5). This suggests that elevated liver STAT3 activation in STAT3 mice likely contributes to the resistance Selleckchem Depsipeptide of these mice to CCl4-induced liver necrosis and oxidative stress. This concept is further supported by conclusive evidence showing that deletion of STAT3 in hepatocytes restores liver necrosis in STAT3 mice after CCl4 administration (Fig. 7). Interestingly, STAT3 mice are resistant to CCl4-induced liver necrosis as demonstrated in the current study but more susceptible to Con A–induced T cell hepatitis despite enhanced STAT3 activation in the liver (Fig. 2 in Lafdil et al.28). This discrepancy could be attributable

to the deletion of STAT3 in myeloid cells preferentially enhancing the Th1 cytokine (IFN-γ) response during Con A–induced T cell hepatitis, dominating over the hepatoprotective effect of STAT3 and resulting in accelerated liver injury in this model.28 Such preferential induction of IFN-γ was not observed in STAT3 mice in the NVP-BEZ235 CCl4-induced liver injury model (2500 pg/mL serum IFN-γ in Con A model28 versus 25 pg/mL IFN-γ in CCl4 model in STAT3 mice in the current study). In addition, STAT3 mice are also more susceptible to chronic ethanol feeding-induced liver inflammation and injury.27 It has been well documented that chronic ethanol consumption inhibits STAT3 activation in the liver.30 Therefore, it is probable that chronic ethanol feeding

diminishes hepatic STAT3 activation and abolishes the hepatoprotective effect of STAT3 in STAT3 mice, 上海皓元 resulting in enhanced liver injury in this alcohol-induced liver injury model.27 We have previously shown that STAT3 activation in hepatocytes promotes liver inflammation in alcohol-induced liver injury.27 Our findings in current studies showed that STAT3 activation in hepatocytes also plays a proinflammatory

role in CCl4-induced liver injury because deletion of STAT3 reduced systemic and hepatic inflammation although it enhanced CCl4-induced liver damage (Fig. 5). In addition, an additional deletion of STAT3 in hepatocytes enhanced CCl4-induced liver necrosis but partially counteracted the strong inflammation in STAT3 mice after CCl4 administration (Fig. 8). This is probably because deletion of STAT3 in hepatocytes reduced the hepatic expression of several STAT3-controlled inflammatory mediators (such as complement 3/5, IL-1, macrophage inflammatory protein 2, monocyte chemotactic protein 1, and intercellular adhesion molecule 1) in STAT3 mice (Fig. 7). Taken together, these findings suggest that enhanced hepatocellular STAT3 activation in STAT3 mice may contribute to not only the reduced liver necrosis but also the enhanced inflammation after CCl4 administration in these mice. In addition, elevated nuclear factor kappaB activation (Supporting Fig. S3) also may contribute to the reduced necrosis in STAT3 mice because of the hepatoprotective functions of nuclear factor kappaB.

Early studies of patients with IBD reported conflicting results regarding the risks for NMSC and the importance of immunosuppressive medications.

One series of IBD patients reported increasing risks of NMSC, but immunosuppression as a causative factor was not specifically evaluated.7,8 In contrast, a prospective cohort study did not find an increase in skin cancer incidence in patients with ulcerative colitis.9 More recent epidemiological studies MAPK inhibitor continue to report contradictory results: Long and colleagues found that recent and ongoing exposure to thiopurines was associated with increased risk of NMSC,10 while a Dutch study of 2887 patients reported that thiopurine use was not associated with increased risk of NMSC.11 A recent meta-analysis, which included a number of population-based studies consisting of IBD patients on thiopurines, reported an overall increased incidence of NMSC.12 This is supported

by a CESAME study from France, which prospectively studied a cohort of nearly 20 000 patients over a median period of 35 months and showed that ongoing thiopurine treatment (hazard ratio, 5.9; 95% confidence interval, 2.1–16.4, P = 0.0006) and past thiopurine exposure (HR, 3.9; 95% CI, 1.3–12.1, P = 0.02) were risk factors for NMSC.13 This study also found that drug-induced immunosuppression this website reverses the ratio of squamous-cell to basal-cell carcinoma. In this issue of Journal of Gastroenterology and Hepatology,14 Shetsedi and colleagues retrospectively reviewed records of IBD patients between 1960 and 2007 and concluded that patients with IBD who receive thiopurines are at increased risk of NMSC; further, the risk is highest among Caucasian patients. This study was conducted in Cape Town, South Africa, a place with high incidence of skin cancers. However the majority in the study were of mixed ethnicity. Out of a total cohort of 1084, 11% of patients were on thiopurines; the duration of thiopurine exposure and the temporal relationship between

