Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

PubMed

Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

2016-07-15

The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation.

A fluorimetric readout reporting the kinetics of nucleotide-induced human ribonucleotide reductase oligomerization.

PubMed

Fu, Yuan; Lin, Hongyu; Wisitpitthaya, Somsinee; Blessing, William A; Aye, Yimon

2014-11-24

Human ribonucleotide reductase (hRNR) is a target of nucleotide chemotherapeutics in clinical use. The nucleotide-induced oligomeric regulation of hRNR subunit α is increasingly being recognized as an innate and drug-relevant mechanism for enzyme activity modulation. In the presence of negative feedback inhibitor dATP and leukemia drug clofarabine nucleotides, hRNR-α assembles into catalytically inert hexameric complexes, whereas nucleotide effectors that govern substrate specificity typically trigger α-dimerization. Currently, both knowledge of and tools to interrogate the oligomeric assembly pathway of RNR in any species in real time are lacking. We therefore developed a fluorimetric assay that reliably reports on oligomeric state changes of α with high sensitivity. The oligomerization-directed fluorescence quenching of hRNR-α, covalently labeled with two fluorophores, allows for direct readout of hRNR dimeric and hexameric states. We applied the newly developed platform to reveal the timescales of α self-assembly, driven by the feedback regulator dATP. This information is currently unavailable, despite the pharmaceutical relevance of hRNR oligomeric regulation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase.

PubMed

Iman, Maryam; Khansefid, Zeynab; Davood, Asghar

2016-01-01

Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.

Ribonucleotide reductase class III, an essential enzyme for the anaerobic growth of Staphylococcus aureus, is a virulence determinant in septic arthritis.

PubMed

Kirdis, Ebru; Jonsson, Ing-Marie; Kubica, Malgorzata; Potempa, Jan; Josefsson, Elisabet; Masalha, Mahmud; Foster, Simon J; Tarkowski, Andrzej

2007-01-01

Staphylococcus aureus is the most common cause of joint infections. It also contributes to several other diseases such as pneumonia, osteomyelitis, endocarditis, and sepsis. Bearing in mind that S. aureus becomes rapidly resistant to new antibiotics, many studies survey the virulence factors, with the aim to find alternative prophylaxis/treatment regimens. One potential virulence factor is the bacterial ability to survive at different oxygen tensions. S. aureus expresses ribonucleotide reductases (RNRs), which help it to grow under both aerobic and anaerobic conditions, by reducing ribonucleotides to deoxyribonucleotides. In this study, we investigated the role of RNR class III, which is required for anaerobic growth, as a virulence determinant in the pathogenesis of staphylococcal arthritis. The wild-type S. aureus strain and its isogenic mutant nrdDG mutant were inoculated intravenously into mice. Mice inoculated with the wild-type strain displayed significantly more severe arthritis, with significantly more synovitis and destruction of the bone and cartilage versus mutant strain inoculated mice. Further, the persistence of bacteria in the kidneys was significantly more pronounced in the group inoculated with the wild-type strain. Together these results indicate that RNR class III is an important virulence factor for the establishment of septic arthritis.

Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

PubMed

Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

2015-01-20

The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

The Active Form of the Saccharomyces cerevisiae Ribonucleotide Reductase Small Subunit Is a Heterodimer in Vitro and in Vivo†

PubMed Central

Perlstein, Deborah L.; Ge, Jie; Ortigosa, Allison D.; Robblee, John H.; Zhang, Zhen; Huang, Mingxia; Stubbe, JoAnne

2015-01-01

The class I ribonucleotide reductases (RNRs) are composed of two homodimeric subunits: R1 and R2. R2 houses a diferric-tyrosyl radical (Y•) cofactor. Saccharomyces cerevisiae has two R2s: Y2 (β2) and Y4 (β′2). Y4 is an unusual R2 because three residues required for iron binding have been mutated. While the heterodimer (ββ′) is thought to be the active form, several rnr4Δ strains are viable. To resolve this paradox, N-terminally epitope-tagged β and β′ were expressed in E. coli or integrated into the yeast genome. In vitro exchange studies reveal that when apo-(His6)-β2 (Hisβ2) is mixed with β′2, apo-Hisββ′ forms quantitatively within 2 min. In contrast, holo-ββ′ fails to exchange with apo-Hisβ2 to form holo-Hisββ and β′2. Isolation of genomically encoded tagged β or β′ from yeast extracts gave a 1:1 complex of β and β′, suggesting that ββ′ is the active form. The catalytic activity, protein concentrations, and Y• content of the rnr4Δ and wild type (wt) strains were compared to clarify the role of β′ in vivo. The Y• content of rnr4Δ is 15-fold less than that of wt, consistent with the observed low activity of rnr4Δ extracts (<0.01 nmol min−1 mg−1) versus wt (0.06 ± 0.01 nmol min−1 mg−1). FLAGβ2 isolated from the rnr4Δ strain has a specific activity of 2 nmol min−1 mg−1, similar to that of reconstituted apo-Hisβ2 (10 nmol min−1 mg−1), but significantly less than holo-Hisββ′ (~2000 nmol min−1 mg−1). These studies together demonstrate that β′ plays a crucial role in cluster assembly in vitro and in vivo and that the active form of the yeast R2 is ββ′. PMID:16285741

Differentiation of functional constipation and constipation predominant irritable bowel syndrome based on Rome III criteria: a population-based study.

PubMed

Koloski, N A; Jones, M; Young, M; Talley, N J

2015-05-01

While the Rome III classification recognises functional constipation (FC) and constipation predominant IBS (IBS-C) as distinct disorders, recent evidence has suggested that these disorders are difficult to separate in clinical practice. To identify whether clinical and lifestyle factors differentiate Rome III-defined IBS-C from FC based on gastrointestinal symptoms and lifestyle characteristics. 3260 people randomly selected from the Australian population returned a postal survey. FC and IBS-C were defined according to Rome III. The first model used logistic regression to differentiate IBS-C from FC based on lifestyle, quality-of-life and psychological characteristics. The second approach was data-driven employing latent class analysis (LCA) to identify naturally occurring clusters in the data considering all symptoms involved in the Rome III criteria for IBS-C and FC. We found n = 206 (6.5%; 95% CI 5.7-7.4%) people met strict Rome III FC whereas n = 109 (3.5%; 95% CI 2.8-4.1%) met strict Rome III IBS-C. The case-control approach indicated that FC patients reported an older age at onset of constipation, were less likely to exercise, had higher mental QoL and less health care seeking than IBS-C. LCA yielded one latent class that was predominantly (75%) FC, while the other class was approximately half IBS-C and half FC. The FC-dominated latent class had clearly lower levels of symptoms used to classify IBS (pain-related symptoms) and was more likely to be male (P = 0.046) but was otherwise similar in distribution of lifestyle factors to the mixed class. The latent class analysis approach suggests a differentiation based more on symptom severity rather than the Rome III view. © 2015 John Wiley & Sons Ltd.

NrdH Redoxin Enhances Resistance to Multiple Oxidative Stresses by Acting as a Peroxidase Cofactor in Corynebacterium glutamicum

PubMed Central

Si, Mei-Ru; Zhang, Lei; Yang, Zhi-Fang; Xu, Yi-Xiang; Liu, Ying-Bao; Jiang, Cheng-Ying; Wang, Yao; Liu, Shuang-Jiang

2014-01-01

NrdH redoxins are small protein disulfide oxidoreductases behaving like thioredoxins but sharing a high amino acid sequence similarity to glutaredoxins. Although NrdH redoxins are supposed to be another candidate in the antioxidant system, their physiological roles in oxidative stress remain unclear. In this study, we confirmed that the Corynebacterium glutamicum NrdH redoxin catalytically reduces the disulfides in the class Ib ribonucleotide reductases (RNR), insulin and 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB), by exclusively receiving electrons from thioredoxin reductase. Overexpression of NrdH increased the resistance of C. glutamicum to multiple oxidative stresses by reducing ROS accumulation. Accordingly, elevated expression of the nrdH gene was observed when the C. glutamicum wild-type strain was exposed to oxidative stress conditions. It was discovered that the NrdH-mediated resistance to oxidative stresses was largely dependent on the presence of the thiol peroxidase Prx, as the increased resistance to oxidative stresses mediated by overexpression of NrdH was largely abrogated in the prx mutant. Furthermore, we showed that NrdH facilitated the hydroperoxide reduction activity of Prx by directly targeting and serving as its electron donor. Thus, we present evidence that the NrdH redoxin can protect against the damaging effects of reactive oxygen species (ROS) induced by various exogenous oxidative stresses by acting as a peroxidase cofactor. PMID:24375145

HLA class Ib in pregnancy and pregnancy-related disorders.

PubMed

Persson, Gry; Melsted, Wenna Nascimento; Nilsson, Line Lynge; Hviid, Thomas Vauvert F

2017-08-01

The HLA class Ib genes, HLA-E, HLA-F, and HLA-G, were discovered long after the classical HLA class Ia genes. The elucidation of their functions had a modest beginning. However, their basic functions and involvement in pathophysiology and a range of diseases are now emerging. Although results from a range of studies support the functional roles for the HLA class Ib molecules in adult life, especially HLA-G and HLA-F have most intensively been, and were also primarily, studied in relation to reproduction and pregnancy. The expression of HLA class Ib proteins at the feto-maternal interface in the placenta seems to be important for the maternal acceptance of the semi-allogenic fetus. In contrast to the functions of HLA class Ia, HLA-G possesses immune-modulatory and tolerogenic functions. Here, we review an accumulating amount of data describing the functions of HLA class Ib molecules in relation to fertility, reproduction, and pregnancy, and a possible role for these molecules in certain pregnancy complications, such as implantation failure, recurrent spontaneous abortions, and pre-eclampsia. The results from different kinds of studies point toward a role for HLA class Ib, especially HLA-G, throughout the reproductive cycle from conception to the birth weight of the child.

The International Baccalaureate and a Framework for Class Consciousness: The Potential Outcomes of a "Class-for-Itself"

ERIC Educational Resources Information Center

Bunnell, Tristan

2010-01-01

The International Baccalaureate (IB) examination system in early 2010 was on offer in 2700 schools in 139 countries. Since 1999, the Geneva-registered IB has created a platform for image consolidation, product standardization, and technological linkage. Out of this has emerged a globally branded "IB World", educating the "IB Learner", using an…

Rats' Anticipation of Current and Future Trial Outcomes in the Ordered RNR/RNN Serial Pattern Task

ERIC Educational Resources Information Center

Cohen, Jerome; Mohamoud, Sirad; Szelest, Izabela; Kani, Tammy

2008-01-01

In the ordered RNR/RNN serial pattern task, rats often reduce their running speeds on trial 2 less within the RNR than within the RNN series. Initially, investigators (Capaldi, 1985; Capaldi et al., 1983) considered this trial 2 differential speed effect evidence for rats' anticipation of inter-trial outcomes within each series. Later findings,…

Implementation of the Risk-Need-Responsivity Framework across the Juvenile Justice Agencies in Singapore.

PubMed

Chua, Jonathan Raphacis; Chu, Chi Meng; Yim, Grace; Chong, Dominic; Teoh, Jennifer

2014-11-02

The Risk-Need-Responsivity (RNR) framework is regarded as the forefront of offender rehabilitation in guiding youth offender risk assessment and interventions. This article discusses the juvenile justice system in Singapore and the local research that has been conducted in relation to the RNR framework and the associated Youth Level of Service (YLS) measures. It describes a journey that saw the implementation of the RNR framework across the juvenile justice agencies and highlights the challenges that were faced during the implementation process on the ground. Finally, the article concludes by providing future directions for the implementation of the RNR framework in Singapore.

Implementation of the Risk–Need–Responsivity Framework across the Juvenile Justice Agencies in Singapore

PubMed Central

Chua, Jonathan Raphacis; Chu, Chi Meng; Yim, Grace; Chong, Dominic; Teoh, Jennifer

2014-01-01

The Risk–Need–Responsivity (RNR) framework is regarded as the forefront of offender rehabilitation in guiding youth offender risk assessment and interventions. This article discusses the juvenile justice system in Singapore and the local research that has been conducted in relation to the RNR framework and the associated Youth Level of Service (YLS) measures. It describes a journey that saw the implementation of the RNR framework across the juvenile justice agencies and highlights the challenges that were faced during the implementation process on the ground. Finally, the article concludes by providing future directions for the implementation of the RNR framework in Singapore. PMID:25866464

TMS combined with EEG in genetic generalized epilepsy: A phase II diagnostic accuracy study.

PubMed

Kimiskidis, Vasilios K; Tsimpiris, Alkiviadis; Ryvlin, Philippe; Kalviainen, Reetta; Koutroumanidis, Michalis; Valentin, Antonio; Laskaris, Nikolaos; Kugiumtzis, Dimitris

2017-02-01

(A) To develop a TMS-EEG stimulation and data analysis protocol in genetic generalized epilepsy (GGE). (B) To investigate the diagnostic accuracy of TMS-EEG in GGE. Pilot experiments resulted in the development and optimization of a paired-pulse TMS-EEG protocol at rest, during hyperventilation (HV), and post-HV combined with multi-level data analysis. This protocol was applied in 11 controls (C) and 25 GGE patients (P), further dichotomized into responders to antiepileptic drugs (R, n=13) and non-responders (n-R, n=12).Features (n=57) extracted from TMS-EEG responses after multi-level analysis were given to a feature selection scheme and a Bayesian classifier, and the accuracy of assigning participants into the classes P-C and R-nR was computed. On the basis of the optimal feature subset, the cross-validated accuracy of TMS-EEG for the classification P-C was 0.86 at rest, 0.81 during HV and 0.92 at post-HV, whereas for R-nR the corresponding figures are 0.80, 0.78 and 0.65, respectively. Applying a fusion approach on all conditions resulted in an accuracy of 0.84 for the classification P-C and 0.76 for the classification R-nR. TMS-EEG can be used for diagnostic purposes and for assessing the response to antiepileptic drugs. TMS-EEG holds significant diagnostic potential in GGE. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Effect of type and content of tackifier on adhesion of natural rubber and reclaimed natural rubber based sealant

NASA Astrophysics Data System (ADS)

Raethong, P.; Boonkerd, K.

2017-07-01

Adhesion property of natural rubber (NR) and reclaimed natural rubber (RNR) based sealant with concrete was studied here. The effect of tackifier type and loading on the tensile properties of the rubber based sealant sandwished between two flat cements was evaluated. There are three different tackifiers including Coumarone-indene resin (CI), petro resin (PE) and gum rosin (GR). The result initially showed that at the 20 phr of tackifier both NR and RNR sealant mixed with CI consumed the highest force to separate the rubber based sealant from the concrete. This might be due to the highest compatiblility between CI and rubber. Regardless of the tackifier type, all NR based sealants showed the cohesive failure while all RNR based sealants only showed the adhesive failure. Moreover, the NR based sealant seemed to be stronger than the RNR based one. When considering the effect of CI loading on the adhesion, it was shown that for both NR and RNR based sealents, the highest stress was observed when the rubber based sealant loaded with the 20 phr of CI.

Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus

USGS Publications Warehouse

Landis, E.D.; Purcell, M.K.; Thorgaard, G.H.; Wheeler, P.A.; Hansen, J.D.

2008-01-01

Major histocompatibility complex (MHC) molecules are important mediators of cell-mediated immunity in vertebrates. MHC class IA molecules are important for host anti-viral immunity as they present intracellular antigens and regulate natural killer cell (NK) activity. MHC class Ib molecules on the other hand are less understood and have demonstrated diverse immune and non-immune functions in mammals. Rainbow trout possess a single classical MHC IA locus (Onmy-UBA) that is believed to function similar to that of mammalian MHC class Ia. Numerous MHC class Ib genes with undetermined functions have also been described in trout. Here we utilize quantitative reverse transcriptase PCR (qRT-PCR) techniques to survey the levels of basal and inducible transcription for selected trout MHC class Ib genes, sIgM and sentinels of IFN induction in response to viral infection. Basal transcription of all the class Ib genes examined in this study was lower than Onmy-UBA in nai??ve fish. UBA, along with all of the non-classical genes were induced in fish infected with virus but not in control fish. Our results support a non-classical designation for the majority of the class IB genes surveyed in this study based upon expression levels while also indicating that they may play an important role in anti-viral immunity in trout.

Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus

USGS Publications Warehouse

Landis, Eric D.; Purcell, Maureen K.; Thorgaard, Gary H.; Wheeler , Paul A.; Hansen, John D.

2008-01-01

Major histocompatibility complex (MHC) molecules are important mediators of cell-mediated immunity in vertebrates. MHC class IA molecules are important for host anti-viral immunity as they present intracellular antigens and regulate natural killer cell (NK) activity. MHC class Ib molecules on the other hand are less understood and have demonstrated diverse immune and non-immune functions in mammals. Rainbow trout possess a single classical MHC IA locus (Onmy-UBA) that is believed to function similar to that of mammalian MHC class Ia. Numerous MHC class Ib genes with undetermined functions have also been described in trout. Here we utilize quantitative reverse transcriptase PCR (qRT-PCR) techniques to survey the levels of basal and inducible transcription for selected trout MHC class Ib genes, sIgM and sentinels of IFN induction in response to viral infection. Basal transcription of all the class Ib genes examined in this study was lower than Onmy-UBA in naïve fish. UBA, along with all of the non-classical genes were induced in fish infected with virus but not in control fish. Our results support a non-classical designation for the majority of the class IB genes surveyed in this study based upon expression levels while also indicating that they may play an important role in anti-viral immunity in trout.

COP9 signalosome subunit 7 from Arabidopsis interacts with and regulates the small subunit of ribonucleotide reductase (RNR2).

PubMed

Halimi, Yair; Dessau, Moshe; Pollak, Shaul; Ast, Tslil; Erez, Tamir; Livnat-Levanon, Nurit; Karniol, Baruch; Hirsch, Joel A; Chamovitz, Daniel A

2011-09-01

The COP9 Signalosome protein complex (CSN) is a pleiotropic regulator of plant development and contains eight-subunits. Six of these subunits contain the PCI motif which mediates specific protein interactions necessary for the integrity of the complex. COP9 complex subunit 7 (CSN7) contains an N-terminal PCI motif followed by a C-terminal extension which is also necessary for CSN function. A yeast-interaction trap assay identified the small subunit of ribonucelotide reductase (RNR2) from Arabidopsis as interacting with the C-terminal section of CSN7. This interaction was confirmed in planta by both bimolecular fluorescence complementation and immuoprecipitation assays with endogenous proteins. The subcellular localization of RNR2 was primarily nuclear in meristematic regions, and cytoplasmic in adult cells. RNR2 was constitutively nuclear in csn7 mutant seedlings, and was also primarily nuclear in wild type seedlings following exposure to UV-C. These two results correlate with constitutive expression of several DNA-damage response genes in csn7 mutants, and to increased tolerance of csn7 seedlings to UV-C treatment. We propose that the CSN is a negative regulator of RNR activity in Arabidopsis.

Post-surgical functional recovery, lumbar lordosis, and range of motion associated with MR-detectable redundant nerve roots in lumbar spinal stenosis.

PubMed

Chen, Jinshui; Wang, Juying; Wang, Benhai; Xu, Hao; Lin, Songqing; Zhang, Huihao

2016-01-01

T1- and T2-weighted magnetic resonance images (MRI) can reveal lumbar redundant nerve roots (RNRs), a result of chronic compression and nerve elongation associated with pathogenesis of cauda equina claudication (CEC) in degenerative lumbar canal stenosis (DLCS). The study investigated effects of lumbar lordosis angle and range of motion on functional recovery in lumbar stenosis patents with and without RNRs. A retrospective study was conducted of 93 lumbar spinal stenosis patients who underwent decompressive surgery. Eligible records were assessed by 3 independent blinded radiologists for presence or absence of RNRs on sagittal T2-weighted MR (RNR and non-RNR groups), pre- and post-operative JOA score, lumbar lordosis angle, and range of motion. Of 93 total patients, the RNR group (n=37, 21/37 female) and non-RNR group (n=56; 31/56 female) had similar preoperative conditions (JOA score) and were not significantly different in age (mean 64.19 ± 8.25 vs. 62.8 ± 9.41 years), symptom duration (30.92 ± 22.43 vs. 28.64 ± 17.40 months), or follow-up periods (17.35 ± 4.02 vs. 17.75 ± 4.29 mo) (all p>0.4). The non-RNR group exhibited significantly better final JOA score (p=0.015) and recovery rate (p=0.002). RNR group patients exhibited larger lumbar lordosis angles in the neutral position (p=0.009) and extension (p=0.021) and larger range of motion (p=0.008). Poorer surgical outcomes in patients with RNRs indicated that elevated lumbar lordosis angle and range of motion increased risks of RNR formation, which in turn may cause poorer post-surgical recovery, this information is possibly useful in prognostic assessment of lumbar stenosis complicated by RNRs. Copyright © 2015 Elsevier B.V. All rights reserved.

Regulation of Bacteriophage T5 Development by ColI Factors

PubMed Central

Moyer, R. W.; Fu, A. S.; Szabo, C.

1972-01-01

The I-type colicinogenic factor ColIb transforms Escherichia coli from a permissive to a nonpermissive host for bacteriophage T5 reproduction by preventing complete expression of the phage genome. T5-infected ColIb+ cells synthesize only class I (early) phage protein and ribonucleic acid (RNA). Neither phage-specific class II proteins [associated with viral deoxyribonucleic acid (DNA) replication] nor class III proteins (phage structural components) are formed due to the failure of the infected ColIb+ cells to synthesize class II or class III phage-specific messenger RNA. Comparable studies with T5-infected cells colicinogenic for the related ColIa factor revealed no decrease in the yield of progeny phage although the presence of the ColIa factor leads to a significant reduction in the amount of phage-directed class III protein synthesis. Images PMID:4554465

Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase.

PubMed

Boronat, Susanna; Domènech, Alba; Carmona, Mercè; García-Santamarina, Sarela; Bañó, M Carmen; Ayté, José; Hidalgo, Elena

2017-06-01

The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR). RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation. Here, we show that cytosolic thioredoxins Trx1 and Trx3 are the primary electron donors for RNR in fission yeast. Unexpectedly, trx1 transcript and Trx1 protein levels are up-regulated in a G1-to-S phase-dependent manner, indicating that the supply of electron donors is also cell cycle-regulated. Indeed, genetic depletion of thioredoxins triggers a DNA replication checkpoint ruled by Rad3 and Cds1, with the final goal of up-regulating transcription of S phase genes and constitutive RNR synthesis. Regarding the thioredoxin and glutaredoxin cascades, one combination of gene deletions is synthetic lethal in fission yeast: cells lacking both thioredoxin reductase and cytosolic dithiol glutaredoxin. We have isolated a suppressor of this lethal phenotype: a mutation at the Tpx1-coding gene, leading to a frame shift and a loss-of-function of Tpx1, the main client of electron donors. We propose that in a mutant strain compromised in reducing equivalents, the absence of an abundant and competitive substrate such as the peroxiredoxin Tpx1 has been selected as a lethality suppressor to favor RNR function at the expense of the non-essential peroxide scavenging function, to allow DNA synthesis and cell growth.

Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms

PubMed Central

Liu, Cong; Powell, Kelly A.; Mundt, Kirsten; Wu, LeJung; Carr, Antony M.; Caspari, Thomas

2003-01-01

The signalosome is implicated in regulating cullin-dependent ubiquitin ligases. We find that two signalosome subunits, Csn1 and Csn2, are required to regulate ribonucleotide reductase (RNR) through the degradation of a small protein, Spd1, that acts to anchor the small RNR subunit in the nucleus. Spd1 destruction correlates with the nuclear export of the small RNR subunit, which, in turn, correlates with a requirement for RNR in replication and repair. Spd1 degradation is promoted by two separate CSN-dependent mechanisms. During unperturbed S phase, Spd1 degradation is independent of checkpoint proteins. In irradiated G2 cells, Spd1 degradation requires the DNA damage checkpoint. The signalosome copurifies with Pcu4 (cullin 4). Pcu4, Csn1, and Csn2 promote the degradation of Spd1, identifying a new function for the signalosome as a regulator of Pcu4-containing E3 ubiquitin ligase. PMID:12695334

Regulation of Small Mitochondrial DNA Replicative Advantage by Ribonucleotide Reductase in Saccharomyces cerevisiae

PubMed Central

Bradshaw, Elliot; Yoshida, Minoru; Ling, Feng

2017-01-01

Small mitochondrial genomes can behave as selfish elements by displacing wild-type genomes regardless of their detriment to the host organism. In the budding yeast Saccharomyces cerevisiae, small hypersuppressive mtDNA transiently coexist with wild-type in a state of heteroplasmy, wherein the replicative advantage of the small mtDNA outcompetes wild-type and produces offspring without respiratory capacity in >95% of colonies. The cytosolic enzyme ribonucleotide reductase (RNR) catalyzes the rate-limiting step in dNTP synthesis and its inhibition has been correlated with increased petite colony formation, reflecting loss of respiratory function. Here, we used heteroplasmic diploids containing wild-type (rho+) and suppressive (rho−) or hypersuppressive (HS rho−) mitochondrial genomes to explore the effects of RNR activity on mtDNA heteroplasmy in offspring. We found that the proportion of rho+ offspring was significantly increased by RNR overexpression or deletion of its inhibitor, SML1, while reducing RNR activity via SML1 overexpression produced the opposite effects. In addition, using Ex Taq and KOD Dash polymerases, we observed a replicative advantage for small over large template DNA in vitro, but only at low dNTP concentrations. These results suggest that dNTP insufficiency contributes to the replicative advantage of small mtDNA over wild-type and cytosolic dNTP synthesis by RNR is an important regulator of heteroplasmy involving small mtDNA molecules in yeast. PMID:28717049

How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors.

PubMed

Aziz, Imran; Törnblom, Hans; Palsson, Olafur S; Whitehead, William E; Simrén, Magnus

2018-06-08

The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.

An International Model of World-Class Education: The International Baccalaureate

ERIC Educational Resources Information Center

Hill, Ian

2012-01-01

This article posits that world-class education is international education, as defined by UNESCO, and presents International Baccalaureate (IB) programmes as examples of this phenomenon. It begins with the IB's 1960s origins in international schools, which educated the children of globally mobile parents who worked principally in the UN and its…

Comparative study to develop a single method for retrieving wide class of recombinant proteins from classical inclusion bodies.

PubMed

Padhiar, Arshad Ahmed; Chanda, Warren; Joseph, Thomson Patrick; Guo, Xuefang; Liu, Min; Sha, Li; Batool, Samana; Gao, Yifan; Zhang, Wei; Huang, Min; Zhong, Mintao

2018-03-01

The formation of inclusion bodies (IBs) is considered as an Achilles heel of heterologous protein expression in bacterial hosts. Wide array of techniques has been developed to recover biochemically challenging proteins from IBs. However, acquiring the active state even from the same protein family was found to be an independent of single established method. Here, we present a new strategy for the recovery of wide sub-classes of recombinant protein from harsh IBs. We found that numerous methods and their combinations for reducing IB formation and producing soluble proteins were not effective, if the inclusion bodies were harsh in nature. On the other hand, different practices with mild solubilization buffers were able to solubilize IBs completely, yet the recovery of active protein requires large screening of refolding buffers. With the integration of previously reported mild solubilization techniques, we proposed an improved method, which comprised low sarkosyl concentration, ranging from 0.05 to 0.1% coupled with slow freezing (- 1 °C/min) and fast thaw (room temperature), resulting in greater solubility and the integrity of solubilized protein. Dilution method was employed with single buffer to restore activity for every sub-class of recombinant protein. Results showed that the recovered protein's activity was significantly higher compared with traditional solubilization/refolding approach. Solubilization of IBs by the described method was proved milder in nature, which restored native-like conformation of proteins within IBs.

The RNase R from Campylobacter jejuni Has Unique Features and Is Involved in the First Steps of Infection*

PubMed Central

Haddad, Nabila; Matos, Rute G.; Pinto, Teresa; Rannou, Pauline; Cappelier, Jean-Michel; Prévost, Hervé; Arraiano, Cecília M.

2014-01-01

Bacterial pathogens must adapt/respond rapidly to changing environmental conditions. Ribonucleases (RNases) can be crucial factors contributing to the fast adaptation of RNA levels to different environmental demands. It has been demonstrated that the exoribonuclease polynucleotide phosphorylase (PNPase) facilitates survival of Campylobacter jejuni in low temperatures and favors swimming, chick colonization, and cell adhesion/invasion. However, little is known about the mechanism of action of other ribonucleases in this microorganism. Members of the RNB family of enzymes have been shown to be involved in virulence of several pathogens. We have searched C. jejuni genome for homologues and found one candidate that displayed properties more similar to RNase R (Cj-RNR). We show here that Cj-RNR is important for the first steps of infection, the adhesion and invasion of C. jejuni to eukaryotic cells. Moreover, Cj-RNR proved to be active in a wide range of conditions. The results obtained lead us to conclude that Cj-RNR has an important role in the biology of this foodborne pathogen. PMID:25100732

Comprehensive analysis of MHC class I genes from the U-, S-, and Z-lineages in Atlantic salmon.

PubMed

Lukacs, Morten F; Harstad, Håvard; Bakke, Hege G; Beetz-Sargent, Marianne; McKinnel, Linda; Lubieniecki, Krzysztof P; Koop, Ben F; Grimholt, Unni

2010-03-05

We have previously sequenced more than 500 kb of the duplicated MHC class I regions in Atlantic salmon. In the IA region we identified the loci for the MHC class I gene Sasa-UBA in addition to a soluble MHC class I molecule, Sasa-ULA. A pseudolocus for Sasa-UCA was identified in the nonclassical IB region. Both regions contained genes for antigen presentation, as wells as orthologues to other genes residing in the human MHC region. The genomic localisation of two MHC class I lineages (Z and S) has been resolved. 7 BACs were sequenced using a combination of standard Sanger and 454 sequencing. The new sequence data extended the IA region with 150 kb identifying the location of one Z-lineage locus, ZAA. The IB region was extended with 350 kb including three new Z-lineage loci, ZBA, ZCA and ZDA in addition to a UGA locus. An allelic version of the IB region contained a functional UDA locus in addition to the UCA pseudolocus. Additionally a BAC harbouring two MHC class I genes (UHA) was placed on linkage group 14, while a BAC containing the S-lineage locus SAA (previously known as UAA) was placed on LG10. Gene expression studies showed limited expression range for all class I genes with exception of UBA being dominantly expressed in gut, spleen and gills, and ZAA with high expression in blood. Here we describe the genomic organization of MHC class I loci from the U-, Z-, and S-lineages in Atlantic salmon. Nine of the described class I genes are located in the extension of the duplicated IA and IB regions, while three class I genes are found on two separate linkage groups. The gene organization of the two regions indicates that the IB region is evolving at a different pace than the IA region. Expression profiling, polymorphic content, peptide binding properties and phylogenetic relationship show that Atlantic salmon has only one MHC class Ia gene (UBA), in addition to a multitude of nonclassical MHC class I genes from the U-, S- and Z-lineages.

Sustainability of Routine Notification and Request legislation on eye bank tissue supply and corneal transplantation wait times in Canada.

PubMed

Lee, Kenneth; Boimer, Corey; Hershenfeld, Samantha; Sharpen, Linda; Slomovic, Allan R

2011-10-01

To assess whether provinces with Routine Notification and Request (RNR) legislation have sustained increases in corneal tissue supply and decreases in wait times for corneal transplantation surgery. Cross-sectional survey of Canadian corneal transplant (CT) surgeons and eye banks. Canadian CT surgeons and representatives from the 10 Canadian eye banks. Voluntary and anonymous surveys were distributed between July and October 2009. Eligible CT surgeons were defined as ophthalmologists who practice in Canada; currently perform Penetrating keratoplasty (PKP), Deep anterior lamellar keratoplasty (DALK), Deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet membrane endothelial keratoplasty (DMEK); and have obtained tissues from a Canadian eye bank. From 2006 to 2009, for provinces with RNR legislation and where data are available, mean wait times from date of diagnosis to date of CT surgery have increased: in Ontario, from 31 ± 34 weeks to 36 ± 27 weeks; in British Columbia, from 39 ± 20 weeks to 42 ± 35 weeks; in Manitoba, from 32 ± 23 weeks to 49 ± 36 weeks. In addition, the amount of corneal tissue in RNR provinces suitable for transplant, with the exception of British Columbia, has declined between 2006 and 2008: in Ontario, 1186 tissues to 999 tissues (16% decline); in Manitoba, 92 tissues to 83 tissues (10% decline); in New Brunswick, 129 tissues to 98 tissues (24% decline). Although initially effective, RNR legislation has not sustained an increase in corneal tissue availability nor has it shortened wait times in most provinces. Incorporation of community hospitals into the RNR catchment, improved enforcement, and continued education of hospital staff regarding the RNR process may be effective in making this legislation more sustainable in the long term. Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Applicability of the Risk-Need-Responsivity Model to Persons With Mental Illness Involved in the Criminal Justice System.

PubMed

Skeem, Jennifer L; Steadman, Henry J; Manchak, Sarah M

2015-09-01

National efforts to improve responses to persons with mental illness involved with the criminal justice system have traditionally focused on providing mental health services under court supervision. However, a new policy emphasis has emerged that focuses on providing correctional treatment services consistent with the risk-need-responsivity (RNR) model to reduce recidivism. The objective of this review was to evaluate empirical support for following the RNR model (developed with general offenders) with this group and to pose major questions that the field needs to address. A comprehensive search using PubMed and PsycINFO yielded 18 studies that addressed the applicability of the RNR model to the target population. The results of these studies were synthesized. There is strong support for using general risk assessment tools to assess this group's risk of recidivism. Preliminary evidence indicates that cognitive-behavioral programs targeting general risk factors are more effective than psychiatric treatment alone. However, there is as yet no direct support for the applicability of the three core RNR principles to treat this population. Although the new policy emphasis shows substantial promise, the field must avoid rushing to the next "evidence base" too rapidly and with too little data. There must be explicit recognition that RNR principles are being applied to a new population with unique characteristics (mental illness combined with justice system involvement), such that generalizability from general offender samples is uncertain. Moreover, public safety goals for the target population should not eclipse those related to public health. This group's unique features may affect both the process and outcomes of treatment.

OUTLINE OF MATHEMATICS - LEVELS I-A AND I-B FOR TALENT PRESERVATION CLASSES IN GRADE SEVEN.

ERIC Educational Resources Information Center

Houston Public Schools, TX.

LEVEL I-A UNIT AREAS COVER THE MEANING OF "NUMBER," ADDITION, MULTIPLICATION, SUBTRACTION, AND DIVISION. LEVEL I-B COVERS INTRODUCTION TO COMMON FRACTIONS, COMBINING FRACTION, FRACTIONAL PARTS, SEPARATING FRACTIONS, AND APPLICATIONS. EACH UNIT UNDER I-B HAS SUBDIVISIONS, WITH A PARAGRAPH OF TEACHING HINTS AND EXAMPLES. STRESS IS UPON…

The Risk Need Responsivity Model of Offender Rehabilitation: Is There Really a Need for a Paradigm Shift?

ERIC Educational Resources Information Center

Looman, Jan; Abracen, Jeffrey

2013-01-01

The current paper critically reviews the Risk-Need-Responsivity (RNR) and Good Lives Model (GLM) approaches to correctional treatment. Research, or the lack thereof, is discussed in terms of whether there is a need for a new model of offender rehabilitation. We argue that although there is a wealth of research in support of RNR approaches, there…

Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.

PubMed

Mohanty, Partha Sarathi; Bansal, Avi Kumar; Naaz, Farah; Gupta, Umesh Datta; Dwivedi, Vivek Dhar; Yadava, Umesh

2018-06-01

Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification and Characterization of Alternative Promoters, Transcripts and Protein Isoforms of Zebrafish R2 Gene

PubMed Central

Shang, Hanqiao; Li, Qing; Feng, Guohui; Cui, Zongbin

2011-01-01

Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5′ termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress. PMID:21887375

Identification and characterization of alternative promoters, transcripts and protein isoforms of zebrafish R2 gene.

