Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Association Between Cigarette Smoking and Alcohol Consumption and Sessile Serrated Polyps in Subjects 30 to 49 Years Old.

BACKGROUND & AIMS: We investigated the prevalence of sessile serrated polyps (SSPs) and the association between SSP risk and modifiable lifestyle factors in asymptomatic young adults. METHODS: We performed a cross-sectional study using a screening colonoscopy database of 13,618 asymptomatic subjects age 30 to 49 years, and 17,999 subjects age 50 to 75 years. We investigated risk factors of SSP by multivariable analyses of clinical data that included cigarette smoking and alcohol consumption. RESULTS: In subjects age 30 to 49 years, the prevalence of SSP was 2.0% (275 of 13,618 individuals). Of all SSPs, 40.7% (112 of 275 SSPs) were large (≥10 mm). Smoking for 20 or more pack-years was associated with overall SSPs (odds ratio [OR], 1.87; 95% CI, 1.17-2.99) and large SSPs (OR, 3.03; 95% CI, 1.62-5.66). The association between anatomic location and 20 or more pack-years of smoking was stronger for distal SSPs than for proximal SSPs (OR, 2.71; 95% CI, 1.27-5.77 vs OR, 1.60; 95% CI, 1.00-2.54). Cessation of smoking for 5 years or more decreased the risk of SSPs (OR, 0.49; 95% CI, 0.28-0.86) and of large SSPs (OR, 0.23; 95% CI, 0.10-0.54). Alcohol consumption was associated with large SSPs. These findings were similar for subjects age 50 to 75 years. CONCLUSIONS: In an analysis of a screening colonoscopy database, we found that in asymptomatic young adults, smoking and alcohol consumption were associated with any SSPs and large SSPs. Cessation of smoking decreased the risk of SSPs. Therefore, early lifestyle modification may be recommended for primary prevention of SSPs in young adults.

Venom allergen-like protein 28 in Clonorchis sinensis: four epitopes on its surface and the potential role of Cys124 for its conformational stability.

Venom allergen-like (VAL) proteins are important to host-parasite interactions. We previously demonstrated that a Clonorchis sinensis VAL (CsVAL) protein-derived synthetic peptide suppresses allergic and inflammatory responses. However, little is known regarding the physicochemical and antigenic properties of CsVAL proteins. Here, we identified a novel 194 amino acid VAL protein, named C. sinensis VAL 28 (CsVAL28), and characterized its functional motifs and structural details as a new member of the CAP superfamily. Unlike members of the Schistosoma mansoni VAL (SmVAL) family, CsVAL28 has a single CAP1 motif and six highly conserved disulfide bond-forming cysteines. Tertiary models of wild-type CsVAL28 and mutants were built using SmVAL4 as template via homology modeling. Normal mode analysis predicted that disulfide bond breaking by mutation of cysteine 124 to serine would greatly affect protein mobility. Four major immunoreactive linear epitopes were identified in the surface-exposed region or its vicinity via epitope mapping, using sera from clonorchiasis patients and healthy controls. Our findings provide in-depth knowledge on the structure-function properties of VAL proteins and may help determine highly antigenic regions for developing new diagnostic approaches.

Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3.

BACKGROUND AND AIM: Recent studies suggest that the anti-inflammatory agent balsalazide (BSZ) and probiotic agent VSL#3 have potential therapeutic benefits for the treatment of patients with inflammatory bowel disease. However, their effectiveness in preventing colitis-associated carcinogenesis (CAC) remains uncertain. The aim of the present study was to determine the chemopreventive effects of BSZ and VSL#3 in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. METHODS: C57B/L6J mice were randomly divided into four groups: CAC group, BSZ group, VSL#3 group, and BSZ + VSL#3 group. After 2 weeks, the AOM/DSS model was induced by AOM injection followed by two cycles of 2% DSS. RESULTS: During first and second cycles of DSS, the number of F4/80-positive macrophages was significantly lower in the drug-treated groups compared with the CAC group (P < 0.05). At the endpoint, the total numbers of tumors in the drug-treated groups were significantly low compared with the CAC group (P < 0.05), and the drug-treated groups had significantly lower F4/80-positive macrophages in the tumor stroma (P < 0.01). The protein production of macrophage inflammatory protein 1 beta, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-10 in the colon tissues decreased in concordance with the plasma concentrations of the cytokines (P < 0.05). The drug-treated groups revealed lower expression of p-STAT3 compared with the CAC group. In addition, BCL2 decreased, and BAX increased markedly in the BSZ + VSL#3 group. CONCLUSIONS: These results revealed that BSZ and VSL#3 have chemopreventive effects against CAC through IL-6/STAT3 suppression. BSZ and VSL#3 could be suitable options for chemoprevention of colorectal cancer.

