Questionnaire-Based Survey Conducted in 2011 concerning Endoscopic Management of Barrett's Esophagus in East Asian Countries

Background/Aims: Endoscopic definitions and management of Barrett's esophagus vary widely among countries. To examine the current situation regarding diagnosis, epidemiology, management and treatment of Barrett's esophagus in East Asian countries using a questionnaire-based survey. Methods: Representative members of the Committee of the International Gastrointestinal Consensus Symposium developed and sent a questionnaire to major institutions in China, South Korea, Japan, Thailand, Indonesia, and the Philippines. Results: A total of 56 institutions in the 6 countries participated in the survey. We found that the presence of specialized columnar metaplasia is considered to be important for diagnosing Barrett's esophagus in East Asian countries except for Japan. C&M criteria have not been well accepted in East Asia. The palisade vessels are mainly used as a landmark for the esophagogastric junction in Japan. The prevalence of long segment Barrett's esophagus is extremely low in East Asia, while the prevalence of short segment Barrett's esophagus is very high only in Japan, likely due to different diagnostic criteria. Conclusion: Among East Asian countries, we found both similarities and differences regarding diagnosis and management of Barrett's esophagus. The findings in the present survey are helpful to understand the current situation of Barrett's esophagus in East Asian countries.     

The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters

Oxidative stress has been implicated in the pathogenesis of many human diseases including Fanconi anemia (FA), a genetic disorder associated with BM failure and cancer. Here we show that major antioxidant defense genes are down-regulated in FA patients, and that gene down-regulation is selectively associated with increased oxidative DNA damage in the promoters of the antioxidant defense genes. Assessment of promoter activity and DNA damage repair kinetics shows that increased initial damage, rather than a reduced repair rate, contributes to the augmented oxidative DNA damage. Mechanistically, FA proteins act in concert with the chromatin-remodeling factor BRG1 to protect the promoters of antioxidant defense genes from oxidative damage. Specifically, BRG1 binds to the promoters of the antioxidant defense genes at steady state. On challenge with oxidative stress, FA proteins are recruited to promoter DNA, which correlates with significant increase in the binding of BRG1 within promoter regions. In addition, oxidative stress-induced FANCD2 ubiquitination is required for the formation of a FA-BRG1-promoter complex. Taken together, these data identify a role for the FA pathway in cellular antioxidant defense.     

Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model

The high rate of mortality and frequent incidence of recurrence associated with hepatocellular carcinoma (HCC) reveal the need for new therapeutic approaches. In this study we evaluated the efficacy of a novel chemoimmunotherapeutic strategy to control HCC and investigated the underlying mechanism that increased the antitumor immune response. We developed a novel orthotopic mouse model of HCC through seeding of tumorigenic hepatocytes from SV40 T antigen (Tag) transgenic MTD2 mice into the livers of syngeneic C57BL/6 mice. These MTD2-derived hepatocytes form Tag-expressing HCC tumors specifically within the liver. This approach provides a platform to test therapeutic strategies and antigen-specific immune-directed therapy in an immunocompetent murine model. Using this model we tested the efficacy of a combination of oral sunitinib, a small molecule multitargeted receptor tyrosine kinase (RTK) inhibitor, and adoptive transfer of tumor antigen-specific CD8(+) T cells to eliminate HCC. Sunitinib treatment alone promoted a transient reduction in tumor size. Sunitinib treatment combined with adoptive transfer of tumor antigen-specific CD8(+) T cells led to elimination of established tumors without recurrence. In vitro studies revealed that HCC growth was inhibited through suppression of STAT3 signaling. In addition, sunitinib treatment of tumor-bearing mice was associated with suppression of STAT3 and a block in T-cell tolerance. CONCLUSION: These findings indicate that sunitinib inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor antigen-specific CD8(+) T-cell tolerance, thus defining a synergistic chemoimmunotherapeutic approach for HCC.     

The relationship of major depressive disorder and gender to changes in smoking for current and former smokers: longitudinal evaluation in the US population

Aims Although depression and smoking are correlated highly, the relationship of major depressive disorder (MDD) to smoking cessation and relapse remains unclear. This study compared changes in smoking for current and former smokers with and without current and life‐time MDD over a 3‐year period. Design Analysis of two waves of longitudinal data from the National Institute on Alcohol Abuse and Alcoholism's National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001–02; wave 2, 2004–05). Setting Data were collected through face‐to‐face interviews from non‐institutionalized United States civilians, aged 18 years and older, in 50 states and the District of Columbia. Participants A total of 11 973 adults (54% male) classified as current or former daily smokers at wave 1 and completed wave 2. Measurements Classification as current or former smokers at wave 1 and wave 2. Findings Smoking status remained stable for most participants. Wave 1 current daily smokers with current MDD [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.03, 1.85] and life‐time MDD (OR = 1.52, 95% CI: 1.15, 2.01) were more likely than those without the respective diagnosis to report continued smoking at wave 2. Wave 1 former daily smokers with current MDD (OR = 0.44, 95% CI: 0.26, 0.76) were less likely to report continued abstinence at wave 2. None of the gender × MDD diagnosis interactions were significant. Patterns of results remained similar when analyses were limited to smokers with nicotine dependence. Conclusions Current and life‐time major depressive disorders are associated with a lower likelihood of quitting smoking and current major depressive disorder is associated with greater likelihood of smoking relapse.     

