Comparison of Effective Imaging Modalities for Detecting Gastric Neoplasms: A Randomized 3-Arm Phase II Trial.

INTRODUCTION: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI. METHODS: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%. RESULTS: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively. DISCUSSION: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection.

Non-atrophic gastric mucosa is an independently associated factor for superficial non-ampullary duodenal epithelial tumors: a multicenter, matched, case-control study.

BACKGROUND/AIMS: The etiology of superficial non-ampullary duodenal epithelial tumors (SNADETs) remains unclear. Recent studies have reported conflicting associations between duodenal tumor development and Helicobacter pylori infection or endoscopic gastric mucosal atrophy. As such, the present study aimed to clarify the relationship between SNADETs and H. pylori infection and/or endoscopic gastric mucosal atrophy. METHODS: This retrospective case-control study reviewed data from 177 consecutive patients with SNADETs who underwent endoscopic or surgical resection at seven institutions in Japan over a three-year period. The prevalence of endoscopic gastric mucosal atrophy and the status of H. pylori infection were compared in 531 sex- and age-matched controls selected from screening endoscopies at two of the seven participating institutions. RESULTS: For H. pylori infection, 85 of 177 (48.0%) patients exhibited SNADETs and 112 of 531 (21.1%) control patients were non-infected (p<0.001). Non-atrophic mucosa (C0 to C1) was observed in 96 of 177 (54.2%) patients with SNADETs and 112 of 531 (21.1%) control patients (p<0.001). Conditional logistic regression analysis revealed that non-atrophic gastric mucosa was an independent risk factor for SNADETs (odds ratio, 5.10; 95% confidence interval, 2.44-8.40; p<0.001). CONCLUSION: Non-atrophic gastric mucosa, regardless of H. pylori infection status, was a factor independently associated with SNADETs.

Usefulness of third-generation narrow band imaging and texture and color enhancement imaging in improving visibility of superficial early gastric cancer: A study using color difference.

Objectives: Overlooking early gastric cancer (EGC) during endoscopy is an issue to be resolved. Image-enhanced endoscopy is expected to improve EGC detection. This study investigated the usefulness of third-generation narrow band imaging (3G-NBI) and texture and color enhancement imaging (TXI) in improving the visibility of EGC using the color difference between EGC and its surrounding gastric mucosa. Methods: In this retrospective observational study, we examined 51 superficial EGCs that underwent endoscopic submucosal dissection and were observed by all three methods: 3G-NBI, TXI, and white light imaging (WLI). The primary endpoint was to compare the color difference of each method. For each EGC, we prepared one non-magnifying image for each method so that the location and size of the lesion in each image were the same. The L*a*b* color space was used to evaluate the color values. When the color values of the cancerous lesion and its surrounding mucosa were (L*c, a*c, b*c) and (L*s, a*s, b*s), respectively, the color difference was defined to be [(L*c-L*s)2+(a*c-a*s)2+(b*c-b*s)2]1/2. Results: The median color difference was 9.2 (interquartile range, 5.3-15.7) in WLI, 13.5 (interquartile range, 9.4-19.5) in 3G-NBI, and 15.3 (interquartile range, 9.1-22.1) in TXI. Statistically, the color difference was significantly larger in 3G-NBI than in WLI (p < 0.001) and TXI compared with WLI (p < 0.001). However, there was no significant difference between 3G-NBI and TXI (p = 0.330). Conclusions: Regarding color difference, both 3G-NBI and TXI were estimated to be more useful than WLI in improving the visibility of superficial EGC.

Collection of Xylem Exudates from the Model Plant Arabidopsis and the Crop Plant Soybean.

A number of molecules, such as secreted peptides, have been shown to mediate root-to-shoot signaling in response to various conditions. The xylem is a pathway for water and molecules that are translocated from roots to shoots. Therefore, collecting and analyzing xylem exudates is an efficient approach to study root-to-shoot long-distance signaling. Here, we describe a step-by-step protocol for the collection of xylem exudate from the model plant Arabidopsis and the crop plant soybean ( Glycine max ). In this protocol, we can collect xylem exudate from plants cultured under normal growth conditions without using special equipment. Graphical abstract: Xylem exudates on the cut surfaces of an Arabidopsis hypocotyl and a soybean internode.

Resection depth and layer of underwater versus conventional endoscopic mucosal resection of intermediate-sized colorectal polyps: A pilot study.

