Associations between gastric histopathology and the occurrence of colonic polyps.

AIM: Compromise of the gastric acid barrier may facilitate bacterial invasion of the lower intestinal tract and promote the development of colonic neoplasia. Our study aimed to test the associations between histopathological abnormalities of the upper and lower gastrointestinal tract in patients undergoing bidirectional endoscopy. METHOD: The Inform Diagnostics database is a national electronic repository of histopathological records of patients distributed throughout the USA. A case-control study of 302 061 patients, 163 168 of whom had colonic polyps, evaluated whether the occurrence of colonic polyps was influenced by the presence of the following gastro-oesophageal diagnoses: gastric Helicobacter pylori infection, gastric intestinal metaplasia, fundic gland polyps and gastric hyperplastic polyps. The influence of individual diagnoses on the occurrence of colonic polyps was expressed as odds ratios with their 95% confidence intervals. RESULTS: The odds ratio for tubular adenomas being associated with gastric H. pylori was 1.53 (1.49-1.58), with intestinal metaplasia 1.65 (1.59-1.71), with fundic gland polyps 1.49 (1.45-1.54) and with gastric hyperplastic polyps 1.85 (1.75-1.96). The odds ratio for sessile serrated polyps being associated with gastric H. pylori was 1.03 (0.96-1.10), with intestinal metaplasia 1.21 (1.13-1.30), with fundic gland polyps 1.79 (1.69-1.89) and with gastric hyperplastic polyps 1.52 (1.35-1.71. CONCLUSION: A diminished gastric acid barrier function, which occurs in various upper gastrointestinal diseases associated with lowered gastric acid output, may promote the development of colonic neoplasia.

Screening of white-rot fungi for bioprocessing of wheat straw into ruminant feed.

AIM: In this study, the biological variation for improvement of the nutritive value of wheat straw by 12 Ceriporiopsis subvermispora, 10 Pleurotus eryngii and 10 Lentinula edodes strains was assessed. Screening of the best performing strains within each species was made based on the in vitro degradability of fungal-treated wheat straw. METHODS AND RESULTS: Wheat straw was inoculated with each strain for 7 weeks of solid state fermentation. Weekly samples were evaluated for in vitro gas production (IVGP) in buffered rumen fluid for 72 h. Out of the 32 fungal strains studied, 17 strains showed a significantly higher (P < 0·05) IVGP compared to the control after 7 weeks (227·7 ml g-1 OM). The three best Ceriporiopsis subvermispora strains showed a mean IVGP of 297·0 ml g-1 OM, while the three best P. eryngii and L. edodes strains showed a mean IVGP of 257·8 and 291·5 ml g-1 OM, respectively. CONCLUSION: Ceriporiopsis subvermispora strains show an overall high potential to improve the ruminal degradability of wheat straw, followed by L. edodes and P. eryngii strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Large variation exists within and among different fungal species in the valorization of wheat straw, which offers opportunities to improve the fungal genotype by breeding.

Decreased risk for microscopic colitis and inflammatory bowel disease among patients with reflux disease.

AIM: Previous studies have found an increased risk for microscopic colitis (MC) associated with proton pump inhibitors. In patients with ulcerative colitis (UC) or Crohn's disease (CD), proton pump inhibitors have been associated with an increased risk for IBD flares and impaired outcomes. The aim of this study was to test the epidemiological associations between gastro-oesophageal reflux disease (GERD) and MC, UC or CD in a large database. METHOD: The Miraca Life Sciences Database is a national electronic repository of histopathological records of patients distributed throughout the entire USA. A case-control study evaluated whether the presence of Barrett's metaplasia, erosive oesophagitis on endoscopy or histological signs of reflux oesophagitis, clinical diagnosis of GERD or any GERD type affected the occurrence of MC, UC or CD among 228 506 subjects undergoing bidirectional endoscopy. Multivariate logistic regression analyses were used to calculate ORs and their 95% CI for the risk of MC, UC or CD associated with various types of GERD and were adjusted for age, sex and presence of Helicobacter pylori. RESULTS: The analysis revealed an inverse relationship between GERD and different types of inflammatory bowel disease. The inverse relationships applied similarly to MC (mean = 0.62, 95% CI: 0.58-0.66), UC (mean = 0.89, 95% CI: 0.81-0.97) and CD (mean = 0.76, 95% CI: 0.69-0.85). It also applied to different forms of GERD, with a trend towards more pronounced inverse relationships associated with Barrett's metaplasia or erosive oesophagitis than clinical diagnosis of GERD. CONCLUSION: Gastro-oesophageal reflux disease is inversely associated with all forms of inflammatory bowel disease, such as MC, UC, or CD.

