Multilocus phylogenetic analysis of the first molecular data from the rare and monotypic Amarsipidae places the family within the Pelagia and highlights limitations of existing data sets in resolving pelagian interrelationships.

The Pelagia is a recently delineated group of fishes, comprising fifteen families formerly placed in six perciform suborders. The Pelagia was lately recognized as it encompasses huge morphological diversity and only in the last few years have large-scale molecular phylogenetic studies been undertaken that could unite such morphologically disparate lineages. Due to the recent erection of Pelagia, the composition of the taxon is not entirely certain. Five families of the former perciform suborder Stromateoidei have been identified as pelagians. However, the sixth stromateoid subfamily Amarsipidae is a rare monotypic family that has distinctive meristic and morphological characteristics from that of other stromateoids such as the lack of a pharyngeal sac. We examine molecular data generated from the sole species in Amarsipidae, Amarsipus carlsbergi, and demonstrate that it is clearly nested within Pelagia. As with two previous studies that have the breadth of sampling to evaluate pelagian intra-relationships, we find high support for monophyly of most family-level taxonomic units but statistical support for early-branching nodes in the pelagian tree is very low. We conduct the first analyses of Pelagia incorporating the multispecies coalescent and are limited by a high degree of missing loci, or, incomplete taxon sampling. The high degree of missing data across a complete sampling of pelagian lineages along with the deep time scale and rapid radiation of the lineage contribute to poor resolution of early-branching relationships within Pelagia that cannot be resolved with current data sets. Currently available data are either mitochondrial genomes or a super matrix of relatively few loci with a high degree of missing data. A new and independent dataset of numerous phylogenetic loci derived from high-throughput sequencing technology may reduce uncertainty within the Pelagia and provide insights into this adaptive radiation.

Etiology and long-term rebleeding of endoscopic ulcerative lesions in the small bowel in patients with obscure gastrointestinal bleeding: A multicenter cohort study.

BACKGROUND: Among patients with obscure gastrointestinal bleeding (OGIB), endoscopic ulcerative lesions in the small bowel have diverse etiologies and often cause rebleeding. Certain characteristics of patients or ulcerations may be reasonable indications for diagnostic balloon-assisted endoscopy (BAE) to assess etiology and may be risks of rebleeding; however, these characteristics are unclear. We aimed to elucidate appropriate indications for diagnostic BAE and predictors of long-term rebleeding in patients with small bowel ulcerative lesions. METHODS: We conducted a multicenter retrospective cohort study of 68 patients with OGIB, in whom small bowel ulcerative lesions were detected by capsule endoscopy (n = 60) and/or BAE (n = 43). Patients' characteristics, including medications and endoscopic findings, were evaluated. Predictors of the need for diagnostic BAE to determine ulceration etiology were identified by logistic regression analysis. Rebleeding risks were evaluated using Cox proportional hazards analysis. RESULTS: Single ulcerations were diagnosed in 26 patients, and multiple ulcerations were diagnosed in 42 patients. Among 43 patients who underwent BAE, ulceration etiology was identified in 12 (28%) patients. In the etiology identification, BAE was more useful for a single ulceration than for multiple ulcerations (P < 0.001). Among the 68 patients, rebleeding occurred in 14 (21%) patients during a mean follow-up period of 17 months. Aspirin use and multiple ulcerations were significant predictors of rebleeding (P < 0.05). CONCLUSIONS: When we manage small bowel ulcerative lesions in OGIB patients, a single ulceration is a reasonable indication for the diagnostic BAE. The rebleeding rate was lower for single ulcerations than for multiple ulcerations.

New predictive model of rebleeding during follow-up of patents with obscure gastrointestinal bleeding: A multicenter cohort study.