thiopurine use and diagnosis of NMSC was not explored. Interestingly this study did not find the known increased MCE公司 risk of lymphoma among those treated with thiopurines that has been found in other bigger studies. However, the results of the present study do confirm the findings of the recent largest prospective CESAME cohort,13 that NMSC is increased with immunosuppression. An understanding of the “photobiology” of thiopurines helps explain the increased risk of non-melanotic skin cancer, while the risk of solid cancers other than lymphoma may be reduced.15 The major components of the ultraviolet spectrum are UVB (wavelength 280–320 nm) and UVA (320–400 nm) light; visible light is above 400 nm. The carcinogenic effects of UV radiation are mainly attributable to UVB,16 which can cause direct DNA damage and is responsible for sunburn.

Conclusion: Our data suggest that HGF and HPC may act synergistically in inhibiting the toxicant-induced liver fibrosis in rats.

Therefore, the HGF-expressing fetal HPC may be used as a new therapeutic approach for the treatment of liver fibrosis. Key Word(s): 1. Hepatic fibrosis; Stem Cell Compound Library 2. fetal hepatic cells; 3. HGF; 4. gene therapy; Presenting Author: YINGDI LIU Additional Authors: YUNSHENG YANG, GUOJUN CHAI, GUOHUI SUN, HUA JIANG, JUAN WANG Corresponding Author: YINGDI LIU Affiliations: Chinese PLA General Hospital Objective: To evaluate the hemostatic effects of emergent endoscopic variceal sclerotherapy(EIS) combined with acrylate glue (N-butyl-2-cyanoacrylate, NBCA) injection (ESCI) on esophageal variceal bleeding, and to investigate glue extrusion after endoscopic injection. Methods: Thirty patients with esophageal variceal bleeding which failed in EIS before combined with NBCA injection were consecutively observed in the past 10 years. The clinical characteristics of patients, and hemostasis rate of ESCI were

observed, which compared the success rate of hemostasis and blood transfusion with the same period of 16 patients who were performed intervention treatment after failed in endoscopic therapy, hemostatic effect of ESCI, glue extrusion time and complications were analyzed. Results: A total of 30 patients with esophageal AUY-922 chemical structure variceal bleeding were recruited in our study (20:10 males/females) and 31 times of ESCI therapy were conducted, including 30 cases of successful therapy. No heterotopic embolism or serious infection was recorded. Transient fever was found in 6 cases and dysphagia was turned out

in 9 cases, sever dysphagia was found in 2 of them and released by endoscopic treatment afterwards. NBCA (1∼4 vials, mean 2.03 ± 0.182 vials) were injected into esophageal varices and glue extrusion from varices mainly started from 2 weeks (9 cases, 36.00%) to 3 weeks (15 cases, 60.00%) after the injection, mainly completed at week 2∼4 (88%). In comparison to 16 cases failed in endoscopic sclerotherapy, hemostasis 上海皓元 were abtained with balloon tamponade during the same period, no significant difference was found with respect to hemostatic success rate, but the unit of blood transfusion and hospitalization costs were reduced. Twenty five cases were followed up for 12 months to 36 months, the average time was 20.23 ± 19.77 months. For one patient who was performed TIPSS after failed in endoscopic therapy, no rebleeding occurred in the following 30 months years. One patient with congenital hepatic arterioportal fistula died of massive upper gastrointestinal bleeding 2 months after treatment. Three patients with hepatocellular carcinoma died of liver failure 3∼7 months after the operation respectively. EV recurred within 6 months and 12 months after the operation in 4 and 2 cases respectively.