PubMed

Shang, Hanqiao; Li, Qing; Feng, Guohui; Cui, Zongbin

2011-01-01

Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2) functions exclusively in DNA replication of normal cells due to its S phase-specific expression and late mitotic degradation. Herein, we demonstrate the control of R2 expression through alternative promoters, splicing and polyadenylation sites in zebrafish. Three functional R2 promoters were identified to generate six transcript variants with distinct 5' termini. The proximal promoter contains a conserved E2F binding site and two CCAAT boxes, which are crucial for the transcription of R2 gene during cell cycle. Activity of the distal promoter can be induced by DNA damage to generate four transcript variants through alternative splicing. In addition, two novel splice variants were found to encode distinct N-truncated R2 isoforms containing residues for enzymatic activity but no KEN box essential for its proteolysis. These two N-truncated R2 isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit (R1). Thus, our results suggest that multilayered mechanisms control the differential expression and function of zebrafish R2 gene during cell cycle and under genotoxic stress.

Allosteric Inhibition of Human Ribonucleotide Reductase by dATP Entails the Stabilization of a Hexamer

PubMed Central

2015-01-01

Ribonucleotide reductases (RNRs) are responsible for all de novo biosynthesis of DNA precursors in nature by catalyzing the conversion of ribonucleotides to deoxyribonucleotides. Because of its essential role in cell division, human RNR is a target for a number of anticancer drugs in clinical use. Like other class Ia RNRs, human RNR requires both a radical-generation subunit (β) and nucleotide-binding subunit (α) for activity. Because of their complex dependence on allosteric effectors, however, the active and inactive quaternary forms of many class Ia RNRs have remained in question. Here, we present an X-ray crystal structure of the human α subunit in the presence of inhibiting levels of dATP, depicting a ring-shaped hexamer (α6) where the active sites line the inner hole. Surprisingly, our small-angle X-ray scattering (SAXS) results indicate that human α forms a similar hexamer in the presence of ATP, an activating effector. In both cases, α6 is assembled from dimers (α2) without a previously proposed tetramer intermediate (α4). However, we show with SAXS and electron microscopy that at millimolar ATP, the ATP-induced α6 can further interconvert with higher-order filaments. Differences in the dATP- and ATP-induced α6 were further examined by SAXS in the presence of the β subunit and by activity assays as a function of ATP or dATP. Together, these results suggest that dATP-induced α6 is more stable than the ATP-induced α6 and that stabilization of this ring-shaped configuration provides a mechanism to prevent access of the β subunit to the active site of α. PMID:26727048

Color-color diagrams in near infrared: (J-H)/(H-K). I

NASA Astrophysics Data System (ADS)

Gyulbudaghian, Armen L.; Baloian, N.; Sanchez, I. A.

2017-12-01

In the paper are presented the color-color diagrams (J-H)/(H-K) for all stars with visible values B<11, for which in the known catalogs the values of J, H, K, and also spectral classes and luminosity classes of these stars are given. The diagrams are constructed for luminosity classes Ia, Ib, II, III, IV, V. The similarity of diagrams for classes Ia and Ib (super giants) and II (giants), is obvious from these diagrams. The diagrams obtained by us can be used for discovering of new young stars and also for determining of color excesses of investigating stars. Maximal amounts of stars are registered in the classes V and III. There is a tendency of increasing of J-H and H-K along the sequence of spectral classes O - M, which is correct for all luminosity classes.

Classification of ulnar triangular fibrocartilage complex tears. A treatment algorithm for Palmer type IB tears.

PubMed

Atzei, A; Luchetti, R; Garagnani, L

2017-05-01

The classical definition of 'Palmer Type IB' triangular fibrocartilage complex tear, includes a spectrum of clinical conditions. This review highlights the clinical and arthroscopic criteria that enable us to categorize five classes on a treatment-oriented classification system of triangular fibrocartilage complex peripheral tears. Class 1 lesions represent isolated tears of the distal triangular fibrocartilage complex without distal radio-ulnar joint instability and are amenable to arthroscopic suture. Class 2 tears include rupture of both the distal triangular fibrocartilage complex and proximal attachments of the triangular fibrocartilage complex to the fovea. Class 3 tears constitute isolated ruptures of the proximal attachment of the triangular fibrocartilage complex to the fovea; they are not visible at radio-carpal arthroscopy. Both Class 2 and Class 3 tears are diagnosed with a positive hook test and are typically associated with distal radio-ulnar joint instability. If required, treatment is through reattachment of the distal radio-ulnar ligament insertions to the fovea. Class 4 lesions are irreparable tears due to the size of the defect or to poor tissue quality and, if required, treatment is through distal radio-ulnar ligament reconstruction with tendon graft. Class 5 tears are associated with distal radio-ulnar joint arthritis and can only be treated with salvage procedures. This subdivision of type IB triangular fibrocartilage complex tear provides more insights in the pathomechanics and treatment strategies. II.

Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or 'psychomarkers'?

PubMed

Sood, Ruchit; Law, Graham R; Ford, Alexander C

2014-11-01

IBS is estimated to have a prevalence of up to 20% in Western populations and results in substantial costs to health-care services worldwide, estimated to be US$1 billion per year in the USA. IBS remains difficult to diagnose due to its multifactorial aetiology, heterogeneous nature and overlap of symptoms with organic pathologies, such as coeliac disease and IBD. As a result, IBS often continues to be a diagnosis of exclusion, resulting in unnecessary investigations. Available methods for the diagnosis of IBS-including the current gold standard, the Rome III criteria-perform only moderately well. Visceral hypersensitivity and altered pain perception do not discriminate between IBS and other functional gastrointestinal diseases or health with any great accuracy. Attention has now turned to developing novel biomarkers and using psychological markers (so-called psychomarkers) to aid the diagnosis of IBS. This Review describes how useful symptoms, symptom-based criteria, biomarkers and psychomarkers, and indeed combinations of all these approaches, are in the diagnosis of IBS. Future directions in diagnosing IBS could include combining demographic data, gastrointestinal symptoms, biomarkers and psychomarkers using statistical methods. Latent class analysis to distinguish between IBS and non-IBS symptom profiles might also represent a promising avenue for future research.

Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

PubMed Central

Jadallah, Khaled A; Kullab, Susan M; Sanders, David S

2014-01-01

Irritable bowel syndrome (IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS (IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators. PMID:25083062

Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

PubMed Central

Kim, Seung-Jin; Choi, Hojung; Park, Sung-Soo; Chang, Chawnshang; Kim, Eungseok

2011-01-01

Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, is highly expressed in prostate cancer although the SCD protein has been known to be rapidly turned over by proteolytic cleavage. The present data demonstrate that SCD can promote proliferation of androgen receptor (AR)-positive LNCaP prostate cancer cells and enhance dihydrotestosterone (DHT)-induced AR transcriptional activity, resulting in increased expression of prostatespecific antigen (PSA) and kallikrein-related peptidase 2 (KLK2). Interestingly, among the previously reported SCDderived peptides produced by proteolytic cleavage of SCD, a peptide spanning amino acids 130-162 of SCD (SCDCoRNR) contained the CoRNR box motif (LFLII) and enhanced AR transcriptional activity. In contrast, a mutant SCD-CoRNR in which Leu136 was replaced by Ala had no effect on AR transcriptional activity. Moreover, SCDCoRNR directly interacted with AR and inhibited RIP140 suppression of AR transactivation. Knockdown of the SCD gene by SCD microRNA suppressed AR transactivation with decreased cell proliferation, suggesting that SCD may regulate the proliferation of LNCaP cells via modulation of AR transcriptional activity. Moreover, ectopic expression of SCD in LNCaP cells facilitated LNCaP tumor formation and growth in nude mice. Together, the data indicate that SCD plays a key role in the regulation of AR transcriptional activity in prostate cancer cells. PMID:21331774

Vibrio cholerae InV117, a Class 1 Integron Harboring aac(6′)-Ib and blaCTX-M-2, Is Linked to Transposition Genes

PubMed Central

Soler Bistué, Alfonso J. C.; Martín, Fernando A.; Petroni, Alejandro; Faccone, Diego; Galas, Marcelo; Tolmasky, Marcelo E.; Zorreguieta, Angeles

2006-01-01

A ca. 150-kbp Vibrio cholerae O1 biotype El Tor plasmid includes blaCTX-M-2 and a variant of aac(6′)-Ib within InV117, an orf513-bearing class 1 integron. InV117 is linked to a tnp1696 module in which IRl carries an insertion of IS4321R. The complete structure could be a potential mobile element. PMID:16641475

Overaccumulation of the chloroplast antisense RNA AS5 is correlated with decreased abundance of 5S rRNA in vivo and inefficient 5S rRNA maturation in vitro

PubMed Central

Sharwood, Robert E.; Hotto, Amber M.; Bollenbach, Thomas J.; Stern, David B.

2011-01-01

Post-transcriptional regulation in the chloroplast is exerted by nucleus-encoded ribonucleases and RNA-binding proteins. One of these ribonucleases is RNR1, a 3′-to-5′ exoribonuclease of the RNase II family. We have previously shown that Arabidopsis rnr1-null mutants exhibit specific abnormalities in the expression of the rRNA operon, including the accumulation of precursor 23S, 16S, and 4.5S species and a concomitant decrease in the mature species. 5S rRNA transcripts, however, accumulate to a very low level in both precursor and mature forms, suggesting that they are unstable in the rnr1 background. Here we demonstrate that rnr1 plants overaccumulate an antisense RNA, AS5, that is complementary to the 5S rRNA, its intergenic spacer, and the downstream trnR gene, which encodes tRNAArg, raising the possibility that AS5 destabilizes 5S rRNA or its precursor and/or blocks rRNA maturation. To investigate this, we used an in vitro system that supports 5S rRNA and trnR processing. We show that AS5 inhibits 5S rRNA maturation from a 5S-trnR precursor, and shorter versions of AS5 demonstrate that inhibition requires intergenic sequences. To test whether the sense and antisense RNAs form double-stranded regions in vitro, treatment with the single-strand-specific mung bean nuclease was used. These results suggest that 5S–AS5 duplexes interfere with a sense-strand secondary structure near the endonucleolytic cleavage site downstream from the 5S rRNA coding region. We hypothesize that these duplexes are degraded by a dsRNA-specific ribonuclease in vivo, contributing to the 5S rRNA deficiency observed in rnr1. PMID:21148395

Yield of diagnostic tests for celiac disease in individuals with symptoms suggestive of irritable bowel syndrome: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Chey, William D; Talley, Nicholas J; Malhotra, Ashish; Spiegel, Brennan M R; Moayyedi, Paul

2009-04-13

Individuals with irritable bowel syndrome (IBS) report abdominal pain, bloating, and diarrhea, symptoms similar to those in celiac disease. Studies suggest that the prevalence of celiac disease is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for celiac disease in these individuals. We conducted a systematic review and meta-analysis to estimate prevalence of celiac disease in unselected adults who met diagnostic criteria for IBS. MEDLINE (1950 to May 31, 2008) and EMBASE (1980 to May 31, 2008) were searched. Case series and case-control studies that used serologic tests for celiac disease were eligible for inclusion. Prevalence of positive serologic indications of celiac disease and biopsy-proved celiac disease were extracted and pooled for all studies and were compared between cases and controls using an odds ratio and 95% confidence interval. Fourteen studies were identified comprising 4204 individuals, of whom 2278 (54%) met diagnostic criteria for IBS. Pooled prevalence of positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease were 4.0% (95% confidence interval, 1.7-7.2), 1.63% (0.7-3.0), and 4.1% (1.9-7.0), respectively. Pooled odds ratios (95% confidence intervals) for positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS compared with controls without IBS were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6). Prevalence of biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS.

A Functional Approach Reveals a Genetic and Physical Interaction between Ribonucleotide Reductase and CHK1 in Mammalian Cells

PubMed Central

Taricani, Lorena; Shanahan, Frances; Malinao, Maria-Christina; Beaumont, Maribel; Parry, David

2014-01-01

Ribonucleotide reductase (RNR) enzyme is composed of the homodimeric RRM1 and RRM2 subunits, which together form a heterotetramic active enzyme that catalyzes the de novo reduction of ribonucleotides to generate deoxyribonucleotides (dNTPs), which are required for DNA replication and DNA repair processes. In this study, we show that ablation of RRM1 and RRM2 by siRNA induces G1/S phase arrest, phosphorylation of Chk1 on Ser345 and phosphorylation of γ-H2AX on S139. Combinatorial ablation of RRM1 or RRM2 and Chk1 causes a dramatic accumulation of γ-H2AX, a marker of double-strand DNA breaks, suggesting that activation of Chk1 in this context is essential for suppression of DNA damage. Significantly, we demonstrate for the first time that Chk1 and RNR subunits co-immunoprecipitate from native cell extracts. These functional genomic studies suggest that RNR is a critical mediator of replication checkpoint activation. PMID:25375241

Linaclotide: a novel therapy for chronic constipation and constipation-predominant irritable bowel syndrome.

PubMed

Lacy, Brian E; Levenick, John M; Crowell, Michael D

2012-10-01

Chronic constipation and irritable bowel syndrome (IBS) are functional gastrointestinal disorders that significantly affect patients' quality of life. Chronic constipation and IBS are prevalent-1 2% of the US population meet the diagnostic criteria for IBS, and 1 5% meet the criteria for chronic constipation- and these conditions negatively impact the healthcare system from an economic perspective. Despite attempts at dietary modification, exercise, or use of over-the-counter medications, many patients have persistent symptoms. Alternative treatment options are limited. This article describes linaclotide (Linzess, Ironwood Pharmaceuticals/Forest Pharmaceuticals), a new, first-in-class medication for the treatment of chronic constipation and constipation-predominant IBS.

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline.

PubMed

Corsetti, Maura; Whorwell, Peter

2017-04-01

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.

Inhibition of CHK1 sensitizes Ewing sarcoma cells to the ribonucleotide reductase inhibitor gemcitabine

PubMed Central

Goss, Kelli L; Koppenhafer, Stacia L; Harmoney, Kathryn M; Terry, William W; Gordon, David J

2017-01-01

Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR. However, clofarabine is a reversible inhibitor of RNR and we found that the effect of clofarabine is limited when using a short (6-hour) drug treatment. Gemcitabine, on the other hand, is an irreversible inhibitor of the RRM1 subunit of RNR and this drug induces apoptosis in Ewing sarcoma cells when used in both 6-hour and longer drug treatments. Treatment of Ewing sarcoma cells with gemcitabine also results in activation of checkpoint kinase 1 (CHK1), which is a critical mediator of cell survival in the setting of impaired DNA replication. Notably, inhibition of CHK1 function in Ewing sarcoma cells using a small-molecule CHK1 inhibitor, or siRNA knockdown, in combination with gemcitabine results in increased toxicity both in vitro and in vivo in a mouse xenograft experiment. Overall, our results provide insight into Ewing sarcoma biology and identify a candidate therapeutic target, and drug combination, in Ewing sarcoma. PMID:29152060

Methyl-hydroxylamine as an efficacious antibacterial agent that targets the ribonucleotide reductase enzyme.

PubMed

Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

2015-01-01

The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme.

Cell Cycle Inhibition To Treat Sleeping Sickness.

PubMed

Epting, Conrad L; Emmer, Brian T; Du, Nga Y; Taylor, Joann M; Makanji, Ming Y; Olson, Cheryl L; Engman, David M

2017-09-19

African trypanosomiasis is caused by infection with the protozoan parasite Trypanosoma brucei During infection, this pathogen divides rapidly to high density in the bloodstream of its mammalian host in a manner similar to that of leukemia. Like all eukaryotes, T. brucei has a cell cycle involving the de novo synthesis of DNA regulated by ribonucleotide reductase (RNR), which catalyzes the conversion of ribonucleotides into their deoxy form. As an essential enzyme for the cell cycle, RNR is a common target for cancer chemotherapy. We hypothesized that inhibition of RNR by genetic or pharmacological means would impair parasite growth in vitro and prolong the survival of infected animals. Our results demonstrate that RNR inhibition is highly effective in suppressing parasite growth both in vitro and in vivo These results support drug discovery efforts targeting the cell cycle, not only for African trypanosomiasis but possibly also for other infections by eukaryotic pathogens. IMPORTANCE The development of drugs to treat infections with eukaryotic pathogens is challenging because many key virulence factors have closely related homologues in humans. Drug toxicity greatly limits these development efforts. For pathogens that replicate at a high rate, especially in the blood, an alternative approach is to target the cell cycle directly, much as is done to treat some hematologic malignancies. The results presented here indicate that targeting the cell cycle via inhibition of ribonucleotide reductase is effective at killing trypanosomes and prolonging the survival of infected animals. Copyright © 2017 Epting et al.

Criminogenic Needs, Substance Use, and Offending among Rural Stimulant Users

PubMed Central

Timko, Christine; Booth, Brenda M.; Han, Xiaotong; Schultz, Nicole R.; Blonigen, Daniel M.; Wong, Jessie J.; Cucciare, Michael A.

2017-01-01

There is a need to understand the determinants of both substance use and criminal activity in rural areas in order to design appropriate treatment interventions for these linked problems. The present study drew on a predominant model used to assess and treat offenders -- the Risk-Need-Responsivity (RNR) model -- to examine risk factors for substance use and criminal activity in a rural drug using sample. This study extends the RNR model’s focus on offenders to assessing rural-dwelling individuals using stimulants (N=462). We examined substance use and criminal justice outcomes at 6-month (91%) and 3-year (79%) follow-ups, and used Generalized Estimating Equations to examine the extent to which RNR criminogenic need factors at baseline predicted outcomes at follow-ups. Substance use and criminal justice outcomes improved at six months, and even more at three years, post-baseline. As expected, higher risk was associated with poorer outcomes. Antisocial personality patterns and procriminal attitudes at baseline predicted poorer legal and drug outcomes measured at subsequent follow-ups. In contrast, less connection to antisocial others and fewer work difficulties predicted lower alcohol problem severity, but more frequent alcohol use. Engagement in social-recreational activities was associated with fewer subsequent arrests and less severe alcohol and drug problems. The RNR model’s criminogenic need factors predicted drug use and crime-related outcomes among rural residents. Services adapted to rural settings that target these factors, such as telehealth and other technology-based resources, may hasten improvement on both types of outcomes among drug users. PMID:29051795

Methyl-Hydroxylamine as an Efficacious Antibacterial Agent That Targets the Ribonucleotide Reductase Enzyme

PubMed Central

Julián, Esther; Baelo, Aida; Gavaldà, Joan; Torrents, Eduard

2015-01-01

The emergence of multidrug-resistant bacteria has encouraged vigorous efforts to develop antimicrobial agents with new mechanisms of action. Ribonucleotide reductase (RNR) is a key enzyme in DNA replication that acts by converting ribonucleotides into the corresponding deoxyribonucleotides, which are the building blocks of DNA replication and repair. RNR has been extensively studied as an ideal target for DNA inhibition, and several drugs that are already available on the market are used for anticancer and antiviral activity. However, the high toxicity of these current drugs to eukaryotic cells does not permit their use as antibacterial agents. Here, we present a radical scavenger compound that inhibited bacterial RNR, and the compound's activity as an antibacterial agent together with its toxicity in eukaryotic cells were evaluated. First, the efficacy of N-methyl-hydroxylamine (M-HA) in inhibiting the growth of different Gram-positive and Gram-negative bacteria was demonstrated, and no effect on eukaryotic cells was observed. M-HA showed remarkable efficacy against Mycobacterium bovis BCG and Pseudomonas aeruginosa. Thus, given the M-HA activity against these two bacteria, our results showed that M-HA has intracellular antimycobacterial activity against BCG-infected macrophages, and it is efficacious in partially disassembling and inhibiting the further formation of P. aeruginosa biofilms. Furthermore, M-HA and ciprofloxacin showed a synergistic effect that caused a massive reduction in a P. aeruginosa biofilm. Overall, our results suggest the vast potential of M-HA as an antibacterial agent, which acts by specifically targeting a bacterial RNR enzyme. PMID:25782003

Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Abhay Kumar; Pantouris, Georgios; Borosch, Sebastian

Macrophage migration inhibitory factor (MIF) is a master regulator of proinflammatory cytokines and plays pathological roles when not properly regulated in rheumatoid arthritis, lupus, atherosclerosis, asthma and cancer. Unlike canonical cytokines, MIF has vestigial keto-enol tautomerase activity. Most of the current MIF inhibitors were screened for the inhibition of this enzymatic activity. However, only some of the enzymatic inhibitors inhibit receptor-mediated biological functions of MIF, such as cell recruitment, through an unknown molecular mechanism. The goal of this study was to understand the molecular basis underlying the pharmacological inhibition of biological functions of MIF. Here, we demonstrate how the structuralmore » changes caused upon inhibitor binding translate into the alteration of MIF-induced downstream signalling. Macrophage migration inhibitory factor activates phosphoinositide 3-kinases (PI3Ks) that play a pivotal role in immune cell recruitment in health and disease. There are several different PI3K isoforms, but little is known about how they respond to MIF. We demonstrate that MIF up-regulates the expression of Class IB PI3Ks in leucocytes. We also demonstrate that MIF tautomerase active site inhibitors down-regulate the expression of Class IB PI3Ks as well as leucocyte recruitment in vitro and in vivo. Finally, based on our MIF:inhibitor complex crystal structures, we hypothesize that the reduction in Class IB PI3K expression occurs because of the displacement of Pro1 towards the second loop of MIF upon inhibitor binding, which results in increased flexibility of the loop 2 and sub-optimal MIF binding to its receptors. These results will provide molecular insights for fine-tuning the biological functions of MIF.« less

A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides

PubMed Central

1994-01-01

Unlike the highly polymorphic major histocompatibility complex (MHC) class Ia molecules, which present a wide variety of peptides to T cells, it is generally assumed that the nonpolymorphic MHC class Ib molecules may have evolved to function as highly specialized receptors for the presentation of structurally unique peptides. However, a thorough biochemical analysis of one class Ib molecule, the soluble isoform of Qa-2 antigen (H-2SQ7b), has revealed that it binds a diverse array of structurally similar peptides derived from intracellular proteins in much the same manner as the classical antigen-presenting molecules. Specifically, we find that SQ7b molecules are heterodimers of heavy and light chains complexed with nonameric peptides in a 1:1:1 ratio. These peptides contain a conserved hydrophobic residue at the COOH terminus and a combination of one or more conserved residue(s) at P7 (histidine), P2 (glutamine/leucine), and/or P3 (leucine/asparagine) as anchors for binding SQ7b. 2 of 18 sequenced peptides matched cytosolic proteins (cofilin and L19 ribosomal protein), suggesting an intracellular source of the SQ7b ligands. Minimal estimates of the peptide repertoire revealed that at least 200 different naturally processed self-peptides can bind SQ7b molecules. Since Qa-2 molecules associate with a diverse array of peptides, we suggest that they function as effective presenting molecules of endogenously synthesized proteins like the class Ia molecules. PMID:8294869

A Summary of Research on the International Baccalaureate Diploma Programme: Perspectives of Students, Teachers, and University Admissions Offices in the USA

ERIC Educational Resources Information Center

Culross, Rita; Tarver, Emily

2011-01-01

This is the summary of a series of research studies into the International Baccalaureate (IB) Diploma Programme (DP) in the USA, beginning with the investigation of how the first class of IB DP graduates in an individual school perceived the impacts and benefits of the programme, through further investigations of teacher perceptions of the…

Charlotte, N.C.'s Project L.I.F.T.: Ranson IB Middle School Launches an Opportunty Culture. An Opportunity Culture Case Study

ERIC Educational Resources Information Center

Barrett, Sharon Kebschull; Han, Jiye Grace

2015-01-01

Principal Alison Harris is blunt in describing what she confronted on her arrival to Ranson IB Middle School in 2011. "I was placed in what many people would call an impossible situation," she says. During her initial visit to the school in 2009-10, she watched as students changed classes--while teachers pressed against the lockers to…

Prevalence of quinolone resistance determinant qnrA6 among broad- and extended-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates with sul1-type class 1 integron association in a Tunisian Hospital.

PubMed

Mahrouki, Sihem; Perilli, Mariagrazia; Bourouis, Amel; Chihi, Hela; Ferjani, Mustapha; Ben Moussa, Mohamed; Amicosante, Gianfranco; Belhadj, Omrane

2013-08-01

The aim of this study was to investigate the prevalence and the emergence of plasmid-mediated quinolone resistance among broad-spectrum beta-lactam-resistant Proteus mirabilis and Morganella morganii clinical isolates recovered in the Military Hospital in Tunisia. Of 200 strains examined, 50 exhibited resistance to quinolones. Quinolone resistance determinants (qnr and aac(6')-Ib-cr) were characterized by multiplex PCR and sequencing. Chromosomal quinolone resistance mutations in the quinolone resistance-determining region (QRDR) and class 1 integron characterization were analysed by PCR and sequencing. The clonal relationship between the isolates was studied by pulsed-field gel electrophoresis (PFGE). Fourteen isolates harboured qnrA6 and among them 8 (57%) were extended-spectrum beta-lactamase (ESBL) producers, whilst 12 (85%) isolates harboured blaDHA-1. Mutations in the QRDR were detected in gyrA (Ser83Ile, Glu87Lys), gyrB (Ser464Phe), and parC (Ser80Ile). qnrA6 and blaDHA-1 genes were found embedded in complex sul1-type class 1 integrons. A gene cassette carrying aac(6')-Ib-cr was found located in the class 1 integron upstream of the qacEΔ1 gene. According to the PFGE analysis, the isolates were clonally unrelated. This is the first description in North Africa of class 1 integrons carrying blaDHA-1, qnrA6 gene, and aac(6')-Ib-cr determinants in clinical strains of Proteus mirabilis and Morganella morganii.

Generation and characterization of koi herpesvirus recombinants lacking viral enzymes of nucleotide metabolism.

PubMed

Fuchs, Walter; Fichtner, Dieter; Bergmann, Sven M; Mettenleiter, Thomas C

2011-06-01

Koi herpesvirus (KHV) causes a fatal disease in koi and common carp, but no reliable and genetically characterized vaccines are available up to now. Therefore, we generated KHV recombinants possessing deletions within the viral ribonucleotide reductase (RNR), thymidine kinase (TK), dUTPase, or TK and dUTPase genes, and their corresponding rescuants. All KHV mutants were replication competent in cultured cells. Whereas plaque sizes and titers of RNR-negative KHV were reduced, replication of the other mutants was not affected. Experimental infection of carp indicated attenuation of TK- or dUTPase-deleted KHV, and PCR analysis of tissue samples permitted differentiation of mutant from wild-type virus.

Lubiprostone: evaluation of the newest medication for the treatment of adult women with constipation-predominant irritable bowel syndrome

PubMed Central

Lunsford, Tisha N; Harris, Lucinda A

2010-01-01

Irritable bowel syndrome (IBS) is a chronic disorder that affects primarily female patients and is thought also to afflict approximately 7%–10% of the population of the Western World. Although bowel habits may change over the course of years, patients with IBS are characterized according to their predominant bowel habit, constipation (IBS-C), diarrhea (IBS-D), or mixed type (IBS-M), and treatments are focused toward the predominant symptom. Current treatments for IBS-C have included fiber, antispasmodics, osmotic and stimulant laxatives, and the now severely limited 5-HT4 agonist tegaserod. No one agent has been universally successful in the treatment of this bothersome syndrome and the search for new agents continues. Lubiprostone (Amitiza®), a novel compound, is a member of a new class of agents called prostones and was approved for the treatment of chronic idiopathic constipation in 2006 at a dose of 24 μg twice daily and then in 2008 for the treatment of IBS-C in women only at a dose of 8 μg twice daily. Its purported mechanism is as a type 2 chloride channel activator, but recent evidence suggests that it may also work at the cystic fibrosis transport receptor. This article will compare the newly proposed mechanism of action of this compound to the purported mechanism and review the structure, pharmacology, safety, efficacy, and tolerability of this new therapeutic option. Clinical trial data leading to the approval of this agent for the treatment of IBS-C and the gender-based understanding of IBS, as well as this agent’s place among existing and emerging therapies, will be examined. PMID:21151683

SN 1994I in M51 and the nature of type Ibc supernovae

NASA Technical Reports Server (NTRS)

Wheeler, J. C.; Harkness, R. P.; Clocchiatti, A.; Benetti, S.; Brotherton, M. S.; Depoy, D. L.; Elias, J.

1994-01-01

Early spectra of SN 1994I in M51 (NGC 5194) are presented along with arguments that is a member of the class of helium-poor Type Ic supernovae. The issue of H and He in the spectra of Type Ib and Ic events is reexamined with the conclusion that Type Ib eject substantially less H than even transition events like SN 1993J and that Type Ic eject substantially less He than Type Ib and their optical spectra are consistent with no H or He. Type Ic show and absorption of the Si II lambda 6355 blend that characterizes Type Ia. This feature requires only a solar abundance of Si. Some Type Ic show an absorption that is probably C II lambda 6580. IR spectra are presented of SN 1990W which show the line of He I lambda 10830. The strength of this feature and the rather slow decay of the late time light curve suggest that this event could be better classified as a Type Ib. Even if trace abundances of H are present in Type Ib and of He in Type Ic the spectral differences still imply a distinctly different evolution for the progenitors of Type Ib from Type Ic and events like SN 1993J.

The treatment of irritable bowel syndrome.

PubMed

Lacy, Brian E; Weiser, Kirsten; De Lee, Ryan

2009-07-01

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder routinely encountered by healthcare providers. Although not life-threatening, this chronic disorder reduces patients' quality of life and imposes a significant economic burden to the healthcare system. IBS is no longer considered a diagnosis of exclusion that can only be made after performing a battery of expensive diagnostic tests. Rather, IBS should be confidently diagnosed in the clinic at the time of the first visit using the Rome III criteria and a careful history and physical examination. Treatment options for IBS have increased in number in the past decade and clinicians should not be limited to using only fiber supplements and smooth muscle relaxants. Although all patients with IBS have symptoms of abdominal pain and disordered defecation, treatment needs to be individualized and should focus on the predominant symptom. This paper will review therapeutic options for the treatment of IBS using a tailored approach based on the predominant symptom. Abdominal pain, bloating, constipation and diarrhea are the four main symptoms that can be addressed using a combination of dietary interventions and medications. Treatment options include probiotics, antibiotics, tricyclic antidepressants, selective serotonin reuptake inhibitors and agents that modulate chloride channels and serotonin. Each class of agent will be reviewed using the latest data from the literature.

MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution

PubMed Central

Huang, Shouxiong; Martin, Emmanuel; Kim, Sojung; Yu, Lawrence; Soudais, Claire; Fremont, Daved H.; Lantz, Olivier; Hansen, Ted H.

2009-01-01

Several nonclassical major histocompatibilty antigens (class Ib molecules) have emerged as key players in the early immune response to pathogens or stress. Class Ib molecules activate subsets of T cells that mount effector responses before the adaptive immune system, and thus are called innate T cells. MR1 is a novel class Ib molecule with properties highly suggestive of its regulation of mucosal immunity. The Mr1 gene is evolutionarily conserved, is non-Mhc linked, and controls the development of mucosal-associated invariant T (MAIT) cells. MAIT cells preferentially reside in the gut, and their development is dependent on commensal microbiota. Although these properties suggest that MAIT cells function as innate T cells in the mucosa, this has been difficult to test, due to the (i) paucity of MAIT cells that display MR1-specific activation in vitro and (ii) lack of knowledge of whether or not MR1 presents antigen. Here we show that both mouse and human MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination. Furthermore, acid eluates from recombinant or cellular MR1 proteins enhance MAIT cell activation in an MR1-specific and cross-species manner. Our findings demonstrate that the presentation pathway of MR1 to MAIT cells is highly evolutionarily conserved. PMID:19416870

Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis-Derived Protein Antigens and Contribute to Protection Against Infection

PubMed Central

Shang, Shaobin; Siddiqui, Sarah; Bian, Yao; Zhao, Jie; Wang, Chyung-Ru

2016-01-01

MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or β2m (β2m-/-) to study the role of M3-restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia-restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly β2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/- mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib-restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID:27272249

Students' perceptions of the non-academic advantages and disadvantages of participation in Advanced Placement courses and International Baccalaureate programs.

PubMed

Foust, Regan Clark; Hertberg-Davis, Holly; Callahan, Carolyn M

2009-01-01

In-depth interviews of students with qualitative analysis of the responses were used to explore perceptions of the non-academic advantages and disadvantages of Advanced Placement (AP) and International Baccalaureate (IB) program participation, and differences between the AP and IB programs in those perceptions. Results revealed that benefits of participation, including pride in completing more challenging work, similarity and special bonds among participants, better treatment (more respect and responsibility) from teachers, better overall class atmosphere, and preference for AP and IB courses were consistent across schools and between programs. Also consistent were the disadvantages students reported, with marked differences in the intensity of disadvantages between the AP and IB programs. Specifically, as the amount of time students spent in homogeneously grouped settings increased, so did the workload, the intensity of the perceived social/emotional disadvantages of the workload, the perceived range of negative feelings between participants and non-participants, and the perceived negativity of participant strereotypes.

HLA-G in human reproduction: aspects of genetics, function and pregnancy complications.

PubMed

Hviid, Thomas Vauvert F

2006-01-01

The non-classical human leukocyte antigen (HLA) class Ib genes, HLA-E, -G and -F, are located on chromosome 6 in the human major histocompatibility complex (MHC). HLA class Ib antigens resemble the HLA class Ia antigens in many ways, but several major differences have been described. This review will, in particular, discuss HLA-G and its role in human reproduction and in the human MHC. HLA-G seems to be important in the modulation of the maternal immune system during pregnancy and thereby the maternal acceptance of the semiallogenic fetus. Recent findings regarding aspects of HLA-G polymorphism, the possible significance of this polymorphism in respect to HLA-G function and certain complications of pregnancy (such as pre-eclampsia and recurrent spontaneous abortions (RSA)) are discussed together with possible importance to IVF. Finally, aspects of a possible role of HLA-G in organ transplantation and in inflammatory or autoimmune disease, and of HLA-G in an evolutionary context, are also briefly examined.

Class of 2015 Advanced Placement and International Baccalaureate Exam Participation and Performance. Memorandum

ERIC Educational Resources Information Center

Navarro, Maria V.

2016-01-01

This memorandum describes the Advanced Placement (AP) and International Baccalaureate (IB) exams participation and performance of 2013 to 2015 public school graduates in Montgomery County Public Schools (MCPS) and the state of Maryland. The results are disaggregated by demographics and high schools. Students in the MCPS Class of 2015 continued to…

A catalog of rotational and radial velocities for evolved stars. V. Southern stars

NASA Astrophysics Data System (ADS)

De Medeiros, J. R.; Alves, S.; Udry, S.; Andersen, J.; Nordström, B.; Mayor, M.

2014-01-01

Rotational and radial velocities have been measured for 1589 evolved stars of spectral types F, G, and K and luminosity classes IV, III, II, and Ib, based on observations carried out with the CORAVEL spectrometers. The precision in radial velocity is better than 0.30 km s-1 per observation, whereas rotational velocity uncertainties are typically 1.0 km s-1 for subgiants and giants and 2.0 km s-1 for class II giants and Ib supergiants. Based on observations collected at the Haute-Provence Observatory, Saint-Michel, France, and at the European Southern Observatory, La Silla, Chile.Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/561/A126

Real-world use of the risk-need-responsivity model and the level of service/case management inventory with community-supervised offenders.