Quantification of the duodenal eosinophil content in adults: a necessary step for an evidence-based diagnosis of duodenal eosinophilia.

BACKGROUND: The normal content of eosinophils in the adult duodenum remains undefined. Therefore, there is no foundation for evidence-based criteria to diagnose eosinophilic duodenitis. AIM: This study aimed at: (1) establishing the range of the eosinophil density in the mucosa of the duodenum of normal adults, and (2) determining the biopsy-based prevalence of isolated eosinophilic duodenitis in a large population of adults. METHODS: We counted intact eosinophils in three separate high-power fields (hpf area = 0.237 mm2 each) with the highest densities of eosinophils from the duodenal biopsy specimens of 370 consecutive adults (60% women) with no history of small intestinal disease and a normal duodenal histology. From a large database we also extracted patients with a diagnosis of elevated duodenal eosinophilia and reviewed their biopsies and clinical history. RESULTS: The mean eosinophil count for the 370 patients was 8.2 eos/hpf with a standard deviation of ± 6.3. Twenty-seven of the 370 had eosinophil counts outside the 95% range, which was calculated as: mean + 1.96 × SD = 20.4 eos/hpf. In a database of 458 668 adult subjects, 31 patients (6.8/100 000) had elevated duodenal eosinophilia; 21 of these had other gastrointestinal organs involved by eosinophilia, suggesting eosinophilic gastroenteritis. No significant association between duodenal eosinophilia and any specific symptom was observed. CONCLUSIONS: This study suggests that in this diverse US population, a cut-off count of 20 eos/hpf would be useful to separate patients with normal from those with elevated duodenal eosinophilic infiltrations. The clinical implications of duodenal eosinophilia, particularly when it is not an expression of eosinophilic gastroenteritis, remain to be established.

Demographic and socioeconomic influences on Helicobacter pylori gastritis and its pre-neoplastic lesions amongst US residents.

BACKGROUND: Gastric infection with Helicobacter pylori (Hp) can lead to chronic inactive gastritis, atrophy and intestinal metaplasia. AIMS: To investigate in a cross-sectional study these changes among different socioeconomic and ethnic groups within the USA. METHODS: We used the Miraca Life Sciences database, an electronic depository of clinicopathological records from patients distributed throughout the USA, to extract data from 487 587 patients who underwent oesophago-gastro-duodenoscopy with biopsy between 1/2008 and 12/2014. We then classified patients into ethnic and socioeconomic categories using previously validated algorithms, as well as ZIP code-based information derived from the 2011-2012 US Census. RESULTS: The prevalence of Hp increased significantly until the age-group 40-49, before it leveled off and started a gradual decrease. The prevalence of chronic inactive gastritis, atrophy, and intestinal metaplasia increased significantly with age. The prevalence of Hp, chronic inactive gastritis, intestinal metaplasia, and atrophy decreased significantly with the percentage of Whites per ZIP code. The prevalence of all four diagnoses also decreased significantly with rising levels of income or college education. Hp, chronic inactive gastritis, atrophy and intestinal metaplasia were more common among Hispanics and the influence of income or college education less pronounced than in the entire population. Hp, chronic inactive gastritis, atrophy, and intestinal metaplasia were also more common among East-Asians, Hp and atrophy decreasing with rising income but remaining unaffected by levels of college education. CONCLUSION: Ethnicity and socioeconomic factors influence the occurrence of Hp gastritis, and its progression to chronic inactive gastritis, atrophy or intestinal metaplasia.

Differences between two strains of Ceriporiopsis subvermispora on improving the nutritive value of wheat straw for ruminants.

AIM: This study evaluated differences between two strains of Ceriporiopsis subvermispora on improving the nutritive value and in vitro degradability of wheat straw. METHODS AND RESULTS: Wheat straw was treated with the fungi for 7 weeks. Weekly samples were analysed for ergosterol content, in vitro gas production (IVGP), chemical composition and lignin-degrading enzyme activity. Ergosterol data showed CS1 to have a faster initial growth than CS2 and reaching a stationary phase after 3 weeks. The IVGP of CS1-treated wheat straw exceeded the control earlier than CS2 (4 vs 5 weeks). CS1 showed a significantly higher (P < 0·001) selectivity in lignin degradation compared to CS2. Both strains showed peak activity of laccase and manganese peroxidase (MnP) at week 1. CS1 showed a significantly higher (P < 0·001) laccase activity, but lower (P = 0·008) MnP activity compared to CS2. CONCLUSION: Both CS strains improved the nutritive value of wheat straw. Variation between strains was clearly demonstrated by their growth pattern and enzyme activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The differences among the two strains provide an opportunity for future selection and breeding programs in improving the extent and selectivity of lignin degradation in agricultural biomass.