Background and study aims Curability of colorectal tumors is associated with resection depth and layer in endoscopic resection. Underwater endoscopic mucosal resection (UEMR) has not undergone sufficient histopathological evaluation. We conducted a pilot study to compare the effectiveness, including resection depth and layer, of UEMR and conventional endoscopic mucosal resection (CEMR). Patients and methods This study was a single-center, retrospective study. Patients with colorectal lesions were treated by UEMR or CEMR between January 2018 and March 2020. Eligible patients were selected from included patients in a 1:1 ratio using propensity score matching. We compared the resection depth and layer and treatment results between the UEMR and CEMR groups. Results We evaluated 55 patients undergoing UEMR and 291 patients undergoing CEMR. Using propensity score matching, we analyzed 54 lesions in each group. The proportion of specimens containing submucosal tissue was 100 % in both groups. The median thickness of the submucosal tissue was significantly greater in the CEMR group than in the UEMR group [1235 µm (95 % confidence interval [CI], 1020-1530 µm) vs. 950 µm (95 % CI, 830-1090 µm), respectively]. However, vertical margins were negative in all lesions in both groups. Conclusions Our findings suggest that the median thickness of submucosal tissue in the UEMR group was about 1,000 µm. Even though the resection depth achieved with UEMR was more superficial than that achieved with CEMR, UEMR may be a treatment option, especially for colorectal lesions ≤ 20 mm in diameter without suspicious findings of submucosal deeply invasive cancer.

Long-distance translocation of CLAVATA3/ESR-related 2 peptide and its positive effect on roots sucrose status.

In vascular plants, roots anchor themselves into the soil and take up water and nutrients to provide them to the shoots. Therefore, continuous growth and development of the roots are important for plant life. To achieve this, photosynthesizing leaves must be able to supply sufficient photoassimilates to the roots. However, the mechanisms by which plants maintain carbon levels in roots remain elusive. Here, we focused on the Arabidopsis (Arabidopsis thaliana) CLAVATA3/ESR-related 2 (CLE2) peptide, which was detected in Arabidopsis xylem exudate, and its homologs. CLE2 and CLE3 genes responded to carbon-deficient conditions. Loss- and gain-of-function mutant analyses showed that CLE genes positively affected root sucrose level. Mutations in the CLE genes resulted in a high shoot/root ratio under sucrose-free conditions. Grafting experiments demonstrated the systemic effect of CLE peptide genes. These findings provide insights into the molecular basis for the relationship between roots and leaves in maintenance of the root sucrose levels and growth.

Characterization of Oligopeptides in Solanum lycopersicum Xylem Exudates.

The xylem is the main pathway for the transport of water and molecules from roots to shoots. To date, it has been reported that secreted oligopeptides mediate root-to-shoot signaling, and some long-distance mobile oligopeptides have been detected in xylem exudates. However, the conservation of a number of oligopeptides and the overall features of peptide fragments contained in xylem exudates are poorly understood. Here, we conducted a comprehensive analysis of small proteins and peptides in tomato (Solanum lycopersicum) xylem exudates and characterized the identified peptide fragments. We found that putative secreted proteins were enriched in xylem exudates compared with all proteins in the tomato protein database. We identified seven oligopeptides that showed common features of bioactive oligopeptides, including homologs of CLV3/ESR-related (CLE), C-TERMINALLY ENCODED PEPTIDE (CEP), and CASPARIAN STRIP INTEGRITY FACTOR (CIF) peptides. Furthermore, five of the identified oligopeptides were homologs of the soybean xylem exudate-associated oligopeptides that we previously reported. Our results suggest that oligopeptides in xylem exudates are conserved across plant species and provide insights into not only root-to-shoot signaling but also the maintenance of the xylem conduit.

[Number of hospitalizations due to colonic diverticular bleeding as a predictive factor for readmission:an exploratory study].

Colonic diverticular bleeding often recurs and requires hospital readmission. This study aimed to examine the relationship between the rate of readmission and the number of hospitalizations due to colonic diverticular bleeding. We retrospectively studied 98 patients first admitted between January 2008 and July 2017 for the treatment of colonic diverticular bleeding. We investigated the subsequent number of hospitalizations due to colonic diverticular bleeding and classified the patients into 3 groups:those admitted for the first time (first group), those admitted for the second time (second group), and those admitted for the third time or later (third group). Generally, the readmission rate increased as the number of hospitalizations increased (P<0.01). The 1-year readmission rates were 11.6%, 23.2%, and 34.2% in the first, second, and third groups, respectively. The 2-year readmission rates were 15.1%, 50.1%, and 62.4% in the first, second, and third groups, respectively. The 3-year readmission rates were 21.7%, 50.1%, and 74.9% in the first, second, and third groups, respectively. Thus, the number of hospitalizations due to colonic diverticular bleeding could be a predictive factor for readmission. We also classified the patients into 2 additional groups:those who had been readmitted (readmission group) and those who had not (no readmission group). Furthermore, we examined background and therapeutic factors, and found hypovolemic shock on admission to be an independent risk factor (odds ratio 14.1). Preventive treatments for such high-risk patients should be considered.