PubMed

Dyck, Heather L; Campbell, Mary Ann; Wershler, Julie L

2018-06-01

The risk-need-responsivity model (RNR; Bonta & Andrews, 2017) has become a leading approach for effective offender case management, but field tests of this model are still required. The present study first assessed the predictive validity of the RNR-informed Level of Service/Case Management Inventory (LS/CMI; Andrews, Bonta, & Wormith, 2004) with a sample of Atlantic Canadian male and female community-supervised provincial offenders (N = 136). Next, the case management plans prepared from these LS/CMI results were analyzed for adherence to the principles of risk, need, and responsivity. As expected, the LS/CMI was a strong predictor of general recidivism for both males (area under the curve = .75, 95% confidence interval [.66, .85]), and especially females (area under the curve = .94, 95% confidence interval [.84, 1.00]), over an average 3.42-year follow-up period. The LS/CMI was predictive of time to recidivism, with lower risk cases taking longer to reoffend than higher risk cases. Despite the robust predictive validity of the LS/CMI, case management plans developed by probation officers generally reflected poor adherence to the RNR principles. These findings highlight the need for better training on how to transfer risk appraisal information from valid risk tools to case plans to better meet the best-practice principles of risk, need, and responsivity for criminal behavior risk reduction. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

40 CFR 90.410 - Engine test cycle.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Engine test cycle. 90.410 Section 90... Procedures § 90.410 Engine test cycle. (a) Follow the appropriate 6-mode test cycle for Class I, I-B and II engines and 2-mode test cycle for Class I-A, III, IV, and V engines when testing spark-ignition engines...

[Therapeutic outcomes in patients with cervical cancer FIGO stage IB1].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish overall and disease-free survival (OS and DFS) for patients with FIGO IB1 stage cervical cancer for median period of follow-up of 41 months. Between 11.2002-11.2011 110 women with histologically confirmed cervical cancer IB1 stage were operated on by the author. Surgery was radical hysterectomy class III (Piver) and pelvic lymphonodulectomy (ovariectomy was optionally). 76 patients were submitted to adjuvant RT (TGT- 52 - 54 Gy). The period of follow-up ranges from 2 to 104 monts, median 41 monts. The acturial OS and DFS in patients with cervical cancer IB1 stage were estimated as 90% and 90.9%, respectively. Eleven patients had died for the period of follow-up and in 10 occurred local or distant recurrences. The time to develop recurrences was estimated as 16.81 months. Four patients developed local recurrences and six--distant metastases. Surgical and combined therapy of cervical cancer patients IB1 stage leads to high rate OS and DFS--90% and 90.9%, respectively. The incidence rate of distant metastases (5.5%)--in six patients in this stage makes pelvic lymph node dissection crucial and the presence of LM in gluteal and presacral lymph nodes requires paraaortic lymph node dissection.

High temperature regenerative H.sub.2 S sorbents

NASA Technical Reports Server (NTRS)

Flytani-Stephanopoulos, Maria (Inventor); Gavalas, George R. (Inventor); Tamhankar, Satish S. (Inventor)

1988-01-01

Efficient, regenerable sorbents for removal of H.sub.2 S from high temperature gas streams comprise porous, high surface area particles. A first class of sorbents comprise a thin film of binary oxides that form a eutectic at the temperature of the gas stream coated onto a porous, high surface area refractory support. The binary oxides are a mixture of a Group VB or VIB metal oxide with a Group IB, IIB or VIII metal oxide such as a film of V-Zn-O, V-Cu-O, Cu-Mo-O, Zn-Mo-O or Fe-Mo-O coated on an alumina support. A second class of sorbents consist of particles of unsupported mixed oxides in the form of highly dispersed solid solutions of solid compounds characterized by small crystallite size, high porosity and relatively high surface area. The mixed oxide sorbents contain one Group IB, IIB or VIIB metal oxide such as copper, zinc or manganese and one or more oxides of Groups IIIA, VIB or VII such as aluminum, iron or molybdenum. The presence of iron or aluminum maintains the Group IB, IIB or VIIB metal in its oxidized state. Presence of molybdenum results in eutectic formation at sulfidation temperature and improves the efficiency of the sorbent.

Furan-2-ylmethylene thiazolidinediones as novel, potent, and selective inhibitors of phosphoinositide 3-kinase gamma.

PubMed

Pomel, Vincent; Klicic, Jasna; Covini, David; Church, Dennis D; Shaw, Jeffrey P; Roulin, Karen; Burgat-Charvillon, Fabienne; Valognes, Delphine; Camps, Montserrat; Chabert, Christian; Gillieron, Corinne; Françon, Bernard; Perrin, Dominique; Leroy, Didier; Gretener, Denise; Nichols, Anthony; Vitte, Pierre Alain; Carboni, Susanna; Rommel, Christian; Schwarz, Matthias K; Rückle, Thomas

2006-06-29

Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kgamma, have become attractive drug targets for inflammatory and autoimmune diseases. Here, we disclose a novel series of furan-2-ylmethylene thiazolidinediones as selective, ATP-competitive PI3Kgamma inhibitors. Structure-based design and X-ray crystallography of complexes formed by inhibitors bound to PI3Kgamma identified key pharmacophore features for potency and selectivity. An acidic NH group on the thiazolidinedione moiety and a hydroxy group on the furan-2-yl-phenyl part of the molecule play crucial roles in binding to PI3K and contribute to class IB PI3K selectivity. Compound 26 (AS-252424), a potent and selective small-molecule PI3Kgamma inhibitor emerging from these efforts, was further profiled in three different cellular PI3K assays and shown to be selective for class IB PI3K-mediated cellular effects. Oral administration of 26 in a mouse model of acute peritonitis led to a significant reduction of leukocyte recruitment.

Frequency and risk factors of functional gastro-intestinal disorders in a rural Indian population.

PubMed

Ghoshal, Uday C; Singh, Rajan

2017-02-01

As best estimates on functional gastrointestinal disorders (FGIDs) prevalence are expected from community studies, which are scanty from Asia, we evaluated the prevalence and risk factors of FGIDs in a rural Indian community. House-to-house survey was undertaken by trained interviewers using translated-validated Rome III and hospital anxiety and depression questionnaires. Among 3426 subjects ≥ 18 years old from 3 villages in Uttar Pradesh, 84% participated, of whom 80% were finally analyzed. Of these 2774 subjects (age 38.4 ± 16.5 years, 1573 [56.7%] male), 2654 [95.7%] were vegetarian and 120 [4.3%] non-vegetarian. Socioeconomic classes were upper (16.7%), upper middle (15.1%), lower middle (22%), upper lower (22.2%), and lower (24%) using Prasad's Classification; 603 (21.7%) had FGIDs (413 [14.9%] dyspepsia, 75 [2.7%] irritable bowel syndrome (IBS) and 115 [4.1%] dyspepsia-IBS overlap), by Rome III criteria. In subjects with dyspepsia, 49/528 (9%) had epigastric pain, 141 (27%) postprandial distress syndromes (EPS, PDS) and 338 (64%) EPS-PDS overlap. IBS was more often diarrhea than constipation-predominant subtype. On univariate analysis, chewing tobacco, aerated drink, tea/coffee, disturbed sleep, vegetarianism, and anxiety parameters and presence of dyspepsia predicting occurrence of IBS were associated with FGIDs. On multivariate analysis, chewing tobacco, aerated soft drink, tea/coffee, vegetarianism, anxiety parameters, and presence of dyspepsia predicting IBS were significant. Functional gastrointestinal disorders, particularly dyspepsia-IBS overlap, are common in rural Indian population; the risk factors included chewing tobacco, aerated soft drink, tea/coffee, vegetarian diet, disturbed sleep, anxiety, and dyspepsia predicting occurrence of IBS. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Development and validation of the irritable bowel syndrome scale under the system of quality of life instruments for chronic diseases QLICD-IBS: combinations of classical test theory and generalizability theory.

PubMed

Lei, Pingguang; Lei, Guanghe; Tian, Jianjun; Zhou, Zengfen; Zhao, Miao; Wan, Chonghua

2014-10-01

This paper is aimed to develop the irritable bowel syndrome (IBS) scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-IBS) by the modular approach and validate it by both classical test theory and generalizability theory. The QLICD-IBS was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, and quantitative statistical procedures. One hundred twelve inpatients with IBS were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability, and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t tests and also G studies and D studies of generalizability theory analysis. Multi-trait scaling analysis, correlation, and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. Test-retest reliability coefficients (Pearson r and intra-class correlation (ICC)) for the overall score and all domains were higher than 0.80; the internal consistency α for all domains at two measurements were higher than 0.70 except for the social domain (0.55 and 0.67, respectively). The overall score and scores for all domains/facets had statistically significant changes after treatments with moderate or higher effect size standardized response mean (SRM) ranging from 0.72 to 1.02 at domain levels. G coefficients and index of dependability (Ф coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-IBS has good validity, reliability, responsiveness, and some highlights and can be used as the quality of life instrument for patients with IBS.

Possible Class of Nearby Gamma-Ray Burst / Gravitational Wave Sources

NASA Astrophysics Data System (ADS)

Norris, Jay P.

2003-10-01

A possible subclass of gamma-ray bursts - those with few, wide pulses, spectral lags of order one to several seconds, and soft spectra - has been identified. Their Log[N]-Log[Fp] distribution approximates a -3/2 power-law, suggesting homogeneity and relatively nearby sources. These mostly dim bursts account for ~ 50% of the BATSE sample of long bursts near that instrument's trigger threshold, suggesting that this subluminous class constitutes a more common variety than the more familiar burst sources which lie at truly cosmological distances. Theoretical scenarios predicted such a class, motivated by their exemplar GRB 980425 (SN 1998bw) lying at a distance of ~ 38 Mpc. The observations are explained by invoking off-axis viewing of the GRB jet and/or bulk Lorentz factors of order a few. Long-lag bursts show a tendency to concentrate near the Supergalactic Plane with a quadrupole moment of -0.10 +/- 0.04, similar to that for SNe type Ib/c within the same volume. The rate of the observed subluminous bursts is of order 14 that of SNe Ib/c. Evidence for a sequential relationship between SNe Ib/c and GRBs is critiqued for two cases, as simultaneity of the SN and GRB events may be important for detection of the expected gravitational wave signal; at most, SN to GRB delays appear to be a few days. SN asymmetries and ultrarelativistic GRB jets suggest the possibility of rapid rotation in the pre-collapse objects, a primary condition required for highly non-axisymmetric SN collapse to produce strong gravitational waves.

Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing.

PubMed

Lee, Carol; Moroldo, Marco; Perdomo-Sabogal, Alvaro; Mach, Núria; Marthey, Sylvain; Lecardonnel, Jérôme; Wahlberg, Per; Chong, Amanda Y; Estellé, Jordi; Ho, Simon Y W; Rogel-Gaillard, Claire; Gongora, Jaime

2018-06-01

The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens.

The Dimanganese(II) Site of Bacillus subtilis Class Ib Ribonucleotide Reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boal, Amie K.; Cotruvo, Jr., Joseph A.; Stubbe, JoAnne

2014-10-02

Class Ib ribonucleotide reductases (RNRs) use a dimanganese-tyrosyl radical cofactor, Mn{sub 2}{sup III}-Y{sm_bullet}, in their homodimeric NrdF ({beta}2) subunit to initiate reduction of ribonucleotides to deoxyribonucleotides. The structure of the Mn{sub 2}{sup II} form of NrdF is an important component in understanding O{sub 2}-mediated formation of the active metallocofactor, a subject of much interest because a unique flavodoxin, NrdI, is required for cofactor assembly. Biochemical studies and sequence alignments suggest that NrdF and NrdI proteins diverge into three phylogenetically distinct groups. The only crystal structure to date of a NrdF with a fully ordered and occupied dimanganese site is thatmore » of Escherichia coli Mn{sub 2}{sup II}-NrdF, prototypical of the enzymes from actinobacteria and proteobacteria. Here we report the 1.9 {angstrom} resolution crystal structure of Bacillus subtilis Mn{sub 2}{sup II}-NrdF, representative of the enzymes from a second group, from Bacillus and Staphylococcus. The structures of the metal clusters in the {beta}2 dimer are distinct from those observed in E. coli Mn{sub 2}{sup II}-NrdF. These differences illustrate the key role that solvent molecules and protein residues in the second coordination sphere of the Mn{sub 2}{sup II} cluster play in determining conformations of carboxylate residues at the metal sites and demonstrate that diverse coordination geometries are capable of serving as starting points for Mn{sub 2}{sup III}-Y{sm_bullet} cofactor assembly in class Ib RNRs.« less

Feasibility of use of fatty acid and triacylglycerol profiles for the authentication of commercial labelling in Iberian dry-cured sausages.

PubMed

Horcada, Alberto; Fernández-Cabanás, Víctor M; Polvillo, Oliva; Botella, Baltasar; Cubiles, M Dolores; Pino, Rafael; Narváez-Rivas, Mónica; León-Camacho, Manuel; Acuña, Rafael Rodríguez

2013-12-15

In the present study, fatty acid and triacylglycerol profiles were used to evaluate the possibility of authenticating Iberian dry-cured sausages according to their label specifications. 42 Commercial brand 'chorizo' and 39 commercial brand 'salchichón' sausages from Iberian pigs were purchased. 36 Samples were labelled Bellota and 45 bore the generic Ibérico label. In the market, Bellota is considered to be a better class than the generic Ibérico since products with the Bellota label are manufactured with high quality fat obtained from extensively reared pigs fed on acorns and pasture. Analyses of fatty acids and triacylglycerols were carried out by gas chromatography and a flame ion detector. A CP-SIL 88 column (highly substituted cyanopropyl phase; 50 m × 0.25 mm i.d., 0.2 µm film thickness) (Varian, Palo Alto, USA) was used for fatty acid analysis and a fused silica capillary DB-17HT column (50% phenyl-50% methylpolysiloxane; 30 m × 0.25 mm i.d., 0.15 µm film thickness) was used for triacylglycerols. Twelve fatty acids and 16 triacylglycerols were identified. Various discriminant models (linear quadratic discriminant analyses, logistic regression and support vector machines) were trained to predict the sample class (Bellota or Ibérico). These models included fatty acids and triacylglycerols separately and combined fatty acid and triacylglycerol profiles. The number of correctly classified samples according to discriminant analyses can be considered low (lower than 65%). The greatest discriminant rate was obtained when triacylglycerol profiles were included in the model, whilst using a combination of fatty acid and triacylglycerol profiles did not improve the rate of correct assignation. The values that represent the reliability of prediction of the samples according to the label specification were higher for the Ibérico class than for the Bellota class. In fact, quadratic and Support Vector Machine discriminate analyses were not able to assign the Bellota class (0%) when combined fatty acids and triacylglycerols were included in the model. The use of fatty acid and triacylglycerol profiles to discriminate Iberian dry-cured sausages in the market according to their labelling information is unclear. In order to ensure the genuineness of Iberian dry-cured sausages in the market, identification of fatty acid and triacylglycerol profiles should be combined with the application of quality standard traceability techniques. © 2013 Published by Elsevier B.V.

Herpes B Virus, Macacine Herpesvirus 1, Breaks Simplex Virus Tradition via Major Histocompatibility Complex Class I Expression in Cells from Human and Macaque Hosts

PubMed Central

Vasireddi, Mugdha

2012-01-01

B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8+ T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions. PMID:22973043

Cilansetron. Solvay.

PubMed

Stacher, G

2001-10-01

Cilansetron is a 5-HT3 antagonist tinder development by Solvay Pharmaceuticals as a potential treatment for irritable bowel syndrome (IBS). The compound targets non-constipated men and women with IBS. Cilansetron is being evaluated in phase III trials, but up to now, only scarce information has been made available and most publications have appeared in abstract form only. In July 2001, it was reported that regulatory submissions were expected in 2003 [416185]. Also in July 2001, after discussion with the FDA, Solvay initiated a revised phase III program in diarrhea-predominant IBS and signed a five-year 'preferred-provider' clinical services agreement with Quintiles Transnational to conduct the trial. At this time, Solvay was also seeking marketing partners for cilansetron [416185]. By October 1999, Solvay was treating cilansetron as one of its main priorities, as it represented a novel class of compound [342434]. Solvay has predicted peak sales of euro 100 m to euro 1000 m [420654].

The role of mental health and specific responsivity in juvenile justice rehabilitation.

PubMed

McCormick, Sarah; Peterson-Badali, Michele; Skilling, Tracey A

2017-02-01

Understanding the role that mental health issues play in justice-involved youth poses challenges for research, policy, and practice. While mental health problems are generally not risk factors for criminal behavior according to the risk-needs-responsivity (RNR) framework of correctional psychology practice, prevalence rates are very high and RNR principles suggest that mental health as a responsivity variable may moderate the success of interventions targeted to criminogenic needs. In this study we investigated the relationships among mental health status, criminogenic needs treatment, and recidivism in a sample of 232 youth referred for court-ordered assessments and followed through their community supervision sentence (probation). Youth with mental health needs were no more likely than youth without these needs to reoffend, regardless of whether those needs were treated. Youth who received mental health treatment also more frequently had their criminogenic needs matched across several domains, suggesting an association between mental health treatment and intermediate treatment targets. However, mental health did not moderate the effect of criminogenic needs treatment: youth who had a greater proportion of criminogenic needs targeted through appropriate services were less likely to reoffend, regardless of mental health status. Findings are consistent with the RNR stance that, within a correctional context in which the primary goal of intervention is preventing recidivism, treatment for mental health needs should be in addition to criminogenic needs treatment, not in replacement of it. They also point to the need for continued research to understand precisely how mental health treatment interacts with intervention targeting criminogenic needs. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Investigating the Molecular Mechanism of TSO1 Function in Arabidopsis cell division and meristem development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhongchi Liu

2004-10-01

Unlike animals, plants are constantly exposed to environmental mutagens including ultraviolet light and reactive oxygen species. Further, plant cells are totipotent with highly plastic developmental programs. An understanding of molecular mechanisms underlying the ability of plants to monitor and repair its DNA and to eliminate damaged cells are of great importance. Previously we have identified two genes, TSO1 and TSO2, from a flowering plant Arabidopsis thaliana. Mutations in these two genes cause callus-like flowers, fasciated shoot apical meristems, and abnormal cell division, indicating that TSO1 and TSO2 may encode important cell cycle regulators. Previous funding from DOE led to themore » molecular cloning of TSO1, which was shown to encode a novel nuclear protein with two CXC domains suspected to bind DNA. This DOE grant has allowed us to characterize and isolate TSO2 that encodes the small subunit of the ribonucleotide reductase (RNR). RNR comprises two large subunits (R1) an d two small subunits (R2), catalyzes a rate-limiting step in the production of deoxyribonucleotides needed for DNA replication and repair. Previous studies in yeast and mammals indicated that defective RNR often led to cell cycle arrest, growth retardation and p53-dependent apoptosis while abnormally elevated RNR activities led to higher mutation rates. Subsequently, we identified two additional R2 genes, R2A and R2B in the Arabidopsis genome. Using reverse genetics, mutations in R2A and R2B were isolated, and double and triple mutants among the three R2 genes (TSO2, R2A and R2B) were constructed and analyzed. We showed that Arabidopsis tso2 mutants, with reduced dNTP levels, were more sensitive to UV-C. While r2a or r2b single mutants did not exhibit any phenotypes, tso2 r2b double mutants were embryonic lethal and tso2 r2a double mutants were seedling lethal indicating redundant functions among the three R2 genes. Furthermore, tso2 r2a double mutants exhibited increased DNA dam age, massive programmed cell death, and the release of transcriptional gene silencing. Our data suggests that plants can initiate programmed cell death to eliminate damaged cells despite the absence of p53 in plant genome.« less

Cloning of murine RNA polymerase I-specific TAF factors: conserved interactions between the subunits of the species-specific transcription initiation factor TIF-IB/SL1.

PubMed

Heix, J; Zomerdijk, J C; Ravanpay, A; Tjian, R; Grummt, I

1997-03-04

Promoter selectivity for all three classes of eukaryotic RNA polymerases is brought about by multimeric protein complexes containing TATA box binding protein (TBP) and specific TBP-associated factors (TAFs). Unlike class II- and III-specific TBP-TAF complexes, the corresponding murine and human class I-specific transcription initiation factor TIF-IB/SL1 exhibits a pronounced selectivity for its homologous promoter. As a first step toward understanding the molecular basis of species-specific promoter recognition, we cloned the cDNAs encoding the three mouse pol I-specific TBP-associated factors (TAFIs) and compared the amino acid sequences of the murine TAFIs with their human counterparts. The four subunits from either species can form stable chimeric complexes that contain stoichiometric amounts of TBP and TAFIs, demonstrating that differences in the primary structure of human and mouse TAFIs do not dramatically alter the network of protein-protein contacts responsible for assembly of the multimeric complex. Thus, primate vs. rodent promoter selectivity mediated by the TBP-TAFI complex is likely to be the result of cumulative subtle differences between individual subunits that lead to species-specific properties of RNA polymerase I transcription.

Development of a duplex droplet digital PCR assay for absolute quantitative detection of "Candidatus Liberibacter asiaticus".

PubMed

Selvaraj, Vijayanandraj; Maheshwari, Yogita; Hajeri, Subhas; Chen, Jianchi; McCollum, Thomas Greg; Yokomi, Raymond

2018-01-01

Huanglongbing (HLB, citrus greening) is a devastating citrus disease affecting citrus production worldwide. It is associated with the bacterium "Candidatus Liberibacter asiaticus" (CLas) and is vectored by the Asian citrus psyllid (ACP). Currently, diagnosis of CLas in regulatory samples is based on real-time quantitative polymerase chain reaction (qPCR) using 16S rRNA gene specific primers/probe. The detection of CLas using qPCR is challenging due to low pathogen titer and uneven distribution in infected plants and exacerbated by sampling issues and presence of inhibitors. This study evaluated a duplex droplet digital polymerase chain reaction (ddPCR) using multi-copy gene targets, 16S and RNR, to simultaneously detect CLas DNA targets in the same sample for unambiguous detection of the HLB pathogen in DNA extracts from citrus leaves and ACP. Standard curve analyses on tenfold dilution series with plasmid, citrus leaf and ACP DNA showed that both ddPCR and qPCR exhibited good linearity and efficiency in the duplex assay. CLas-infected low titer samples were used to validate the duplex ddPCR and qPCR performance and demonstrated that detection rate is higher when both 16S and RNR primers were used in duplex assay. However, the receiver operating characteristic analysis indicated that area under the curve for RNR primer was significantly broader, compared to 16S primers for CLas detection at low target titer. The absolute quantification of CLas at variable titers was reproducible and repeatable for both primer sets and the ddPCR showed higher resilience to PCR inhibitors with citrus leaf and ACP extracts. Hence, the resultant duplex ddPCR assay resulted in a significantly improved detection platform for diagnosis of CLas in samples with low pathogen titer.

Development of a duplex droplet digital PCR assay for absolute quantitative detection of "Candidatus Liberibacter asiaticus"

PubMed Central

Hajeri, Subhas; Chen, Jianchi; McCollum, Thomas Greg

2018-01-01

Huanglongbing (HLB, citrus greening) is a devastating citrus disease affecting citrus production worldwide. It is associated with the bacterium “Candidatus Liberibacter asiaticus” (CLas) and is vectored by the Asian citrus psyllid (ACP). Currently, diagnosis of CLas in regulatory samples is based on real-time quantitative polymerase chain reaction (qPCR) using 16S rRNA gene specific primers/probe. The detection of CLas using qPCR is challenging due to low pathogen titer and uneven distribution in infected plants and exacerbated by sampling issues and presence of inhibitors. This study evaluated a duplex droplet digital polymerase chain reaction (ddPCR) using multi-copy gene targets, 16S and RNR, to simultaneously detect CLas DNA targets in the same sample for unambiguous detection of the HLB pathogen in DNA extracts from citrus leaves and ACP. Standard curve analyses on tenfold dilution series with plasmid, citrus leaf and ACP DNA showed that both ddPCR and qPCR exhibited good linearity and efficiency in the duplex assay. CLas-infected low titer samples were used to validate the duplex ddPCR and qPCR performance and demonstrated that detection rate is higher when both 16S and RNR primers were used in duplex assay. However, the receiver operating characteristic analysis indicated that area under the curve for RNR primer was significantly broader, compared to 16S primers for CLas detection at low target titer. The absolute quantification of CLas at variable titers was reproducible and repeatable for both primer sets and the ddPCR showed higher resilience to PCR inhibitors with citrus leaf and ACP extracts. Hence, the resultant duplex ddPCR assay resulted in a significantly improved detection platform for diagnosis of CLas in samples with low pathogen titer. PMID:29772016

Development and evaluation of yeast-based GFP and luciferase reporter assays for chemical-induced genotoxicity and oxidative damage.

PubMed

Suzuki, Hajime; Sakabe, Takahiro; Hirose, Yuu; Eki, Toshihiko

2017-01-01

We aimed to develop the bioassays for genotixicity and/or oxidative damage using the recombinant yeast. A genotoxicity assay was developed using recombinant Saccharomyces cerevisiae strain BY4741 with a green fluorescent protein (GFP) reporter plasmid, driven by the DNA damage-responsive RNR3 promoter. Enhanced fluorescence induction was observed in DNA repair-deficient strains treated with methyl methanesulfonate, but not with hydrogen peroxide. A GFP reporter yeast strain driven by the oxidative stress-responsive TRX2 promoter was newly developed to assess oxidative damage, but fluorescence was poorly induced by oxidants. In place of GFP, yeast strains with luciferase gene reporter plasmids (luc2 and luc2CP, encoding stable and unstable luciferase, respectively) were prepared. Transient induction of luciferase activity was clearly detected only in a TRX2 promoter-driven luc2CP reporter strain within 90 min of oxidant exposure. However, luciferase was strongly induced by hydroxyurea in the RNR3 promoter-driven luc2 and GFP reporter strains over 8 h after the exposure, suggesting that the RNR3 promoter is continuously upregulated by DNA damage, whereas the TRX2 promoter is transiently activated by oxidative agents. Luciferase activity levels were also increased in a TRX2-promoter-driven luc2CP reporter strain treated with tert-butyl hydroperoxide and menadione and weakly induced with diamide and diethyl maleate. Weakly enhanced luciferase activity induction was detected in the sod1Δ, sod2Δ, and rad27Δ strains treated with hydrogen peroxide compared with that in the wild-type strain. In conclusion, tests using GFP and stable luciferase reporters are useful for genotoxicity, and oxidative damage can be clearly detected by assay with an unstable luciferase reporter.

Iyengar Yoga for Adolescents and Young Adults With Irritable Bowel Syndrome

PubMed Central

Evans, Subhadra; Lung, Kirsten C.; Seidman, Laura C.; Sternlieb, Beth; Zeltzer, Lonnie K.; Tsao, Jennie C.I.

2014-01-01

Objectives Irritable bowel syndrome (IBS) is a chronic, disabling condition that greatly compromises patient functioning. The aim of this study was to assess the impact of a 6-week twice per week Iyengar yoga (IY) program on IBS symptoms in adolescents and young adults (YA) with IBS compared with a usual-care waitlist control group. Methods Assessments of symptoms, global improvement, pain, health-related quality of life, psychological distress, functional disability, fatigue, and sleep were collected pre- and posttreatment. Weekly ratings of pain, IBS symptoms, and global improvement were also recorded until 2-month follow-up. A total of 51 participants completed the intervention (yoga = 29; usual-care waitlist = 22). Results Baseline attrition was 24%. On average, the yoga group attended 75% of classes. Analyses were divided by age group. Relative to controls, adolescents (14–17 years) assigned to yoga reported significantly improved physical functioning, whereas YA (18–26 years) assigned to yoga reported significantly improved IBS symptoms, global improvement, disability, psychological distress, sleep quality, and fatigue. Although abdominal pain intensity was statistically unchanged, 44% of adolescents and 46% of YA reported a minimally clinically significant reduction in pain following yoga, and one-third of YA reported clinically significant levels of global symptom improvement. Analysis of the uncontrolled effects and maintenance of treatment effects for adolescents revealed global improvement immediately post-yoga that was not maintained at follow-up. For YA, global improvement, worst pain, constipation, and nausea were significantly improved postyoga, but only global improvement, worst pain, and nausea maintained at the 2-month follow-up. Conclusions The findings suggest that a brief IY intervention is a feasible and safe adjunctive treatment for young people with IBS, leading to benefits in a number of IBS-specific and general functioning domains for YA. The age-specific results suggest that yoga interventions may be most fruitful when developmentally tailored. PMID:25025601

Iyengar yoga for adolescents and young adults with irritable bowel syndrome.

PubMed

Evans, Subhadra; Lung, Kirsten C; Seidman, Laura C; Sternlieb, Beth; Zeltzer, Lonnie K; Tsao, Jennie C I

2014-08-01

Irritable bowel syndrome (IBS) is a chronic, disabling condition that greatly compromises patient functioning. The aim of this study was to assess the impact of a 6-week twice per week Iyengar yoga (IY) program on IBS symptoms in adolescents and young adults (YA) with IBS compared with a usual-care waitlist control group. Assessments of symptoms, global improvement, pain, health-related quality of life, psychological distress, functional disability, fatigue, and sleep were collected pre- and posttreatment. Weekly ratings of pain, IBS symptoms, and global improvement were also recorded until 2-month follow-up. A total of 51 participants completed the intervention (yoga = 29; usual-care waitlist = 22). Baseline attrition was 24%. On average, the yoga group attended 75% of classes. Analyses were divided by age group. Relative to controls, adolescents (14-17 years) assigned to yoga reported significantly improved physical functioning, whereas YA (18-26 years) assigned to yoga reported significantly improved IBS symptoms, global improvement, disability, psychological distress, sleep quality, and fatigue. Although abdominal pain intensity was statistically unchanged, 44% of adolescents and 46% of YA reported a minimally clinically significant reduction in pain following yoga, and one-third of YA reported clinically significant levels of global symptom improvement. Analysis of the uncontrolled effects and maintenance of treatment effects for adolescents revealed global improvement immediately post-yoga that was not maintained at follow-up. For YA, global improvement, worst pain, constipation, and nausea were significantly improved postyoga, but only global improvement, worst pain, and nausea maintained at the 2-month follow-up. The findings suggest that a brief IY intervention is a feasible and safe adjunctive treatment for young people with IBS, leading to benefits in a number of IBS-specific and general functioning domains for YA. The age-specific results suggest that yoga interventions may be most fruitful when developmentally tailored.

Inhibition of Mutation: A Novel Approach to Preventing and Treating Cancer

DTIC Science & Technology

2007-06-01

Hydroxyurea (HU) is a small molecule chemotherapeutic that is thought to slow tumor growth by inhibiting RNR and thus reducing dNTP...Identification of hydroxyurea as an inhibitor of induced mutation that presumably acts by inhibiting ribonucleotide reductase and thereby decreasing the

ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

DOE PAGES

Le, Thuc M.; Poddar, Soumya; Capri, Joseph R.; ...

2017-08-14

It is known that leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the diseasemore » in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.« less

The Availability and Utility of Services to Address Risk Factors for Recidivism among Justice-Involved Veterans

PubMed Central

Blonigen, Daniel M.; Rodriguez, Allison L.; Manfredi, Luisa; Britt, Jessica; Nevedal, Andrea; Finlay, Andrea K.; Rosenthal, Joel; Smelson, David; Timko, Christine

2016-01-01

The availability and utility of services to address recidivism risk factors among justice-involved veterans is unknown. We explored these issues through qualitative interviews with 63 Specialists from the Department of Veterans Affairs’ (VA) Veterans Justice Programs. To guide the interviews, we utilized the Risk-Need-Responsivity (RNR) model of offender rehabilitation. Specialists reported that justice-involved veterans generally have access to services to address most RNR-based risk factors (substance abuse; lack of positive school/work involvement; family/marital dysfunction; lack of prosocial activities/interests), but have less access to services targeting risk factors of antisocial tendencies and associates and empirically-based treatments for recidivism in VA. Peer-based services, motivational interviewing/cognitive-behavioral therapy, and Veterans Treatment Courts were perceived as useful to address multiple risk factors. These findings highlight potential gaps in provision of evidence-based care to address recidivism among justice-involved veterans, as well as promising policy-based solutions that may have widespread impact on reducing recidivism in this population. PMID:26924887

ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le, Thuc M.; Poddar, Soumya; Capri, Joseph R.

It is known that leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the diseasemore » in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.« less

Alpha-synuclein functions in the nucleus to protect against hydroxyurea-induced replication stress in yeast

PubMed Central

Liu, Xianpeng; Lee, Yong Joo; Liou, Liang-Chun; Ren, Qun; Zhang, Zhaojie; Wang, Shaoxiao; Witt, Stephan N.

2011-01-01

Hydroxyurea (HU) inhibits ribonucleotide reductase (RNR), which catalyzes the rate-limiting synthesis of deoxyribonucleotides for DNA replication. HU is used to treat HIV, sickle-cell anemia and some cancers. We found that, compared with vector control cells, low levels of alpha-synuclein (α-syn) protect S. cerevisiae cells from the growth inhibition and reactive oxygen species (ROS) accumulation induced by HU. Analysis of this effect using different α-syn mutants revealed that the α-syn protein functions in the nucleus and not the cytoplasm to modulate S-phase checkpoint responses: α-syn up-regulates histone acetylation and RNR levels, maintains helicase minichromosome maintenance protein complexes (Mcm2–7) on chromatin and inhibits HU-induced ROS accumulation. Strikingly, when residues 2–10 or 96–140 are deleted, this protective function of α-syn in the nucleus is abolished. Understanding the mechanism by which α-syn protects against HU could expand our knowledge of the normal function of this neuronal protein. PMID:21642386

Advancements in drug development for diarrhea-predominant irritable bowel syndrome.

PubMed

Dothel, Giovanni; Barbaro, Maria Raffaella; Raschi, Emanuel; Barbara, Giovanni; De Ponti, Fabrizio

2018-03-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder characterized by a complex pathophysiology hampering optimal targeted drug development. Recent advances in our understanding of key underlying mechanisms prompted novel therapeutics including novel pharmacological approaches. Areas covered: This review summarizes the latest advancements in the pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and safety of medicinal products considering the recent harmonization of regulatory requirements by the FDA and the EMA. Expert opinion: The new 5-HT 3 receptor antagonist ramosetron appears a promising therapeutic approach devoid of significant adverse events, although it is presently unavailable in Western countries, most likely because of the precautionary approach taken by regulatory agencies with this drug class. New pharmacological concepts on full agonists/antagonists, mixed-receptor activity and novel drug targets may streamline the present drug pipeline along with the adherence on new regulatory guidelines on outcome measures. Eluxadoline can be taken as an example of this paradigm shift. It has now been granted marketing authorization for IBS-D on both sides of the Atlantic, but it is still considered as a second-line agent by the NICE. There is still much work to be done to fully cover clinical needs of patients with IBS-D.

Commitment to the Study of International Business and Cultural Intelligence: A Multilevel Model

ERIC Educational Resources Information Center

Ramsey, Jase R.; Barakat, Livia L.; Aad, Amine Abi

2014-01-01

Adopting a multilevel theoretical framework, we examined how metacognitive and motivational cultural intelligence influence an individual's commitment to the study of international business (IB). Data from 292 undergraduate and graduate business students nested in 12 U.S. business school classes demonstrated that individuals' metacognitive and…

Risk, Need, and Responsivity (RNR): It All Depends

ERIC Educational Resources Information Center

Taxman, Faye S.; Thanner, Meridith

2006-01-01

Target populations have always been a thorny issue for correctional programs. In this experiment of seamless treatment for probationers in two sites, offenders were randomly assigned to the seamless model (drug treatment incorporated into probation supervision) or traditional referral model to services in the community. The experiment blocked on…

Cloning of murine RNA polymerase I-specific TAF factors: Conserved interactions between the subunits of the species-specific transcription initiation factor TIF-IB/SL1

PubMed Central

Heix, Jutta; Zomerdijk, Joost C. B. M.; Ravanpay, Ali; Tjian, Robert; Grummt, Ingrid

1997-01-01

Promoter selectivity for all three classes of eukaryotic RNA polymerases is brought about by multimeric protein complexes containing TATA box binding protein (TBP) and specific TBP-associated factors (TAFs). Unlike class II- and III-specific TBP–TAF complexes, the corresponding murine and human class I-specific transcription initiation factor TIF-IB/SL1 exhibits a pronounced selectivity for its homologous promoter. As a first step toward understanding the molecular basis of species-specific promoter recognition, we cloned the cDNAs encoding the three mouse pol I-specific TBP-associated factors (TAFIs) and compared the amino acid sequences of the murine TAFIs with their human counterparts. The four subunits from either species can form stable chimeric complexes that contain stoichiometric amounts of TBP and TAFIs, demonstrating that differences in the primary structure of human and mouse TAFIs do not dramatically alter the network of protein–protein contacts responsible for assembly of the multimeric complex. Thus, primate vs. rodent promoter selectivity mediated by the TBP–TAFI complex is likely to be the result of cumulative subtle differences between individual subunits that lead to species-specific properties of RNA polymerase I transcription. PMID:9050847

Foods of juvenile ring-necked ducks: Relationship to wetland pH

USGS Publications Warehouse

McAuley, D.G.; Longcore, J.R.