The ethnic distribution of sessile serrated polyps in the United States is inversely associated with Helicobacter pylori prevalence.

AIM: Little is known about the epidemiology of sessile serrated polyps (SSP). Our study aimed to investigate the influence of Helicobacter pylori gastritis and patient demographic characteristics (age, gender, ethnicity) on the prevalence of SSP using a large national database of patients undergoing bi-directional endoscopy. METHOD: De-identified patient data were extracted from the Miraca Life Sciences electronic database of histopathological reports. Using multivariate logistic regression analysis, the influence of H. pylori gastritis and demographic characteristics on the occurrence of SSP were expressed as odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The total study population comprised 228 506 subjects, of whom 28 890 carried a diagnosis of H. pylori gastritis and 11 285 SSP. Age (OR 4.35, 95% CI: 3.82-4.96), female gender (0.92, 0.88-0.95) and H. pylori gastritis (0.94, 0.88-0.99) exerted the strongest influence on the occurrence of SSP. In comparison with the population comprising Caucasians and African Americans, SSP were less common among subjects of Hispanic (0.67, 0.62-0.73), East Asian (0.59, 0.50-0.69), Indian (0.43, 0.27-0.64) or Middle Eastern descent (0.61, 0.41-0.87). All these ethnic subgroups were also characterized by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of SSP (R2  = 0.82, P < 0.001). CONCLUSION: The prevalence of SSP within the United States is characterized by a marked ethnic variation. The inverse correlation between the prevalence of H. pylori and SSP suggests that gastric infection with H. pylori may be partly responsible for the observed ethnic distribution of SSP.

Differences in the socio-economic distribution of inflammatory bowel disease and microscopic colitis.

AIM: Inflammatory bowel disease (IBD) and microscopic colitis are characterized by different geographical distributions across the USA. In this cross-sectional study we utilized demographic and socio-economic information associated with individual ZIP codes to further delineate the epidemiological characteristics of the two diseases. METHOD: A total of 813 057 patients who underwent colonoscopy between 2008 and 2014 were extracted from an electronic database of histopathology reports. The prevalence of patients with IBD or microscopic colitis was expressed as percentage of the population associated with specific demographic (age, sex, ethnicity) and socio-economic characteristics (population size, housing value, annual income, tertiary education). RESULTS: Both diseases were more common among subjects from ZIP codes with predominantly White residents and less common among subjects from ZIP codes with predominantly non-White residents such as Black, Hispanic and Asian. These ethnic variations were more pronounced in microscopic colitis than IBD. Markers of affluence, such as average residential house value and annual income, were positively associated with IBD and negatively with microscopic colitis. The prevalence of both diseases was positively correlated with tertiary education. CONCLUSION: The occurrence of both IBD and microscopic colitis is influenced by environmental risk factors. The differences in the demographic, ethnic and socio-economic distributions of the two diseases suggest that different sets of risk factors affect the two diseases and that their aetiology is unrelated.

The influence of Helicobacter pylori on the ethnic distribution of Barrett's metaplasia.

BACKGROUND: Environmental risk factors associated with ethnicity may contribute to the occurrence of Barrett's metaplasia. AIM: To investigate the interaction between ethnicity and Helicobacter pylori infection in the occurrence of Barrett's metaplasia among patients undergoing oesophago-gastro-duodenoscopy. METHODS: The Miraca Life Sciences Database is an electronic repository of histopathological patient records. A case-control study evaluated the influence of age, gender, ethnicity and histological diagnosis of H. pylori on the occurrence of Barrett's metaplasia. RESULTS: The total study population comprised 596 479 subjects, of whom 76 475 harboured a diagnosis of Barrett's metaplasia. Male sex, age and H. pylori infection in declining order exerted the strongest influence on the occurrence of BM. In comparison with the population comprising Caucasians and African Americans, Barrett's metaplasia was less common among subjects of African (OR = 0.09, 95% CI = 0.01-0.43), Middle Eastern (0.26, 0.20-0.34), East Asian (0.35, 0.31-0.40), Indian (0.39, 0.32-0.47), Hispanic (0.62, 0.59-0.64) or Jewish descent (0.50, 0.45-0.54), but more common among subjects of Northern European descent (1.14, 1.03-1.26). With the exception of Jews and Northern Europeans, all other ethnic subgroups were characterised by a higher prevalence of H. pylori than the comparison group. A low prevalence of H. pylori was significantly associated with a high prevalence of Barrett's metaplasia (R2 = 0.82, P < 0.001), as well as dysplasia or oesophageal adenocarcinoma (R2 = 0.81, P < 0.001). CONCLUSION: Our analysis reveals an inverse relationship between the prevalence of Barrett's metaplasia and H. pylori gastritis among different ethnic groups within the United States.