AAV-DJ is an artificial chimeric AAV vector containing hybrid capsid sequences from three naturally occurring AAV serotypes (AAV2, 8, and 9).28 This and other chimeric AAV vectors are currently being used because of their improved tissue tropism and transduction frequencies.28, 34, 38 However, understanding of the

factors that influence AAV gene targeting are still incomplete and more work in this area will likely improve our ability in the future to modify genes in primary somatic cells. According to the annual report of the American Liver Foundation, hepatitis, cirrhosis, and HCC affect 25 million Americans. However, research in the area of GSI-IX supplier liver disease lags behind other well-studied prominent disorders because of the lack of appropriate animal models. The HT1 pig will potentially address several significant needs, including serving as the first large-animal model of HCC arising

spontaneously in the background of cirrhosis. In addition, the Fah-null mouse has proven an invaluable model for cell and gene therapy work, including its use for hepatocyte and bone marrow transplantation studies, as well as both viral and non-viral-mediated gene therapy approaches.39-42 We anticipate Ivacaftor cost that the pig model will also be extensively used for similar gene and cell therapy studies. Finally, we recently developed a method whereby primary human hepatocytes were efficiently expanded MCE公司 in immune-deficient mice mutant for Fah.43 In these mice, transplanted Fah+/+ primary human hepatocytes were able to engraft and expand to greater than 90% repopulation of the mouse liver. These hepatocytes were fully functioning adult primary hepatocytes capable of performing all the necessary metabolic and synthetic functions that are required in the normal liver. However, a limitation in the repopulated FAH-deficient mouse is related to its small size. The absolute number of primary human hepatocytes that can be obtained from these animals is low, making a large animal

model of FAH deficiency highly desirable. We thank Mark Kay and Leszek Lisowski (Stanford University, Stanford, CA) for supplying the AAV-DJ capsid and helper plasmids, as well as the AAV-DJ GFP virus. We also thank Angela Major of the NIDDK-sponsored Digestive Disease Core Laboratory of the Texas Medical Center (DK56338) for histology support. “
“In 1991 this journal published the report of an international working party to the World Congress of Gastroenterology regarding the clinicopathological staging of colorectal cancer. Since that time staging has continued to evolve as further prognostic factors in colorectal cancer have been elucidated in studies of increasingly large databases in several countries. This review summarizes several of the key issues that have arisen during this evolutionary process and raises matters which still remain controversial in staging at the present time.

AAV-DJ is an artificial chimeric AAV vector containing hybrid capsid sequences from three naturally occurring AAV serotypes (AAV2, 8, and 9).28 This and other chimeric AAV vectors are currently being used because of their improved tissue tropism and transduction frequencies.28, 34, 38 However, understanding of the

factors that influence AAV gene targeting are still incomplete and more work in this area will likely improve our ability in the future to modify genes in primary somatic cells. According to the annual report of the American Liver Foundation, hepatitis, cirrhosis, and HCC affect 25 million Americans. However, research in the area of Romidepsin nmr liver disease lags behind other well-studied prominent disorders because of the lack of appropriate animal models. The HT1 pig will potentially address several significant needs, including serving as the first large-animal model of HCC arising

spontaneously in the background of cirrhosis. In addition, the Fah-null mouse has proven an invaluable model for cell and gene therapy work, including its use for hepatocyte and bone marrow transplantation studies, as well as both viral and non-viral-mediated gene therapy approaches.39-42 We anticipate BMN 673 chemical structure that the pig model will also be extensively used for similar gene and cell therapy studies. Finally, we recently developed a method whereby primary human hepatocytes were efficiently expanded MCE in immune-deficient mice mutant for Fah.43 In these mice, transplanted Fah+/+ primary human hepatocytes were able to engraft and expand to greater than 90% repopulation of the mouse liver. These hepatocytes were fully functioning adult primary hepatocytes capable of performing all the necessary metabolic and synthetic functions that are required in the normal liver. However, a limitation in the repopulated FAH-deficient mouse is related to its small size. The absolute number of primary human hepatocytes that can be obtained from these animals is low, making a large animal

model of FAH deficiency highly desirable. We thank Mark Kay and Leszek Lisowski (Stanford University, Stanford, CA) for supplying the AAV-DJ capsid and helper plasmids, as well as the AAV-DJ GFP virus. We also thank Angela Major of the NIDDK-sponsored Digestive Disease Core Laboratory of the Texas Medical Center (DK56338) for histology support. “
“In 1991 this journal published the report of an international working party to the World Congress of Gastroenterology regarding the clinicopathological staging of colorectal cancer. Since that time staging has continued to evolve as further prognostic factors in colorectal cancer have been elucidated in studies of increasingly large databases in several countries. This review summarizes several of the key issues that have arisen during this evolutionary process and raises matters which still remain controversial in staging at the present time.

