Background & Aims Patients with chronic hepatitis C virus (HCV) infections are treated with pegylated interferon and ribavirin (PEG-IFN/RBV), which is effective in less than 50% of those infected ...with HCV genotype 1. Genome-wide association studies have linked response to PEG-IFN/RBV with common single nucleotide polymorphisms in the vicinity of interferon (IFN)-λ genes on chromosome 19. We investigated the association between the polymorphism rs12979860 and treatment response in a diverse cohort of chronic HCV patients. Methods A cross-sectional study of 1021 consecutive patients enrolled in the Duke Hepatology Clinic Research Database and Biorepository. We analyzed DNA, clinical and demographic data, along with validated data of the response of 231 subjects to PEG-IFN/RBV. The study included Caucasians (n = 178), African Americans (n = 53), and HCV genotypes 1 (n = 186) and 2/3 (n = 45). The rs12979860 genotype was tested for an association with sustained virologic response, defined as undetectable levels of HCV RNA 24 weeks after treatment ended. Results The rs12979860 CC genotype (found in ∼40% of Caucasians) predicted a sustained virologic response to therapy among Caucasians (odds ratio, 5.79; 95% confidence interval, 2.67–12.57; P = 9.0 × 10−6 ), independent of HCV genotype and other covariates. Rs12979860 CC predicted a sustained response with 78% specificity and 65% sensitivity in patients infected with HCV genotype 1). Conclusions rs12979860 genotype is a significant independent predictor of response to PEG-IFN/RBV in patients with chronic HCV infection; tests for this genotype might be used to determine the best course of treatment for patients considering antiviral therapy.
Summary
Background Fructose malabsorption, lactose malabsorption and an early rise in breath hydrogen after lactulose (ERBHAL) may play roles in induction of symptoms in gastrointestinal conditions.
...Aim To compare prevalence and interactions of fructose malabsorption, lactose malabsorption and ERBHAL among healthy subjects and those with chronic intestinal disorders using consistent breath hydrogen testing methodologies.
Methods Consecutive series of Caucasian patients with Crohn’s disease (n = 91), ulcerative colitis (56), functional gastrointestinal disorders (FGID) (201), coeliac disease (136) and 71 healthy volunteers underwent breath hydrogen testing using lactulose, fructose and lactose.
Results Early rise in breath hydrogen after lactulose occurred more commonly in healthy controls (39%) than in Crohn’s disease (20%) and untreated coeliac disease (14%; P < 0.008), but not FGID (27%), ulcerative colitis (26%) or treated coeliac disease (29%). Fructose malabsorption was more frequent in Crohn’s disease (61%) than other groups (33–44%, P < 0.05). Lactose malabsorption was most common in Crohn’s disease (42%) and ulcerative colitis (40%) and uncommon (10%) in 79 patients with newly diagnosed coeliac disease. In Crohn’s disease, concurrent Fructose malabsorption and lactose malabsorption was most common (29%), and the association of fructose malabsorption with ERBHAL seen overall (62%) was not observed (36%, P < 0.0001).
Conclusions Carbohydrate malabsorption and ERBHAL are normal physiological phenomena. The abnormal patterns observed in Crohn’s disease may have pathogenic importance.
Summary
Background
Current evidence suggests that many patients with self‐reported non‐coeliac gluten sensitivity (NCGS) retain gastrointestinal symptoms on a gluten‐free diet (GFD) but continue to ...restrict gluten as they report ‘feeling better’.
Aim
To investigate the notion that a major effect of gluten in those with NCGS is on mental state and not necessarily on gastrointestinal symptoms.
Methods
Twenty‐two subjects (24–62 years, five male) with irritable bowel syndrome who had coeliac disease excluded but were symptomatically controlled on a GFD, undertook a double‐blind cross‐over study. Participants randomly received one of three dietary challenges for 3 days, followed by a minimum 3‐day washout before crossing over to the next diet. Challenge gluten‐free food was supplemented with gluten (16 g/day), whey (16 g/day) or not supplemented (placebo). End‐points included mental state as assessed by the Spielberger State Trait Personality Inventory (STPI), cortisol secretion and gastrointestinal symptoms.
Results
Gluten ingestion was associated with higher overall STPI state depression scores compared to placebo M = 2.03, 95% CI (0.55–3.51), P = 0.010 but not whey M = 1.48, 95% CI (−0.14 to 3.10), P = 0.07. No differences were found for other STPI state indices or for any STPI trait measures. No difference in cortisol secretion was identified between challenges. Gastrointestinal symptoms were induced similarly across all dietary challenges.
Conclusions
Short‐term exposure to gluten specifically induced current feelings of depression with no effect on other indices or on emotional disposition. Gluten‐specific induction of gastrointestinal symptoms was not identified. Such findings might explain why patients with non‐coeliac gluten sensitivity feel better on a gluten‐free diet despite the continuation of gastrointestinal symptoms.
The nature of interaction of the amino acid cysteine (HS–CH2CH(NH2)COOH), as a model multifunctional group amino acid, was studied theoretically on a rutile TiO2 (110) surface using the DFT method. A ...large number of adsorption modes were investigated through the three functional groups: the carboxyl (COOH), thiol (SH) and amino (NH2) groups. Two main stable forms of adsorption via the carboxyl group were found: bridging (O, O) (with adsorption energies, Ea between 1.1 and 1.5eV) and (O, N) (Ea=1.4eV). The bridging (O, O) adsorption mode had zwitterionic forms (with the H atom of the SH transferred to the NH2 group making S− and NH3+) which were nearly isoenergetic with the dissociated form (Ea=1.35eV). The mono-dentate carboxyl adsorption mode had no stable zwitterionic forms. The thiol and amino groups of cysteine affect bonding by creating hydrogen bonds to the surface. These cause small changes of the adsorption energy (up to 0.4eV); they also modify the ordering of the last six (lone pair) orbitals of cysteine which in turn affect its nature as a hole acceptor.