BACKGROUND AND AIM: The long-term recurrence rate of patients with obscure gastrointestinal bleeding (OGIB) who underwent video capsule endoscopy (VCE) remains unknown. Our study aimed to identify the cumulative incidence of rebleeding, develop a predictive model of rebleeding, and evaluate whether the model can be applied in other outcomes among patients with OGIB. METHODS: We conducted a multicenter retrospective cohort study of 320 patients with OGIB who underwent VCE between 2009 and 2014. A rebleeding model was developed using multivariate Cox proportional hazards analysis and evaluated using Harrell's c-index. RESULTS: Rebleeding occurred in 43 patients (13.4%) during a mean follow-up period of 18.3 (standard error, 0.9) months. The rebleeding sources were the small intestine (n = 17), extra-small intestine (n = 13), and unknown (n = 13). The cumulative incidence of rebleeding was 11.0% at 12 months and 35.3% at 60 months. Multivariate analysis revealed that female gender, liver cirrhosis, warfarin use, overt bleeding, and positive VCE findings were significant predictors of rebleeding. The rebleeding rate was 0% in patients with no predictors and 40% in patients with full predictors (P < 0.01). The model presented a high predictive accuracy (c-statistic, 0.733). Patients with higher predictors exhibited higher transfusion requirements, longer length of stay, and higher mortality (P < 0.01). CONCLUSION: The cumulative incidence of rebleeding at 12 and 60 months was 11.0% and 35.3%, respectively. Five factors enable prediction of not only rebleeding but also transfusion requirements, length of stay, and death in OGIB patients.

Endoscopic submucosal dissection is an effective and safe therapy for early gastric neoplasms: a multicenter feasible study.

BACKGROUND AND AIM: The technique of endoscopic submucosal dissection (ESD) was introduced to obtain en bloc specimens of large early gastrointestinal neoplasms. The drawback of ESD is its technical difficulty and, consequently, its higher rate of complication. In this multicenter study, we investigated the therapeutic outcomes of ESD in consecutive patients. METHODS: From January 2002 to December 2008, 485 early gastric neoplasms in 418 patients were consecutively treated by using ESD procedure performed by 6 endoscopists in 4 institutions in Tokyo. Demorgraphics, tumor location, therapeutic outcomes, and complication rates were analyzed. RESULTS: The rates of en bloc resection, complete en bloc resection, submucosal invasion, and piecemeal resection were 93.6%, 85.4%, 10.9%, and 5.4%, respectively. In multivariate analysis, the en bloc resection rate was independently lower in lesions in upper portion than in lower portion (P<0.01), lower in larger lesions (>30 mm, P<0.05; 20 to 30 mm, P<0.05), and lower in lesions with a scar (P<0.01). Delayed bleeding occurrence was independently high in larger lesions (>30 mm, P<0.01; 20 to 29 mm, P<0.01) than in small lesions (<20 mm). Institution and endoscopists were not risk factors of en bloc resection and complications CONCLUSIONS: ESD is an effective and safe therapy in the management of early gastric neoplasms when performed by well-trained endoscopists. Endoscopists should recognize the difficulty to perform ESD for en bloc resection of upper lesion, and the risk of delayed bleeding in cases of lesions >2 cm in size.

Surveillance of small intestinal abnormalities in patients with hepatocellular carcinoma: a prospective capsule endoscopy study.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) sometimes suffer from obscure gastrointestinal bleeding. Portal hypertension (PH), common in cirrhosis, induces esophagogastric varices. Because of the location, PH also may influence mucosal abnormalities in the small intestine. The objective of this study is to estimate the prevalence of small intestinal mucosal abnormalities in HCC patients using capsule endoscopy (CE). PATIENTS AND METHODS: We prospectively conducted CE in HCC patients, and analyzed the findings in relation to hepatic function, the number and size of HCC tumor and findings obtained by conventional endoscopy. RESULTS: Thirty-six patients (aged 66.7 ± 7.5 years, 29 men) underwent CE. Abnormal findings in the small bowel were found in 16 patients (44%), angioectasias in eight patients (22%), erosions in five (14%), varices in four (11%), polyps in four (11%), and submucosal tumor in one (3%). The patients with angioectasia had a larger spleen index than the no abnormal lesions group (85.4 ± 15.8 vs 59.0 ± 24.4, P = 0.02). The former group had been more frequently treated for esophageal varices endoscopically (62% vs 15%, P = 0.02). Large HCC nodules seemed more common in the patients with angioectasia than subjects without abnormal lesions (38% vs 5%, P = 0.06). Small intestinal varices also seemed to have a positive association with large HCC. During the follow up after CE, one patient with small intestinal polyps suffered from obscure gastrointestinal bleeding. CONCLUSIONS: CE revealed that HCC patients frequently have small intestinal mucosal lesions. In particular, small intestinal angioectasia, which may cause obscure gastrointestinal bleeding, seems to be associated with portal hypertension.