1988-01-01

Foods of 37 juvenile ring-necked ducks (Aythya collaris) from 16 different wetlands were examined in eastcentral Maine in 1983-85. Invertebrates made up 70% aggregate dry weight (100% occurrence) of the foods of Class Ia-lla ( 24 days old) ducklings and 32% (86% occurrence) of Class lIb-III ( 25 days old) ducklings. These percentages may be as high as 85% for Ia-lla ducklings and 47% for lIb-III ducklings after adjusting for insect sclerites. Ducklings ate invertebrates from 44 taxa and seeds or fibers from 23 plant taxa. Freshwater sponges (Porifera) were the most important invertebrate and constituted 23% of the foods of all ducklings. Seeds of pondweeds (Potamogeton spp.) were the most important plant foods. Diets of ducklings from high-pH (>6.1) wetlands were more diverse (t = 2.54, P = 0.021) than those from low-pH (<6.1) wetlands and consisted of 33 invertebrate taxa. Only 17 taxa occurred in ducklings from low-pH ponds. Class Ia-lla ducklings from high-pH wetlands ate more invertebrates (77%) than ducklings from lower-pH wetlands (61%), although the difference was not significant (P = 0.21). Sponges made up the largest percentage of the diets and occurred in similar amounts in high- (34%) and low- (31.5%) pH wetlands.

Association of HLA-A and Non-Classical HLA Class I Alleles

PubMed Central

Carlini, Federico; Ferreira, Virginia; Buhler, Stéphane; Tous, Audrey; Eliaou, Jean-François; René, Céline; Chiaroni, Jacques; Picard, Christophe; Di Cristofaro, Julie

2016-01-01

The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region. PMID:27701438

Coevolution of MHC genes (LMP/TAP/class Ia; NKT-class Ib; NKp30-B7H6): Lessons from cold-blooded vertebrates

PubMed Central

Ohta, Yuko; Flajnik, Martin F.

2015-01-01

Summary Comparative immunology provides the long view of what is conserved across all vertebrate taxa versus what is specific to particular organisms or group of organisms. Regarding the major histocompatibility complex (MHC) and coevolution, three striking cases have been revealed in cold-blooded vertebrates: lineages of class Ia antigen-processing and -presenting genes, evolutionary conservation of NKT-class Ib recognition, and the ancient emergence of the natural cytotoxicity receptor NKp30 and its ligand B7H6. While coevolution of transporter associated with antigen processing (TAP) and class Ia has been documented in endothermic birds and two mammals, lineages of LMP7 are restricted to ectotherms. The unambiguous discovery of natural killer T (NKT) cells in Xenopus demonstrated that NKT cells are not restricted to mammals and are likely to have emerged at the same time in evolution as classical α/β and γ/δ T cells. NK cell receptors evolve at a rapid rate, and orthologues are nearly impossible to identify in different vertebrate classes. By contrast, we have detected NKp30 in all gnathostomes, except in species where it was lost. The recently discovered ligand of NKp30, B7H6, shows strong signs of coevolution with NKp30 throughout evolution, i.e. coincident loss or expansion of both genes in some species. NKp30 also offers an attractive IgSF candidate for the invasion of the RAG transposon, which is believed to have initiated T-cell receptor/immunoglobulin adaptive immunity. Besides reviewing these intriguing features of MHC evolution and coevolution, we offer suggestions for future studies and propose a model for the primordial or proto MHC. PMID:26284468

41 CFR 109-38.104 - Fuel efficient passenger automobiles and light trucks.

Code of Federal Regulations, 2011 CFR

2011-01-01

... automobiles and light trucks. 109-38.104 Section 109-38.104 Public Contracts and Property Management Federal... Vehicles § 109-38.104 Fuel efficient passenger automobiles and light trucks. (a) [Reserved] (b) All requests to purchase passenger automobiles larger than class IA, IB, or II (small, subcompact, or compact...

41 CFR 109-38.104 - Fuel efficient passenger automobiles and light trucks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... automobiles and light trucks. 109-38.104 Section 109-38.104 Public Contracts and Property Management Federal... Vehicles § 109-38.104 Fuel efficient passenger automobiles and light trucks. (a) [Reserved] (b) All requests to purchase passenger automobiles larger than class IA, IB, or II (small, subcompact, or compact...

41 CFR 109-38.104 - Fuel efficient passenger automobiles and light trucks.

Code of Federal Regulations, 2014 CFR

2014-01-01

... automobiles and light trucks. 109-38.104 Section 109-38.104 Public Contracts and Property Management Federal... Vehicles § 109-38.104 Fuel efficient passenger automobiles and light trucks. (a) [Reserved] (b) All requests to purchase passenger automobiles larger than class IA, IB, or II (small, subcompact, or compact...

41 CFR 109-38.104 - Fuel efficient passenger automobiles and light trucks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... automobiles and light trucks. 109-38.104 Section 109-38.104 Public Contracts and Property Management Federal... Vehicles § 109-38.104 Fuel efficient passenger automobiles and light trucks. (a) [Reserved] (b) All requests to purchase passenger automobiles larger than class IA, IB, or II (small, subcompact, or compact...

41 CFR 109-38.104 - Fuel efficient passenger automobiles and light trucks.

Code of Federal Regulations, 2012 CFR

2012-01-01

... automobiles and light trucks. 109-38.104 Section 109-38.104 Public Contracts and Property Management Federal... Vehicles § 109-38.104 Fuel efficient passenger automobiles and light trucks. (a) [Reserved] (b) All requests to purchase passenger automobiles larger than class IA, IB, or II (small, subcompact, or compact...

Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

PubMed Central

Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

2014-01-01

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

[Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant gliomas--a new treatment modality].

PubMed

Cortnum, Søren; Laursen, Rene

2013-02-25

5-aminolevulinic acid (ALA) is a precursor of haemoglobin which leads to the synthesis of porphyrins in malignant gliomas which then appears with red fluorescence under blue light. In the literature we see that there is class Ib evidence that 5-ALA guided surgery significantly increases the radicalism of surgery and gives rise to a marked improvement in 6-month progression-free survival and that there is now class II evidence confirming the value of maximal cytoreductive surgery. Furthermore, existing class II evidence indicates that there is a synergistic effect between aggressive cytoreductive surgery and radiochemotherapy.

Is the mu-oxo-mu-peroxodiiron intermediate of a ribonucleotide reductase biomimetic a possible oxidant of epoxidation reactions?

PubMed

de Visser, Sam P

2008-01-01

Density functional calculations on a mu-oxo-mu-peroxodiiron complex (1) with a tetrapodal ligand BPP (BPP=N,N-bis(2-pyridylmethyl)-3-aminopropionate) are presented that is a biomimetic of the active site region of ribonucleotide reductase (RNR). We have studied all low-lying electronic states and show that it has close-lying broken-shell singlet and undecaplet (S=0, 5) ground states with essentially two sextet spin iron atoms. In strongly distorted electronic systems in which the two iron atoms have different spin states, the peroxo group moves considerably out of the plane of the mu-oxodiiron group due to orbital rearrangements. The calculated absorption spectra of (1,11)1 are in good agreement with experimental studies on biomimetics and RNR enzyme systems. Moreover, vibrational shifts in the spectrum due to (18)O(2) substitution of the oxygen atoms in the peroxo group follow similar trends as experimental observations. To identify whether the mu-oxo-mu-1,2-peroxodiiron or the mu-oxo-mu-1,1-peroxodiiron complexes are able to epoxidize substrates, we studied the reactivity patterns versus propene. Generally, the reactions are stepwise via radical intermediates and proceed by two-state reactivity patterns on competing singlet and undecaplet spin state surfaces. However, both the mu-oxo-mu-1,2-peroxodiiron and mu-oxo-mu-1,1-peroxodiiron complex are sluggish oxidants with high epoxidation barriers. The epoxidation barriers for the mu-oxo-mu-1,1-peroxodiiron complex are significantly lower than the ones for the mu-oxo-mu-1,2-peroxodiiron complex but still are too high to be considered for catalytic properties. Thus, theory has ruled out two possible peroxodiiron catalysts as oxidants in RNR enzymes and biomimetics and the quest to find the actual oxidant in the enzyme mechanism continues.

40 CFR 90.410 - Engine test cycle.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Engine test cycle. 90.410 Section 90...) CONTROL OF EMISSIONS FROM NONROAD SPARK-IGNITION ENGINES AT OR BELOW 19 KILOWATTS Gaseous Exhaust Test Procedures § 90.410 Engine test cycle. (a) Follow the appropriate 6-mode test cycle for Class I, I-B and II...

40 CFR 90.410 - Engine test cycle.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Engine test cycle. 90.410 Section 90...) CONTROL OF EMISSIONS FROM NONROAD SPARK-IGNITION ENGINES AT OR BELOW 19 KILOWATTS Gaseous Exhaust Test Procedures § 90.410 Engine test cycle. (a) Follow the appropriate 6-mode test cycle for Class I, I-B and II...

Characterization of In40 of Enterobacter aerogenes BM2688, a Class 1 Integron with Two New Gene Cassettes, cmlA2 and qacF

PubMed Central

Ploy, Marie-Cécile; Courvalin, Patrice; Lambert, Thierry

1998-01-01

Enterobacter aerogenes BM2688, which is resistant to multiple antibiotics, and its aminoglycoside-susceptible derivative BM2688-1 were isolated from the same clinical sample. Strain BM2688 harbored plasmid pIP833, which carries a class 1 integron, In40, containing (in addition to qacEΔ1 and sul1, which are characteristic of class 1 integrons) four gene cassettes: aac(6′)-Ib, qacF, cmlA2, and oxa-9. The cmlA2 gene had 83.7% identity with the previously described nonenzymatic chloramphenicol resistance cmlA1 gene. The qacF gene conferred resistance to quaternary ammonium compounds and displayed a high degree of similarity with qacE (67.8% identity) which, however, has been found as part of a cassette with a very different 59-base element. The oxa-9 gene was not expressed due to a lack of promoter sequences. Study of the antibiotic-susceptible derivative BM2688-1 indicated that a 3,148-bp deletion between the 3′ end of the aac(6′)-Ib gene and the 3′ conserved segment of In40 was responsible for the loss of resistance. The occurrence of this DNA rearrangement, which did not involve homologous sequences, suggests that the In40 integrase could promote recombination at secondary sites. PMID:9756755

Adoption and validation of Ribonucleotide Reductase (RNR)-based real-time assays for detection of HLB ‘Candidatus Liberibacter asiaticus’ (CLas)

USDA-ARS?s Scientific Manuscript database

Huanglongbing (HLB), aka Citrus Greening, is a well-known destructive disease that threatens the multi-billion dollar citrus industry in the United States and citrus production in other countries around the world. The presumptive causal agent of HLB, ‘Candidatus Liberibacter asiaticus' (CLas), is of...

Fine mapping and identification of candidate genes for a QTL affecting Meloidogyne incognita reproduction in Upland cotton

USDA-ARS?s Scientific Manuscript database

The resistant line Auburn 623RNR and a number of elite breeding lines derived from it remain the most important source of root-knot nematode (RKN) resistance because they exhibit the highest level of resistance to RKN known to date in Upland cotton (Gossypium hirsutum L). Prior genetic mapping analy...

The Recent Past and near Future of Risk and/or Need Assessment

ERIC Educational Resources Information Center

Andrews, D. A.; Bonta, James; Wormith, J. Stephen

2006-01-01

The history of risk assessment in criminal justice has been written on several occasions. In this article, the authors assess progress since Andrews, Bonta, and Hoge's statement of the human service principles of risk-need-responsivity (RNR) and professional discretion. The review is conducted in the context of the advent of the fourth generation…

Post-Infectious IBS (IBS-PI)

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

IBS Diet

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Introduction to IBS

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Relaxation Techniques to Manage IBS Symptoms

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Short linear motif acquisition, exon formation and alternative splicing determine a pathway to diversity for NCoR-family co-repressors

PubMed Central

Short, Stephen; Peterkin, Tessa; Guille, Matthew; Patient, Roger; Sharpe, Colin

2015-01-01

Vertebrate NCoR-family co-repressors play central roles in the timing of embryo and stem cell differentiation by repressing the activity of a range of transcription factors. They interact with nuclear receptors using short linear motifs (SLiMs) termed co-repressor for nuclear receptor (CoRNR) boxes. Here, we identify the pathway leading to increasing co-repressor diversity across the deuterostomes. The final complement of CoRNR boxes arose in an ancestral cephalochordate, and was encoded in one large exon; the urochordates and vertebrates then split this region between 10 and 12 exons. In Xenopus, alternative splicing is prevalent in NCoR2, but absent in NCoR1. We show for one NCoR1 exon that alternative splicing can be recovered by a single point mutation, suggesting NCoR1 lost the capacity for alternative splicing. Analyses in Xenopus and zebrafish identify that cellular context, rather than gene sequence, predominantly determines species differences in alternative splicing. We identify a pathway to diversity for the NCoR family beginning with the addition of a SLiM, followed by gene duplication, the generation of alternatively spliced isoforms and their differential deployment. PMID:26289800

Recognizing Symptoms

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Pregnancy and Irritable Bowel Syndrome

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Sleep and Irritable Bowel Syndrome

MedlinePlus

... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ... IBS Patients' Experience and Unmet Needs IBS and Holidays Personal Stories IBS Awareness Month IBS Awareness Month ...

Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities.

PubMed

Kibune Nagasako, Cristiane; Garcia Montes, Ciro; Silva Lorena, Sônia Letícia; Mesquita, Maria Aparecida

2016-02-01

Irritable bowel syndrome (IBS) is classified into subtypes according to bowel habit. To investigate whether there are differences in clinical features, comorbidities, anxiety, depression and body mass index (BMI) among IBS subtypes. The study group included 113 consecutive patients (mean age: 48 ± 11 years; females: 94) with the diagnosis of IBS. All of them answered a structured questionnaire for demographic and clinical data and underwent upper endoscopy. Anxiety and depression were assessed by the Hospital Anxiety and Depression scale (HAD). The distribution of subtypes was: IBS-diarrhea (IBS-D), 46%; IBS-constipation (IBS-C), 32%, and mixed IBS (IBS-M), 22%. IBS overlap with gastroesophageal reflux disease (GERD), functional dyspepsia, chronic headache and fibromyalgia occurred in 65.5%, 48.7%, 40.7% and 22.1% of patients, respectively. Anxiety and/or depression were found in 81.5%. Comparisons among subgroups showed that bloating was significantly associated with IBS-M compared to IBS-D (odds ratio-OR-5.6). Straining was more likely to be reported by IBS-M (OR 15.3) and IBS-C (OR 12.0) compared to IBS-D patients, while urgency was associated with both IBS-M (OR 19.7) and IBS-D (OR 14.2) compared to IBS-C. In addition, IBS-M patients were more likely to present GERD than IBS-D (OR 6.7) and higher scores for anxiety than IBS-C patients (OR 1.2). BMI values did not differ between IBS-D and IBS-C. IBS-M is characterized by symptoms frequently reported by both IBS-C (straining) and IBS-D (urgency), higher levels of anxiety, and high prevalence of comorbidities. These features should be considered in the clinical management of this subgroup.

An Empirical Study on Washback Effects of the Internet-Based College English Test Band 4 in China

ERIC Educational Resources Information Center

Wang, Chao; Yan, Jiaolan; Liu, Bao

2014-01-01

Based on Bailey's washback model, in respect of participants, process and products, the present empirical study was conducted to find the actual washback effects of the internet-based College English Test Band 4 (IB CET-4). The methods adopted are questionnaires, class observation, interview and the analysis of both the CET-4 teaching and testing…

Locking plate and fibular strut-graft augmentation in the reconstruction of unicameral bone cyst of proximal femur in the paediatric population.

PubMed

Jamshidi, Khodamorad; Mirkazemi, Masoud; Izanloo, Azra; Mirzaei, Alireza

2018-01-01

Several therapeutic strategies have been used for managing unicameral bone cyst (UBC) of the proximal femur. However, there is insufficient evidence to support one treatment over another, and the optimal treatment is controversial. This study aims at describing our experience with surgical reconstruction of paediatric UBCs of the proximal femur using a proximal locking plate and fibular strut allograft. In total, 14 consecutive paediatric patients with Dormans types IB (four cases) and IIB (10 cases) UBC were assessed. Mean patient age was 8.6 ± 2.3 years, and mean follow-up period was 41.7 ± 29.8 months. Six patients (42.8%) were referred with a pathologic fracture. Clinical/radiological outcome and complication rates were evaluated at the final follow-up session. No cysts were Capanna's class III (recurrence) or IV (no response). Complete healing (Capanna's class I) was seen in ten cysts, while four other cysts healed with residual radiolucent areas (Capanna's class II). Mean healing period was 14.1 ± 5.1 (9-24 months). One patient had superficial infection, one heterotopic ossification, and one mild coxa vara, and mean Musculoskeletal Tumor Society (MSTS) score was 99.5%. According to our results, locking plate and fibular strut graft in Dormans classification types IB and IIB results in a favorable outcome in managing UBC of the proximal femur in the paediatric population.

A Phylogenomic Investigation of CYCLOIDEA-Like TCP Genes in the Leguminosae1

PubMed Central

Citerne, Hélène L.; Luo, Da; Pennington, R. Toby; Coen, Enrico; Cronk, Quentin C.B.

2003-01-01

Numerous TCP genes (transcription factors with a TCP domain) occur in legumes. Genes of this class in Arabidopsis (TCP1) and snapdragon (Antirrhinum majus; CYCLOIDEA) have been shown to be asymmetrically expressed in developing floral primordia, and in snapdragon, they are required for floral zygomorphy (bilaterally symmetrical flowers). These genes are therefore particularly interesting in Leguminosae, a family that is thought to have evolved zygomorphy independently from other zygomorphic angiosperm lineages. Using a phylogenomic approach, we show that homologs of TCP1/CYCLOIDEA occur in legumes and may be divided into two main classes (LEGCYC group I and II), apparently the result of an early duplication, and each class is characterized by a typical amino acid signature in the TCP domain. Furthermore, group I genes in legumes may be divided into two subclasses (LEGCYC IA and IB), apparently the result of a duplication near the base of the papilionoid legumes or below. Most papilionoid legumes investigated have all three genes present (LEGCYC IA, IB, and II), inviting further work to investigate possible functional difference between the three types. However, within these three major gene groups, the precise relationships of the paralogs between species are difficult to determine probably because of a complex history of duplication and loss with lineage sorting or heterotachy (within-site rate variation) due to functional differentiation. The results illustrate both the potential and the difficulties of orthology determination in variable gene families, on which the phylogenomic approach to formulating hypotheses of function depends. PMID:12644657

Protection of chickens vaccinated with combinations of commercial live infectious bronchitis vaccines containing Massachusetts, Dutch and QX-like serotypes against challenge with virulent infectious bronchitis viruses 793B and IS/1494/06 Israel variant 2.

PubMed

Bru, T; Vila, R; Cabana, M; Geerligs, H J

2017-02-01

Infectious bronchitis virus (IBV) is a coronavirus which affects chickens of all ages. IBV mainly causes respiratory disease but can also result in reduced weight gain, reduced egg production, increased frequency of abnormal eggs and increased rates of mortality. Vaccination is the most important way to control the disease. Nevertheless, novel strains of infectious bronchitis (IB) continue to emerge in the field. In order to respond promptly, combinations of existing IB vaccines are frequently tested to see whether they can provide cross-protection. The efficacy of a combination of vaccines based on Massachusetts, Dutch and QX-like IB strains against emerging IB Israel variant 2 and IB 793B strains was assessed by means of four challenge studies. At least 80% of the birds vaccinated with IB H120 (Mass type) combined with IB D274 (Dutch type) followed by a QX-like IB vaccine booster or vaccinated with a combination of IB H120, IB D274 and QX-like IB were protected against a challenge with IB 793B. In addition, IB 1263 (Mass type) boosted by QX-like IB showed an 85% protection following challenge with IB 793B. A combination of IB H120 and IB D274 boosted by QX-like IB vaccine conferred 70% protection whilst H120 and IB D274 combination on its own showed 61.1% protection against Israel variant 2 challenge. IB 1263 boosted by a QX-like IB vaccine showed 50% protection against IB Israel variant 2. Therefore, it can be concluded that a combination of the IB H120, IB D274 and QX-like IB confers broad protection against different non-related virulent IB strains.

Characterization of Symptoms in Irritable Bowel Syndrome with Mixed Bowel Habit Pattern

PubMed Central

Su, Andrew; Shih, Wendy; Presson, Angela P.; Chang, Lin

2013-01-01

Background Irritable bowel syndrome (IBS) with mixed bowel habits (IBS-M) is a heterogeneous subtype with varying symptoms of constipation and diarrhea, and has not been well characterized. We aimed to characterize gastrointestinal (GI) and non-GI symptoms in IBS-M patients from a U.S. community, and to compare them with IBS with constipation (IBS-C) and diarrhea (IBS-D). Methods Subjects answering community advertisements and meeting Rome III criteria for IBS completed symptom questionnaires. Key Results Of the initial 289 IBS patients identified, one-third (n=51, 32.5%) who met Rome III criteria for IBS-M endorsed having either loose stools or hard stools due to medication. These patients had more severe symptoms and longer duration of flares compared to the rest of the IBS-M group (p = 0.014, p = 0.005). Excluding IBS-M patients with medication-related extremes in stool form who could not be reclassified by medical history, 247 IBS patients were assessed. IBS-M was the most common (44.1%), followed by IBS-C (27.9%), IBS-D (26.3%), and IBS-U (unsubtyped, 1.6%). IBS-M shared symptoms with both IBS-C and IBS-D (p-value range: <0.001–0.002). IBS-M patients reported most bothersome symptoms more similarly to IBS-D, with the most common being irregular bowel habits (27.5%), bloating (26.6%), and abdominal pain (20.2%). There were no differences in non-GI symptoms between subtypes. Conclusions & Inferences IBS-M is a heterogeneous symptom group and thus requires that subclassification criteria be better defined. Use of laxative/anti-diarrheal medications adds to the diagnostic complexity in a potentially more severe subset of IBS-M and should be assessed for accurate subclassification. PMID:23991913

Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability.

PubMed

O'Rourke, Thomas W; Doudican, Nicole A; Zhang, Hong; Eaton, Jana S; Doetsch, Paul W; Shadel, Gerald S

2005-07-18

With the exception of base excision repair, conserved pathways and mechanisms that maintain mitochondrial genome stability have remained largely undelineated. In the budding yeast, Saccharomyces cerevisiae, Pif1p is a unique DNA helicase that is localized both to the nucleus and mitochondria, where it is involved in maintaining DNA integrity. We previously elucidated a role for Pif1p in oxidative mtDNA damage resistance that appears to be distinct from its postulated function in mtDNA recombination. Strains lacking Pif1p (pif1Delta) exhibit an increased rate of formation of petite mutants (an indicator of mtDNA instability) and elevated mtDNA point mutagenesis. Here we show that deletion of the RRM3 gene, which encodes a DNA helicase closely related to Pif1p, significantly rescues the petite-induction phenotype of a pif1Delta strain. However, suppression of this phenotype was not accompanied by a corresponding decrease in mtDNA point mutagenesis. Instead, deletion of RRM3 alone resulted in an increase in mtDNA point mutagenesis that was synergistic with that caused by a pif1Delta mutation. In addition, we found that over-expression of RNR1, encoding a large subunit of ribonucleotide reductase (RNR), rescued the petite-induction phenotype of a pif1Delta mutation to a similar extent as deletion of RRM3. This, coupled to our finding that the Rad53p protein kinase is phosphorylated in the rrm3Delta pif1Delta double-mutant strain, leads us to conclude that one mechanism whereby deletion of RRM3 influences mtDNA stability is by modulating mitochondrial deoxynucleoside triphosphate pools. We propose that this is accomplished by signaling through the conserved Mec1/Rad53, S-phase checkpoint pathway to induce the expression and activity of RNR. Altogether, our results define a novel role for Rrm3p in mitochondrial function and indicate that Pif1p and Rrm3p influence a common process (or processes) involved in mtDNA replication, repair, or stability.

Pharmacy benefit forecast for a new interferon Beta-1a for the treatment of multiple sclerosis: development of a first-line decision tool for pharmacy-budget planning using administrative claims data.

PubMed

Meyer, Christina M; Phipps, Robert; Cooper, Deborah; Wright, Alan

2003-01-01

To estimate the incremental change in pharmacy per-member-permonth (PMPM) costs, according to various formulary designs, for a new interferon beta-1a product (IB1a2) using administrative claims data. Cross-sectional sex- and age-specific disease prevalence and treatment rates for relapsing, remitting multiple sclerosis (RRMS) patients were measured using integrated medical and pharmacy claims data from a 500,000- member employer group in the southern United States. Migration to IB1a2 from other drugs in the class was based on market-share data for new and existing RRMS patients. Duration of therapy was estimated by analyzing claims for current RRMS therapies. Daily therapy cost was provided by the manufacturer of IB1a2, adjusted for migration from other therapies, and multiplied by estimated volume to predict incremental and total PMPM cost impact. Market-share estimates were used to develop a PMPM cost forecast for the next 2 years. PMPM cost estimates were calculated for preferred (copayment tier 2) and nonpreferred (copayment tier 3) formulary designs with and without prior authorization (PA). One-way sensitivity analysis was performed to assess the influence of product pricing, duration of therapy, and other market factors. Annual incremental PMPM change was $0.047 for the scenario of third copayment tier with PA. The incremental change was greatest for those aged 55 to 65 years ($0.056 PMPM) and did not vary greatly by benefit design. Duration of therapy had the greatest impact on the PMPM estimate across benefit designs. IB1a2 will not cause a significant change in managed care pharmacy budgets under a variety of formulary conditions, according to this crosssectional analysis of current care-seeking behavior by RRMS patients. Economic impact may differ if IB1a2 expands RRMS patients. treatment-seeking behavior.

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation

PubMed Central

Singh, Prashant; Staller, Kyle; Barshop, Kenneth; Dai, Elaine; Newman, Jennifer; Yoon, Sonia; Castel, Shahar; Kuo, Braden

2015-01-01

AIM: To determine effect of irritable bowel syndrome (IBS) subtype on IBS-specific quality of life (QOL) questionnaire and its subscales. METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States. IBS and IBS subtype were diagnosed using Rome-III questionnaire. QOL was assessed using IBS-QOL questionnaire. IBS-QOL assesses quality of life along eight subscales: dysphoria, interference with activities, body image, health worry, food avoidance, social reactions, sexual health, and effect on relationships. IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL. Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI. We compared mean IBS-QOL score and its subscales among various IBS-subtypes. Analysis of variance (ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender. A post-hoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05. RESULTS: Of 542 patients screened, 243 had IBS as per Rome-III criteria. IBS-mixed (IBS-M) was the most common IBS subtype (121 patients, 49.8%) followed by IBS- diarrhea (IBS-D) (56 patients, 23.1%), IBS-constipation (IBS-C) (54 patients, 22.2%) and IBS-unspecified (IBS-U) (12 patients, 4.9%). Overall IBS-QOL scores were significantly different among various IBS-subtypes (P = 0.01). IBS-QOL of patients with IBS-D (61.6, 95%CI: 54.0-69.1) and IBS-M (63.0, 95%CI: 58.1-68.0) was significantly lower than patients with IBS-C (74.5, 95%CI: 66.9-82.1) (P = 0.03 and 0.02 respectively). IBS-D patients scored significantly lower than IBS-C on food avoidance (45.0, 95%CI: 34.8-55.2 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and interference with activity (59.6, 95%CI: 51.4-67.7 vs 82.3, 95%CI: 74.1-90.6, P < 0.001). IBS-M patients had more interference in their activities (61.6, 95%CI: 56.3-66.9 vs 82.3, 95%CI: 74.1-90.6, P = 0.001) and greater impact on their relationships (73.3, 95%CI: 68.4-78.2 vs 84.7, 95%CI: 77.2-92.2, P = 0.02) than IBS-C patients. Patients with IBS-M also scored significantly lower than IBS-C on food avoidance (47.2, 95%CI: 40.7-53.7 vs 61.1, 95%CI: 50.8-71.3, P = 0.04) and social reaction (66.1, 95%CI: 61.1-71.1 vs 80.0, 95%CI: 72.1-87.7, P = 0.005). CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients. Clinicians should recognize food avoidance, effects on daily activities and relationship problems in these patients. PMID:26185382

Intermittent Fermi-Pasta-Ulam Dynamics at Equilibrium

NASA Astrophysics Data System (ADS)

Campbell, David; Danieli, Carlo; Flach, Sergej

The equilibrium value of an observable defines a manifold in the phase space of an ergodic and equipartitioned many-body syste. A typical trajectory pierces that manifold infinitely often as time goes to infinity. We use these piercings to measure both the relaxation time of the lowest frequency eigenmode of the Fermi-Pasta-Ulam chain, as well as the fluctuations of the subsequent dynamics in equilibrium. We show that previously obtained scaling laws for equipartition times are modified at low energy density due to an unexpected slowing down of the relaxation. The dynamics in equilibrium is characterized by a power-law distribution of excursion times far off equilibrium, with diverging variance. The long excursions arise from sticky dynamics close to regular orbits in the phase space. Our method is generalizable to large classes of many-body systems. The authors acknowledge financial support from IBS (Project Code IBS-R024-D1).

Reduced E-cadherin expression is associated with abdominal pain and symptom duration in a study of alternating and diarrhea predominant IBS.

PubMed

Wilcz-Villega, E; McClean, S; O'Sullivan, M

2014-03-01

Increased intestinal permeability and altered expression of tight junction (TJ) proteins may be implicated in the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the expression of adherens junction (AJ) protein E-cadherin and TJ proteins zonula occludens (ZO)-1 and claudin (CLD)-1 and associations with IBS symptoms. Junctional proteins were immunostained in cecal biopsy tissue of Rome II IBS patients (n = 34) comprising both alternating (IBS-A) and diarrhea predominant (IBS-D) subtypes, and controls (n = 12). IBS symptom duration, abdominal pain severity and stool frequency were assessed for IBS patients. Protein expression was determined by immunofluorescence. E-cadherin and ZO-1 protein expression was significantly lower (p = 0.03 and p = 0.016, respectively) in the cecal surface epithelium of the IBS group comprising both IBS-A and IBS-D subtypes. CLD-1 expression was not significantly altered compared with controls. On subtype analysis, ZO-1 expression was significantly reduced in both IBS-A and IBS-D compared with controls, whereas E-cadherin was reduced only in IBS-A. Lower E-cadherin expression was associated with longer symptoms duration specifically in IBS-A patients (rs = -0.76, p = 0.004). Reduced E-cadherin associated with abdominal pain severity in the overall IBS group (rs = -0.36, p = 0.041), but this association was unrelated to IBS subtype. E-cadherin protein expression in the cecum was significantly lower in IBS-A compared with controls and associated with longstanding symptoms. E-cadherin was further associated with abdominal pain severity in the IBS group overall, but unrelated to IBS subtype. Altered E-cadherin expression may provide novel insights into mechanisms underlying intestinal barrier dysfunction in IBS. © 2013 John Wiley & Sons Ltd.

The integrated bispectrum in modified gravity theories

NASA Astrophysics Data System (ADS)

Munshi, Dipak

2017-01-01

Gravity-induced non-Gaussianity can provide important clues to Modified Gravity (MG) Theories. Several recent studies have suggested using the Integrated Bispectrum (IB) as a probe for squeezed configuration of bispectrum. Extending previous studies on the IB, we include redshift-space distortions to study a class of (parametrised) MG theories that include the string-inspired Dvali, Gabadadze & Porrati (DGP) model. Various contributions from redshift-space distortions are derived in a transparent manner, and squeezed contributions from these terms are derived separately. Results are obtained using the Zel'dovich Approximation (ZA). Results are also presented for projected surveys (2D). We use the Press-Schechter (PS) and Sheth-Tormen (ST) mass functions to compute the IB for collapsed objects that can readily be extended to peak-theory based approaches. The cumulant correlators (CCs) generalise the ordinary cumulants and are known to probe collapsed configurations of higher order correlation functions. We generalise the concept of CCs to halos of different masses. We also introduce a generating function based approach to analyse more general non-local biasing models. The Fourier representations of the CCs, the skew-spectrum, or the kurt-spctra are discussed in this context. The results are relevant for the study of the Minkowski Functionals (MF) of collapsed tracers in redshift-space.

The integrated bispectrum in modified gravity theories

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munshi, Dipak, E-mail: D.Munshi@sussex.ac.uk

2017-01-01

Gravity-induced non-Gaussianity can provide important clues to Modified Gravity (MG) Theories. Several recent studies have suggested using the Integrated Bispectrum (IB) as a probe for squeezed configuration of bispectrum. Extending previous studies on the IB, we include redshift-space distortions to study a class of (parametrised) MG theories that include the string-inspired Dvali, Gabadadze and Porrati (DGP) model. Various contributions from redshift-space distortions are derived in a transparent manner, and squeezed contributions from these terms are derived separately. Results are obtained using the Zel'dovich Approximation (ZA). Results are also presented for projected surveys (2D). We use the Press-Schechter (PS) and Sheth-Tormenmore » (ST) mass functions to compute the IB for collapsed objects that can readily be extended to peak-theory based approaches. The cumulant correlators (CCs) generalise the ordinary cumulants and are known to probe collapsed configurations of higher order correlation functions. We generalise the concept of CCs to halos of different masses. We also introduce a generating function based approach to analyse more general non-local biasing models. The Fourier representations of the CCs, the skew-spectrum, or the kurt-spctra are discussed in this context. The results are relevant for the study of the Minkowski Functionals (MF) of collapsed tracers in redshift-space.« less

Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice

PubMed Central

1996-01-01

Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin- associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP- 1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development. PMID:8879233

Alternative splicing of class Ib major histocompatibility complex transcripts in vivo leads to the expression of soluble Qa-2 molecules in murine blood.

PubMed Central

Tabaczewski, P; Shirwan, H; Lewis, K; Stroynowski, I

1994-01-01

Class Ib Qa-2 molecules are expressed in tissue culture cells as approximately 40-kDa membrane-bound, glycophosphatidylinositol-linked antigens and as approximately 39-kDa soluble polypeptides. Recently, alternative splicing events which delete exon 5 from a portion of Qa-2 transcripts were demonstrated to give rise to truncated secreted Qa-2 molecules in transfected cell lines. To determine whether this mechanism operates in vivo and to find out whether Qa-2 can be detected in soluble form in circulation, murine blood samples were analyzed. Critical to these experiments was preparation of an anti-peptide antiserum against an epitope encoded by a junction of exon 4 and exon 6. We find that supernatants of splenocytes cultured in vitro as well as serum or plasma contain two forms of soluble Qa-2 molecules. One form corresponds to a secreted molecule translated from transcripts from which exon 5 has been deleted; the other is derived from membrane-bound antigens or their precursors. The levels of both soluble forms of Qa-2 are inducible upon stimulation of the immune system, suggesting an immunoregulatory role for these molecules or for the mechanism leading to the reduction of cell-associated Qa-2 antigens in vivo. Images PMID:8127900

Motility response to colonic distention is increased in postinfectious irritable bowel syndrome (PI-IBS).