Isolated terminal ileal ulcerations in asymptomatic individuals: natural course and clinical significance.

BACKGROUND: Although isolated terminal ileal ulcerations (ITIUs) are occasionally observed on colonoscopic examination of asymptomatic individuals, their clinical course and guidelines for treatment are unclear. OBJECTIVE: To evaluate the clinical course and significance of ITIUs in asymptomatic individuals. DESIGN: Single-center retrospective analysis. SETTING: University hospital. PATIENTS AND INTERVENTIONS: All patients diagnosed with ITIUs on colonoscopy from July 2001 to December 2007 were identified. Patients with colorectal symptoms, a history of nonsteroidal anti-inflammatory drug consumption, a history of colorectal surgery, oral or genital ulcerations, and coincidental ulceration in the ileocecal valve or colon were excluded. MAIN OUTCOME MEASUREMENTS: Colonoscopic findings and clinical courses of patients were analyzed. RESULTS: Of the 148 included patients, 93 were followed (mean duration, 29.9 months). Of these, 62 showed resolution of ITIU on follow-up colonoscopy, including 60 who resolved without any treatment and 2 who resolved after antituberculosis medication. Follow-up colonoscopy continued to show ITIUs in the remaining 31 patients, only 1 of whom developed typical Crohn's disease, whereas the other 30 showed no significant changes in the lesions (n = 22), partial improvement (n = 6), or waxing and waning endoscopic appearance (n = 2). LIMITATIONS: Retrospective design, relatively short-term follow-up. CONCLUSIONS: Most ITIUs incidentally observed in asymptomatic individuals resolve without any treatment. Even if these lesions persist, it is unusual for them to progress or to cause any symptoms.

The Characteristics and Prognosis of Diffuse-Type Early Gastric Cancer Diagnosed during Health Check-Ups.

BACKGROUND/AIMS: Because of the poor prognosis of diffuse-type gastric cancer, early detection is important. We investigated the clinical characteristics and prognosis of diffuse-type early gastric cancer (EGC) diagnosed in subjects during health check-ups. METHODS: Among 121,111 subjects who underwent gastroscopy during a routine health check-up, we identified 282 patients with 286 EGC lesions and reviewed their clinical and tumor-specific parameters. RESULTS: Patients with diffuse-type EGC were younger, and 48.1% of them were female. Serum anti-Helicobacter pylori IgG (Hp-IgG) was positive in 90.7% of diffuse-type EGC patients (vs 75.9% of intestinal-type EGC, p=0.002), and the proportion of diffuse-type EGC cases increased significantly with increasing Hp-IgG serum titers (p<0.001). Diffuse-type EGC had pale discolorations on the tumor surface (26.4% vs 4.0% in intestinal-type EGC, p<0.001) and were often located in the middle third of the stomach. Submucosal invasion or regional nodal metastasis was observed more commonly in patients with diffuse-type EGC. However, during the median follow-up period of 50 months, 5-year disease-free survival rates did not differ between the groups. CONCLUSIONS: Diffuse-type EGC shows different clinical and endoscopic characteristics. Diffuse-type EGC is more closely associated with Hp-IgG seropositivity and a higher serum titer. Early detection results in excellent prognosis.

Combination of metformin and VSL#3 additively suppresses western-style diet induced colon cancer in mice.