Macroscopic morphologic subtypes of laterally spreading colorectal tumors showing distinct molecular alterations.

Recent advances in colonoscopic techniques have resulted in more frequent detection of superficial-type colorectal tumors, that is, laterally spreading tumors (LSTs), although little is known about the characteristic clinical features and genetic alterations of LSTs. To elucidate the molecular characteristics of LSTs, genetic alterations in the KRAS, BRAF and PIK3CA genes and abnormal expression of the p53, beta-catenin and MYC proteins were analyzed using direct DNA sequencing and immunohistochemistry for 50 protruded-type tumors (Protruded), 35 granular-type LSTs (LST-G) and 19 nongranular-type LSTs (LST-NG). In addition, loss of heterozygosity (LOH) close to the adenomatous polyposis coli (APC) gene (5q21) was examined in these tumors. In univariate analyses, significant differences were noted in the percentages with KRAS mutations (Protruded, LST-G, LST-NG = 30.0%, 54.3%, 21.1%, respectively, p = 0.0156), nuclear accumulation of beta-catenin (Protruded, LST-G, LST-NG = 50.0%, 37.1%, 68.4%, respectively, p = 0.0267), expression of MYC (Protruded, LST-G, LST-NG = 26.0%, 17.1%, 42.1%, respectively, p = 0.0456) and LOH at the APC gene locus (Protruded, LST-G, LST-NG = 22.0%, 20.0%, 47.4%, respectively, p = 0.0302). Multivariate analysis demonstrated that the macroscopic subtype of LST was significantly associated with KRAS mutation (for LST-NG: odds ratio [OR] 0.23, 95% CI 0.06-0.90) and nuclear accumulation of beta-catenin (for LST-NG: OR 4.05, 95% CI 1.11-14.8). Our data revealed that the 2 subtypes of LST have different molecular characteristics, suggesting that 2 or more different molecular mechanisms result in colorectal tumors with a similar growth pattern.

Stability analysis of gliding flight of a swallowtail butterfly Papilio xuthus.

Preliminary observation of the flights of swallowtail butterfly Papilio xuthus revealed that its dihedral angle is larger than 30 degrees and that the section of its left hind wing close to its body and the counterpart of its right hind wing actually clap and form a "vertical tail". In this study, the effects of these two features on the lateral-directional dynamic flight stability of these butterflies were analyzed theoretically and revealed the following: (a) when the dihedral angle is larger than 30 degrees , the lateral-directional motion of the swallowtail becomes stable; (b) the vertical tail stabilizes the dutch roll mode; (c) the effects of the dihedral angle on the roll and spiral modes of a swallowtail are qualitatively the same as those of a meter-sized airplane; and (d) with increasing dihedral angle, the stability of the dutch roll mode decreases for a meter-sized airplane with vertical and horizontal tails but increases for the swallowtail. A possible explanation for the latter effect is the smaller Reynolds number of the insect that causes the drag coefficient of the swallowtail wings to increase more rapidly with an increasing angle of attack compared to a large airplane.

Study of association between atrophic gastritis and body mass index: a cross-sectional study in 10,197 Japanese subjects.

OBJECTIVES: The aim of this study was to elucidate the association between body mass index (BMI) and both Helicobacter pylori and atrophic gastritis. METHODS: The study involved 10,197 subjects participating in a Japanese mass endoscopic gastric cancer screening program. Atrophic gastritis was assessed by pepsinogen I to II ratio. RESULTS: In logistic regression models, BMI had an inverse association with atrophic gastritis, with the odds ratios (OR) decreasing progressively to 0.67 (95% confidence interval [CI] 0.57-0.79, P<0.0001) in the highest BMI quintiles (BMI >or=25.66) group compared with the lowest BMI quintiles (BMI <20.97) group. In linear regression models, atrophic gastritis predicted BMI (regression coefficient -0.326, 95% CI -0.469, -0.184, P<0.0001), whereas H. pylori antibody was not a predictor (regression coefficient 0.072, 95% CI -0.053, 0.198, P=0.3). CONCLUSIONS: A small, inverse association between BMI and atrophic gastritis was found in the general population. In contrast, no association was observed between H. pylori seropositivity and BMI.