Taurine attenuates the development of hepatic steatosis through the inhibition of oxidative stress in a model of nonalcoholic fatty liver disease in vivo and in vitro.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is characterized by the accumulation of triglyceride within hepatocytes. Taurine is a sulfur-containing-ß-amino acid that is widely distributed in mammalian tissues. The objective of this study was to examine the effects of taurine on the development of hepatic steatosis in a model of NAFLD in vivo and in vitro. Male C57BL/6J mice were fed a high-fat diet (HFD) supplemented with 2% (w/v) or 5% (w/v) taurine for 12 weeks. An in vitro study was performed in HepG2 cells loaded with fatty acids. Twelve weeks of supplementation with an HFD increased the hepatic lipid levels and oxidative stress as well as the body weight and liver weight. Taurine significantly suppressed these changes, which was accompanied by a decrease in the hepatic level of thiobarbituric acid-reactive substances (TBARS). In addition, taurine treatment suppressed the HFD-induced reduction of the enzyme activity of hepatic superoxide dismutase and catalase and the reduction of the hepatic level of reduced glutathione and ATP. In HepG2 cells, taurine suppressed the fatty acid-induced lipid accumulation, production of reactive oxygen species and TBARS level, and amelioration of the fatty acid-induced disruption of the mitochondrial membrane potential. These results showed that taurine was effective in alleviating hepatic steatosis by reducing oxidative stress. Taurine may, therefore, be of therapeutic value in reducing the risks associated with NAFLD.

Multiple Small Intestine Ulcers with Desquamation of the Fingers.

A 73-year-old female was admitted to our hospital with abdominal pain and diarrhea. Computed tomography detected distension of the small intestine. A palmar erythema, multiple oral ulcers, and desquamation of the fingers appeared after hospitalization. Small-bowel endoscopic images showed multiple ulcers. We attributed this case to infection with Yersinia pseudotuberculosis based on the changes in Y. pseudotuberculosis antibody titers throughout the course of the illness. This report is valuable, as it illustrates the endoscopic characteristics of a Y. pseudotuberculosis infection with skin lesion and ileus, which may enable us to deepen the pathologic understanding of this disease.

The Taurine Content of Japanese Seaweed.

Japanese and South Koreans have a dietary habit of eating seaweed. Although it is known that some seaweed contains taurine, there have been few detailed analyses on the taurine content of seaweed other than the major types of edible seaweed. In the present study, we determined the content of free amino acids, including taurine, in seaweed obtained along the Sea of Japan coast. The taurine content in the seaweed varied according to the species. Among the 29 different types of seaweed that were studied, red algae contained relatively high concentrations of taurine. In contrast, the taurine content was low or undetectable in brown and green algae. The algal alanine level was relatively higher in brown sea algae, which was in sharp contrast to its taurine level. No clear trends were observed with regards to the distribution of the other free amino acids, including aspartic acid, glutamic acid, and phenylalanine. Considering the physiological role of taurine in cellular homeostasis, the algal taurine content may be associated with the growing environment. Taurine-rich red edible algae such as mafunori (Gloiopeltis tenax)/fukurofunori (Gloiopeltis furcata), kabanori (Gracilaria textorii), and ogonori (Gracilaria vermiculophylla) may be used to create functional foods that are rich in naturally occurring taurine.

Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting ß-amyloid aggregates.

In vivo imaging of ß-amyloid (Aß) aggregates consisting of Aß(1-40) and Aß(1-42) peptides by positron emission tomography (PET) contributes to the diagnosis and therapy for Alzheimer's disease (AD). Because (64)Cu (t1/2=12.7h) is a radionuclide for PET with a longer physical half-life than (11)C (t1/2=20min) and (18)F (t1/2=110min), it is an attractive radionuclide for the development of Aß imaging probes that are suitable for routine use. In the present study, we designed and synthesized two novel (64)Cu labeled benzofuran derivatives and evaluated their utility as PET imaging probes for Aß aggregates. In an in vitro binding assay, 6 and 8 showed binding affinity for Aß(1-42) aggregates with a Ki value of 33 and 243nM, respectively. In addition, these probes bound to Aß plaques deposited in the brain of an AD model mouse in vitro. In a biodistribution experiment using normal mice, these probes showed low brain uptake (0.33% and 0.36% ID/g) at 2min post-injection. Although refinement to enhance brain uptake is needed, [(64)Cu]6 and [(64)Cu]8 demonstrated the feasibility of developing novel PET probes for imaging Aß aggregates.

An EF-hands protein, centrin-1, is an EGTA-sensitive SUMO-interacting protein in mouse testis.

A multifunctional calcium-binding protein, centrin-1, is specifically expressed in male germ cells, certain neurons and ciliated cells. We identified centrin-1 as a protein interacting with SUMO-2/3 using yeast two-hybrid screening of a mouse testicular cDNA library. In bead halo assays, the interaction between centrin-1 and SUMO-2/3 was reduced in the presence of EGTA and facilitated by the addition of CaCl2. immunostaining of seminiferous tubules in 35-day-old mouse testes revealed that cells in the layer containing spermatogonia showed colocalization of SUMO-2/3 with centrin-1 in cytoplasmic spots. Identification of centrin-1 as the EGTA-sensitive SUMO-2/3-interacting protein indicates the possible role of calcium in modulating the centrin-1-SUMO-2/3 interaction and suggests the importance of this interaction in mouse testis.