Western-style diet (WD) and dysbiosis are known to be associated with colonic inflammation, which contributes to carcinogenesis. Metformin (Met) exerts anti-inflammatory effects to induce AMP-activated protein kinase (AMPK), resulting in suppressed protein synthesis and reduced cell proliferation. Probiotic VSL#3 (V) modifies microbial composition. We investigated the chemopreventive mechanisms of Met and V in WD-induced colitis-associated colon carcinogenesis. Male BALB/c mice were randomly divided into five groups: a control diet (CD) group, WD group, WD+ Met (250mg/kg/day) group, WD+V (1.3 million bacteria/day) group, and WD+Met+V group. All mice were exposed to azoxymethane (10mg/kg) followed by 2% dextran sodium sulfate (DSS) for 7 days. Using HCT-116 human colon cancer cell line, expression of AMPK, extracellular signal-regulated kinase (ERK), cyclin D1, and Bcl-2 was investigated and cell cycle arrest was assessed. WD enhanced the severity of colitis and tumor growth compared with CD. The combination of Met and V significantly ameliorated colitis and tumor growth by inhibiting macrophage infiltration and maintaining epithelial integrity. In vitro assays showed that the combination therapy promoted late apoptosis by inhibiting cyclin D1 and Bcl-2 and activating pro-apoptotic ERK. A combination therapy with Met and V attenuates tumor growth in a mouse model of WD-induced colitic cancer, suggesting that this strategy could be useful for the chemoprevention of colon cancer.

Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm.

BACKGROUND/AIMS: Helicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN. METHODS: This cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy. RESULTS: A total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not. CONCLUSIONS: H. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.

Colonic Chicken Skin Mucosa is an Independent Endoscopic Predictor of Advanced Colorectal Adenoma.

BACKGROUND/AIMS: Chicken skin mucosa (CSM), surrounding colorectal adenoma, is an endoscopic finding with pale yellow-speckled mucosa; however, its clinical significance is unknown. This study aimed to evaluate the prevalence and clinical characteristics of CSM, and the association between colorectal carcinogenesis and CSM. METHODS: This cross-sectional study was performed in 733 consecutive patients who underwent endoscopic polypectomy for colorectal adenoma after the screening of colonoscopy at the Asan Health Promotion Center between June 2009 and December 2011. The colonoscopic and pathological findings of colorectal adenoma including number, size, location, dysplasia, morphology, and clinical parameters were reviewed. RESULTS: The prevalence of CSM was 30.7% (225 of 733 patients), and most CSM-related adenomas were located in the distal colon (93.3%). Histological analysis revealed lipid-laden macrophages in the lamina propria of the mucosa. Multivariate analyses showed that CSM was significantly associated with advanced pathology, including villous adenoma and high-grade dysplasia (odds ratio [OR], 2.078; 95% confidence interval [CI], 1.191-3.627; P=0.010), multiple adenomas (i.e., ≥2 adenomas; OR, 1.692; 95% CI, 1.143-2.507; P=0.009), and a protruding morphology (OR, 1.493; 95% CI, 1.027-2.170; P=0.036). There were no significant differences in polyp size or clinical parameters between patients with and without CSM. CONCLUSIONS: CSM-related adenoma was mainly found in the distal colon, and was associated with advanced pathology and multiple adenomas. CSM could be a potential predictive marker of the carcinogenetic progression of distally located colorectal adenomas.

Screening colonoscopy in asymptomatic average-risk Koreans: analysis in relation to age and sex.

BACKGROUND AND AIMS: Although the incidence of colorectal cancer is rising in Asian countries, there are no guidelines for its screening in this region due in part to the lack of epidemiological data regarding colorectal neoplasms. This study aimed to evaluate the prevalence of colorectal neoplasms in average-risk Koreans and to assess the effectiveness of screening colonoscopy in Korea. METHODS: The prevalence of colorectal neoplasms was assessed by primary screening colonoscopy in 5,086 consecutive asymptomatic adults (males 70.5%; age 20-84 years) with no risk factors for colorectal cancer. RESULTS: The overall prevalence of colorectal neoplasms in the 5,086 subjects was 21.9% and this increased linearly with age. Among the 2,435 subjects aged >or=50 years (males 66.7%; mean age 57.7 years), the prevalence of all colorectal neoplasms was 30.2% (males 35.9% vs females 18.7%; P < 0.001), while advanced neoplasms accounted for only 4.1% (males 5.1% vs females 2.0%; P < 0.001). The prevalence of advanced neoplasms in Korean men of a specific age group was similar to that of Korean women in the 10-years older age group. Also, Koreans in a specific age group showed a prevalence of advanced neoplasms similar to that of Westerners in the 10-years younger age group. CONCLUSIONS: Colonoscopy is a useful modality for colorectal cancer screening in Korea, as established in Western countries. However, the screening colonoscopy may begin at an older age for Koreans than for Westerners. Similarly, the optimal starting age for screening in Korean women may be higher than that in men by 10 years.