Alpha-Blockers As Colorectal Cancer Chemopreventive: Findings from a Case-Control Study, Human Cell Cultures, and In Vivo Preclinical Testing.

A retrospective case-controlled analysis was performed to identify drug candidates in the current use that may prevent colorectal cancer, outside of aspirin. A total of 37,510 patients aged ≥20 years were assessed to identify subjects who had been diagnosed with colorectal cancer by colonoscopy without a previous diagnosis of colorectal cancer, inflammatory bowel disease (IBD), or gastrointestinal symptoms; 1,560 patients were identified who were diagnosed with colorectal cancer by colonoscopy. The patients with colorectal cancer were matched with 1,560 age, gender, family history of colorectal cancer and comorbidity-matched control patients who were not diagnosed with colorectal cancer at colonoscopy. The medication histories were compared between the two groups. Next, candidate drugs that were more frequently used by the control patients were selected and their effects on human colorectal cancer cell lines in vitro and an inflammation-induced mouse model of colorectal cancer were tested. Putative colorectal cancer preventative agents were identified, including aspirin, vitamin D, vitamin B, vitamin C, vitamin E, xanthine oxidase inhibitor, alpha-blockers, angiotensin receptor blocker, nateglinide, probiotics, thienopyridine, folic acid, nitrovasodilators, bisphosphonates, calcium channel blockers, steroids, and statins (P < 0.05). Alpha-blockers and xanthine oxidase inhibitors were selected for further study because these agents have not been analyzed previously as factors that may affect colorectal cancer outcomes. In vitro doxazosin (alpha-blocker), but not febuxostat (xanthine oxidase inhibitor), suppressed the proliferation of human colorectal cancer cells. Doxazosin also decreased tumorigenesis in an AOM/DSS mouse colorectal cancer model. Alpha-blockers may prevent colorectal cancer.

Cholelithiasis is a risk factor for colorectal adenoma.

OBJECTIVES: Postcholecystectomy patients show moderate risk of colorectal cancer. However, few studies have investigated the relationship between cholelithiasis and colorectal adenoma. We examined this possibility through a combination of colonoscopy and ultrasonography in asymptomatic Japanese. METHODS: We reviewed a subgroup of subjects drawn from a prospective annual colonoscopy screening survey. Subjects who underwent both ultrasonography and colonoscopy, and completed a questionnaire regarding lifestyle habits were entered. We investigated whether subjects with cholelithiasis or a previous cholecystectomy showed an increased risk of colorectal adenoma, as compared with subjects with normal gallbladders. RESULTS: Data of 4,458 subjects (men 3,053, women 1,405, mean age +/- SD 46.1 +/- 8.62 yr) were analyzed. Cholelithiasis was detected in 206 subjects, 4,189 subjects had normal gallbladders, and 63 subjects had cholecystectomies. The prevalence of colorectal adenoma was 29.6% (61/206) in subjects with cholelithiasis, which was significantly higher when compared with normal subjects, with a prevalence of 17.7% (741/4,189, P < 0.001). In cholecystectomy patients, only 15.9% (10/63) developed colorectal adenomas, which was not significantly different from the control group. In a multivariate analysis controlling for sex, age, family history of colorectal cancer, alcohol, smoking, and body mass index, cholelithiasis was shown to be an independent risk factor for colorectal adenoma (adjusted OR 1.57, 95% CI 1.14-2.18). Cholelithiasis was strongly associated with multiple (> or = 3 lesions, adjusted OR 2.39, 95% CI 1.21-4.72) and left-sided colorectal adenomas (adjusted OR 1.82, 95% CI 1.28-2.59). CONCLUSIONS: Cholelithiasis is a risk factor for colorectal adenoma.