Oesophageal signet ring cell carcinoma as complication of gastro-oesophageal reflux disease.

BACKGROUND: Signet ring cell carcinoma occurs as a histological variant of oesophageal adenocarcinoma. AIM: In a cross-sectional study, to pursue the hypothesis that oesophageal signet ring cell cancers constitute a complication of gastro-oesophageal reflux disease. METHODS: In a large national database of histopathology records, we accumulated 91 802 patients with Barrett's oesophagus (BE), 2817 with oesophageal nonsignet ring adenocarcinoma (EAC) and 278 with oesophageal signet ring cell carcinoma (SRC). The three groups were compared with respect to their clinical and demographic characteristics, as well as socio-economic risk factors (associated with patients' place of residence). RESULTS: About 9% of all oesophageal adenocarcinomas harboured features of signet ring cell carcinoma. Patients with oesophageal adenocarcinoma and signet ring cell carcinoma were characterised by almost identical epidemiological patterns. Patients with either cancer type were slightly older than those with Barrett's oesophagus (EAC 68.0, SRC 66.7 vs. BE 63.7 years), and both showed a striking male predominance (EAC and SRC 85% vs. BE 67%). Both cancer types were associated with a similar set of alarm symptoms, such as dysphagia, pain and weight loss. The distribution by race (Whites vs. Blacks) and socio-economic parameters, such as levels of college education and family income, were similar among the three groups of patients. CONCLUSIONS: Signet ring cell carcinoma is a rare variant of oesophageal adenocarcinoma with similar epidemiological characteristics. The reasons why a minority of reflux patients progress to develop signet ring cell carcinoma, rather than the usual type of oesophageal adenocarcinoma, remain unknown.

The stomach in health and disease.

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.

Seasonal variation in detection of oesophageal eosinophilia and eosinophilic oesophagitis.

BACKGROUND: Seasonal variation has been reported in diagnosis of eosinophilic oesophagitis (EoE), but results are not consistent across studies and there are no national-level data in the USA. AIM: To determine if there is seasonal variation in diagnosis of oesophageal eosinophilia and EoE in the USA, while accounting for factors such as climate zone and geographic variation. METHODS: This was a cross-sectional study using a USA national pathology database. Patients with oesophageal eosinophilia (≥15 eosinophils per high-power field) comprised the primary case definition and were compared to those with normal oesophageal biopsies. We calculated the crude and adjusted odds of oesophageal eosinophilia by season, as well as by day of the year. Sensitivity analyses were performed using more restrictive case definitions of EoE, and after stratification by climate zone. RESULTS: Exactly, 14 524 cases with oesophageal eosinophilia and 90 459 normal controls were analysed. The adjusted odds of oesophageal eosinophilia were higher in the late spring and summer months, with the highest odds in July (aOR: 1.13; 95% CI: 1.03-1.24). These findings persisted with increasing levels of oesophageal eosinophilia, as well as across EoE case definitions. Seasonal variation was strongest in temperate and cold climates, and peak diagnosis varied by climate zone. CONCLUSIONS: There is a mild but consistent seasonal variation in the diagnosis of oesophageal eosinophilia and EoE, with cases more frequently diagnosed during summer months. These findings take into account climate and geographic differences, suggesting that aeroallergens may contribute to disease development or flare.

Fungal treated lignocellulosic biomass as ruminant feed ingredient: a review.