Despite increasing interest and research, there remains uncertainty around the mechanism of HCV-associated cognitive impairment and other CNS effects. Imaging studies have suggested evidence of CNS immune activation[1, 9, 10] and alterations in neurotransmission in HCV infection,[11] yet it is unclear whether this is associated

with a direct effect of viral penetration into the CNS[12] or a result of peripheral factors acting across the blood-brain barrier. HCV genomes have isolated by a number of groups in human microglial cells[13] and recent data show that human brain endothelial cells support productive but low-level infection by HCV.[14] The potential importance of an extrahepatic, immune-privileged site goes beyond the neurocognitive symptoms in this infection, particularly ABT-888 purchase as we move into the era of interferon-free, direct-acting antiviral therapy. The expected major improvements in sustained virological responses after finite short-course combination therapies will depend on adequate drug penetration to all sites. The era of interferon-free regimens will greatly reduce the neurocognitive burden posed by interferon and offers further opportunities to test the relationships between HCV infection and

CNS symptoms. In the absence of the deleterious effect of interferon, we should expect an accelerated improvement in neurocognitive symptoms if, as suggested, they are directly attributable to BMN 673 solubility dmso HCV per se and the promise of high-level, permanent viral eradication

becomes reality. Jasmohan S. Bajaj, M.D., M.Sc.1 “
“Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and MCE公司 levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P < 0.05), and fibrosis (2.1 ± 0.35 vs 2.9 ± 0.84, P < 0.05). Transforming growth factor-β and α-SMA expressions were also reduced by caffeine. Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation.

The mean follow-up time was 320 days, the overall mortality rate was 62% and previous aspiration pneumonia (p = 0.006), higher levels of C-reactive protein (p = 0.002) and leucocytosis (p = 0.005) are among the predictive

factors of mortality found. The 30-day mortality rate was 19% and the only predictive factor of mortality found was higher urea levels (p = 0.046). Ninety-six BYL719 percent of patients had a follow-up period superior to 90-days and 91% superior to 180-days: mortality rates were 30% and 43%, respectively, and the predictive factors of mortality observed were: diabetes mellitus (90-days : p = 0.013;180-days : p = 0.040) and higher levels of C-reactive protein (90-days : p = 0.002; 180-days : p = 0.008). Conclusion: The mortality rate

after PEG placement is high. Past history of aspiration pneumonia, presence of diabetes mellitus and higher levels of C-reactive protein significantly influenced the prognosis of these patients. These factors should be considered in the decision making of PEG insertion. Key Word(s): 1. PEG; Presenting Author: ENQIANG LINGHU Additional Authors: YAQI ZHAI, HUIKAI LI, ZHICHU QIN, LIHUA PENG, XIAOLIN SHI, XIAOYU QIU, QIYANG HUANG, YONGWEI ZHAO Corresponding Author: ENQIANG LINGHU Affiliations: Department of Gastroenterology and Hepatology,The Chinese PLA General Hospital; Department of Gastroenterology and Hepatology,The PLA General Hospital GDC941 Objective: Peroral endoscopic myotomy (POEM) is a new-developed minimally invasive endoscopic technique, expected to be the first choice for achalasia (AC).Not only is POEM technically challenging and time consuming, but incidence of complications is fairly high,such as pneumoderm and even pneumothorax. Therefore, we have initially developed a new POEM with longitudinal entry incision to settle above-mentioned

上海皓元医药股份有限公司 problems.Our aim was to compare the safety and efficiency of transverse-incision POEM with longitudinal-incision POEM. Methods: This is a prospective controlled trial, but not randomized.POEM,with transverse or longitudinal entry incision, was performed on 53 consecutive patients confirmed achalasia (AC) between December 2010 and Septemper 2012. Data of those patients was recorded, including time in different procedures, complications. Results: All the 53 patients underwent POEM successfully, among whom 41 patients was performed with transverse entry incision and 12 for longitudinal incision. Treatment success (Eckardt score≤3), with a median 5 month follow-up,was achieved in 96.2 % of cases (mean score pre-treatment vs. post-treatment: 7.5 vs. 0.6,P < 0.001). The whole operation time of transverse-incision group is a little shorter than that of longitudinal-incision((65.0 ± 18.0)min vs (74.1 ± 18.2)min,P = 0.142). But it took much less time in the process of tunnel built-up and muscle dissection in the transverse-incision group((36.3 ± 9.0)min vs (45.4 ± 10.5)min; (10.2 ± 4.6)min vs 15.5 ± 5.5 min P < 0.05).