PubMed

Kanazawa, M; Palsson, O S; van Tilburg, M A L; Gangarosa, L M; Fukudo, S; Whitehead, W E

2014-05-01

Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether postinfectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone, and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). Two hundred and eighteen Rome III-positive IBS patients and 43 HC participated. IBS patients were designated PI-IBS, if their IBS symptoms began following an episode of gastroenteritis characterized by two or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). Twenty two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p < 0.05) or HC (p < 0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability. © 2014 John Wiley & Sons Ltd.

Motility Response to Colonic Distention is Increased in Post-infectious Irritable Bowel Syndrome (PI-IBS)

PubMed Central

Kanazawa, Motoyori; Palsson, Olafur S.; van Tilburg, Miranda A.L.; Gangarosa, Lisa M.; Fukudo, Shin; Whitehead., William E.

2015-01-01

Background Acute intestinal infection leads to persistent intestinal smooth muscle hypercontractility and pain hypersensitivity after resolution of the infection in animal models. We investigated whether post-infectious irritable bowel syndrome (PI-IBS) is associated with abnormalities in phasic contractions of the colon, smooth muscle tone and pain sensitivity compared to non-PI-IBS (NI-IBS) or healthy controls (HC). Methods 218 Rome III positive IBS patients and 43 healthy controls participated. IBS patients were designated PI-IBS if their IBS symptoms began following an episode of gastroenteritis characterized by 2 or more of: fever, vomiting, or diarrhea. Pain threshold to phasic distentions of the descending colon was assessed using a barostat. Colonic motility was assessed with the barostat bag minimally inflated to the individual operating pressure (IOP), at 20 mmHg above the IOP, and following a test meal. IBS symptom severity and psychological symptoms were assessed by the IBS Severity Scale (IBS-SS) and the Brief Symptom Inventory-18 (BSI-18). Key Results Twenty-two (10.1%) met criteria for PI-IBS. Both IBS and HC groups showed a significant increase in motility index during intraluminal distention and following meals. The magnitude of the response to distention above (orad to) the balloon was significantly greater in PI-IBS compared with NI-IBS (p<0.05) or HC (p<0.01). Differences between PI-IBS and NI-IBS were not significant for IBS symptom severity, pain threshold, barostat bag volumes, or any psychological score on the BSI-18. Conclusions & Inferences Patients with PI-IBS have greater colonic hypercontractility than NI-IBS. We speculate that sustained mild mucosal inflammation may cause this colonic irritability. PMID:24602083

Serotonin Transporter Gene (SLC6A4) Polymorphism and Mucosal Serotonin Levels in Southeastern Iranian Patients with Irritable Bowel Syndrome

PubMed Central

Mohammadi, Mojgan; Tahmasebi Abdar, Hossein; Mollaei, Hamid Reza; Hajghani, Hossein; Baneshi, Mohammad Reza; Hayatbakhsh, Mohammad Mahdi

2017-01-01

BACKGROUND Irritable bowel syndrome (IBS) is a digestive system disorder with an unknown etiology. Serotonin has a key role in the secretion and motility of the intestine. Polymorphism in serotonin re-uptake transporter (SERT or SLC6A4) gene may have a functional role in the gut of patients with IBS. The aims of the present study were to investigate the association between SLC6A4 gene polymorphism and IBS and to detect the correlation between rectal serotonin levels and IBS sub-types. METHODS SLC6A4 gene polymorphism in 131 patients with IBS and 211 healthy controls were analysed using the quantitative polymerase chain reaction high-resolution melting (qPCR-HRM) curve technique. Serotonin was measured in rectal biopsies of patients with IBS using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS The patients were categorized into three groups: IBS with diarrhoea (IBS-D): 70 patients, IBS with constipation (IBS-C): 18 patients, and IBS with mixed symptoms (IBS-M): 43 patients. The frequency of SLC6A4 s/s and l/s genotypes was significantly higher in IBS-C than IBS-D, IBS-M, and controls (p=0.036). Serotonin levels were similar in IBS sub-types. CONCLUSION SLC6A4 polymorphism is a possible candidate gene associated with the pathogenesis of IBS-C. Although serotonin levels did not differ in rectal biopsies of IBS sub-types, further investigation is recommended. PMID:28316763

The effect of sample size and disease prevalence on supervised machine learning of narrative data.

PubMed Central

McKnight, Lawrence K.; Wilcox, Adam; Hripcsak, George

2002-01-01

This paper examines the independent effects of outcome prevalence and training sample sizes on inductive learning performance. We trained 3 inductive learning algorithms (MC4, IB, and Naïve-Bayes) on 60 simulated datasets of parsed radiology text reports labeled with 6 disease states. Data sets were constructed to define positive outcome states at 4 prevalence rates (1, 5, 10, 25, and 50%) in training set sizes of 200 and 2,000 cases. We found that the effect of outcome prevalence is significant when outcome classes drop below 10% of cases. The effect appeared independent of sample size, induction algorithm used, or class label. Work is needed to identify methods of improving classifier performance when output classes are rare. PMID:12463878

Differential effects on nematode development of two QTLs for resistance to Meloidogyne incognita in cotton

USDA-ARS?s Scientific Manuscript database

QTLs qMi-C11 and qMi-C14 impart resistance to Meloidogyne incognita in cotton. Breeders had backcrossed both QTLs into Coker 201 (C201; susceptible) to create M-120 RNR (M-120; highly resistant), and we crossed C201 and M-120 to create near isogenic lines with either qMi-C11 or qMi-C14. Previous wor...

Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study.

PubMed

Hawrelak, Jason A; Myers, Stephen P

2010-10-01

The study objective was to assess the effects and tolerability of two novel natural medicine formulations in improving bowel habit and abdominal symptoms in patients with irritable bowel syndrome (IBS). The DA-IBS formula was designed to treat diarrhea-predominant and alternating bowel habit IBS, and the C-IBS formula was designed to treat constipation-predominant IBS. This was a two arm, open-label, uncontrolled pilot study. Subjects were recruited from the greater Lismore area (NSW, Australia) in 2001. The study included 31 patients who fulfilled the Rome II criteria for IBS. Twenty-one (21) patients were classified as suffering from diarrhea-predominant or alternating bowel habit IBS and 10 patients were classified with constipation-predominant IBS. The DA-IBS formula consisted of a mixture of dried, powdered bilberry fruit, slippery elm bark, agrimony aerial parts, and cinnamon quills. The C-IBS formula consisted of a mixture of dried powdered slippery elm bark, lactulose, oat bran, and licorice root. The aim of each formula was to normalize stool frequency and stool consistency. Ingestion of the DA-IBS formula was associated with a small, but significant increase in bowel movement frequency (p = 0.027). Subjects in the DA-IBS group also experienced reductions in straining (p = 0.004), abdominal pain (p = 0.006), bloating (p < 0.0001), flatulence (p = 0.0001), and global IBS symptoms (p = 0.002) during the treatment phase of the trial. Subjects in the C-IBS group experienced a 20% increase in bowel movement frequency (p = 0.016) and significant reductions in straining (p < 0.0001), abdominal pain (p = 0.032), bloating (p = 0.034), and global IBS symptom severity (p = 0.0005), as well as improvements in stool consistency (p < 0.0001). Both formulas were well-tolerated. The DA-IBS formula was not effective in improving bowel habit in individuals with diarrhea-predominant or alternating bowel habit IBS, although it did significantly improve a number of IBS symptoms. The C-IBS formula significantly improved both bowel habit and IBS symptoms in patients with constipation-predominant IBS. Further research is warranted on C-IBS, as a potentially useful therapeutic formula.

[An analysis for the clinical difference between post infectious irritable bowel syndrome and non post infectious irritable bowel syndrome].

PubMed

Shi, Hui; Wan, Jun; Liu, Wenhui; Su, Binbin

2015-04-01

To study the clinical discrepancy between patients with post infectious irritable bowel syndrome (PI-IBS) and non post infectious irritable bowel syndrome (NPI-IBS) , and assess the value of serum intestinal fatty acid binding protein (I-FABP) for differential diagnosis. A total of 117 patients with PI-IBS, 201 patients with NPI-IBS and 31 healthy controls were prospectively recruited in General Liberation Army Hospital from 2010 to 2013. Plasma samples and clinical data were collected. Serum I-FABP level was measured by an enzyme-linked immunosorbent assay. The median age of patients with PI-IBS was 36 years. The median time to diagnosis in PI-IBS group was significantly longer than that in NPI-IBS group [(19.7 ± 10.3)months vs (11.4 ± 5.3) months, P < 0.05]. Similarly, the proportion of anxiety [58.1%(68/117) vs 28.9%(58/201), P < 0.05] and the value of I-FABP [(42.6 ± 14.8) µg/L vs (17.3 ± 11.5) µg/L, P < 0.05] in PI-IBS group were significant higher than NPI-IBS patients. The level of I-FABP of healthy controls [(10.6 ± 8.2) µg/L] was also significantly lower than that of PI-IBS patients (P < 0.05), yet no difference from that of NPI-IBS group. The I-FABP value of subgroup PI-IBS patients with diarrhoea (IBS-D) was significant higher than that of NPI-IBS group [(54.8 ± 9.3)µg/L vs (12.3 ± 6.2) µg/L, P < 0.05]. However, other parameters including gender, age, GSRS score, and I-FABP value of subgroup constipation (IBS-C) and mix (IBS-M), were not different between PI-IBS group and NPI-IBS group (all P > 0.05). PI-IBS is an occult intestinal inflammation disease with mucosa injury. I-FABP might be a potential testing marker for the diagnosis of PI-IBS.

A prospective study of the psychobehavioral factors responsible for a change from non-patient irritable bowel syndrome to IBS patient status

PubMed Central

Fujii, Yasushi; Nomura, Shinobu

2008-01-01

Background To investigate non-patient irritable bowel syndrome (IBS) change to IBS and to determine factors predictive of the onset of IBS, individual biological factors, psychological factors, behavioral factors, and environmental factors were examined. Methods The subjects were 105 non-patient IBS (male = 59, female = 46, average age:21.49 ± 2.37), including 68 of the diarrhea-predominant type and 37 of the constipation-predominant type selected from 1,409 university and technical college students by use of a questionnaire based on the Rome II diagnostic criteria. The subjects were followed for three years, and various characteristics and IBS symptoms were serially observed (12 times). The IBS incidence rate was calculated. Results During the three years, 37 non-patient IBS (35.24%) changed to IBS: 28 diarrhea-predominant type and 9 constipation-predominant type. All IBS symptoms disappeared in 26 non-patient IBS subjects (24.76%). According to quantification method II (discriminant analysis), seven factors (stressor, two kinds of stress coping styles, cognitive appraisal, eating habits, sleeping time, and psychologically abuse) were adopted as a predictive model for IBS incidence and were confirmed as predictive of IBS. Conclusion The results of this research show that non-patient IBS is a changeable state that can change into IBS or persons without symptoms. Most of the non-patient IBS subjects who became asymptomatic had had symptoms for six months or less. Furthermore, the longer a non-patient IBS subject had symptoms, the higher the risk of a change to IBS became. The findings suggest the usefulness of identifying and approaching non-patient IBS as early as possible to prevent the onset of IBS. It must be noted that the persons surveyed in the present study had only the diarrhea-predominant and constipation-predominant types. Therefore, the findings of the present study are limited only these two types. Further study including the mixed type is needed. PMID:18817571

Integrated Baseline System (IBS). Version 1.03, System Management Guide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, J.R.; Bailey, S.; Bower, J.C.

This IBS System Management Guide explains how to install or upgrade the Integrated Baseline System (IBS) software package. The IBS is an emergency management planning and analysis tool that was developed under the direction of the Federal Emergency Management Agency (FEMA). This guide includes detailed instructions for installing the IBS software package on a Digital Equipment Corporation (DEC) VAX computer from the IBS distribution tapes. The installation instructions include procedures for both first-time installations and upgrades to existing IBS installations. To ensure that the system manager has the background necessary for successful installation of the IBS package, this guide alsomore » includes information on IBS computer requirements, software organization, and the generation of IBS distribution tapes. When special utility programs are used during IBS installation and setups, this guide refers you to the IBS Utilities Guide for specific instructions. This guide also refers you to the IBS Data Management Guide for detailed descriptions of some IBS data files and structures. Any special requirements for installation are not documented here but should be included in a set of installation notes that come with the distribution tapes.« less

Effects of Disturbed Sleep on Gastrointestinal and Somatic Pain Symptoms in IBS

PubMed Central

Patel, Ami; Hasak, Stephen; Cassell, Benjamin; Ciorba, Matthew A.; Vivio, Emily E.; Kumar, Mrudula; Gyawali, C. Prakash; Sayuk, Gregory S.

2016-01-01

Summary Background Sleep disturbances are common, and perhaps are even more prevalent in irritable bowel syndrome (IBS). Aim To determine the effect of measured sleep on: 1) IBS symptoms the following day, and IBS-specific quality of life (IBS-QOL), and 2) non-GI pain symptoms. Methods IBS patients’ sleep patterns were compared to healthy individuals via wrist-mounted actigraphy over 7 days. Daily bowel pain logs (severity, distress; 10-point Likert), stool pattern (Bristol scale) and supporting symptoms (e.g., bloating, urgency; 5-point Likert) were kept. Validated measures, including the GI Symptom Rating Scale-IBS, Visceral Sensitivity Index, Pittsburgh Sleep Quality Index and the IBS-Quality of Life were collected. Mediation analysis explored the relationship between sleep, mood, and bowel symptoms. Results 50 subjects (38.6±1.0years old, 44 female; 24 IBS and 26 healthy controls) completed sleep monitoring. IBS patients slept more hours per day (7.7±0.2 vs 7.1±0.1, p=0.008), but felt less well-rested. IBS patients demonstrated more waking episodes during sleep (waking episodes; 12.1 vs 9.3, p<0.001). Waking episodes predicted worse abdominal pain (p≤0.01) and GI distress (p<0.001), but not bowel pattern or accessory IBS symptoms (p>0.3 for each). Waking episodes negatively correlated with general- and IBS-specific QOL in IBS (r= −0.58 and −0.52, p<0.001 for each). Disturbed sleep effects on abdominal pain were partially explained by mood as an intermediate. Conclusion Sleep disturbances are more common in IBS, and correlate with IBS-related pain, distress, and poorer IBS-related QOL. Disturbed sleep effects extend beyond the bowel, leading to worse mood and greater somatic pain in IBS patients. PMID:27240555

Anxiety and IBS revisited: ten years later.

PubMed

Popa, Stefan-Lucian; Dumitrascu, Dan Lucian

2015-01-01

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological and psychiatric disorders. However, the association between IBS and each of its subtypes (diarrhea IBS-D, constipation IBS-C, mixed IBS-M) with anxiety still remains unclear. The purpose of this study was to perform a comparative analysis of the association between anxiety and IBS on a period of ten years. PubMed was searched for studies analyzing IBS and anxiety, published at 10 years interval. The study presents a comparative analysis of the articles that were published between 2003-2005 and 2013-2015, investigating the correlation between anxiety and IBS. The initial search identified 220 articles, from which 156 were published between 2013 and 2015, and 64 were published between 2003 and 2005. Of these articles, 15 articles were included in the review. Out of these 15 articles, 10 articles analyzed the correlation between anxiety-depression status in IBS patients using specific questionnaires, 2 articles analyzed genetic variables in IBS, 1 article analyzed serotonin and monoamine oxidase levels in IBS, 1 article analyzed serum levels of IL-1β and IL-10 in IBS, 1 article analyzed somatostatin and vasoactive intestinal peptide levels in IBS. The result was a review of 15 studies that analyzed the association between IBS and anxiety. IBS is a heterogeneous disorder caused by numerous psychological, immunological, infectious, endocrine and genetic factors. In recent years, the number of studies concentrating on genetic factors, cytokines and hormones has increased in comparison with the 2003-2005 period, when clinical investigation, using mainly questionnaires was the essential method. Also, the total number of papers investigating anxiety and IBS, considerably increased. The recent studies have confirmed the fact that IBS symptoms are often exacerbated during stressful events and the psychiatric treatment has a positive effect on gastro-intestinal symptomatology.

Evaluation of the Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire in diarrheal-predominant irritable bowel syndrome patients

PubMed Central

2013-01-01

Background Diarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients. The current paper assesses this previously-validated instrument employing data collected from 754 patients who participated in a randomized clinical trial of a novel treatment, eluxadoline, for IBS-d. Methods Psychometric methods common to HRQOL research were employed to evaluate the IBS-QOL. Many of the historical analyses of the IBS-QOL validations were used. Other techniques that extended the original methods were applied where more appropriate for the current dataset. In IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item reduction, factor structure, internal consistency, reproducibility, construct validity, and ability to detect change. Results This study supports the IBS-QOL as a psychometrically valid measure. Factor analyses suggested that IBS-specific QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity was further buttressed by significant correlations between IBS-QOL total scores and related measures of IBS-d severity including the historically-relevant Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA’s Clinical Responder definition. The IBS-QOL also showed a significant ability to detect change as evidenced by analysis of treatment effects. A minority of the items, unrelated to the IBS-d, performed less well by the standards set by the original authors. Conclusions We established that the IBS-QOL total score is a psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study. Our analyses suggest that the IBS-QOL items demonstrate very good construct validity and ability to detect changes due to treatment effects. Furthermore, our analyses suggest that the IBS-QOL items measure a univariate construct and we believe further modeling of the IBS-QOL from an item response theory (IRT) approach under both non-treatment and treatment conditions would greatly further our understanding as item-based methods could be used to develop a short form. PMID:24330412

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

PubMed

Jarrett, M E; Han, C J; Cain, K C; Burr, R L; Shulman, R J; Barney, P G; Naliboff, B D; Zia, J; Heitkemper, M M

2016-07-01

Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures. © 2016 John Wiley & Sons Ltd.

Comparison of the Rome IV and Rome III criteria for IBS diagnosis: A cross-sectional survey.

PubMed

Bai, Tao; Xia, Jing; Jiang, Yudong; Cao, Huan; Zhao, Yong; Zhang, Lei; Wang, Huan; Song, Jun; Hou, Xiaohua

2017-05-01

The aims of this study were to investigate the proportion of clinical irritable bowel syndrome (IBS) at a tertiary hospital in China, to compare the Rome III and Rome IV criteria with regard to IBS diagnosis, to describe the agreement between the Rome III and Rome IV criteria, and to identify differences between Rome IV-positive and -negative IBS patients. A cross-sectional survey was performed among outpatients in the gastrointestinal (GI) department of a tertiary hospital. The patients were categorized as having IBS using Rome III and Rome IV criteria. In total, 1,376 (91.7%) patients completed a GI symptom questionnaire. Among them, 352 were suspected of having IBS and 175 were diagnosed with IBS using the Rome III or Rome IV criteria. In particular, 170 (12.4%) patients were diagnosed with IBS using the Rome III criteria, and 84 (6.1%) patients were diagnosed using the Rome IV criteria. Rome IV IBS patients experienced more pain symptoms (P<0.01) and showed higher IBS severity scores. In contrast, no significant differences were noted for demographic characteristics, stool frequency, IBS subtype, disease course, operation history or GI infection history between Rome IV IBS patients and IBS patients not diagnosed with the Rome IV criteria. Rome IV-positive IBS patients represented approximately half of Rome III-positive IBS patients at a tertiary hospital in China. More specifically, Rome IV-positive IBS was mainly a subgroup of Rome III-positive IBS with more serious symptoms. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Blastocystis sp. in Irritable Bowel Syndrome (IBS)--Detection in Stool Aspirates during Colonoscopy.

PubMed

Ragavan, Nanthiney Devi; Kumar, Suresh; Chye, Tan Tian; Mahadeva, Sanjiv; Shiaw-Hooi, Ho

2015-01-01

Blastocystis is one of the most common gut parasites found in the intestinal tract of humans and animals. Its' association with IBS is controversial, possibly as a result of irregular shedding of parasites in stool and variation in stool detection. We aimed to screen for Blastocystis in colonic stool aspirate samples in adult patients with and without IBS undergoing colonoscopy for various indications and measure the interleukin levels (IL-8, IL-3 and IL-5). In addition to standard stool culture techniques, polymerase chain reaction (PCR) techniques were employed to detect and subtype Blastocystis. All the serum samples collected were subjected for ELISA studies to measure the interleukin levels (IL-8, IL-3 and IL-5). Among 109 (IBS n = 35 and non-IBS n = 74) adults, direct stool examination and culture of colonic aspirates were initially negative for Blastocystis. However, PCR analysis detected Blastocystis in 6 (17%) IBS and 4 (5.5%) non-IBS patients. In the six positive IBS patients by PCR method, subtype 3 was shown to be the most predominant (3/6: 50%) followed by subtype 4 (2/6; 33.3%) and subtype 5 (1/6; 16.6%). IL-8 levels were significantly elevated in the IBS Blasto group and IBS group (p<0.05) compared to non-IBS and non-IBS Blasto group. The level of IL-3 in were seen to be significantly higher in than IBS Blasto group and IBS group (p<0.05) compared to non-IBS. Meanwhile, the IL-5 levels were significantly higher in IBS Blasto group (p<0.05) compared to non-IBS and non-IBS Blasto group. This study implicates that detecting Blastosystis by PCR method using colonic aspirate samples during colonoscopy, suggests that this may be a better method for sample collection due to the parasite's irregular shedding in Blastocystis-infected stools. Patients with IBS infected with parasite showed an increase in the interleukin levels demonstrate that Blastocystis does have an effect in the immune system.

Intracellular Trafficking of Clostridium perfringens Iota-Toxin b

PubMed Central

Umezaki, Mariko; Tashiro, Ryo; Oda, Masataka; Kobayashi, Keiko; Shibutani, Masahiro; Takagishi, Teruhisa; Ishidoh, Kazumi; Fukuda, Mitsunori; Sakurai, Jun

2012-01-01

Clostridium perfringens iota-toxin is composed of an enzymatic component (Ia) and a binding component (Ib). Ib binds to a cell surface receptor, undergoes oligomerization in lipid rafts, and binds Ia. The resulting complex is then endocytosed. Here, we show the intracellular trafficking of iota-toxin. After the binding of the Ib monomer with cells at 4°C, oligomers of Ib formed at 37°C and later disappeared. Immunofluorescence staining of Ib revealed that the internalized Ib was transported to early endosomes. Some Ib was returned to the plasma membrane through recycling endosomes, whereas the rest was transported to late endosomes and lysosomes for degradation. Degraded Ib was delivered to the plasma membrane by an increase in the intracellular Ca2+ concentration caused by Ib. Bafilomycin A1, an endosomal acidification inhibitor, caused the accumulation of Ib in endosomes, and both nocodazole and colchicine, microtubule-disrupting agents, restricted Ib's movement in the cytosol. These results indicated that an internalized Ia and Ib complex was delivered to early endosomes and that subsequent delivery of Ia to the cytoplasm occurs mainly in early endosomes. Ib was either sent back to the plasma membranes through recycling endosomes or transported to late endosomes and lysosomes for degradation. Degraded Ib was transported to plasma membranes. PMID:22825447

Stabilities of nitrogen containing heterocyclic radicals and geometrical influences on non-radiative processes in organic molecules

NASA Technical Reports Server (NTRS)

Evleth, E. M.

1972-01-01

Stabilities of nitrogen containing heterocyclic radicals were studied to detect radicals of the type R-N-R, and to theoretically rationalize their electronic structure. The computation of simple potential energy surfaces for ground and excited states is discussed along with the photophysical properties of indolizine. Methods of calculation and problems associated with the calculations are presented. Results, tables, diagrams, discussions, and references are included.

Advances in IBS 2016: A Review of Current and Emerging Data.

PubMed

Schoenfeld, Philip S

2016-08-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide.

Advances in IBS 2016: A Review of Current and Emerging Data

PubMed Central

Schoenfeld, Philip S.

2016-01-01

Irritable bowel syndrome (IBS) is characterized by chronic intermittent abdominal pain and associated diarrhea (IBS-D), constipation (IBS-C), or both. IBS can significantly impact patient function and quality of life. The diagnosis of IBS is based on the presence of characteristic symptoms, the exclusion of concerning features, and selected tests to exclude organic diseases that can mimic IBS. The pathophysiology of IBS remains incompletely understood, and new contributing factors have been identified over the past decade. Altered gut immune activation, intestinal permeability, and the intestinal and colonic microbiome may be important factors. Poorly absorbed carbohydrates have been implicated in triggering IBS symptoms. Increasing evidence supports the benefit of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). Although there are several randomized controlled trials of probiotics in IBS, they are typically poorly designed and have not consistently demonstrated efficacy. Until recently, there were few effective treatments for IBS-D. Data from recent clinical trials support the use of rifaximin, eluxadoline, and peppermint oil. Options for the treatment of IBS-C include lubiprostone and linaclotide. PMID:28070176

Impact of Comorbid Irritable Bowel Syndrome on Treatment Outcome in Non-Erosive Reflux Disease on Long-Term Proton Pump Inhibitor in Japan.

PubMed

Funaki, Yasushi; Kaneko, Hiroshi; Kawamura, Yurika; Yoshimine, Takashi; Tamura, Yasuhiro; Izawa, Shinya; Ebi, Masahide; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

2017-01-01

Irritable bowel syndrome (IBS) frequently coexists with non-erosive reflux disease (NERD). Efficacy of long-term proton pump inhibitor (PPI) treatment on NERD with or without IBS is controversial. The impact of comorbid IBS in NERD on quality of life (QOL) remains uncertain. We verified the hypothesis that NERD patients with IBS symptoms demonstrated poor responses to long-term PPI treatments, deteriorated QOL, and high frequency of psychological deviations in Japan. In all, 141 NERD patients who had been taking PPIs for more than 6 months were enrolled and analyzed. Patient profiles were assessed by GerdQ, IBS Severity Index (IBSSI-J)/Gastrointestinal Symptoms Rating Scale (GSRS)/SF-8, and Hospital Anxiety and Depression Scale (HADS). IBS existed in 37 out of 141 NERD patients. Patients with IBS (the positive-IBS group) demonstrated significantly higher frequencies of extant reflux symptoms than those without IBS (64.9 vs. 40.4%). In the positive-IBS group, 40.5% were classified as middle grade by IBSSI-J. The SF-8 and GSRS scores in this group were significantly lower than those without IBS (the negative-IBS group). Prevalence of depression and anxiety by HADS in the positive-IBS group was significantly higher than that in the negative-IBS group. These results proved the hypothesis that considering comorbid IBS among NERD patients on long-term PPI seems recommended in Japan. © 2017 S. Karger AG, Basel.

Endocannabinoid and cannabinoid-like fatty acid amide levels correlate with pain-related symptoms in patients with IBS-D and IBS-C: a pilot study.

PubMed

Fichna, Jakub; Wood, Jodianne T; Papanastasiou, Malvina; Vadivel, Subramanian K; Oprocha, Piotr; Sałaga, Maciej; Sobczak, Marta; Mokrowiecka, Anna; Cygankiewicz, Adam I; Zakrzewski, Piotr K; Małecka-Panas, Ewa; Krajewska, Wanda M; Kościelniak, Piotr; Makriyannis, Alexandros; Storr, Martin A

2013-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients. AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D) and constipation-predominant (IBS-C) patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls. Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C. IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.

The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity.

PubMed

Sullivan, L C; Clements, C S; Rossjohn, J; Brooks, A G

2008-11-01

The non-classical major histocompatibility complex (MHC) class I molecule human leucocyte antigen (HLA)-E is the least polymorphic of all the MHC class I molecules and acts as a ligand for receptors of both the innate and the adaptive immune systems. The recognition of self-peptides complexed to HLA-E by the CD94-NKG2A receptor expressed by natural killer (NK) cells represents a crucial checkpoint for immune surveillance by NK cells. However, HLA-E can also be recognised by the T-cell receptor expressed by alphabeta CD8 T cells and therefore can play a role in the adaptive immune response to invading pathogens. The recent resolution of HLA-E in complex with both innate and adaptive ligands has provided insight into the dual role of this molecule in immunity.

Pattern of irritable bowel syndrome and its impact on quality of life in primary health care center attendees, Suez governorate, Egypt

PubMed Central

Abdulmajeed, Ahmed; Rabab, Mohamed A; Sliem, Hamdy A; Hebatallah, Nour Eldein

2011-01-01

Introduction Irritable bowel syndrome (IBS) is one of the most common disorders diagnosed by gastroenterologists and a common cause of general practice visits. Although this disease is not life threatening, patients with IBS seem to be seriously affected in their everyday life. The study was designed to explore the pattern of IBS in clinical practice and the impact on the quality of life. Methods This is a case control descriptive study. 117 individuals were included in this study. Rome II criteria were used for the diagnosis of IBS. Impact of IBS on patient's quality of life was determined by irritable bowel syndrome quality of life (IBS-QOL) questionnaire. Results Prevalence of IBS among the study sample was 34.2%. 10% were IBS-Diarrhea, 37.5% were IBS-Constipation and 52.5% were alternators. There is statistical insignificant relationship between IBS (+) and age while it was a significant relation regarding gender (more common among women 80%). There is statistical significance relationship between IBS (+) on one hand and marital status and occupational status on the other hand. Patients with IBS had statistically significant lower scores for all IBS- QOL domains compared with the control group. Conclusion IBS is a prevalent disorder that affects females more than males and it has significant impacts on work, lifestyle and social well-being. PMID:22145053

Pattern of irritable bowel syndrome and its impact on quality of life in primary health care center attendees, Suez governorate, Egypt.

PubMed

Abdulmajeed, Ahmed; Rabab, Mohamed A; Sliem, Hamdy A; Hebatallah, Nour Eldein

2011-01-01

Irritable bowel syndrome (IBS) is one of the most common disorders diagnosed by gastroenterologists and a common cause of general practice visits. Although this disease is not life threatening, patients with IBS seem to be seriously affected in their everyday life. The study was designed to explore the pattern of IBS in clinical practice and the impact on the quality of life. This is a case control descriptive study. 117 individuals were included in this study. Rome II criteria were used for the diagnosis of IBS. Impact of IBS on patient's quality of life was determined by irritable bowel syndrome quality of life (IBS-QOL) questionnaire. Prevalence of IBS among the study sample was 34.2%. 10% were IBS-Diarrhea, 37.5% were IBS-Constipation and 52.5% were alternators. There is statistical insignificant relationship between IBS (+) and age while it was a significant relation regarding gender (more common among women 80%). There is statistical significance relationship between IBS (+) on one hand and marital status and occupational status on the other hand. Patients with IBS had statistically significant lower scores for all IBS- QOL domains compared with the control group. IBS is a prevalent disorder that affects females more than males and it has significant impacts on work, lifestyle and social well-being.

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

PubMed Central

El-Salhy, Magdy; Gilja, Odd Helge; Gundersen, Doris; Hausken, Trygve

2014-01-01

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS). METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7). RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm2, respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001). CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility. PMID:24891930

Active inclusion bodies of acid phosphatase PhoC: aggregation induced by GFP fusion and activities modulated by linker flexibility

PubMed Central

2013-01-01

Background Biologically active inclusion bodies (IBs) have gained much attention in recent years. Fusion with IB-inducing partner has been shown to be an efficient strategy for generating active IBs. To make full use of the advantages of active IBs, one of the key issues will be to improve the activity yield of IBs when expressed in cells, which would need more choices on IB-inducing fusion partners and approaches for engineering IBs. Green fluorescent protein (GFP) has been reported to aggregate when overexpressed, but GFP fusion has not been considered as an IB-inducing approach for these fusion proteins so far. In addition, the role of linker in fusion proteins has been shown to be important for protein characteristics, yet impact of linker on active IBs has never been reported. Results Here we report that by fusing GFP and acid phosphatase PhoC via a linker region, the resultant PhoC-GFPs were expressed largely as IBs. These IBs show high levels of specific fluorescence and specific PhoC activities (phosphatase and phosphotransferase), and can account for up to over 80% of the total PhoC activities in the cells. We further demonstrated that the aggregation of GFP moiety in the fusion protein plays an essential role in the formation of PhoC-GFP IBs. In addition, PhoC-GFP IBs with linkers of different flexibility were found to exhibit different levels of activities and ratios in the cells, suggesting that the linker region can be utilized to manipulate the characteristics of active IBs. Conclusions Our results show that active IBs of PhoC can be generated by GFP fusion, demonstrating for the first time the potential of GFP fusion to induce active IB formation of another soluble protein. We also show that the linker sequence in PhoC-GFP fusion proteins plays an important role on the regulation of IB characteristics, providing an alternative and important approach for engineering of active IBs with the goal of obtaining high activity yield of IBs. PMID:23497261

Glioplasticity in irritable bowel syndrome.

PubMed

Lilli, N L; Quénéhervé, L; Haddara, S; Brochard, C; Aubert, P; Rolli-Derkinderen, M; Durand, T; Naveilhan, P; Hardouin, J-B; De Giorgio, R; Barbara, G; Bruley des Varannes, S; Coron, E; Neunlist, M

2018-04-01

Growing evidence indicates a wide array of cellular remodeling in the mucosal microenvironment during irritable bowel syndrome (IBS), which possibly contributes to pathophysiology and symptom generation. Here, we investigated whether enteric glial cells (EGC) may be altered, and which factors/mechanisms lead to these changes. Colonic mucosal biopsies of IBS patients (13 IBS-Constipation [IBS-C]; 10 IBS-Diarrhea [IBS-D]; 11 IBS-Mixed [IBS-M]) and 24 healthy controls (HC) were analyzed. Expression of S100β and GFAP was measured. Cultured rat EGC were incubated with supernatants from mucosal biopsies, then proliferation and Ca 2+ response to ATP were analyzed using flow cytometry and Ca 2+ imaging. Histamine and histamine 1-receptor (H1R) involvement in the effects of supernatant upon EGC was analyzed. Compared to HC, the mucosal area immunoreactive for S100β was significantly reduced in biopsies of IBS patients, independently of the IBS subtype. IBS-C supernatants reduced EGC proliferation and IBS-D and IBS-M supernatants reduced Ca 2+ response to ATP in EGC. EGC expressed H1R and the effects of supernatant upon Ca 2+ response to ATP in EGC were blocked by pyrilamine and reproduced by histamine via H1R. IBS supernatants reduced mRNA expression of connexin-43. The S100β-stained area was negatively correlated with the frequency and intensity of pain and bloating. Changes in EGC occur in IBS, involving mucosal soluble factors. Histamine, via activation of H1R-dependent pathways, partly mediates altered Ca 2+ response to ATP in EGC. These changes may contribute to the pathophysiology and the perception of pain and bloating in patients with IBS. © 2017 John Wiley & Sons Ltd.

Resilience is decreased in irritable bowel syndrome and associated with symptoms and cortisol response.

PubMed

Park, S H; Naliboff, B D; Shih, W; Presson, A P; Videlock, E J; Ju, T; Kilpatrick, L; Gupta, A; Mayer, E A; Chang, L

2018-01-01

Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated with early adverse life events (EALs) and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. Resilience is the ability to recover and adapt positively to stress but has not been well studied in IBS. The aims of this study are to compare resilience in IBS and healthy controls (HCs) and to assess its relationships with IBS symptom severity, quality of life (QOL), EALs, and HPA axis response. Two hundred fifty-six subjects (154 IBS, 102 HCs) completed questionnaires for resilience (Connor-Davidson Resilience Scale [CD-RISC] and Brief Resilience Scale [BRS]), IBS symptoms, IBS-QOL, and EALs. Ninety-six of these subjects had serial serum adrenocorticotropic hormone (ACTH) and cortisol levels to exogenous corticotrophin-releasing hormone (CRH) and ACTH measured. The relationship between IBS status, resilience, and other variables of interest was assessed by regression analysis after adjusting for demographics and neuroticism, a predictor of resilience. Resilience was significantly lower in IBS compared to HCs (CD-RISC: 72.16±14.97 vs 77.32±12.73, P=.003; BRS: 3.29±0.87 vs 3.93±0.69, P<.001); however, only BRS was significant after controlling for neuroticism (P=.001). Lower BRS scores were associated with greater IBS symptom severity (P=.002), poorer IBS-QOL (P<.001), and a higher number of EALs (P=.01). There was a significant interaction between BRS resilience and IBS status for ACTH-stimulated cortisol response (P=.031); more resilient IBS subjects had lower cortisol response, and more resilient HCs had higher cortisol response. Lower resilience is associated with IBS status, worse IBS symptom severity, lower IBS-QOL, greater EALs, and stress hyperresponsiveness. © 2017 John Wiley & Sons Ltd.