In ruminant nutrition, there is an increasing interest for ingredients that do not compete with human nutrition. Ruminants are specialists in digesting carbohydrates in plant cell walls; therefore lignocellulosic biomass has potential in ruminant nutrition. The presence of lignin in biomass, however, limits the effective utilization of cellulose and hemicellulose. Currently, most often chemical and/or physical treatments are used to degrade lignin. White rot fungi are selective lignin degraders and can be a potential alternative to current methods which involve potentially toxic chemicals and expensive equipment. This review provides an overview of research conducted to date on fungal pretreatment of lignocellulosic biomass for ruminant feeds. White rot fungi colonize lignocellulosic biomass, and during colonization produce enzymes, radicals and other small compounds to breakdown lignin. The mechanisms on how these fungi degrade lignin are not fully understood, but fungal strain, the origin of lignocellulose and culture conditions have a major effect on the process. Ceriporiopsis subvermispora and Pleurotus eryngii are the most effective fungi to improve the nutritional value of biomass for ruminant nutrition. However, conclusions on the effectiveness of fungal delignification are difficult to draw due to a lack of standardized culture conditions and information on fungal strains used. Methods of analysis between studies are not uniform for both chemical analysis and in vitro degradation measurements. In vivo studies are limited in number and mostly describing digestibility after mushroom production, when the fungus has degraded cellulose to derive energy for fruit body development. Optimization of fungal pretreatment is required to shorten the process of delignification and make it more selective for lignin. In this respect, future research should focus on optimization of culture conditions and gene expression to obtain a better understanding of the mechanisms involved and allow the development of superior fungal strains to degrade lignin in biomass.

Helicobacter-negative gastritis: a distinct entity unrelated to Helicobacter pylori infection.

BACKGROUND: Helicobacter-negative gastritis is diagnosed when no organisms are detected in a gastric mucosa with typical features of Helicobacter gastritis (Hp-gastritis). If Helicobacter-negative gastritis consisted mostly of 'missed' Helicobacter infections, its prevalence should represent a constant percentage of these infections in a population, and their clinico-epidemiological features would overlap. AIM: To compare the epidemiologic patterns of Hp-positive and Hp-negative gastritis. METHODS: From a pathology database, we extracted demographic, clinical and histopathological data from patients with gastric biopsies (1.2008-12.2013). We allocated patients to high (≥12%) and low (≤6%) H. pylori prevalence regions defined by ZIP code-based data. The prevalence of H. pylori-positive and -negative gastritis by sex, age and state were expressed as a per cent of the total study population stratified accordingly. RESULTS: Of 895 323 patients, 10.6% had Hp-gastritis and 1.5% Helicobacter-negative gastritis. Hp-gastritis, but not Helicobacter-negative gastritis, was more common in males than females (OR 1.17, 95% CI: 1.16-1.19). While Hp-gastritis was more prevalent in high than in low-prevalence areas (OR 3.65, 95% CI: 3.57-3.74), Helicobacter-negative gastritis was only minimally affected by the underlying H. pylori prevalence (1.7% vs. 1.5%). The age-specific prevalence of Hp-gastritis peaked in the 4th to 5th decades; Helicobacter-negative gastritis exhibited a low and relatively flat pattern. The geographic distribution of H. pylori-positive and -negative gastritis showed no significant correlation. Intestinal metaplasia was found in 13.0% of patients with Hp-gastritis and in 6.1% of those with Helicobacter-negative gastritis (OR 0.43, 95% CI: 0.40-0.47). CONCLUSION: These data suggest that Helicobacter-negative gastritis is, in the vast majority of cases, a nosologically and epidemiologically distinct entity that deserves further investigation.

Signaling events mediated by α3ß1 integrin are essential for mammary tumorigenesis.

The constitutive activation of ß-catenin signaling in the mammary basal epithelial cell layer in transgenic K5ΔNßcat mice leads to basal-type tumor development. Integrins of the ß1 family and integrin-mediated signaling events have an important role in breast tumor growth and progression. We show here that the deletion of α3ß1 integrin, a major laminin receptor, from the basal layer of the mammary epithelium of K5ΔNßcat mice completely prevented the tumorigenesis induced by ß-catenin signaling. Moreover, the depletion of α3ß1 integrin from a spontaneously transformed mouse mammary basal epithelial cell line (MEC) prevented the cells from forming colonies in soft agar and greatly reduced tumor development in orthotopic grafts. Inhibition of the integrin signaling intermediates Rac1 or PAK1 (P21-activated Kinase 1) in MEC affected tumor cell growth in soft agar, whereas the expression of activated forms of these effectors in α3-depleted cells rescued the capacity of these cells to grow in non-adherent conditions. Similarly, the tumorigenic potential of α3-depleted cells was restored by the expression of activated PAK1, as assessed by orthotopic transplantation assay. In three-dimensional Matrigel culture, MEC survival and proliferation were affected by the depletion of α3ß1 integrin, which also significantly decreased the activation of focal adhesion kinase (FAK), mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK). Our data suggest that the activation of signaling cascades downstream from α3ß1 and involving the Rac1/PAK1 pathway, MAPK and JNK, promotes prosurvival and proproliferative signals required for the malignant growth of basal mammary epithelial cells, providing further insight into the molecular mechanisms underlying breast cancer initiation and progression.