Furthermore, the disparity between fluorescent and O2 flux measurement is not solved by reference to respiration rates (Rdark or Light-enhanced dark respiration, results not shown for the latter) as they follow a similar trend as Pnmax and Pgross. C. implexa grew profusely under November-PI conditions,

but, Pnmax was greatest under November-A1FI conditions. An uncoupling between biomass accumulation and growth rate has been observed in other studies (e.g., Israel et al. 1999 and Xu and Gao 2012) and in at least one species this has been attributed to changes in carbon allocation (Gordillo et al. 2001). Likewise, changes in resource allocation may have occurred in C. implexa, where Rdark tended to be greater under November-A1FI, suggesting that much of the carbon accumulated by day is respired by night, as opposed to converted into biomass for growth. Furthermore, Tamoxifen clinical trial there is a tendency for the amount of carbon per dry weight of tissue to be less in the PI and present-day treatments than in the B1 or A1FI treatments, suggesting a bias against the formation of carbon storage compounds such as laminarin and fatty acids (Michel et al. 2010, Gardner et al. 2013). This bias is especially noticeable in the contrast between nutrient-enriched

versus ambient treatments. In this case, algal tissue from enriched treatments, irrespective of experimental time point or scenario, are relatively deplete in carbon and enriched in both selleck nitrogen and phosphorus, clearly demonstrating that the enrichment was assimilated by the algae, even if it did not lead to differential

growth. The reduction in tissue carbon content observed under nutrient addition may have been caused by its release as dissolved organic carbon; this has been suggested for various other tropical algal species under seasonal nutrient enrichment (Wild et al. 2008). The nitrogen assimilated into the tissue of C. implexa can be stored as inorganic nitrogen, used MCE公司 in nitrogen rich pigments such as Chl a, or amino acids and proteins (Chapman and Craigie 1977, Wheeler and North 1980, Bird et al. 1982). The present results suggest that the additional nitrogen is not used for Chl a synthesis in C. implexa because (i) no increase was observed with nutrient addition and (ii) winter Chl a concentration decreased under nutrient addition. This leaves proteins, amino acids, and inorganic nitrogen storage as possible nutrient sinks. The relative xanthophyll pool, that does not include nitrogen as a component, increased with nutrient enrichment, but this response was principally driven by the reduction in Chl a levels, rather than an increase in xanthophyll synthesis. Interestingly, neither reduction in Chl a nor the increase in the relative xanthophyll pool appeared to have consistent effects on either dark-adapted Fv/Fm or Pnmax.

Results: Group I: Genotype 1 was the most common 59.98% (genotype 1: 9.39%, 1a: 12.96%, 1b: 37.63%); genotype 6: 24.15% (genotype 6: 1.28%, 6a: 22.68%, 6b: 0.19%), genotype 2: Dabrafenib manufacturer 15.82% (genotype 2: 0.3%, 2a: 13.67%, 2b: 0.52%, 2c:1.19% and 2d: 0.14%), and

genotype 3: 0.05% ( genotype 3a: 0.025% and 3b: 0.025%). Group II: Genotype 6 was the most common: 46.59% (genotype 6: 1.14%, 6a: 19.31%, 6e: 23.86%, 6h: 1.14%, 6r: 1.14%); genotype 1: 42.05% (genotype 1a: 29.55%, 1b: 12.50%); genotype 2: 11.36% ( genotype 2a: 1.14%, 2m: 10.22%). Group III: Genotype 1 was the most common: 78.21% (genotype 1a: 36.63%, 1b: 41.58 %); genotype 6: 19.80 % (genotype 6a: 0.99%, 6e: 14.85%, 6h: 1.98%, 6p: 0.99%, 6t: 0.99%); genotype 2: 1.98% (only genotype 2m). Conclusion: Using 5′NC suggested that genotype 1 was the most common in Vietnam. However using NS5B region the rate of HCV genotype 6 was higher than using 5′NC region, and was the most common genotype in Vietnam. The rate of mis-classification of genotype 6 into genotype 1 when using 5′NC was 19.80%. GSI-IX ic50 In this group genotype 6e had the highest rate at 75%. Disclosures: The following people have nothing to disclose: Thu Thuy Pham Thi, Tan Dat Ho,