Ehealth: Low FODMAP diet vs Lactobacillus rhamnosus GG in irritable bowel syndrome

PubMed Central

Pedersen, Natalia; Andersen, Nynne Nyboe; Végh, Zsuzsanna; Jensen, Lisbeth; Ankersen, Dorit Vedel; Felding, Maria; Simonsen, Mette Hestetun; Burisch, Johan; Munkholm, Pia

2014-01-01

AIM: To investigate the effects of a low fermentable, oligosaccharides, disaccharides, monosaccharides and polyols diet (LFD) and the probiotic Lactobacillus rhamnosus GG (LGG) in irritable bowel syndrome (IBS). METHODS: Randomised, unblinded controlled trial on the effect of 6-wk treatment with LFD, LGG or a normal Danish/Western diet (ND) in patients with IBS fulfilling Rome III diagnostic criteria, recruited between November 2009 and April 2013. Patients were required to complete on a weekly basis the IBS severity score system (IBS-SSS) and IBS quality of life (IBS-QOL) questionnaires in a specially developed IBS web self-monitoring application. We investigated whether LFD or LGG could reduce IBS-SSS and improve QOL in IBS patients. RESULTS: One hundred twenty-three patients (median age 37 years, range: 18-74 years), 90 (73%) females were randomised: 42 to LFD, 41 to LGG and 40 to ND. A significant reduction in mean ± SD of IBS-SSS from baseline to week 6 between LFD vs LGG vs ND was revealed: 133 ± 122 vs 68 ± 107, 133 ± 122 vs 34 ± 95, P < 0.01. Adjusted changes of IBS-SSS for baseline covariates showed statistically significant reduction of IBS-SSS in LFD group compared to ND (IBS-SSS score 75; 95%CI: 24-126, P < 0.01), but not in LGG compared to ND (IBS-SSS score 32; 95%CI: 18-80, P = 0.20). IBS-QOL was not altered significantly in any of the three groups: mean ± SD in LFD 8 ± 18 vs LGG 7 ± 17, LFD 8 ± 18 vs ND 0.1 ± 15, P = 0.13. CONCLUSION: Both LFD and LGG are efficatious in patients with IBS. PMID:25473176

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

PubMed

Jonefjäll, Börje; Simrén, Magnus; Öhman, Lena; Lasson, Anders; Svedlund, Jan; Strid, Hans

2015-09-01

Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Object-based connectedness facilitates matching.

PubMed

Koning, Arno; van Lier, Rob

2003-10-01

In two matching tasks, participants had to match two images of object pairs. Image-based (IB) connectedness refers to connectedness between the objects in an image. Object-based (OB) connectedness refers to connectedness between the interpreted objects. In Experiment 1, a monocular depth cue (shadow) was used to distinguish different relation types between object pairs. Three relation types were created: IB/OB-connected objects, IB/OB-disconnected objects, and IB-connected/OB-disconnected objects. It was found that IB/OB-connected objects were matched faster than IB/OB-disconnected objects. Objects that were IB-connected/OB-disconnected were matched equally to IB/OB-disconnected objects. In Experiment 2, stereoscopic presentation was used. With relation types comparable to those in Experiment 1, it was again found that OB connectedness determined speed of matching, rather than IB connectedness. We conclude that matching of projections of three-dimensional objects depends more on OB connectedness than on IB connectedness.

Depression, anxiety and anger in subtypes of irritable bowel syndrome patients.

PubMed

Muscatello, Maria Rosaria A; Bruno, Antonio; Pandolfo, Gianluca; Micò, Umberto; Stilo, Simona; Scaffidi, Mariagrazia; Consolo, Pierluigi; Tortora, Andrea; Pallio, Socrate; Giacobbe, Giuseppa; Familiari, Luigi; Zoccali, Rocco

2010-03-01

The present study aimed to elucidate the differences in depression, anxiety, anger, and quality of life in a sample of non-psychiatric IBS patients, starting from the hypothesis that IBS subtypes may have different symptomatic expressions of negative emotions with different outcomes on quality of life measures. Forty-two constipation-predominant IBS (C-IBS) subjects and 44 diarrhea-predominant IBS (D-IBS) subjects, after an examination by a gastroenterologist and a total colonoscopy, underwent a clinical interview and psychometric examination for the assessment of depression, anxiety, anger and quality of life. IBS subtypes showed different symptomatic profiles in depression, anxiety and anger, with C-IBS patients more psychologically distressed than D-IBS subjects. Affective and emotional symptoms should be considered as specific and integral to the syndrome, and recognizing the differences between IBS subtypes may have relevant implications for treatment options and clinical outcome.

A Swedish national adoption study of risk of irritable bowel syndrome (IBS)

PubMed Central

Waehrens, Rasmus; Sundquist, Jan; Sundquist, Kristina; Pirouzifard, MirNabi

2017-01-01

Objectives Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. Methods We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964–2012 and the Swedish Outpatient Care Register for 2001–2012, and the Swedish Primary Healthcare register for 1989–2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h 2 (±SE) was also determined. Results The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. Conclusions The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees. PMID:29119001

A Swedish national adoption study of risk of irritable bowel syndrome (IBS).

PubMed

Waehrens, Rasmus; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina; Pirouzifard, MirNabi

2017-01-01

Irritable bowel syndrome (IBS) clusters in families, but the familial risk of IBS has not been determined in adoptees. Studying adoptees and their biological and adoptive parents is a strong study design for separating genetic from environmental causes of familial clustering. This nationwide study aimed to separate the biological (genetic) and familial environmental contribution to the familial transmission of IBS. We performed a family study for Swedish-born adoptees born from 1951 until 1995, and their biological and adoptive parents. The Swedish Multigeneration Register was linked to the Hospital Register (inpatients and outpatients) for the period 1964-2012 and the Swedish Outpatient Care Register for 2001-2012, and the Swedish Primary Healthcare register for 1989-2012. ORs for IBS were calculated for adoptees with an affected biological parent with IBS compared with adoptees without a biological parent with IBS. The OR for IBS was also determined in adoptees with an adoptive parent with IBS compared with adoptees without an adoptive parent with IBS. Heritability h 2 (±SE) was also determined. The ORs for IBS were 1.67 in adoptees (95% CI 1.06 to 2.62) of biological parents diagnosed with IBS. The ORs for IBS were 0.88 in adoptees (95% CI 0.48 to 1.63) of adoptive parents diagnosed with IBS. The heritability was 19.5%±8.5%. The present study indicates that biological (genetic) factors are important for the familial clustering of IBS. The heritability calculated is in the range from twin studies and suggests that heritability may be estimated in adoptees.

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

[Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin].

PubMed

Liu, Z J; Wei, H; Duan, L P; Zhu, S W; Zhang, L; Wang, K

2016-06-28

To investigate the prevalence and clinical features of small intestinal bacterial overgrowth (SIBO) in diarrhea-predominant irritable bowel syndrome (IBS-D) patients detected by hydrogen and methane in lactulose breath test (LBT), and to study the effects of rifaximin in IBS-D patients. Consecutive patients with IBS-D who met Rome Ⅲ criteria, and gender- and age-matched healthy volunteers were enrolled from March 2015 to January 2016 in Peking University Third Hospital. All the ISB-D patients underwent LBT to detect the prevalence of SIBO. The clinical and LBT features of IBS with SIBO (IBS-P group) and without SIBO (IBS-N group) were analyzed. The effects of rifaximin therapy (0.4 g, twice per day for 4 weeks) in IBS-D patients were evaluated by comparing changes in clinical features and LBT results after treatment. (1) Eighty-four IBS-D patients and 22 healthy controls were enrolled. The prevalence of SIBO in IBS-D patients was 41.67% (35/84), with 27 (77.14%) only hydrogen-positive, 5 (14.29%) methane-positive, and 3 (8.57%) both methane- and hydrogen-positive. (2) The body mass index (BMI) in the IBS-P group was lower than in the IBS-N group [(21.61±0.57) vs (23.44±0.54) kg/m(2,) P<0.05], the maximum stool frequency was also less than in the IBS-N group [(3.85±0.23) vs (4.88±0.35) times/day, P<0.05]. (3) No significant difference was found in oro-cecal transit time (OCTT) among IBS-P, IBS-N and healthy controls. The hydrogen concentration in small intestinal and colonic sections in breath of the IBS-P group was higher than that of both healthy controls and the IBS-N group, while methane concentration in small intestinal and colonic sections (160 min) was higher than that of the IBS-N group (all P<0.05). (4) There was no linear relationship between mean hydrogen and methane concentrations in LBT among the IBS-P, the IBS-N and healthy control groups (all r<0.35, P>0.05). (5) Totally 13 IBS-P patients received rifaximin therapy, in whom the symptoms of abdomen pain, bloating, fecal consistency, stool frequency, and stool satisfactory were significantly improved after treatment (all P<0.05); 8 IBS-N patients received rifaximin therapy, in whom fecal consistency, stool frequency, and satisfactory were significantly improved (all P<0.05). (6) And 5/13 of the IBS-P patients receiving rifaximin presented negative LBT results after rifaximin therapy, with lower hydrogen concentration at all the time points, especially in colonic section (120 min) [(34.54±7.32) ×10(-6) vs (52.23±9.40) ×10(-6,) P<0.05] and lower methane concentration especially in small intestinal section (80 min) [(8.54±0.95) ×10(-6) vs (11.31±0.94) ×10(-6,) P<0.05]. About 41.67% of the IBS-D patients meeting Rome Ⅲ criteria have SIBO, which can be better screened by combining hydrogen and methane in LBT compared with only hydrogen in LBT. SIBO can affect nutritional status in IBS-D patients. Rifaximin can improve the systematic symptoms of IBS-D patients with SIBO, also reduce hydrogen and methane concentration in breath, while only improving diarrhea in IBS-D patients without SIBO. Some differences in gut microbiota may exist between IBS-D with and without SIBO.

Lifestyle and psychological factors related to irritable bowel syndrome in nursing and medical school students.

PubMed

Okami, Yukiko; Kato, Takako; Nin, Gyozen; Harada, Kiyomi; Aoi, Wataru; Wada, Sayori; Higashi, Akane; Okuyama, Yusuke; Takakuwa, Susumu; Ichikawa, Hiroshi; Kanazawa, Motoyori; Fukudo, Shin

2011-12-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder comprising abdominal pain, abdominal discomfort, and disordered defecation. The prevalence of IBS is 10-15% in the general population. This study investigated the prevalence of IBS and the relationship between IBS and stress, lifestyle, and dietary habits among nursing and medical school students. A blank self-administrated questionnaire was used to survey 2,639 students studying nursing or medicine. This questionnaire asked about IBS symptoms, lifestyle, dietary intake, life events, anxiety, and depression. The questionnaires were collected from 2,365 students (89.6%) and the responses of 1,768 students (74.8%) were analyzed. The prevalence of IBS was 35.5% as a whole, 25.2% in males and 41.5% in females. Significantly higher stress scores (anxiety and depression) and life events were found in the IBS group than in the non-IBS group. Sleep disorders and the time spent sitting were also higher in males with IBS. In the IBS group, females ate less fish, fruit, milk, and green-yellow vegetables, and more processed food products than the non-IBS group (p = 0.001, p = 0.002, p = 0.032, p = 0.037, p < 0.001). The rates of missed meals and irregular mealtimes were significantly higher in females in the IBS group (p = 0.001, p = 0.013). The prevalence of IBS was higher among nursing and medical students, and further interventional studies are needed to improve IBS symptoms.

Emerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS.

PubMed

Lacy, B E

2016-01-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder worldwide. The global prevalence of IBS is estimated to be as high as 15%. For many patients, IBS is a chronic disorder which can significantly reduce quality of life. Just as important as the effects on any one individual, IBS also places a significant impact on the population as a whole with its negative effects on the health care system. Irritable bowel syndrome is categorized into one of three main categories: IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. A number of therapeutic options exist to treat the symptoms of abdominal pain, bloating, diarrhea, and fecal urgency, including non-pharmacologic therapies such as dietary changes and probiotics, or pharmacologic therapies such as loperamide and alosetron. However, many patients have persistent symptoms despite these therapies. This unmet need led to the development of eluxadoline, a mu-opioid receptor agonist/delta-opioid receptor antagonist/kappa-receptor agonist. Approved by the FDA in May 2015, this medication shows promise in the treatment of diarrhea-predominant IBS for both men and women. This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed. © 2015 John Wiley & Sons Ltd.

Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan.

PubMed

Kanazawa, Motoyori; Miwa, Hiroto; Nakagawa, Ayako; Kosako, Masanori; Akiho, Hiraku; Fukudo, Shin

2016-01-01

Abdominal bloating is a common symptom in patients with irritable bowel syndrome with constipation (IBS-C). However, it is not included among the required items in the Rome III diagnostic criteria for IBS. Little is known about an impact of abdominal bloating seen in patients with IBS-C. Using a large population-based sample, the aim of the present study was to investigate what is the most bothersome symptom in subjects with IBS-C. An Internet survey of 30,000 adults drawn from the general public throughout Japan was conducted to identify subtypes of IBS using the Rome III diagnostic questionnaire. Consecutively, the screened subjects with IBS-C and the same number of age- and sex-matched non-IBS subjects who were randomly selected as controls were asked to answer a questionnaire on the degree of anxiety they experienced in their daily lives, thoughts about bowel habit, and their dominant gastrointestinal symptoms together with exacerbation factors (for IBS-C only). The screening survey showed that the prevalence of overall IBS was 16.5 % (female 17.4 %, male 15.5 %) and that 2.8 % met the criteria for IBS-C, 4.5 % for IBS with diarrhea (IBS-D) and 8.2 % for mixed IBS (IBS-M). Seven hundred and fifty-nine of 835 (90.9 %) subjects with IBS-C and 746 of 830 (89.9 %) control subjects completed the consecutive questionnaire. IBS-C subjects felt a higher degree of anxiety in their daily lives (p < 0.01) and considered bowel habit to be an indicator of health (p < 0.01) to a greater extent than control subjects. In IBS-C, the degree of anxiety was significantly associated with abdominal discomfort (p < 0.01), pain (p < 0.01) and bloating (p = 0.02), but not with the frequency of bowel habit (p > 0.1). Abdominal bloating was the most bothersome symptom (27.5 %), which was more likely to occur after a meal (52.2 %), at work/school (29.2 %) and during times of stress (26.8 %). Only 4.5 % of IBS-C subjects reported abdominal pain as the 'most bothersome' symptom. A large population-based Internet survey suggests that abdominal bloating has a great impact on the daily lives of subjects diagnosed with IBS-C. Not only bowel movement/abdominal pain but also abdominal bloating should be evaluated in patients with IBS-C.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

PubMed

Ghoshal, Uday C; Gwee, Kok-Ann

2017-07-01

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Pressure induced structural phase transition in IB transition metal nitrides compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soni, Shubhangi; Kaurav, Netram, E-mail: netramkaurav@yahoo.co.uk; Jain, A.

2015-06-24

Transition metal mononitrides are known as refractory compounds, and they have, relatively, high hardness, brittleness, melting point, and superconducting transition temperature, and they also have interesting optical, electronic, catalytic, and magnetic properties. Evolution of structural properties would be an important step towards realizing the potential technological scenario of this material of class. In the present study, an effective interionic interaction potential (EIOP) is developed to investigate the pressure induced phase transitions in IB transition metal nitrides TMN [TM = Cu, Ag, and Au] compounds. The long range Coulomb, van der Waals (vdW) interaction and the short-range repulsive interaction upto second-neighbormore » ions within the Hafemeister and Flygare approach with modified ionic charge are properly incorporated in the EIOP. The vdW coefficients are computed following the Slater-Kirkwood variational method, as both the ions are polarizable. The estimated value of the phase transition pressure (Pt) and the magnitude of the discontinuity in volume at the transition pressure are consistent as compared to the reported data.« less

Investigating intermolecular forces associated with thrombus initiation using optical tweezers

NASA Astrophysics Data System (ADS)

Arya, Maneesh; Lopez, Jose A.; Romo, Gabriel M.; Dong, Jing-Fei; McIntire, Larry V.; Moake, Joel L.; Anvari, Bahman

2002-05-01

Thrombus formation occurs when a platelet membrane receptor, glycoprotein (GP) Ib-IX-V complex, binds to its ligand, von Willebrand factor (vWf), in the subendothelium or plasma. To determine which GP Ib-IX-V amino acid sequences are critical for bond formation, we have used optical tweezers to measure forces involved in the binding of vWf to GP Ib-IX-V variants. Inasmuch as GP Ib(alpha) subunit is the primary component in human GP Ib-IX-V complex that binds to vWf, and that canine GP Ib(alpha) , on the other hand, does not bind to human vWf, we progressively replaced human GP Ib(alpha) amino acid sequences with canine GP Ib(alpha) sequences to determine the sequences essential for vWf/GP Ib(alpha) binding. After measuring the adhesive forces between optically trapped, vWf-coated beads and GP Ib(alpha) variants expressed on mammalian cells, we determined that leucine- rich repeat 2 of GP Ib(alpha) was necessary for vWf/GP Ib-IX- V bond formation. We also found that deletion of the N- terminal flanking sequence and leucine-rich repeat 1 reduced adhesion strength to vWf but did not abolish binding. While divalent cations are known to influence binding of vWf, addition of 1mM CaCl2 had no effect on measured vWf/GP Ib(alpha) bond strengths.

Diagnostics for Intelligent Control of MPD Engines

DTIC Science & Technology

1988-11-15

Comparison of finite and infinite dimensional systems. -29- V r eAtvo which satisfies - ( eAtv ,,) =AeAtvo -Av where eAt is the transition matrix defined by, eA...Bu (6-1) and v(o) =v o where vER’, ueRm, Ae2(Rn,R’), and Bei(Rm,Ra). The solution of this equation at time t is t v(t) = eAtv + f eA(t-S)Bu(s) ds (6-2

From Risk Assessment to Risk Management: Matching Interventions to Adolescent Offenders’ Strengths and Vulnerabilities

PubMed Central

Singh, Jay P.; Desmarais, Sarah L.; Sellers, Brian G.; Hylton, Tatiana; Tirotti, Melissa; Van Dorn, Richard A.

2013-01-01

Though considerable research has examined the validity of risk assessment tools in predicting adverse outcomes in justice-involved adolescents, the extent to which risk assessments are translated into risk management strategies and, importantly, the association between this link and adverse outcomes has gone largely unexamined. To address these shortcomings, the Risk-Need-Responsivity (RNR) model was used to examine associations between identified strengths and vulnerabilities, interventions, and institutional outcomes for justice-involved youth. Data were collected from risk assessments completed using the Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV) for 120 adolescent offenders (96 boys and 24 girls). Interventions and outcomes were extracted from institutional records. Mixed evidence of adherence to RNR principles was found. Accordant to the risk principle, adolescent offenders judged to have more strengths had more strength-based interventions in their service plans, though adolescent offenders with more vulnerabilities did not have more interventions targeting their vulnerabilities. With respect to the need and responsivity principles, vulnerabilities and strengths identified as particularly relevant to the individual youth's risk of adverse outcomes were addressed in the service plans about half and a quarter of the time, respectively. Greater adherence to the risk and need principles was found to predict significantly the likelihood of externalizing outcomes. Findings suggest some gaps between risk assessment and risk management and highlight the potential usefulness of strength-based approaches to intervention. PMID:25346561

Impaired mitochondrial Fe-S cluster biogenesis activates the DNA damage response through different signaling mediators.

PubMed

Pijuan, Jordi; María, Carlos; Herrero, Enrique; Bellí, Gemma

2015-12-15

Fe-S cluster biogenesis machinery is required for multiple DNA metabolism processes. In this work, we show that, in Saccharomyces cerevisiae, defects at different stages of the mitochondrial Fe-S cluster assembly machinery (ISC) result in increased spontaneous mutation rate and hyper-recombination, accompanied by an increment in Rad52-associated DNA repair foci and a higher phosphorylated state of γH2A histone, altogether supporting the presence of constitutive DNA lesions. Furthermore, ISC assembly machinery deficiency elicits a DNA damage response that upregulates ribonucleotide reductase activity by promoting the reduction of Sml1 levels and the cytosolic redistribution of Rnr2 and Rnr4 enzyme subunits. Depending on the impaired stage of the ISC machinery, different signaling pathway mediators contribute to such a response, converging on Dun1. Thus, cells lacking the glutaredoxin Grx5, which are compromised at the core ISC system, show Mec1- and Rad53-independent Dun1 activation, whereas both Mec1 and Chk1 are required when the non-core ISC member Iba57 is absent. Grx5-null cells exhibit a strong dependence on the error-free post-replication repair and the homologous recombination pathways, demonstrating that a DNA damage response needs to be activated upon ISC impairment to preserve cell viability. © 2015. Published by The Company of Biologists Ltd.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article

PubMed Central

Chen, Longtu; Ilham, Sheikh J.; Feng, Bin

2017-01-01

Context Visceral pain is a leading symptom for patients with irritable bowel syndrome (IBS) that affects 10% - 20 % of the world population. Conventional pharmacological treatments to manage IBS-related visceral pain is unsatisfactory. Recently, medications have emerged to treat IBS patients by targeting the gastrointestinal (GI) tract and peripheral nerves to alleviate visceral pain while avoiding adverse effects on the central nervous system (CNS). Several investigational drugs for IBS also target the periphery with minimal CNS effects. Evidence of Acquisition In this paper, reputable internet databases from 1960 - 2016 were searched including Pubmed and ClinicalTrials.org, and 97 original articles analyzed. Search was performed based on the following keywords and combinations: irritable bowel syndrome, clinical trial, pain, visceral pain, narcotics, opioid, chloride channel, neuropathy, primary afferent, intestine, microbiota, gut barrier, inflammation, diarrhea, constipation, serotonin, visceral hypersensitivity, nociceptor, sensitization, hyperalgesia. Results Certain conventional pain managing drugs do not effectively improve IBS symptoms, including NSAIDs, acetaminophen, aspirin, and various narcotics. Anxiolytic and antidepressant drugs (Benzodiazepines, TCAs, SSRI and SNRI) can attenuate pain in IBS patients with relevant comorbidities. Clonidine, gabapentin and pregabalin can moderately improve IBS symptoms. Lubiprostone relieves constipation predominant IBS (IBS-C) while loperamide improves diarrhea predominant IBS (IBS-D). Alosetron, granisetron and ondansetron can generally treat pain in IBS-D patients, of which alosetron needs to be used with caution due to cardiovascular toxicity. The optimal drugs for managing pain in IBS-D and IBS-C appear to be eluxadoline and linaclotide, respectively, both of which target peripheral GI tract. Conclusions Conventional pain managing drugs are in general not suitable for treating IBS pain. Medications that target the GI tract and peripheral nerves have better therapeutic profiles by limiting adverse CNS effects. PMID:28824858

Neither self-reported atopy nor IgE-mediated allergy are linked to gastrointestinal symptoms in patients with irritable bowel syndrome.

PubMed

Nybacka, S; Öhman, L; Störsrud, S; Mybeck, M; Böhn, L; Wilpart, K; Winkvist, A; Bengtsson, U; Törnblom, H; Simrén, M

2018-06-01

Among patients with irritable bowel syndrome (IBS), atopic disease has been proposed as a common comorbidity increasing the IBS symptom burden. We therefore assessed the prevalence of self-reported atopy among patients with IBS as compared to non-IBS controls, and whether atopy and higher serum IgE levels were associated with increased IBS symptom severity. Levels of total and specific IgE in serum were measured and questionnaires assessing the presence of atopic disease (ie, eczema, asthma, rhinoconjunctivitis, and pollen allergy), gastrointestinal symptom burden, food intolerance, somatic, and psychological symptoms were completed. In total, 223 patients with IBS and 47 controls participated. Presence of atopic disease was reported in 55% of patients with IBS compared to 40% of controls (P = .07). IBS patients with atopic manifestations (N = 123) had higher total serum IgE levels (median 31 vs 16 kU A /L, P < .001) and higher prevalence of self-reported food intolerance (28% vs 9%, P = .002) than non-atopic IBS patients (N = 100), respectively, but no major difference in gastrointestinal or psychological symptom burden was noted. However, severe somatic symptoms were more common among atopic than non-atopic patients with IBS (38% vs 27%, P = .028). We found no associations between self-reported atopy and IBS symptom severity using linear regression models. Atopic disease is common in patients with IBS, but that is also true for subjects without IBS. The presence of atopic disease in IBS is associated with self-reported food intolerance and somatic symptom severity, but unrelated to IBS symptom severity. © 2018 John Wiley & Sons Ltd.

Irritable bowel syndrome among nurses working in King Abdulaziz University Hospital, Jeddah, Saudi Arabia

PubMed Central

Ibrahim, Nahla Khamis; Al-Bloushy, Randa Ibrahim; Sait, Salma Hani; Al-Azhary, Hatoon Wahid; Al Bar, Nusaybah Hussain; Mirdad, Ghazal A.

2016-01-01

Background Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that can cause disability and economic burden. Nurses are a vital part of the medical team and their well-being is an important issue. Yet, few studies have been done concerning IBS among nurses. Objectives To determine the prevalence, severity, and predictors of IBS among nurses working at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Materials and methods A cross-sectional study was conducted among 229 nurses who fulfilled the eligibility criteria. They were selected by stratified random sampling during 2014–2015. A validated, confidential, self-administered data collection sheet was used for collection of personal and sociodemographic data. Rome III Criteria, IBS Severity Scoring System (IBS-SSS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were included. Both descriptive and inferential statistics were done. A multiple logistic regression analysis was done to determine the predictors of IBS. Results The prevalence of IBS among nurses was 14.4%, and IBS-Mixed type was the commonest variety (54.5%). Positive family history of IBS, working in outpatient clinics, having day shift, poor sleep quality, and high anxiety and depression scale scores were significantly associated with IBS. After controlling for confounding factors in regression analysis, the predictors of IBS were food hypersensitivity (aOR=4.52; 95% CI: 1.80−11.33), morbid anxiety (aOR=4.34; 95% CI: 1.49–12.67), and positive family history of IBS (aOR=3.38; 95% CI: 1.12–13.23). Conclusion The prevalence of IBS was 14.4%. Food hypersensitivity, morbid anxiety, and family history were the predictors of IBS. Screening and management of IBS, food hypersensitivity, and psychological problems among nurses are recommended. PMID:27032964

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

PubMed

Li, Mei; Huang, Xiao-Guang; Yang, Zhi-Ning; Lu, Jia-Yang; Zhan, Yi-Zhou; Xie, Wen-Jia; Zhou, Dong-Jie; Wang, Li; Zhu, Di-Xia; Lin, Zhi-Xiong

2016-09-01

To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends

PubMed Central

Zhang, Pingze; Xie, Guangyao; Liu, Xinxin; Ai, Lili; Chen, Yanyu; Meng, Xin; Bi, Yuhai; Chen, Jianjun; Sun, Yuzhang; Stoeger, Tobias; Ding, Zhuang

2015-01-01

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future. PMID:26712543

High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends.

PubMed

Zhang, Pingze; Xie, Guangyao; Liu, Xinxin; Ai, Lili; Chen, Yanyu; Meng, Xin; Bi, Yuhai; Chen, Jianjun; Sun, Yuzhang; Stoeger, Tobias; Ding, Zhuang; Yin, Renfu

2015-12-28

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b.

PubMed

Zeng, Li; Sullivan, Lucy C; Vivian, Julian P; Walpole, Nicholas G; Harpur, Christopher M; Rossjohn, Jamie; Clements, Craig S; Brooks, Andrew G

2012-01-01

The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1(b) function is unclear. We have assessed the interaction between Qa-1(b) and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1(b) bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1(b). Whereas the Qa-1(b-AMAPRTLLL) complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1(b) was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1(b) and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1(b) and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1(b) with CD94-NKG2 receptors.

A randomized, double-blind, placebo-controlled multicenter trial of saccharomyces boulardii in irritable bowel syndrome: effect on quality of life.

PubMed

Choi, Chang Hwan; Jo, Sun Young; Park, Hyo Jin; Chang, Sae Kyung; Byeon, Jeong-Sik; Myung, Seung-Jae

2011-09-01

Probiotics confer health benefits to the host. However, its clinical effect on irritable bowel syndrome (IBS) is controversial. This study was aimed to evaluate the effects of Saccharomyces boulardii on quality of life (QOL) and symptoms in patients with diarrhea-predominant IBS or mixed-type IBS. Sixty-seven patients with IBS were randomized either to receive S. boulardii at 2×10 live cells as a daily dose (n=34), or placebo (n=33) for 4 weeks. IBS-QOL was assessed at the beginning and end of the treatment phase. IBS-related symptoms, bowel movement frequency, and stool consistency were recorded on a daily basis and assessed each week. The overall improvement in IBS-QOL was higher in S. boulardii group than placebo (15.4% vs 7.0%; P<0.05). All eight domains of IBS-QOL were significantly improved in S. boulardii group; however, placebo group only showed improvements in dysphoria and health worry. Composite scores for IBS symptoms were significantly reduced in both groups to a similar extent. Bowel frequency and stool consistency did not change in either group. S. boulardii improved IBS-QOL better than placebo but was not superior for individual symptoms in patients with diarrhea-predominant IBS or mixed-type IBS.

Orange protein has a role in phytoene synthase stabilization in sweetpotato.

PubMed

Park, Seyeon; Kim, Ho Soo; Jung, Young Jun; Kim, Sun Ha; Ji, Chang Yoon; Wang, Zhi; Jeong, Jae Cheol; Lee, Haeng-Soon; Lee, Sang Yeol; Kwak, Sang-Soo

2016-09-16

Carotenoids have essential roles in light-harvesting processes and protecting the photosynthetic machinery from photo-oxidative damage. Phytoene synthase (PSY) and Orange (Or) are key plant proteins for carotenoid biosynthesis and accumulation. We previously isolated the sweetpotato (Ipomoea batatas) Or gene (IbOr), which is involved in carotenoid accumulation and salt stress tolerance. The molecular mechanism underlying IbOr regulation of carotenoid accumulation was unknown. Here, we show that IbOr has an essential role in regulating IbPSY stability via its holdase chaperone activity both in vitro and in vivo. This protection results in carotenoid accumulation and abiotic stress tolerance. IbOr transcript levels increase in sweetpotato stem, root, and calli after exposure to heat stress. IbOr is localized in the nucleus and chloroplasts, but interacts with IbPSY only in chloroplasts. After exposure to heat stress, IbOr predominantly localizes in chloroplasts. IbOr overexpression in transgenic sweetpotato and Arabidopsis conferred enhanced tolerance to heat and oxidative stress. These results indicate that IbOr holdase chaperone activity protects IbPSY stability, which leads to carotenoid accumulation, and confers enhanced heat and oxidative stress tolerance in plants. This study provides evidence that IbOr functions as a molecular chaperone, and suggests a novel mechanism regulating carotenoid accumulation and stress tolerance in plants.

Faecal biomarker patterns in patients with symptoms of irritable bowel syndrome

PubMed Central

Emmanuel, Anton; Landis, Darryl; Peucker, Mark; Hungin, A Pali S

2016-01-01

Objective To determine rates of faecal biomarker results capable of suggesting potentially treatable causes of irritable bowel syndrome (IBS) symptomatology in a population of patients with symptoms of IBS who meet Rome III criteria for that condition. Design Descriptive, retrospective study in which faecal biomarker results (dichotomised into ‘normal’ and ‘abnormal’ values) were related to data from patient-completed questionnaire data identifying demographics, Rome III criteria for IBS and IBS phenotype (IBS-D, IBS-C, IBS-M and IBS-U). Setting Commercial reference laboratory. Patients Individuals whose physicians ordered faecal biomarker testing for evaluation of chronic abdominal symptoms consistent with IBS. Interventions None. Main outcome measures Rates of occurrence of abnormal results on any of seven faecal biomarkers suggesting a treatable cause for IBS symptoms. Results Abdominal symptoms meeting Rome III criteria for IBS were present in 3553 records (the population), which were subjected to further analysis. Abnormal biomarker results (the outcomes) occurred in 94% of cases; 73% and 65% of records indicated growth of a bacterial potential pathogen and low growth of beneficial organisms, respectively. Abnormal results for all other faecal biomarkers occurred with frequencies from 5% to 13%. Frequency of abnormal results for elastase, calprotectin, eosinophil protein X, and beneficial organisms rose significantly with age, and differed significantly across IBS phenotypes. Conclusions A large proportion of patients manifesting symptoms meeting Rome III IBS diagnostic criteria have faecal biomarker results indicating potential underlying, treatable causes of their symptoms. Faecal biomarker testing is an appropriate means of identifying potentially treatable causes of IBS symptoms. PMID:27761231

Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome

PubMed Central

Zeber-Lubecka, Natalia; Kulecka, Maria; Ambrozkiewicz, Filip; Paziewska, Agnieszka; Goryca, Krzysztof; Karczmarski, Jakub; Rubel, Tymon; Wojtowicz, Wojciech; Mlynarz, Piotr; Marczak, Lukasz; Tomecki, Roman; Mikula, Michal; Ostrowski, Jerzy

2016-01-01

ABSTRACT Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10–12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance (1H-NMR) and gas chromatography–mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment. PMID:27662586

High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

PubMed

Wadhwa, A; Al Nahhas, M F; Dierkhising, R A; Patel, R; Kashyap, P; Pardi, D S; Khanna, S; Grover, M

2016-09-01

Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. To determine the incidence and risk factors for PI-IBS following CDI. A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI. © 2016 John Wiley & Sons Ltd.

IBS suppression lattice in RHIC: theory and experimental verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedotov,A.V.; Bai, M.; Bruno, D.

Intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for Relativistic Heavy Ion Collider (RHIC) operation with heavy ions. Over the last few years the process of IBS was carefully studied in RHIC with dedicated IBS measurements and their comparison with the theoretical models. A new lattice was recently designed and implemented in RHIC to suppress transverse IBS growth, which lowered the average arc dispersion by about 20% [1]. This lattice became operational during RHIC Run-8. We review the IBS suppression mechanism, IBS measurements before and after the lattice change, and comparisons with predictions.

The fundamental ribosomal RNA transcription initiation factor-IB (TIF-IB, SL1, factor D) binds to the rRNA core promoter primarily by minor groove contacts.

PubMed

Geiss, G K; Radebaugh, C A; Paule, M R

1997-11-14

Acanthamoeba castellanii transcription initiation factor-IB (TIF-IB) is the TATA-binding protein-containing transcription factor that binds the rRNA promoter to form the committed complex. Minor groove-specific drugs inhibit TIF-IB binding, with higher concentrations needed to disrupt preformed complexes because of drug exclusion by bound TIF-IB. TIF-IB/DNA interactions were mapped by hydroxyl radical and uranyl nitrate footprinting. TIF-IB contacts four minor grooves in its binding site. TIF-IB and DNA wrap around each other in a right-handed superhelix of high pitch, so the upstream and downstream contacts are on opposite faces of the helix. Dimethyl sulfate protection assays revealed limited contact with a few guanines in the major groove. This detailed analysis suggests significant DNA conformation dependence of the interaction.

Maladjustment to Academic Life and Employment Anxiety in University Students with Irritable Bowel Syndrome

PubMed Central

2015-01-01

The present study tested our hypothesis that university students with irritable bowel syndrome (IBS) may experience less satisfactory academic lives than those of students without IBS. We also verified the hypothesis that university students with IBS might have higher employment anxiety than students without IBS might. We conducted a cross-sectional study of 1,686 university students. Presence or absence of IBS was assessed via the Rome III Questionnaire. Two original items were used to evaluate academic life. The prevalence rates of IBS with diarrhea, IBS with constipation, mixed IBS, and unsubtyped IBS in the study population were 5%, 2%, 10%, and 3%, respectively. Regarding academic life, the proportions of participants who experienced maladjustment and employment anxiety were 29% and 50%, respectively. After adjusting for age, sex, and faculty, the odds ratios for maladjustment and employment anxiety were significantly higher in students who screened positively, relative to those who screened negatively, for IBS (OR, 1.62; 95% CI, 1.24–2.21; OR, 2.16; 95% CI, 1.68–2.81, respectively). In conclusion, maladjustment and anxiety over future employment were higher in university students with IBS relative to those without. PMID:26083662

Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity.