Dual roles of hemidesmosomal proteins in the pancreatic epithelium: the phosphoinositide 3-kinase decides.

Given the failure of chemo- and biotherapies to fight advanced pancreatic cancer, one major challenge is to identify critical events that initiate invasion. One priming step in epithelia carcinogenesis is the disruption of epithelial cell anchorage to the basement membrane which can be provided by hemidesmosomes (HDs). However, the existence of HDs in pancreatic ductal epithelium and their role in carcinogenesis remain unexplored. HDs have been explored in normal and cancer pancreatic cells, and patient samples. Unique cancer cell models where HD assembly can be pharmacologically manipulated by somatostatin/sst2 signaling have been then used to investigate the role and molecular mechanisms of dynamic HD during pancreatic carcinogenesis. We surprisingly report the presence of mature type-1 HDs comprising the integrin α6ß4 and bullous pemphigoid antigen BP180 in the human pancreatic ductal epithelium. Importantly, HDs are shown to disassemble during pancreatic carcinogenesis. HD breakdown requires phosphoinositide 3-kinase (PI3K)-dependent induction of the matrix-metalloprotease MMP-9, which cleaves BP180. Consequently, integrin α6ß4 delocalizes to the cell-leading edges where it paradoxically promotes cell migration and invasion through S100A4 activation. As S100A4 in turn stimulates MMP-9 expression, a vicious cycle maintains BP180 cleavage. Inactivation of this PI3K-MMP-9-S100A4 signaling loop conversely blocks BP180 cleavage, induces HD reassembly and inhibits cell invasion. We conclude that mature type-1 HDs are critical anchoring structures for the pancreatic ductal epithelium whose disruption, upon PI3K activation during carcinogenesis, provokes pancreatic cancer cell migration and invasion.

Review article: historic changes of Helicobacter pylori-associated diseases.

BACKGROUND: The long-term time trends of multiple gastrointestinal diseases are characterised by a striking rise and fall. These temporal changes provide important clues about disease aetiology. AIM: To highlight the importance of Helicobacter pylori infection in shaping the temporal trends of many common gastrointestinal diseases. METHODS: Literature review of the time trends associated with common digestive diseases. RESULTS: The general trends of gastric ulcer, duodenal ulcer, gastric cancer, colon cancer, rectum cancer have all been shaped by a similar underlying birth-cohort phenomenon. Mortality associated with these diagnoses increased in all generations born during the nineteenth century. It peaked among generations born shortly before the turn of the century and then decreased in all subsequent generations born throughout the twentieth century. These patterns can be observed in the incidence, hospitalisation and mortality data from many different countries. They reflect similar rising and falling trends of H. pylori infection in the general population. Diseases that are inversely associated with H. pylori, such as reflux disease, erosive oesophagitis, Barrett's oesophagus, and oesophageal adenocarcinoma, have seen a striking rise during the recent decline of H. pylori infection. CONCLUSION: The temporal variations of H. pylori infection have affected the occurrence of gastroenterology's most common disorders.

Effect of fungal treatments of fibrous agricultural by-products on chemical composition and in vitro rumen fermentation and methane production.

Maize stover, rice straw, oil palm fronds and sugarcane bagasse were treated with the white-rot fungi Ceriporiopsis subvermispora, Lentinula edodes, Pleurotus eryngii, or Pleurotus ostreatus at 24 °C for 0-6 weeks. The fungi increased total gas production from oil palm fronds by 68-132%, but none of the fungi improved the in vitro rumen fermentability of maize stover. C. subvermispora and L. edodes increased total gas production of sugarcane bagasse by 65-71%, but P. eryngii and P. ostreatus decreased it by 22-50%. There was a linear relationship (P<0.05) between the proportion of lignin in the original substrate and the increase in in vitro gas production observed for C. subvermispora and L. edodes treatments (R2=0.92 and 0.96, respectively). It is concluded that C. subvermispora and L. edodes have a particularly high potential to improve the nutritive value of highly lignified ruminant feeds.