Bao Toan Nguyen Introduction: Veterans have historically had low rates of antiviral treatment for the hepatitis C virus (HCV). Due to the rapidly-shifting landscape of pharmacotherapy for HCV, there is an increased urgency to understand how patients and providers interact to make treatment decisions. We hypothesized that patient-physician rapport and patient’s psychiatric history would be important determinants of treatment eligibility. Methods: This prospective cohort study was conducted within the VA Healthcare

System. Participants medchemexpress were recruited between December 2006-June 2010 after referral for HCV treatment. They completed semi-structured interviews and the following validated measures: the Medical Interview Satisfaction Scale (MISS), Patient Education About Hepatitis C (PEAHC), the Center for Epidemiologic Studies-Depression Survey (CES-D), the Alcohol Use Disorders Identification Test (AUDIT), and the Drug Abuse Screening Test (DAST). Two qualitative coders analyzed the semi-structured interviews. Factors associated with patient eligibility for interferon-based therapy were assessed using multivariate logistic regression. Results: Of 339 participants, only 56 (16.5%) were deemed eligible for HCV therapy by gastroenterology (GI) providers. Factors associated with ineligibility in univariate testing were living alone (40% vs. 22%, p=0.02), meeting CES-D criteria for depression (50% vs. 30%, p<0.01) and patient-expressed concerns about the relationship with the consulting GI provider (32% vs. 17%, p=0.03).

19 As the low FODMAP diet was lower in RS than the high FODMAP diet, wheat muffins containing high amylose maize (high in RS) were added to balance the RS content. An example of the test diets provided on day 2 of the study is shown in Table 1. All food used was purchased from the local supermarket with the exception of the 355 mL can of soda that was sweetened with high fructose corn syrup (imported from the USA) and was

obtained from a specialty supermarket. Samples of food and drinks used in the study were separately analyzed for their content of fructose, glucose, lactose, sugar polyols (sorbitol and mannitol), JQ1 solubility dmso galacto-oligosaccharides (GOS, raffinose and stachyose) by high performance liquid chromatography

(HPLC) as previously described.20 Total fructan content was measured using an enzymatically-based assay kit (Megazyme International Ireland Ltd, Wicklow, Ireland), as per the manufacturer’s instructions.21 Results from laboratory analysis were added to the Foodworks database (Foodworks Professional 2007, Xyris Software, Highgate Hill, QLD, Australia) to enable the complete assessment of the macronutrient Afatinib and FODMAP dietary intake during the study. Breath samples were collected every hour for 14 h into 250 mL sample holding bags (Quintron Instrument Co., Milwaukee, Wisconsin). The first sample of the day was a fasting sample and taken prior to breakfast. Samples were then taken hourly for a total of 14 h. All of the supplied food was to be consumed within the 14-h time period. The exact time each subject consumed their meals varied slightly between individuals but was kept constant within each individual during the two dietary MCE periods (i.e. each person was their own control in the crossover design). Breath samples were analyzed for

hydrogen and methane within 24 h using a Quintron Microlyzer Model DP Plus (Quintron Instrument Co., Milwaukee, WI, USA). Total breath gas production over the 14-h period was then calculated from the graphed area-under-the-curve (AUC) using the trapezium rule and expressed in parts per million over 14 h (ppm.14 h). A subject was considered to produce hydrogen or methane if the AUC was more than 10 ppm.14 h during at least one of the dietary periods. All subjects were asked to complete the gastrointestinal symptom questionnaire at the same time in the evening of each day. The questionnaire comprised five categories for general gastrointestinal symptoms (abdominal pain/discomfort, abdominal bloating/distension, wind, nausea, heartburn and lethargy). Bowel function was noted but not analyzed due to the heterogeneity of bowel habits across the subjects. The symptoms were rated using a Likert scale 0 to 3, where 0 = none, 1 = mild, 2 = moderate and 3 = severe.