PubMed

Mansueto, Pasquale; D'Alcamo, Alberto; Seidita, Aurelio; Carroccio, Antonio

2015-06-21

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.

Maladjustment to Academic Life and Employment Anxiety in University Students with Irritable Bowel Syndrome.

PubMed

Tayama, Jun; Nakaya, Naoki; Hamaguchi, Toyohiro; Saigo, Tatsuo; Takeoka, Atsushi; Sone, Toshimasa; Fukudo, Shin; Shirabe, Susumu

2015-01-01

The present study tested our hypothesis that university students with irritable bowel syndrome (IBS) may experience less satisfactory academic lives than those of students without IBS. We also verified the hypothesis that university students with IBS might have higher employment anxiety than students without IBS might. We conducted a cross-sectional study of 1,686 university students. Presence or absence of IBS was assessed via the Rome III Questionnaire. Two original items were used to evaluate academic life. The prevalence rates of IBS with diarrhea, IBS with constipation, mixed IBS, and unsubtyped IBS in the study population were 5%, 2%, 10%, and 3%, respectively. Regarding academic life, the proportions of participants who experienced maladjustment and employment anxiety were 29% and 50%, respectively. After adjusting for age, sex, and faculty, the odds ratios for maladjustment and employment anxiety were significantly higher in students who screened positively, relative to those who screened negatively, for IBS (OR, 1.62; 95% CI, 1.24-2.21; OR, 2.16; 95% CI, 1.68-2.81, respectively). In conclusion, maladjustment and anxiety over future employment were higher in university students with IBS relative to those without.

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads.

PubMed

Jones, M P; Chey, W D; Singh, S; Gong, H; Shringarpure, R; Hoe, N; Chuang, E; Talley, N J

2014-02-01

The development of a reliable biomarker for irritable bowel syndrome (IBS) remains one of the major aims of research in functional gastrointestinal disorders (FGIDs) and is complicated by the absence of a perfect reference standard. Previous efforts based on genetic and immune markers have showed promise, but have not been robust. To evaluate an extensive panel of gene expression and serology markers combined with psychological measures in differentiating IBS from health and between subtypes of IBS. Of subjects eligible for analysis (N = 244), 168 met criteria for IBS (60 IBS-C, 57 IBS-D and 51 mixed), while 76 were free of any FGID. A total of 34 markers were selected based on pathways implicated in pathophysiology of IBS or whole human genome screening. Psychological measures were recorded that covered anxiety, depression and somatisation. Models differentiating disease and health were based on unconditional logistic regression and performance assessed through area under the receiver-operator characteristic curve (AUC), sensitivity and specificity. The performance of a combination of 34 markers was good in differentiating IBS from health (AUC = 0.81) and was improved considerably with the addition of four psychological markers (combined AUC = 0.93). Of the 34 markers considered, discrimination was derived largely from a small subset. Good discrimination was also obtained between IBS subtypes with the best being observed for IBS-C vs. IBS-D (AUC = 0.92); however, psychological variables provided almost no incremental discrimination subtypes over biological markers (combined AUC = 0.94). A combination of gene expression and serological markers in combination with psychological measures shows exciting progress towards a diagnostic test for IBS compared with healthy subjects, and to discriminate IBS-C from IBS-D. © 2014 John Wiley & Sons Ltd.

More negative self-esteem and inferior coping strategies among patients diagnosed with IBS compared with patients without IBS--a case-control study in primary care.

PubMed

Grodzinsky, Ewa; Walter, Susanna; Viktorsson, Lisa; Carlsson, Ann-Kristin; Jones, Michael P; Faresjö, Åshild

2015-01-28

Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder, that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care. A case-control study in primary care setting among IBS patients meeting the ROME III criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any present or previous gastrointestinal complaints. The data were collected through self-reported questionnaires of psychosocial factors. IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report 'good' health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation in negative self-esteem among IBS patients remained statistically significant (p = 0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04). The more frequently reported negative self-esteem and inferior coping strategies among IBS patients found in this study suggest the possibility that psychological therapies might be helpful for these patients. However these data do not indicate the causal direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients.

Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Fond, Guillaume; Loundou, Anderson; Hamdani, Nora; Boukouaci, Wahid; Dargel, Aroldo; Oliveira, José; Roger, Matthieu; Tamouza, Ryad; Leboyer, Marion; Boyer, Laurent

2014-12-01

Irritable bowel syndrome (IBS) has been associated with high prevalence of psychological disorders. However, it remains unclear whether IBS and each of its subtypes (predominant diarrhea IBS-D, constipation IBS-C, mixed IBS-M) are associated with higher anxiety and depressive symptoms levels. This study aimed to determine the associations of IBS and each of its subtypes with anxiety and/or depression. We conducted a systematic review and meta-analysis using five electronic databases (PubMed, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL). We selected case-control studies comparing anxiety and depression levels of patients with IBS to healthy controls, using standardized rating scales. Outcomes were measured as random pooled standardized mean differences (SMD). Ten studies were included in our analysis (885 patients and 1,384 healthy controls). Patients with IBS had significant higher anxiety and depression levels than controls (respectively, SMD = 0.76, 95 % CI 0.47; 0.69, p < 0.01, I2 = 81.7 % and SMD = 0.80, 95 % CI 0.42; 1.19, p < 0.01, I2 = 90.7 %). This significant difference was confirmed for patients with IBS-C and -D subtypes for anxiety, and only in IBS-D patients for depression. However, other IBS subtypes had a statistical trend to be associated with both anxiety and depressive symptomatology, which suggests a lack of power due to the small number of studies included. Patients with IBS had significantly higher levels of anxiety and depression than healthy controls. Anxiety and depression symptomatology should be systematically checked and treated in IBS patients, as psychological factors are important moderators of symptom severity, symptom persistence, decisions to seek treatment, and response to treatment.

Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome

PubMed Central

Yu, Lei-Min; Zhao, Ke-Jia; Wang, Shuang-Shuang; Wang, Xi; Lu, Bin

2018-01-01

AIM To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome (IBS). METHODS In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum (C. butyricum) treatment. C57BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress (WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry (GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS (days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A (CoA) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways. CONCLUSION The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism. PMID:29491683

Reduced interstitial cells of Cajal and increased intraepithelial lymphocytes are associated with development of small intestinal bacterial overgrowth in post-infectious IBS mouse model.

PubMed

Chen, Binrui; Zhu, Shuwen; Du, Lijun; He, Huiqin; Kim, John J; Dai, Ning

2017-10-01

Intestinal dysmotility and immune activation are likely involved in the pathogenesis of small intestinal bacteria overgrowth (SIBO) in irritable bowel syndrome (IBS). We aimed at investigating the role of interstitial cells of Cajal (ICC) and intestinal inflammation in the development of SIBO using a post-infectious IBS (PI-IBS) mouse model. NIH mice were randomly infected with Trichinella spiralis. Visceral sensitivity and stool pattern were assessed at 8-weeks post-infection (PI). Intestinal bacteria counts from jejunum and ileum were measured by quantitative real-time PCR to evaluate the presence of SIBO. ICC density, intraepithelial lymphocytes (IELs) counts, and intestinal cytokine levels (IL1-β, IL-6, toll-like receptor-4 (TLR-4), IL-10) in the ileum were examined. PI-IBS mice demonstrated increased visceral sensitivity compared with the control group. One-third of the PI-IBS mice developed SIBO (SIBO+/PI-IBS) and was more likely to have abnormal stool form compared with SIBO negative PI-IBS (SIBO-/PI-IBS) mice but without difference in visceral sensitivity. SIBO+/PI-IBS mice had decreased ICC density and increased IELs counts in the ileum compared with SIBO-/PI-IBS mice. No difference in inflammatory cytokine expression levels were detected among the groups except for increased TLR-4 in PI-IBS mice compared with the control group. Development of SIBO in PI-IBS mice was associated with reduced ICC density and increased IELs counts in the ileum. Our findings support the role of intestinal dysmotility and inflammation in the pathogenesis of SIBO in IBS and may provide potential therapeutic targets.

Saturn Apollo Program

NASA Image and Video Library

1975-01-01

This montage illustrates the various configurations and missions of the three classes of the Saturn vehicles developed by the Marshall Space Flight Center. The missions for the Saturn I included atmospheric science investigations and the deployment of the Pegasus meteroid-detection satellite as well as launch vehicle development. The Saturn IB vehicle tested the Apollo spacecraft and launched the three marned Skylab missions as well as the Apollo Soyuz test project. The Saturn V vehicle launched the manned lunar orbital/landing missions, and the Skylab Orbital Workshop in 1973.

Psychosocial factors at work and in every day life are associated with irritable bowel syndrome.

PubMed

Faresjö, Ashild; Grodzinsky, Ewa; Johansson, Saga; Wallander, Mari-Ann; Timpka, Toomas; Akerlind, Ingemar

2007-01-01

The etiology of irritable bowel syndrome (IBS) tends to be complex and multi-factorial and there is still a lack of understanding of how different psychosocial factors are associated with the syndrome. Our aim was to examine the occurrence of psychosocial and behavioural factors among patients diagnosed with IBS in primary care. The study had an epidemiological population-based case-control design comparing 347 IBS cases to 1041 age and sex matched controls from the general population. A survey was directed to cases and controls based on validated questions asking for mood status, job strain, family history of IBS, and sleeping habits as well as education, nutritional and exercise habits and medication. In multivariate analyses, independent associations were found between IBS and lack of influence on work planning, a family history of IBS, anxiety, and sleeping disturbances. Important factors associated with IBS diagnosis among females were anxiety as well as family history of IBS and lack of co-determination at work. For males, only lack of influence on working pace and family history of IBS remained independently associated with an IBS diagnosis. The causal associations of the complex risk factor panorama for IBS warrants further study. This study indicates that there should be a special focus on investigating the psychosocial working conditions and their associations to IBS.

The impact of irritable bowel syndrome on daily functioning: Characterizing and understanding daily consequences of IBS.

PubMed

Ballou, S; Keefer, L

2017-04-01

Despite the well-documented economic and psychosocial burden of irritable bowel syndrome (IBS), few studies have focused on the impact of IBS on daily activities. This study aims to quantitate impairment in daily activities among IBS patients and to evaluate the relationship between impairment, IBS, quality of life, and psychiatric symptoms. A total of 179 participants meeting ROME-III criteria for IBS completed an online research survey evaluating the following variables: (i) the impact of IBS on daily activities, (ii) comorbid psychiatric diagnoses, (iii) symptom severity, (iv) quality of life, and (v) symptom-specific cognitive affective factors related to IBS. This sample reported a high degree of impairment due to IBS, with 76% of the sample reporting some degree of IBS-related impairment in at least five different domains of daily life. Rates of impairment were significantly higher for participants who met criteria for anxiety, depression, and/or panic disorder. This study contributes to existing literature by demonstrating a high level of daily impairment among patients with IBS, particularly those who meet criteria for anxiety, depression, and panic disorder. These findings support the importance of integrated psychosocial and medical care for IBS patients, and highlight the utility of evaluation and intervention for behavioral avoidance/impairment especially among those who exhibit signs or symptoms of psychiatric diagnoses. © 2016 John Wiley & Sons Ltd.

Protein misfolding specifies recruitment to cytoplasmic inclusion bodies.

PubMed

Bersuker, Kirill; Brandeis, Michael; Kopito, Ron R

2016-04-25

Inclusion bodies (IBs) containing aggregated disease-associated proteins and polyubiquitin (poly-Ub) conjugates are universal histopathological features of neurodegenerative diseases. Ub has been proposed to target proteins to IBs for degradation via autophagy, but the mechanisms that govern recruitment of ubiquitylated proteins to IBs are not well understood. In this paper, we use conditionally destabilized reporters that undergo misfolding and ubiquitylation upon removal of a stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IBs that are composed of an N-terminal fragment of mutant huntingtin, the causative protein of Huntington's disease. We show that reporters are excluded from IBs in the presence of the stabilizing ligand but are recruited to IBs after ligand washout. However, we find that Ub conjugation is not necessary to target reporters to IBs. We also report that forced Ub conjugation by the Ub fusion degradation pathway is not sufficient for recruitment to IBs. Finally, we find that reporters and Ub conjugates are stable at IBs. These data indicate that compromised folding states, rather than conjugation to Ub, can specify recruitment to IBs. © 2016 Bersuker et al.

Pediatric IBS: an overview on pathophysiology, diagnosis and treatment.

PubMed

Chogle, Ashish; Mintjens, Stijn; Saps, Miguel

2014-04-01

Irritable bowel syndrome (IBS) is a common disorder in children and adults. The pathogenesis and pathophysiology of IBS remains incompletely understood. The biopsychosocial model, which conceptualizes chronic pain as a dysregulation of the gut-brain-homeostasis with peripheral and central factors mutually influencing each other, is the most accepted framework to explain IBS. Twin and family aggregation studies suggest a genetic component that does not exclusively explain the higher prevalence of IBS in certain families. Social learning (environmental factors) and maladaptive coping predispose children to develop IBS with greater disability and more frequent medical consultations. Early-life events constitute an additional risk factor for the development of IBS and other functional gastrointestinal disorders (FGIDs). Children with a history of cow's milk protein hypersensitivity or abdominal surgeries have a higher prevalence of IBS and other FGIDs years later. IBS frequently follows an episode of acute gastrointestinal inflammation (infectious or non-infectious). This article discusses the importance, known pathophysiological mechanisms, clinical approach, and evidence-based therapeutic options for the management of IBS in children and adolescents. Copyright 2014, SLACK Incorporated.

How does comorbidity affect cost of health care in patients with irritable bowel syndrome? A cohort study in general practice.

PubMed

Johansson, Per A; Farup, Per G; Bracco, Andrea; Vandvik, Per O

2010-03-17

Irritable bowel syndrome (IBS) is associated with other disorders (comorbidity), reduced quality of life and increased use of health resources. We aimed to explore the impact of comorbidity on cost of health care in patients with IBS in general practice. In this cohort study 208 consecutive patients with IBS (Rome II) were recruited. Sociodemographic data, IBS symptoms, and comorbidity (somatic symptoms, organic diseases and psychiatric disorders) were assessed at baseline. Based on a follow up interview after 6-9 months and use of medical records, IBS and non-IBS related health resource use were measured as consultations, hospitalisations, use of medications and alternative health care products and sick leave days. Costs were calculated by national tariffs and reported in Norwegian Kroner (NOK, 1 EURO equals 8 NOK). Multivariate analyses were performed to identify predictors of costs. A total of 164 patients (mean age 52 years, 69% female, median duration of IBS 17 years) were available at follow up, 143 patients (88%) had consulted their GP of whom 31 (19%) had consulted for IBS. Mean number of sick- leave days for IBS and comorbidity were 1.7 and 16.3 respectively (p < 0.01), costs related to IBS and comorbidity were 954 NOK and 14854 NOK respectively (p < 0.001). Age, organic diseases and somatic symptoms, but not IBS severity, were significant predictors for total costs. Costs for health resource use among patients with IBS in general practice were largely explained by comorbidity, which generated ten times the costs for IBS.

Ethnic and gender differences in ideal body size and related attitudes among Asians, Native Hawaiians, and Whites.

PubMed

Townsend, Claire; Takishima-Lacasa, Julie Y; Latner, Janet D; Grandinetti, Andrew; Keawe'aimoku Kaholokula, Joseph

2014-08-01

Often overlooked explanations for the varied obesity rates across ethno-cultural groups include differences in attitudes toward excess weight, with certain populations assumed to have larger ideal body sizes (IBS). Past studies found ethnic and gender difference in IBS across and within different groups. This study examined the effects of ethnicity and gender, and their interaction, in accounting for differences in IBS and attitudes toward those ideals. Multiple regression analyses were used to better understand the effects of ethnicity and gender in accounting for differences in perceived IBS according to ethnic-specific and Western ideals and attitudes in 1,124 people of Native Hawaiian, Filipino, Japanese, and White ancestry. The analyses controlled for socio-demographics, body mass index, health-related behaviors, and psychosocial variables. The results indicated that Native Hawaiians selected larger ethnic IBS, Filipinos selected smaller ethnic IBS, and Native Hawaiians selected slightly smaller Western IBS than other ethnic groups. Overall, males selected larger IBS compared to females. Interaction analyses indicated that the relationship between ethnic IBS and attitude toward that IBS varied as a function of ethnicity, such that Native Hawaiians who selected a larger ethnic IBS held less favorable attitudes toward that IBS. The discrepancy between Native Hawaiians' selection of larger ethnic IBS as ideal and their less positive attitude toward that selection warrants more investigation. However, it does suggest that Native Hawaiians, on a personal level, do not prefer larger body sizes, which contradicts their perceptions of social norms. These findings have important implications for obesity interventions among Native Hawaiians.

How does comorbidity affect cost of health care in patients with irritable bowel syndrome? A cohort study in general practice

PubMed Central

2010-01-01

Background Irritable bowel syndrome (IBS) is associated with other disorders (comorbidity), reduced quality of life and increased use of health resources. We aimed to explore the impact of comorbidity on cost of health care in patients with IBS in general practice. Methods In this cohort study 208 consecutive patients with IBS (Rome II) were recruited. Sociodemographic data, IBS symptoms, and comorbidity (somatic symptoms, organic diseases and psychiatric disorders) were assessed at baseline. Based on a follow up interview after 6-9 months and use of medical records, IBS and non-IBS related health resource use were measured as consultations, hospitalisations, use of medications and alternative health care products and sick leave days. Costs were calculated by national tariffs and reported in Norwegian Kroner (NOK, 1 EURO equals 8 NOK). Multivariate analyses were performed to identify predictors of costs. Results A total of 164 patients (mean age 52 years, 69% female, median duration of IBS 17 years) were available at follow up, 143 patients (88%) had consulted their GP of whom 31 (19%) had consulted for IBS. Mean number of sick- leave days for IBS and comorbidity were 1.7 and 16.3 respectively (p < 0.01), costs related to IBS and comorbidity were 954 NOK and 14854 NOK respectively (p < 0.001). Age, organic diseases and somatic symptoms, but not IBS severity, were significant predictors for total costs. Conclusion Costs for health resource use among patients with IBS in general practice were largely explained by comorbidity, which generated ten times the costs for IBS. PMID:20233451

Ethnic and Gender Differences in Ideal Body Size and Related Attitudes among Asians, Native Hawaiians, and Whites

PubMed Central

Takishima-Lacasa, Julie Y; Latner, Janet D; Grandinetti, Andrew; Keawe‘aimoku Kaholokula, Joseph

2014-01-01

Often overlooked explanations for the varied obesity rates across ethno-cultural groups include differences in attitudes toward excess weight, with certain populations assumed to have larger ideal body sizes (IBS). Past studies found ethnic and gender difference in IBS across and within different groups. This study examined the effects of ethnicity and gender, and their interaction, in accounting for differences in IBS and attitudes toward those ideals. Multiple regression analyses were used to better understand the effects of ethnicity and gender in accounting for differences in perceived IBS according to ethnic-specific and Western ideals and attitudes in 1,124 people of Native Hawaiian, Filipino, Japanese, and White ancestry. The analyses controlled for socio-demographics, body mass index, health-related behaviors, and psychosocial variables. The results indicated that Native Hawaiians selected larger ethnic IBS, Filipinos selected smaller ethnic IBS, and Native Hawaiians selected slightly smaller Western IBS than other ethnic groups. Overall, males selected larger IBS compared to females. Interaction analyses indicated that the relationship between ethnic IBS and attitude toward that IBS varied as a function of ethnicity, such that Native Hawaiians who selected a larger ethnic IBS held less favorable attitudes toward that IBS. The discrepancy between Native Hawaiians' selection of larger ethnic IBS as ideal and their less positive attitude toward that selection warrants more investigation. However, it does suggest that Native Hawaiians, on a personal level, do not prefer larger body sizes, which contradicts their perceptions of social norms. These findings have important implications for obesity interventions among Native Hawaiians. PMID:25157324

Intestinal Membrane Permeability and Hypersensitivity In the Irritable Bowel Syndrome

PubMed Central

Zhou, QiQi; Zhang, Buyi; Verne, G. Nicholas

2009-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the underlying pathophysiology is poorly understood; however, increased intestinal permeability in diarrhea-predominant IBS patients has been reported. Here we demonstrate diarrhea-predominant IBS patients (D-IBS) that display increased intestinal permeability. We have also found that increased intestinal membrane permeability is associated with visceral and thermal hypersensitivity in this subset of D-IBS patients. We evaluated 54 D-IBS patients and 22 controls for intestinal membrane permeability using the lactulose / mannitol method. All subjects ingested 5 g laclulose and 2 g mannitol in 100 ml of water after which their urine was collected. We also evaluated the mean mechanical visual analogue (MVAS) pain rating to nociceptive thermal and visceral stimulation in all subjects. All study participants also completed the FBDSI scale. Approximately 39% of diarrhea-predominant IBS patients have increased intestinal membrane permeability as measured by the lactulose / mannitol ratio. These IBS patients also demonstrated higher M-VAS pain intensity reading scale. Interestingly, the IBS patients with hypersensitivity and increased intestinal permeability had a higher FBDSI score (100.8±5.4) compared to IBS patients with normal membrane permeability and sensitivity (51.6±12.7) and controls (6.1 ± 5.6) (p<0.001). A subset of D-IBS patients have increased intestinal membrane permeability that is associated with an increased FBDSI score and increased hypersensitivity to visceral and thermal nociceptive pain stimuli. Thus, increased intestinal membrane permeability in D-IBS patients may lead to more severe IBS symptoms and hypersensitivity to somatic and visceral stimuli. PMID:19595511

Quality of life in patients with Irritable Bowel Syndrome (IBS), assessed using the IBS-Quality of Life (IBS-QOL) measure after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide: results of an international prospective observational cohort study in Poland, Egypt, Mexico and China.

PubMed

Hou, Xiaohua; Chen, Shengliang; Zhang, Yali; Sha, Weihong; Yu, Xiaofeng; Elsawah, Hesham; Afifi, Afifi Fahmy; El-Khayat, Hisham Raafat; Nouh, Alaa; Hassan, Mohamed Fathalla; Fatah, Ayman Abdel; Rucker Joerg, Isabel; Sánchez Núñez, Juan Manuel; Osthoff Rueda, Rodolfo; Jurkowska, Grazyna; Walczak, Michal; Malecka-Panas, Ewa; Linke, Krzysztof; Hartleb, Marek; Janssen-van Solingen, Gwendolyn

2014-11-01

Irritable Bowel Syndrome (IBS) has a substantial impact on health-related quality of life (HR-QoL) but high-quality data pre- and post-treatment using the IBS-Quality of Life (IBS-QOL) measure are limited. The objective of this study was to evaluate the changes from baseline of the IBS-QOL scores, symptom scores and health economic data in IBS patients, after 4 and 8 weeks of treatment with mebeverine hydrochloride or pinaverium bromide. This was a prospective observational cohort study in patients with IBS, diagnosed using the Rome III criteria in four countries (Poland, Egypt, Mexico and China). A total of 607 patients were enrolled. At baseline, the IBS-QOL total scores were 52.0 in Poland, 48.9 in Egypt, 51.9 in Mexico, 76.4 in China and 56.4 overall. Increases in IBS-QOL total score were statistically significant at Weeks 4 and 8 overall and in each country (overall: 11.8 at Week 4, 24.3 at Week 8; p < 0.001). Improvements were shown in all IBS-QOL subscales and scores. Symptoms and health economic outcomes were improved. Furthermore, the favourable safety profile of these treatments was confirmed in this study. This study demonstrated that IBS patients have a substantially reduced HR-QoL and that treatment with mebeverine hydrochloride or pinaverium bromide improved HR-QoL.

Electron Microscopy of Intracellular Protozoa.

DTIC Science & Technology

1980-08-01

D . C . 20012, and Institute of Pathology, Case Western Reserve University, Clevelai| d , 011 44106 .4 2-%? Studies of immunity...0 00 0 0 0 00 00 c N wT co D - -5, * z L 0 N)~v ~. ~~ . * . ~ .. .-. * 4 .. rnr I. *~, a~rn ~ ~ .’* c * ’** * *- . .--. .-U. ’I pg . c ~ $) vs .4 N 0 it...NIH, Bethesda, Maryland. BHK21 (clone-15) was obtained from Dr. Joel Dalrymple of Walter Reed Army Institute of Research, Washington, D . C . Vero

On Line Digitizer Software.

DTIC Science & Technology

1984-06-01

UNSOLINTERRUPT: ; Dismiss unsolicited Interrupt. POPR M<RI,RI,R2,R3,R4,R5> ; Restore RZ-R5 REI ; Return from interrupt. .SBTTL AVCANCEL. Cancel I/O routine...Dismiss unsolicited Interrupt. POPR M<R8,RI.R2,R3,R4,R5> ; Restore RN-R5 REI ; Return from interrupt. .SBTTL ODCANCEL, Cancel I/0 routine ++ I ODCANCEL...output buffer. ODREGDU4P: i Dump device registers MOVZBL ODNUMREGS,(Rg)+ i Store device register count. NOVZWL UCBSWODBYTCNT(RS),- aStore BYTE count

Association between Symptoms of Irritable Bowel Syndrome and Methane and Hydrogen on Lactulose Breath Test

PubMed Central

Lee, Kang Nyeong; Koh, Dong Hee; Sohn, Won; Lee, Sang Pyo; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon; Hahm, Joon Soo

2013-01-01

Whether hydrogen and methane gas produced during lactulose breath test (LBT) are associated with symptoms of irritable bowel syndrome (IBS) is not determined. We aimed to investigate whether hydrogen and methane on LBT are associated with IBS symptoms. Sixty-eight IBS patients meeting the Rome III criteria for IBS, and 55 healthy controls, underwent LBT. The IBS subjects recorded their customary gastrointestinal symptoms on a questionnaire using visual analogue scales. LBT positivity was defined to be above 20 ppm rise of hydrogen or 10 ppm rise of methane within 90 min. Gas amounts produced during LBT were determined by calculating area under the curve of hydrogen and methane excretion. Symptom severity scores were not different between the LBT (+) IBS and LBT (-) IBS subjects and also between methane producers and non-methane producers. Gas amounts produced during LBT were not associated with IBS symptoms, except a weak correlation between total gas amounts and a few IBS symptoms such as bloating (r = 0.324, P = 0.039), flatulence (r = 0.314, P = 0.046) and abdominal pain (r = 0.364, P = 0.018) only in LBT (+) IBS. In conclusion, hydrogen and methane gas on LBT are not useful for predicting the customary symptoms and subtypes of IBS. PMID:23772156

Imaging biomarker roadmap for cancer studies

PubMed Central

O’Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; deSouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, John R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

2017-01-01

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing ‘translational gaps’ through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored ‘roadmap’. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use. PMID:27725679

[Validation of the IBS-SSS].

PubMed

Betz, C; Mannsdörfer, K; Bischoff, S C

2013-10-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterised by abdominal pain, associated with stool abnormalities and changes in stool consistency. Diagnosis of IBS is based on characteristic symptoms and exclusion of other gastrointestinal diseases. A number of questionnaires exist to assist diagnosis and assessment of severity of the disease. One of these is the irritable bowel syndrome - severity scoring system (IBS-SSS). The IBS-SSS was validated 1997 in its English version. In the present study, the IBS-SSS has been validated in German language. To do this, a cohort of 60 patients with IBS according to the Rome III criteria, was compared with a control group of healthy individuals (n = 38). We studied sensitivity and reproducibility of the score, as well as the sensitivity to detect changes of symptom severity. The results of the German validation largely reflect the results of the English validation. The German version of the IBS-SSS is also a valid, meaningful and reproducible questionnaire with a high sensitivity to assess changes in symptom severity, especially in IBS patients with moderate symptoms. It is unclear if the IBS-SSS is also a valid questionnaire in IBS patients with severe symptoms because this group of patients was not studied. © Georg Thieme Verlag KG Stuttgart · New York.

Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction.

PubMed

Rodiño-Janeiro, Bruno K; Martínez, Cristina; Fortea, Marina; Lobo, Beatriz; Pigrau, Marc; Nieto, Adoración; González-Castro, Ana María; Salvo-Romero, Eloísa; Guagnozzi, Danila; Pardo-Camacho, Cristina; Iribarren, Cristina; Azpiroz, Fernando; Alonso-Cotoner, Carmen; Santos, Javier; Vicario, Maria

2018-02-02

Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBS-D. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS.

Integrated Baseline System (IBS), Version 1. 03. [Chemical Stockpile Emergency Preparedness Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, B.M.; Burford, M.J.; Downing, T.R.

The Integrated Baseline System (IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planing and analysis. This document is the user guide for the IBS and explains how to operate the IBS system. The fundamental function of the IBS is to provide tools that civilian emergency management personnel can use in developing emergency plans and in supporting emergency management activities to cope with a chemical-releasing event at a military chemical stockpile. Emergency management planners can evaluate concepts and ideas using the IBS system. The results of that experience can then be factoredmore » into refining requirements and plans. This document provides information for the general system user, and is the primary reference for the system features of the IBS. It is designed for persons who are familiar with general emergency management concepts, operations, and vocabulary. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other LBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary. IBS is a dynamic system. Its capabilities are in a state of continuing expansion and enhancement.« less

The effect of PDIA3 gene knockout on the mucosal immune function in IBS rats.

PubMed

Zhuang, Zhao-Meng; Wang, Xiao-Teng; Zhang, Lu; Tao, Li-Yuan; Lv, Bin

2015-01-01

To observe the changes of intestinal inflammation on PDIA3 gene knockout IBS rats and its effect on immune function. 36 SD rats were randomly divided into four groups: the control group (n = 8); IBS- empty virus group (IBS-GFP, which); IBS-PDIA3 knockout group (n = 12); IBS- the control group (n = 12). After modeling, colon and ileocecal tissue pathology in each group were observed separately. Changes of immune and inflammatory markers were measured. At the same time, ultrastructural changes in each group were observed by electron microscopy. Compared with the IBS control group, inflammation was reduced significantly in IBS-PDIA3 knockout group. IgE, IL-4 and IL-9 and the level of intestinal trypsin type were decreased significantly. Furthermore, mast cell degranulation and PAR 2 receptor reduced significantly. PDIA3 may play an important role in the development of IBS by mediating through immune responses of mucosal abnormalities. However, the mechanism needs to be confirmed in further study.

The impact of irritable bowel syndrome on health-related quality of life: a Singapore perspective.

PubMed

Wang, Yu Tien; Lim, Hwee Yong; Tai, David; Krishnamoorthy, Thinesh L; Tan, Tira; Barbier, Sylvaine; Thumboo, Julian

2012-08-09

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. The prevalence of IBS in Asian countries varies from 2.9% to 15.6%. IBS does not result in increased mortality, but is associated with psychological distress and disruption of work and sleep. Consequently, the evaluation of health-related quality of life (HRQoL) is an important outcome measure for patients with IBS since it provides a holistic assessment of the patient's emotional, social and physical function. However, some HRQoL tools can be time-consuming to apply. EQ-5D is a brief HRQoL tool which has been validated in the Western IBS population but has thus far not been used in Asia. This study was conducted to determine whether persons with self-reported symptoms that met the Rome III criteria for IBS had a poorer quality of life than those without these symptoms. We also aimed to determine which specific aspects of quality of life were most affected and whether any risk factors distinguished those with and without IBS. Self-administered questionnaires which included the Rome III diagnostic questionnaire modules for IBS and the EQ-5D questionnaire were obtained from participants of a health symposium in Singapore on 31th October 2010. IBS was diagnosed based on the Rome III Criteria. The main outcome measure was the EQ-5D index score. The relationship between the presence of IBS and the EQ-5D index score, individual dimensions of EQ-5D and demographic risk factors were examined. 449 completed questionnaires were analyzed. The mean EQ-5D index score for IBS was 0.739 which was a significant reduction compared to non-IBS participants [-0.11 (95% CI: -0.15 to -0.07), p<0.001]. Multivariate analysis showed that IBS was significantly associated with younger age and higher education level. Of the five EQ-5D dimensions, IBS sufferers were significantly affected in mobility, anxiety or depression, usual activity and pain. There was a "dose related" increase in likelihood of having IBS with increased severity of pain and anxiety or depression. IBS sufferers have significantly poorer quality of life. Assessment of HRQoL in IBS using the EQ-5D should be considered in further studies and routine clinical practice.

Antidysrhythmic agents at the turn of the twenty-first century: a current review.

PubMed

Haugh, Kathy Henley

2002-03-01

The use of class IA agents is gradually on the decline, primarily as a result of its unfavorable risk-to-benefit ratio. Lidocaine, a class IB agent, has been widely used in the acute treatment of VT. However, alternate drugs are being considered increasingly as first-line agents in the acute treatment of VT. Class IC drugs are contraindicated in patients with structural cardiac abnormalities and have a limited usefulness in the management of dysrhythmias. Beta-blockers continue to increase their role in cardiology, and subsequently their use in managing dysrhythmias. Class III agents, including amiodarone, sotalol, ibutilide, and dofetilide, are among the most widely used antidysrhythmics. Class IV calcium channel blockers have a limited usefulness in tachydysrhythmias. Digoxin and adenosine have unique antidysrhythmic properties and will likely retain their roles as antidysrhythmic agents. In the wake of the effectiveness of amiodarone, the drug that crosses all classes, some now question the benefit of pure agents that block a single, specific ion channel in the heart. After CAST8 demonstrated that antidysrhythmics can increase mortality while seemingly suppressing dysrhythmias, new drugs will continue to undergo intense scrutiny with regard to their efficacy, safety, and usefulness in treating dysrhythmias.

Gastrointestinal permeability (GIPerm) is increased in family members of children with functional abdominal pain (FAP) and irritable bowel syndrome (IBS)

USDA-ARS?s Scientific Manuscript database

Increased GIPerm has been described in children with FAP/IBS and adults with IBS. We sought to determine if baseline GIPerm is increased and if ibuprofen induces a greater increase in GIPerm in parents and siblings of children with FAP/IBS vs. control families without children with FAP/IBS. Site spe...

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.

PubMed

Jin, Duo-Chen; Cao, Hai-Long; Xu, Meng-Que; Wang, Si-Nan; Wang, Yu-Ming; Yan, Fang; Wang, Bang-Mao

2016-09-28

Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.

Positive and negative affect mediate the bidirectional relationship between emotional processing and symptom severity and impact in irritable bowel syndrome.

PubMed

Sibelli, Alice; Chalder, Trudie; Everitt, Hazel; Chilcot, Joseph; Moss-Morris, Rona

2018-02-01

Individuals with IBS report higher levels of psychological distress compared to healthy controls. Distress has been associated with emotional processing difficulties but studies have not explored how the relationship between distress and emotional processing affects IBS. There is little research on the role of positive affect (PA) in IBS. (a) If difficulties in self-reported emotional processing are associated with affect and IBS measures (i.e., symptom severity, interference in life roles) (b1) If affect mediates the relationship between emotional processing and IBS measures (b2) Alternative model: if affect mediates the relationship between IBS and emotional processing (c) If PA moderates the relationship between distress and IBS. Participants with a confirmed diagnosis of IBS (n=558) completed a questionnaire including measures of emotional processing (i.e., unhelpful beliefs about negative emotions, impoverished emotional experience), distress, PA, and IBS symptoms/interference. Mediation and moderation analyses were conducted with Maximum Likelihood Estimation. Distress and PA mediated or partly mediated the relationship between unhelpful beliefs about negative emotions/impoverished emotional experience and both IBS measures. The alternative models were also valid, suggesting a two-way relationship between emotional processing and IBS through affect. PA did not moderate the relationship between distress and IBS. Future interventions in IBS may benefit from not only targeting the management of physical symptoms and their daily impact but also aspects related to the experience of both negative and positive affect, and the acceptance and expression of negative emotions. Longitudinal studies are needed to confirm causal relationships within the explored models. Copyright © 2017 Elsevier Inc. All rights reserved.