Investigation of SLC2A1 26177A/G gene polymorphism via high resolution melting curve analysis in Malaysian patients with diabetic retinopathy

PurposeIn this study, we aimed to investigate the possible association between SLC2A1 26177A/G polymorphism and diabetic retinopathy (DR) in Malaysian patients with type 2 diabetes.MethodsGenomic DNA was extracted from 211 Malaysian type 2 diabetic patients (100 without retinopathy [DNR], 111 with retinopathy) and 165 healthy controls. A high resolution melting assay developed in this study was used to detect SLC2A1 26177A/G polymorphism followed by statistical analysis.ResultsA statistically significant difference in 26177 G minor allele frequency between healthy controls (19.7 %) and total patient group (26.1 %) (p < 0.05, Odd ratio = 1.437, 95% Confidence interval = 1.015–2.035) as well as between healthy controls (19.7 %) and DNR patients (27.5%) (p < 0.05, Odd ratio = 1.546, 95% Confidence interval = 1.024–2.336) was shown in this study. However, when compared between DR and DNR patients, there was no significant difference (p > 0.05).ConclusionsThis is the first study which shows that SLC2A1 26177G allele is associated with type 2 diabetes in Malaysian population but not with DR.     

A Formative Evaluation of Two Evidence‐Based Psychotherapies for PTSD in VA Residential Treatment Programs

Between July 2008 and March 2011, 38 U.S. Department of Veterans Affairs (VA) residential treatment programs for posttraumatic stress disorder (PTSD) participated in a formative evaluation of their programmatic services, including evidenced‐based treatments (EBTs). Face‐to‐face qualitative interviews were conducted with over 250 staff by an independent psychologist along with onsite participant observations. This evaluation coincided with a national VA dissemination initiative to train providers in two EBTs for PTSD: prolonged exposure (PE) and cognitive processing therapy (CPT). A substantial proportion of eligible (based on professional background) residential treatment providers received training in PE (37.4%) or CPT (64.2%), with 9.5% completing case consultation or becoming national trainers in each therapy respectively. In semistructured interviews, providers reported that their clinical programs had adopted these EBTs at varying levels ranging from no adoption to every patient receiving the full protocol. Suggestions for improving the adoption of PE and CPT are noted, including distilling manualized treatments to essential common elements.     

Pain interference and incident mood,anxiety, and substance-use disorders: Findings from a representative sample of men and women in the general population

To examine gender differences in the longitudinal relationship between past-month pain interference and incident mood, anxiety, and substance-use disorders, chi-square tests and binomial logistic regression analyses were performed on data obtained from the National Epidemiologic Survey on Alcohol and Related Conditions from 34,465 adult respondents (47.9% men; 52.1% women) who completed waves 1 (2000–2001) and 2 (2004–2005) data collection. Models were adjusted for potentially confounding factors (i.e., age, race, marital status, educational level, employment, household income, number of stressful life events, number of general medical conditions, and wave-1 psychopathology). Respondents were categorized at wave 1 according to their past-month level of pain interference (i.e., no or low pain interference, moderate pain interference, severe pain interference). Moderate and severe pain interference (as compared to no or low pain interference) in male and female respondents was associated with the incidence of several psychiatric disorders. A stronger relationship was observed in male respondents as compared to female ones between past-month moderate pain interference and a new onset of any mood disorder (OR = 1.57, p = 0.03) and major depressive disorder (OR = 1.60, p = 0.03), and between past-month severe pain interference and a new onset of alcohol abuse or dependence (OR = 1.69, p = 0.045) and nicotine dependence (OR = 1.48, p = 0.04). These findings suggest that providers should consider screening patients with past-month moderate or severe pain interference for mood, anxiety, and substance-use problems and monitor the possible development of subsequent comorbid psychiatric disorders.     

Differences in gambling problem severity and gambling and health/functioning characteristics among Asian-American and Caucasian high-school students

Studies of Asian-American adults have found high estimates of problematic gambling. However, little is known about gambling behaviors and associated measures among Asian-American adolescents. This study examined gambling perceptions and behaviors and health/functioning characteristics stratified by problem-gambling severity and Asian-American and Caucasian race using cross-sectional survey data of 121 Asian-American and 1659 Caucasian high-school students. Asian-American and Caucasian adolescents significantly differed on problem-gambling severity, with Asian-American adolescents more often reporting not gambling (24.8% vs. 16.4%), but when they did report gambling, they showed higher levels of at-risk/problem gambling (30.6% vs. 26.4%). Parental approval or disapproval of adolescent gambling also significantly differed between races, with Asian-American adolescents more likely to perceive both parental disapproval (50.0% vs. 38.2%) and approval (19.3% vs. 9.6%) of gambling. Asian-American adolescents were also more likely to express concern about gambling among close family members (25.2% vs. 11.6%). Among Asian-American adolescents, stronger associations were observed between at-risk/problem gambling and smoking cigarettes (interaction odds ratio=12.6). In summary, differences in problem-gambling severity and gambling perceptions indicate possible cultural differences in familial attitudes towards gambling. Stronger links between cigarette smoking and risky/problematic gambling amongst Asian-American adolescents suggest that prevention and treatment efforts targeting youth addictions consider cultural differences.