•DFT computation of Cysteine on TiO2 (110) is studied.•Adsorption through the carboxyl, thiol and amino groups was tested.•The carboxyl group adsorption mode was found to be the most stable.•Two main stable modes of carboxyl group adsorption were found; (O, O) and (O, N).•Some configurations of adsorbed cysteine may act as hole trapping centres.
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Summary
Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up ...to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine.
The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short‐chain poorly absorbed carbohydrates such as sorbitol.
The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking.
It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.
Studies of the modes of adsorption and the associated changes in electronic structures of renewable organic compounds are needed in order to understand the fundamentals behind surface reactions of ...catalysts for future energies. Using planewave density functional theory (DFT) calculations, the adsorption of ethanol on perfect and O-defected TiO(2) rutile (110) surfaces was examined. On both surfaces the dissociative adsorption mode on five-fold coordinated Ti cations (Ti(4+)(5c)) was found to be more favourable than the molecular adsorption mode. On the stoichiometric surface E(ads) was found to be equal to 0.85 eV for the ethoxide mode and equal to 0.76 eV for the molecular mode. These energies slightly increased when adsorption occurred on the Ti(4+)(5c) closest to the O-defected site. However, both considerably increased when adsorption occurred at the removed bridging surface O; interacting with Ti(3+) cations. In this case the dissociative adsorption becomes strongly favoured (E(ads) = 1.28 eV for molecular adsorption and 2.27 eV for dissociative adsorption). Geometry and electronic structures of adsorbed ethanol were analysed in detail on the stoichiometric surface. Ethanol does not undergo major changes in its structure upon adsorption with its C-O bond rotating nearly freely on the surface. Bonding to surface Ti atoms is a σ type transfer from the O2p of the ethanol-ethoxide species. Both ethanol and ethoxide present potential hole traps on O lone pairs. Charge density and work function analyses also suggest charge transfer from the adsorbate to the surface, in which the dissociative adsorptions show a larger charge transfer than the molecular adsorption mode.
Summary
Background
A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is effective in treating irritable bowel syndrome (IBS).
Aim
To compare the effects of ...gut‐directed hypnotherapy to the low FODMAP diet on gastrointestinal symptoms and psychological indices, and assess additive effects.
Methods
Irritable bowel syndrome patients were randomised (computer‐generated list), to receive hypnotherapy, diet or a combination. Primary end‐point: change in overall gastrointestinal symptoms across the three groups from baseline to week 6. Secondary end‐points: changes in psychological indices, and the durability of effects over 6 months.
Results
Of 74 participants, 25 received hypnotherapy, 24 diet and 25 combination. There were no demographic differences at baseline across groups. Improvements in overall symptoms were observed from baseline to week 6 for hypnotherapy mean difference (95% CI): −33 (−41 to −25), diet −30 (−42 to −19) and combination −36 (−45 to −27) with no difference across groups (P = 0.67). This represented ≥20 mm improvement on visual analogue scale in 72%, 71% and 72%, respectively. This improvement relative to baseline symptoms was maintained 6 months post‐treatment in 74%, 82% and 54%. Individual gastrointestinal symptoms similarly improved. Hypnotherapy resulted in superior improvements on psychological indices with mean change from baseline to 6 months in State Trait Personality Inventory trait anxiety of −4(95% CI −6 to −2) P < 0.0001; −1(−3 to 0.3) P = ns; and 0.3(−2 to 2) P = ns, and in trait depression of −3(−5 to −0.7) P = 0.011; −0.8(−2 to 0.2) P = ns; and 0.6(−2 to 3) P = ns, respectively. Groups improved similarly for QOL (all p ≤ 0.001).
Conclusions
Durable effects of gut‐directed hypnotherapy are similar to those of the low FODMAP diet for relief of gastrointestinal symptoms. Hypnotherapy has superior efficacy to the diet on psychological indices. No additive effects were observed.
The scan-line corrector (SLC) for the Enhanced Thematic Mapper Plus (ETM+) sensor, on board the Landsat 7 satellite, failed permanently in 2003. The consequence of the SLC failure (or
SLC-off) is ...that about 20% of the pixels in an ETM+ image are not scanned. We aim to develop a geostatistical method that estimates the missing values. Our rationale is to collect three cloud-free images for a particular Landsat scene, taken within a few weeks of each other: the middle image is the target whose un-scanned locations we wish to estimate; the earlier and later images are used as secondary information. We visit each un-scanned location in the target image and, for each reflectance band in turn, predict the missing value with cokriging (resorting to kriging when there is not enough local secondary information to justify cokriging). For three Landsat scenes in different bio-regions of Queensland, Australia, we compared the performance of geostatistical interpolation with image compositing. Geostatistics was a generally superior estimator. In contrast to compositing, geostatistics was able to estimate accurately values at all un-scanned locations, and was able to quantify the variance associated with each prediction. SLC-off images interpolated with geostatistics were visually sensible, although changes in land-use from pixel to pixel affected adversely the accuracy of prediction. The primary disadvantage of geostatistics was its relatively slow computing speed. We recommend the geostatistical method over compositing, but, if speed takes priority over statistical rigour, a hybrid technique–whereby composites are corrected to the local means and variances of the bands in the target image, and any un-estimable locations are interpolated geostatistically–is an adequate compromise.
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