus. Despite substantial evidence linking amyloidogenic hIAPP to loss of ß-cell mass and decreased pancreatic function, the molecular mechanism of hIAPP cytotoxicity is poorly understood. We here investigated the binding of hIAPP and nonamyloidogenic rat IAPP to substrate-supported planar bilayers and examined the membrane-mediated amyloid aggregation. The membrane binding of IAPP in soluble and fibrillar states was characterized using quartz crystal microbalance with dissipation monitoring, revealing significant differences in the binding abilities among different species and conformational states of IAPP. Patterned model membranes composed of polymerized and fluid lipid bilayer domains were used to microscopically observe the amyloid aggregation of hIAPP in its membrane-bound state. The results have important implications for lipid-mediated aggregation following the penetration of hIAPP into fluid membranes. Using the fluorescence recovery after photobleaching method, we show that the processes of membrane binding and subsequent amyloid aggregation are accompanied by substantial changes in membrane fluidity and morphology. Additionally, we show that the fibrillar hIAPP has a potential ability to perturb the membrane structure in experiments of the fibril-mediated aggregation of lipid vesicles. The results obtained in this study using model membranes reveal that membrane-bound hIAPP species display a pronounced membrane perturbation ability and suggest the potential involvement of the oligomeic forms of hAPP in membrane dysfunction.

Optimized enhanced acceleration selective arterial spin labeling (eAccASL) for non-gated and non-enhanced MR angiography of the hands.

PURPOSE: Enhanced acceleration selective arterial spin labeling (eAccASL) was introduced as non-enhanced and non-gated magnetic resonance angiography (MRA). This technique has not been applied to hand MRA. The objective of this study was to optimize the eAccASL for MRA of the hands and to investigate the factors for MRA visibility of the hands. METHODS: Twenty healthy volunteers were examined on a 1.5 T MR system. To evaluate arterial visualization, we compared four different acceleration-encoding (AENC) values (i.e., 0.12, 0.29, 0.58, and 0.87 m/s2). Image quality score regarding the MRA depiction of the proximal artery (range, 0-10), the distal artery (0-5), and venous contamination (0-5) was evaluated by three radiologists. We measured the peak to peak arterial blood flow velocity (Vpp) measured by phase contrast cine MRI and hand temperature as the factors for arterial visualization. Qualitative scores were compared with Friedman's tests. Spearman's correlation of qualitative scores with Vpp and hand temperature was performed to analyze influencing factors. RESULTS: For the distal arterial depiction, scores at AENC 0.12 (median, 9.0) and AENC 0.29 (8.0) were significantly better (both P < 0.0001) than those at AENC 0.87 (5.5). For the proximal arterial depiction, scores at AENC 0.12 (2.25) and AENC 0.29 (2.0) were significantly better (P < 0.001 and P < 0.01, respectively) than those at AENC 0.87 (1.5). Conversely, venous contamination scores at AENC 0.12 (3.0) and AENC 0.29 (3.0) were significantly worse (both P < 0.0001) than those at AENC 0.87 (4.0). There were significantly negative correlations between venous contamination and Vpp at AENC 0.12 (ρ = -0.56, P = 0.01), and 0.29 (ρ = -0.68, P = 0.001), whereas hand temperatures were not significantly correlated with scores (all P > 0.05). CONCLUSION: eAccASL MRA of the hands was optimized by using low AENC values (0.12-0.29 m/s2). Venous contamination may increase with elevation of arterial blood flow.

Non-enhanced and Non-gated MR Angiography for Robust Visualization of Peripheral Arteries Using Enhanced Acceleration-selective Arterial Spin Labeling (eAccASL).

This study aimed to assess the feasibility for applying enhanced acceleration-selective arterial spin labeling (eAccASL) to non-electrocardiogram-gated and non-enhanced peripheral MRA. We compared eAccASL and background suppressed single shot turbo field echo (TFE)-triggered angiography non-contrast-enhanced sequence (BASS TRANCE) required electrocardiographic-gating in eight volunteers and three patients. In the volunteer study, eAccASL demonstrated a comparable arterial visualization compared with BASS TRANCE. In patient observation, the advantages with eAccASL were found in arterial visualization on the collateral vessels and without artifacts affected by arrhythmia events.