High Frequency of Chronic Bacterial and Non-Inflammatory Prostatitis in Infertile Patients with Prostatitis Syndrome Plus Irritable Bowel Syndrome

PubMed Central

Vicari, Enzo; La Vignera, Sandro; Arcoria, Domenico; Condorelli, Rosita; Vicari, Lucia O.; Castiglione, Roberto; Mangiameli, Andrea; Calogero, Aldo E.

2011-01-01

Background Although prostatitis syndrome (PS) and irritable bowel syndrome (IBS) are common disorders, information on the prevalence of IBS in infertile patients with PS is relatively scanty. Therefore, this study was undertaken to estimate the frequency of PS and IBS and to evaluate the prevalence of the various diagnostic categories of prostatitis. Methodology/Principal Findings This study enrolled 152 patients with PS, diagnosed by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) in an andrological setting, and 204 patients with IBS, diagnosed according to the Rome III diagnostic criteria in a gastroenterological setting. The patients with PS were asked to fulfill the Rome III questionnaire for IBS, whereas patients with IBS were asked to complete the NIH-CPSI. The simultaneous presence of PS and IBS was observed in 30.2% and 31.8% of the patients screened by andrologists and gastroenterologists, respectively. Altogether, 111 patients had PS plus IBS (31.2%). They had a total NIH-CPSI and pain subscale scores significantly higher than patients with PS alone. Gastrointestinal symptoms in patients with PS plus IBS were similar to those reported by patients with IBS alone and significantly greater in patients with PS alone. Patients with PS plus IBS had a significantly higher frequency of chronic bacterial prostatitis (category II) and lower of non-inflammatory prostatitis (category IIIB), compared to patients with PS alone. The frequency of inflammatory prostatitis (category IIIA) resulted similar. Conclusions/Significance Prostatitis syndromes and IBS are frequently associated in patients with PS- or IBS-related symptoms. These patients have an increased prevalence of chronic bacterial and non-inflammatory prostatitis. PMID:21494624

Kinetic study of bone ingrowth and ceramic resorption associated with the implantation of different injectable calcium-phosphate bone substitutes.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Daculsi, G; Aguado, E

1999-10-01

This study investigated the in vivo performance of two composite injectable bone substitutes (IBS), each with different calcium-phosphate particles granulometries [40-80 (IBS 40-80) and 200-500 microm (IBS 200-500)]. These biomaterials were obtained by associating a biphasic calcium-phosphate (BCP) ceramic mineral phase with a 3% aqueous solution of a cellulosic polymer (hydroxy-propyl-methyl-cellulose). Both materials were injected for periods of 2, 3, 8, or 12 weeks into bone defects at the distal end of rabbit femurs. Quantitative results on new bone formation, BCP resorption, and staining for tartrate-resistant acid phosphatase (TRAP) activity were studied for statistical purposes. Measurements with scanning electron microscopy and image analysis showed that the final rates of newly formed bone were similar for both tested IBS after 12 weeks of implantation. Bone colonization occurred more extensively during early implantation times for IBS 40-80 than for IBS 200-500. For the latter, BCP degradation occurred regularly throughout the implantation period, whereas it was very intensive during the first 2 weeks for IBS 40-80. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than for IBS 200-500 regardless of implantation time. With the granulometry of either mineral phase, both tested IBS supported extensive bone colonization, which was greater than that previously reported for an equivalent block of macroporous BCP. The resorption-bone substitution process seemed to occur earlier and faster for IBS 40-80 than for IBS 200-500. Both tested IBS expressed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Copyright 1999 John Wiley & Sons, Inc.

Molecular characterization of tocopherol biosynthetic genes in sweetpotato that respond to stress and activate the tocopherol production in tobacco.

PubMed

Ji, Chang Yoon; Kim, Yun-Hee; Kim, Ho Soo; Ke, Qingbo; Kim, Gun-Woo; Park, Sung-Chul; Lee, Haeng-Soon; Jeong, Jae Cheol; Kwak, Sang-Soo

2016-09-01

Tocopherol (vitamin E) is a chloroplast lipid that is presumed to be involved in the plant response to oxidative stress. In this study, we isolated and characterized five tocopherol biosynthetic genes from sweetpotato (Ipomoea batatas [L.] Lam) plants, including genes encoding 4-hydroxyphenylpyruvate dioxygenase (IbHPPD), homogentisate phytyltransferase (IbHPT), 2-methyl-6-phytylbenzoquinol methyltransferase (IbMPBQ MT), tocopherol cyclase (IbTC) and γ-tocopherol methyltransferase (IbTMT). Fluorescence microscope analysis indicated that four proteins localized into the chloroplast, whereas IbHPPD observed in the nuclear. Quantitative RT-PCR analysis revealed that the expression patterns of the five tocopherol biosynthetic genes varied in different plant tissues and under different stress conditions. All five genes were highly expressed in leaf tissues, whereas IbHPPD and IbHPT were highly expressed in the thick roots. The expression patterns of these five genes significantly differed in response to PEG, NaCl and H2O2-mediated oxidative stress. IbHPPD was strongly induced following PEG and H2O2 treatment and IbHPT was strongly induced following PEG treatment, whereas IbMPBQ MT and IbTC were highly expressed following NaCl treatment. Upon infection of the bacterial pathogen Pectobacterium chrysanthemi, the expression of IbHPPD increased sharply in sweetpotato leaves, whereas the expression of the other genes was reduced or unchanged. Additionally, transient expression of the five tocopherol biosynthetic genes in tobacco (Nicotiana bentamiana) leaves resulted in increased transcript levels of the transgenes expressions and tocopherol production. Therefore, our results suggested that the five tocopherol biosynthetic genes of sweetpotato play roles in the stress defense response as transcriptional regulators of the tocopherol production. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Health-related quality of life of irritable bowel syndrome patients in different cultural settings.

PubMed

Faresjö, Ashild; Anastasiou, Foteini; Lionis, Christos; Johansson, Saga; Wallander, Mari-Ann; Faresjö, Tomas

2006-03-27

Persons with Irritable bowel syndrome (IBS) are seriously affected in their everyday life. The effect across different cultural settings of IBS on their quality of life has been little studied. The aim was to compare health-related quality of life (HRQOL) of individuals suffering from IBS in two different cultural settings; Crete, Greece and Linköping, Sweden. This study is a sex and age-matched case-control study, with n = 30 Cretan IBS cases and n = 90 Swedish IBS cases and a Swedish control group (n = 300) randomly selected from the general population. Health-related quality of life, measured by SF-36 and demographics, life style indicators and co-morbidity, was measured. Cretan IBS cases reported lower HRQOL on most dimensions of SF-36 in comparison to the Swedish IBS cases. Significant differences were found for the dimensions mental health (p < 0.0001) and general health (p = 0.05) even after adjustments for educational level and co-morbidity. Women from Crete with IBS scored especially low on the dimensions general health (p = 0.009) and mental health (p < 0.0001) in comparison with Swedish women with IBS. The IBS cases, from both sites, reported significantly lower scores on all HRQOL dimensions in comparison with the Swedish control group. The results from this study tentatively support that the claim that similar individuals having the same disease, e.g. IBS, but living in different cultural environments could perceive their disease differently and that the disease might affect their everyday life and quality of life in a different way. The Cretan population, and especially women, are more seriously affected mentally by their disease than Swedish IBS cases. Coping with IBS in everyday life might be more problematic in the Cretan environment than in the Swedish setting.

Initial Breakdown Pulse Amplitudes in Intracloud and Cloud-to-Ground Lightning Flashes

NASA Astrophysics Data System (ADS)

Marshall, T. C.; Smith, E. M.; Stolzenburg, M.; Karunarathne, S.; Siedlecki, R. D., II

2017-12-01

This study analyzes the largest initial breakdown (IB) pulse in flashes from three storms in Florida. The study was motivated in part by the possibility that IB pulses of IC flashes may cause of terrestrial gamma-ray flashes (TGFs). The range-normalized, zero-to-peak amplitude of the largest IB pulse within each flash was determined along with its altitude, duration, and occurrence time in the flash. Appropriate data were available for 40 intracloud (IC) and 32 cloud-to-ground (CG) flashes. Histograms of the magnitude of the largest IB pulse amplitude by flash type were similar, with mean (median) values of 1.49 (1.05) V/m for IC flashes and -1.35 (-0.87) V/m for CG flashes. The mean amplitude of the largest IC IB pulses are substantially smaller (roughly an order of magnitude smaller) than the few known pulse amplitudes of TGF events and TGF candidate events. The largest IB pulse in 30 IC flashes showed a weak inverse relation between pulse amplitude and altitude. Amplitude of the largest IB pulse for 25 CG flashes showed no altitude correlation. Duration of the largest IB pulse in ICs averaged twice as long as in CGs (96 μs versus 46 μs); all of the CG durations were <100 μs. Among the ICs, there is a positive relation between largest IB pulse duration and amplitude; the linear correlation coefficient is 0.385 with outliers excluded. The largest IB pulse in IC flashes typically occurred at a longer time after the first IB pulse (average 4.1 ms) than was the case in CG flashes (average 0.6 ms). In both flash types, the largest IB pulse was the first IB pulse in about 30% of the cases.

Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.

PubMed

Martinowitz, U; Shapiro, A; Quon, D V; Escobar, M; Kempton, C; Collins, P W; Chowdary, P; Makris, M; Mannucci, P M; Morfini, M; Valentino, L A; Gomperts, E; Lee, M

2012-11-01

IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥ 12 years weighing ≥ 40 kg, with severe or moderately severe haemophilia B (FIX activity ≤ 2 IU dL (-1) ). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4-18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8-59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg(-1) or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC(0-t) and AUC(0-∞) (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non-inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B. © 2012 Blackwell Publishing Ltd.

Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome.

PubMed

Barmeyer, Christian; Schumann, Michael; Meyer, Tim; Zielinski, Christina; Zuberbier, Torsten; Siegmund, Britta; Schulzke, Jörg-Dieter; Daum, Severin; Ullrich, Reiner

2017-01-01

Irritable bowel syndrome (IBS) is common but therapies are unsatisfactory. Food is often suspected as cause by patients, but diagnostic procedures, apart from allergy testing, are limited. Based on the hypothesis of non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8 expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed-type IBS (IBS-M). The response to a GFD served as reference test for WS and HLA-DQ2/8 expression was determined as index test. Patients were classified as responders if they reported complete or considerable relief of IBS symptoms on at least 75 % of weeks over a 4-month period of gluten-free diet. Established questionnaires (IBS-Quality of Life (IBS-QoL), IBS Symptom Severity Scale (IBS-SSS), European Quality of Life-5 Dimensions (EQ-5D)) were used for secondary outcome measures. Thirty-five patients finished the study. Of these, 12 (34 %) were responders and classified as having WS (95 % CI 21-51 %). HLA-DQ2/8 expression had a specificity of 52 % (95 % CI 33-71 %) and sensitivity of 25 % (95 % CI 8-54 %) for WS. Responders showed improvement in quality of life and symptom scores. At 1-year follow-up, all responders and 55 % of non-responders were still on GFD and reported symptom relief. Using strict criteria as recommended for IBS studies, about one third of patients with IBS-D or IBS-M are wheat sensitive, with a similar proportion in both IBS types. Expression of HLA-DQ2/8 is not useful as diagnostic marker for WS. Long-term adherence to a GFD is high and can sustain symptomatic improvement.

Protease signaling through protease activated receptor 1 mediate nerve activation by mucosal supernatants from irritable bowel syndrome but not from ulcerative colitis patients

PubMed Central

Buhner, Sabine; Hahne, Hannes; Hartwig, Kerstin; Li, Qin; Vignali, Sheila; Ostertag, Daniela; Meng, Chen; Hörmannsperger, Gabriele; Braak, Breg; Pehl, Christian; Frieling, Thomas; Barbara, Giovanni; De Giorgio, Roberto; Demir, Ihsan Ekin; Ceyhan, Güralp Onur; Zeller, Florian; Boeckxstaens, Guy; Haller, Dirk; Kuster, Bernhard

2018-01-01

Background & aims The causes of gastrointestinal complaints in irritable bowel syndrome (IBS) remain poorly understood. Altered nerve function has emerged as an important pathogenic factor as IBS mucosal biopsy supernatants consistently activate enteric and sensory neurons. We investigated the neurally active molecular components of such supernatants from patients with IBS and quiescent ulcerative colitis (UC). Method Effects of supernatants from 7 healthy controls (HC), 20 IBS and 12 UC patients on human and guinea pig submucous neurons were studied with neuroimaging techniques. We identify differentially expressed proteins with proteome analysis. Results Nerve activation by IBS supernatants was prevented by the protease activated receptor 1 (PAR1) antagonist SCHE79797. UC supernatants also activated enteric neurons through protease dependent mechanisms but without PAR1 involvement. Proteome analysis of the supernatants identified 204 proteins, among them 17 proteases as differentially expressed between IBS, UC and HC. Of those the four proteases elastase 3a, chymotrypsin C, proteasome subunit type beta-2 and an unspecified isoform of complement C3 were significantly more abundant in IBS compared to HC and UC supernatants. Of eight proteases, which were upregulated in IBS, the combination of elastase 3a, cathepsin L and proteasome alpha subunit-4 showed the highest prediction accuracy of 98% to discriminate between IBS and HC groups. Elastase synergistically potentiated the effects of histamine and serotonin–the two other main neuroactive substances in the IBS supernatants. A serine protease inhibitor isolated from the probiotic Bifidobacterium longum NCC2705 (SERPINBL), known to inhibit elastase-like proteases, prevented nerve activation by IBS supernatants. Conclusion Proteases in IBS and UC supernatants were responsible for nerve activation. Our data demonstrate that proteases, particularly those signalling through neuronal PAR1, are biomarker candidates for IBS, and protease profiling may be used to characterise IBS. PMID:29529042

Recent developments in the pathophysiology of irritable bowel syndrome

PubMed Central

El-Salhy, Magdy

2015-01-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, the pathophysiology of which is not completely known, although it has been shown that genetic/social learning factors, diet, intestinal microbiota, intestinal low-grade inflammation, and abnormal gastrointestinal endocrine cells play a major role. Studies of familial aggregation and on twins have confirmed the heritability of IBS. However, the proposed IBS risk genes are thus far nonvalidated hits rather than true predisposing factors. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, with the effect exerted by diet seemingly caused by intake of poorly absorbed carbohydrates and fiber. Obesity is a possible comorbidity of IBS. Differences in the microbiota between IBS patients and healthy controls have been reported, but the association between IBS symptoms and specific bacterial species is uncertain. Low-grade inflammation appears to play a role in the pathophysiology of a major subset of IBS, namely postinfectious IBS. The density of intestinal endocrine cells is reduced in patients with IBS, possibly as a result of genetic factors, diet, intestinal microbiota, and low-grade inflammation interfering with the regulatory signals controlling the intestinal stem-cell clonogenic and differentiation activities. Furthermore, there is speculation that this decreased number of endocrine cells is responsible for the visceral hypersensitivity, disturbed gastrointestinal motility, and abnormal gut secretion seen in IBS patients. PMID:26167065

Mental Strain and Chronic Stress among University Students with Symptoms of Irritable Bowel Syndrome.

PubMed

Gulewitsch, Marco D; Enck, Paul; Schwille-Kiuntke, Juliane; Weimer, Katja; Schlarb, Angelika A

2013-01-01

Aim. To investigate the degree of mental strain and chronic stress in a German community sample of students with IBS-like symptoms. Methods and Materials. Following an internet-based survey about stress, this study recruited 176 German university students (23.45 ± 2.48 years; 48.3% males) with IBS-like symptoms according to Rome III and 181 students without IBS (23.55 ± 2.82 years; 50.3% males) and compared them regarding current mental strain (SCL-90-R) and the extend of chronic stress. Beyond this, IBS subtypes, IBS severity, and health care utilization were assessed. Results. Students fulfilling IBS criteria showed significantly elevated values of mental strain and chronic stress. Nearly 40% of the IBS group (versus 20% of the controls) reached a clinically relevant value on the SCL-90-R global severity scale. IBS subtypes did not differ in terms of mental distress or chronic stress. Somatization, anxiety, and the chronic stressors "work overload," "social tension," and "dissatisfaction with job" were most closely connected to IBS symptom severity. Regarding health care utilization, our results show that consulting a physician frequently was not associated significantly with elevated mental strain or chronic stress but with IBS symptom severity. Conclusion. Our data contribute additional evidence to the distinct association between psychological stress and IBS in community samples.

Integrated Baseline System (IBS), Version 1.03. User guide: Chemical Stockpile Emergency Preparedness Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bailey, B.M.; Burford, M.J.; Downing, T.R.

The Integrated Baseline System (IBS), operated by the Federal Emergency Management Agency (FEMA), is a system of computerized tools for emergency planing and analysis. This document is the user guide for the IBS and explains how to operate the IBS system. The fundamental function of the IBS is to provide tools that civilian emergency management personnel can use in developing emergency plans and in supporting emergency management activities to cope with a chemical-releasing event at a military chemical stockpile. Emergency management planners can evaluate concepts and ideas using the IBS system. The results of that experience can then be factoredmore » into refining requirements and plans. This document provides information for the general system user, and is the primary reference for the system features of the IBS. It is designed for persons who are familiar with general emergency management concepts, operations, and vocabulary. Although the IBS manual set covers basic and advanced operations, it is not a complete reference document set. Emergency situation modeling software in the IBS is supported by additional technical documents. Some of the other LBS software is commercial software for which more complete documentation is available. The IBS manuals reference such documentation where necessary. IBS is a dynamic system. Its capabilities are in a state of continuing expansion and enhancement.« less

Patient educational media preferences for information about irritable bowel syndrome (IBS).

PubMed

Halpert, Albena; Dalton, Christine B; Palsson, Olafur; Morris, Carolyn; Hu, Yuming; Bangdiwala, Shrikant; Hankins, Jane; Norton, Nancy; Drossman, Douglas A

2008-12-01

To identify the educational media preferences of patients with irritable bowel syndrome (IBS). The IBS-Patient Education Questionnaire (PEQ) was administered to a national sample of IBS patients. Frequencies of item endorsements were compared and meaningful clinical differences were used to identify differences among subgroups. 1,242 patients completed the survey, mean age 39.3 years, 85% female, IBS duration 6.9 years, 79% had seen an MD for IBS within 6 months, and 92.6% used the web for medical information. The most desired source of education was "my doctor" (68%), followed by Internet (62%) and brochure (45%). Notably, patients favored an increase in use of media in the future (past vs. future): doctor (43 vs. 68%); Internet (36 vs. 62%); and brochures (26 vs. 45%). IBS patients expect more education than they have received. Understanding IBS patients' learning preferences can be highly valuable in the development or implementation of educational interventions.

Molecular screening of antibiotic-resistant determinants among multidrug-resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria.

PubMed

Alabi, Olumuyiwa Samuel; Mendonça, Nuno; Adeleke, Olufemi Ezekiel; da Silva, Gabriela Jorge

2017-06-01

Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. This study screened for presence of transferable resistance genes and mobile genetic elements (MGEs) such as integron among multi-drug resistant (MDR) P. mirabilis . A total of 108 P. mirabilis strains collected from five tertiary hospitals in SouthWest Nigeria were subjected to antibiotic susceptibility study using disc-diffusion method. Transferable resistance genes and MGEs were amplified using Polymerase chain reaction (PCR) analysis and amplicons sequenced. Varied resistance was observed against all the antibiotics tested. About 56% of the isolates were MDR including those from 0-12 years old children. PCR analysis revealed the presence of aac(6')-Ib (33.3%), plasmid mediated quinolone resistance (PMQR) genes [qnrA (36.7%), acc(6')-Ib-cr (5%)], TEM (48.3%), CTX-M (6.7%) and integrons class 1 (58.3%) and class 2 (26.7%). Sequencing analysis revealed bla TEM-1 , bla CTX-M-15 associated with IS Ecp1 and eight different arrays of gene cassettes: aadA1, aadA1-qacH, aadB-aadA2, aadA5, dfrA7, dfrA15, dfrA17, dfrA17-aadA5 . Transferable resistance genes in association with MGEs are present in Nigerian P. mirabilis thus their potential in disseminating resistance.

Life stressors, coping strategies, and social supports in patients with irritable bowel syndrome

PubMed Central

Roohafza, Hamidreza; Keshteli, Ammar Hassanzadeh; Daghaghzadeh, Hamed; Afshar, Hamid; Erfani, Zahra; Adibi, Peyman

2016-01-01

Background: The frequency and the perceived intensity of life stressors, coping strategies, and social supports are very important in everybody's well-being. This study intended to estimate the relation of irritable bowel syndrome (IBS) and these factors. Materials and Methods: This was a cross-sectional study carried out in Isfahan on 2013. Data were extracted from the framework of the study on the epidemiology of psychological, alimentary health, and nutrition. Symptoms of IBS were evaluated by Talley bowel disease questionnaire. Stressful life event, modified COPE scale, and Multidimensional Scale of Perceived Social Support were also used. About 4763 subjects were completed questionnaires. Analyzing data were done by t-test and multivariate logistic regression. Results: Of all returned questionnaire, 1024 (21.5%) were diagnosed with IBS. IBS and clinically-significant IBS (IBS-S) groups have significantly experienced a higher level of perceived intensity of stressors and had a higher frequency of stressors. The mean score of social supports and the mean scores of three coping strategies (problem engagement, support seeking, and positive reinterpretation and growth) were significantly lower in subjects with either IBS-S or IBS than in those with no IBS. Multivariate logistic regression revealed a significant association between frequency of stressors and perceived intensity of stressors with IBS (odds ratio [OR] =1.09 and OR = 1.02, respectively) or IBS-S (OR = 1.09 and OR = 1.03, respectively). Conclusions: People with IBS had higher numbers of stressors, higher perception of the intensity of stressors, less adaptive coping strategies, and less social supports which should be focused in psychosocial interventions. PMID:27761433

Inclusion bodies of recombinant Epstein-Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma.

PubMed

Lim, Chun Shen; Goh, Siang Ling; Kariapper, Leena; Krishnan, Gopala; Lim, Yat-Yuen; Ng, Ching Ching

2015-08-25

Development of indirect enzyme-linked immunosorbent assays (ELISAs) often utilizes synthetic peptides or recombinant proteins from Escherichia coli as immobilized antigens. Because inclusion bodies (IBs) formed during recombinant protein expression in E. coli are commonly thought as misfolded aggregates, only refolded proteins from IBs are used to develop new or in-house diagnostic assays. However, the promising utilities of IBs as nanomaterials and immobilized enzymes as shown in recent studies have led us to explore the potential use of IBs of recombinant Epstein-Barr virus viral capsid antigen p18 (VCA p18) as immobilized antigens in ELISAs for serologic detection of nasopharyngeal carcinoma (NPC). Thioredoxin fusion VCA p18 (VCA-Trx) and IBs of VCA p18 without fusion tags (VCA-IBs) were purified from E. coli. The diagnostic performances of IgG/VCA-IBs, IgG/VCA-Denat-IBs (using VCA-IBs coated in 8mol/l urea), IgG/VCA-Trx, and IgG/VCA-Peptide assays were compared by screening 100 NPC case-control pairs. The IgG/VCA-Denat-IBs assay showed the best area under the receiver operating characteristic curve (AUC: 0.802; p<0.05), while the AUCs for the IgG/VCA-IBs, IgG/VCA-Trx, and IgG/VCA-Peptide assays were comparable (AUC: 0.740, 0.727, and 0.741, respectively). We improved the diagnostic performance of the ELISA significantly using IBs of recombinant VCA p18. Copyright © 2015 Elsevier B.V. All rights reserved.

Life stressors, coping strategies, and social supports in patients with irritable bowel syndrome.

PubMed

Roohafza, Hamidreza; Keshteli, Ammar Hassanzadeh; Daghaghzadeh, Hamed; Afshar, Hamid; Erfani, Zahra; Adibi, Peyman

2016-01-01

The frequency and the perceived intensity of life stressors, coping strategies, and social supports are very important in everybody's well-being. This study intended to estimate the relation of irritable bowel syndrome (IBS) and these factors. This was a cross-sectional study carried out in Isfahan on 2013. Data were extracted from the framework of the study on the epidemiology of psychological, alimentary health, and nutrition. Symptoms of IBS were evaluated by Talley bowel disease questionnaire. Stressful life event, modified COPE scale, and Multidimensional Scale of Perceived Social Support were also used. About 4763 subjects were completed questionnaires. Analyzing data were done by t -test and multivariate logistic regression. Of all returned questionnaire, 1024 (21.5%) were diagnosed with IBS. IBS and clinically-significant IBS (IBS-S) groups have significantly experienced a higher level of perceived intensity of stressors and had a higher frequency of stressors. The mean score of social supports and the mean scores of three coping strategies (problem engagement, support seeking, and positive reinterpretation and growth) were significantly lower in subjects with either IBS-S or IBS than in those with no IBS. Multivariate logistic regression revealed a significant association between frequency of stressors and perceived intensity of stressors with IBS (odds ratio [OR] =1.09 and OR = 1.02, respectively) or IBS-S (OR = 1.09 and OR = 1.03, respectively). People with IBS had higher numbers of stressors, higher perception of the intensity of stressors, less adaptive coping strategies, and less social supports which should be focused in psychosocial interventions.

Initial Breakdown Pulse Parameters in Intracloud and Cloud-to-Ground Lightning Flashes

NASA Astrophysics Data System (ADS)

Smith, E. M.; Marshall, T. C.; Karunarathne, S.; Siedlecki, R.; Stolzenburg, M.

2018-02-01

This study analyzes the largest initial breakdown (IB) pulse in flashes from four storms in Florida; data from three sensor arrays are used. The range-normalized, zero-to-peak amplitude of the largest IB pulse was determined along with its altitude, duration, and timing within each flash. Appropriate data were available for 40 intracloud (IC) and 32 cloud-to-ground (CG) flashes. Histograms of amplitude of the largest IB pulse by flash type were similar, with mean (median) values of 1.49 (1.05) V/m for IC flashes and -1.35 (-0.87) V/m for CG flashes. The largest IB pulse in 30 IC flashes showed a weak inverse relation between pulse amplitude and altitude. Amplitude of the largest IB pulse for 25 CG flashes showed no altitude correlation. Duration of the largest IB pulse in ICs averaged twice as long as in CGs (96 μs versus 46 μs), and all of the CG durations were <100 μs. Among the ICs, there is a positive relation between largest IB pulse duration and amplitude; the linear correlation coefficient is 0.385 with outliers excluded. The largest IB pulse in IC flashes typically occurred at a longer time after the first IB pulse (average 4.1 ms) than was the case in CG flashes (average 0.6 ms). In both flash types, the largest IB pulse was the first IB pulse in about 30% of the cases. In one storm all 42 IC flashes with triggered data had IB pulses.

Targeted therapies for diarrhea-predominant irritable bowel syndrome

PubMed Central

Olden, Kevin W

2012-01-01

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder. PMID:22754282

[Comparison of gut microbiotal compositional analysis of patients with irritable bowel syndrome through different bioinformatics pipelines].

PubMed

Zhu, S W; Liu, Z J; Li, M; Zhu, H Q; Duan, L P

2018-04-18

To assess whether the same biological conclusion, diagnostic or curative effects regarding microbial composition of irritable bowel syndrome (IBS) patients could be reached through different bioinformatics pipelines, we used two common bioinformatics pipelines (Uparse V2.0 and Mothur V1.39.5)to analyze the same fecal microbial 16S rRNA high-throughput sequencing data. The two pipelines were used to analyze the diversity and richness of fecal microbial 16S rRNA high-throughput sequencing data of 27 samples, including 9 healthy controls (HC group), 9 diarrhea IBS patients before (IBS group) and after Rifaximin treatment (IBS-treatment, IBSt group). Analyses such as microbial diversity, principal co-ordinates analysis (PCoA), nonmetric multidimensional scaling (NMDS) and linear discriminant analysis effect size (LEfSe) were used to find out the microbial differences among HC group vs. IBS group and IBS group vs. IBSt group. (1) Microbial composition comparison of the 27 samples in the two pipelines showed significant variations at both family and genera levels while no significant variations at phylum level; (2) There was no significant difference in the comparison of HC vs. IBS or IBS vs. IBSt (Uparse: HC vs. IBS, F=0.98, P=0.445; IBS vs. IBSt, F=0.47,P=0.926; Mothur: HC vs.IBS, F=0.82, P=0.646; IBS vs. IBSt, F=0.37, P=0.961). The Shannon index was significantly decreased in IBSt; (3) Both workshops distinguished the significantly enriched genera between HC and IBS groups. For example, Nitrosomonas and Paraprevotella increased while Pseudoalteromonadaceae and Anaerotruncus decreased in HC group through Uparse pipeline, nevertheless Roseburia 62 increased while Butyricicoccus and Moraxellaceae decreased in HC group through Mothur pipeline.Only Uparse pipeline could pick out significant genera between IBS and IBSt, such as Pseudobutyricibrio, Clostridiaceae 1 and Clostridiumsensustricto 1. There were taxonomic and phylogenetic diversity differences between the two pipelines, Mothur can get more taxonomic details because the count number of each taxonomic level is higher. Both pipelines could distinguish the significantly enriched genera between HC and IBS groups, but Uparse was more capable to identity the difference between IBS and IBSt groups. To increase the reproducibility and reliability and to retain the consistency among similar studies, it is very important to consider the impact on different pipelines.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies.

PubMed

Varjú, Péter; Farkas, Nelli; Hegyi, Péter; Garami, András; Szabó, Imre; Illés, Anita; Solymár, Margit; Vincze, Áron; Balaskó, Márta; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Huszár, Orsolya; Pécsi, Dániel; Czimmer, József

2017-01-01

Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.

Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?

PubMed Central

Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

2015-01-01

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS. PMID:25623659

Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?

PubMed

Rajilić-Stojanović, Mirjana; Jonkers, Daisy M; Salonen, Anne; Hanevik, Kurt; Raes, Jeroen; Jalanka, Jonna; de Vos, Willem M; Manichanh, Chaysavanh; Golic, Natasa; Enck, Paul; Philippou, Elena; Iraqi, Fuad A; Clarke, Gerard; Spiller, Robin C; Penders, John

2015-02-01

Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.

Reduction of butyrate- and methane-producing microorganisms in patients with Irritable Bowel Syndrome

PubMed Central

Pozuelo, Marta; Panda, Suchita; Santiago, Alba; Mendez, Sara; Accarino, Anna; Santos, Javier; Guarner, Francisco; Azpiroz, Fernando; Manichanh, Chaysavanh

2015-01-01

The pathophysiology of irritable bowel syndrome (IBS) remains unclear. Here we investigated the microbiome of a large cohort of patients to identify specific signatures for IBS subtypes. We examined the microbiome of 113 patients with IBS and 66 healthy controls. A subset of these participants provided two samples one month apart. We analyzed a total of 273 fecal samples, generating more than 20 million 16S rRNA sequences. In patients with IBS, a significantly lower microbial diversity was associated with a lower relative abundance of butyrate-producing bacteria (P = 0.002; q < 0.06), in particular in patients with IBS-D and IBS-M. IBS patients who did not receive any treatment harboured a lower abundance of Methanobacteria compared to healthy controls (P = 0.005; q = 0.05). Furthermore, significant correlations were observed between several bacterial taxa and sensation of flatulence and abdominal pain (P < 0.05). Altogether, our findings showed that IBS-M and IBS-D patients are characterized by a reduction of butyrate producing bacteria, known to improve intestinal barrier function, and a reduction of methane producing microorganisms a major mechanism of hydrogen disposal in the human colon, which could explain excess of abdominal gas in IBS. PMID:26239401

Subtle imitation behaviour in convenience samples of normal, demented, and currently depressed elderly subjects.

PubMed

von Gunten, Armin; Duc, René

2007-06-01

The clinical significance of imitation behaviour (IB) is unclear. The aim of this study was to investigate the prevalence of subtle naïve and obstinate IB in convenience samples of normal elderly, demented, and depressed subjects. Subtle IB was assessed using a protocol constructed ad hoc in 146 patients, consecutively referred to a memory clinic having received an ICD-10 diagnosis of either dementia or depression, and in 241 healthy subjects. The prevalence of IB in the three groups was determined and the association with possible demographic, cognitive, and non-cognitive variables analysed. Subtle naïve IB was frequent in the elderly with dementia, intermediate in the depressed, and rare in the normal elderly except that the latter frequently stretched out their arms. Obstinate IB never occurred in the normal elderly. IB was predicted by none of the variables used. The groups included were convenience samples with the depressed being a small group precluding further distinction of depressive subtypes. Although naïve IB is a frequent clinical feature in the demented, it also accompanies depressive disorders in the elderly. It can be observed as context-specific IB in the normal elderly. Obstinate IB does not occur in the normal elderly. Copyright 2006 John Wiley & Sons, Ltd.

Catalytically-active inclusion bodies-Carrier-free protein immobilizates for application in biotechnology and biomedicine.

PubMed

Krauss, Ulrich; Jäger, Vera D; Diener, Martin; Pohl, Martina; Jaeger, Karl-Erich

2017-09-20

Bacterial inclusion bodies (IBs) consist of unfolded protein aggregates and represent inactive waste products often accumulating during heterologous overexpression of recombinant genes in Escherichia coli. This general misconception has been challenged in recent years by the discovery that IBs, apart from misfolded polypeptides, can also contain substantial amounts of active and thus correctly or native-like folded protein. The corresponding catalytically-active inclusion bodies (CatIBs) can be regarded as a biologically-active sub-micrometer sized biomaterial or naturally-produced carrier-free protein immobilizate. Fusion of polypeptide (protein) tags can induce CatIB formation paving the way towards the wider application of CatIBs in synthetic chemistry, biocatalysis and biomedicine. In the present review we summarize the history of CatIBs, present the molecular-biological tools that are available to induce CatIB formation, and highlight potential lines of application. In the second part findings regarding the formation, architecture, and structure of (Cat)IBs are summarized. Finally, an overview is presented about the available bioinformatic tools that potentially allow for the prediction of aggregation and thus (Cat)IB formation. This review aims at demonstrating the potential of CatIBs for biotechnology and hopefully contributes to a wider acceptance of this promising, yet not widely utilized, protein preparation. Copyright © 2017 Elsevier B.V. All rights reserved.

Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity

PubMed Central

Mansueto, Pasquale; D’Alcamo, Alberto; Seidita, Aurelio; Carroccio, Antonio

2015-01-01

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: “food”, “diet”, “food allergy”, “food hypersensitivity”, “food intolerance”, “IBS”, “epidemiology”, “pathogenesis”, “pathophysiology”, “diagnosis”, “treatment”. We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS. PMID:26109796

Measuring IBS patient reported outcomes with an abdominal pain numeric rating scale: results from the proof cohort

PubMed Central

SPIEGEL, B.; BOLUS, R.; HARRIS, L. A.; LUCAK, S.; NALIBOFF, B.; ESRAILIAN, E.; CHEY, W. D.; LEMBO, A.; KARSAN, H.; TILLISCH, K.; TALLEY, J.; MAYER, E.; CHANG, L.

2009-01-01

Background Controversy exists about how to effectively measure patient reported outcomes in IBS clinical trials. Pain numeric rating scales (NRS) are widely used in the non-IBS pain literature. The FDA has proposed using the NRS in IBS. Aim To test the psychometrics of an abdominal pain NRS in IBS. Methods We analyzed data from a longitudinal cohort of Rome III IBS subjects. At entry, subjects completed a 10-point NRS, bowel symptoms, IBS severity measurements (IBSSS, FBDSI), health related quality of life indices (IBS-QOL, EQ5D), and the worker productivity activity index (WPAI). We repeated assessments at 3 months along with a response scale to calculate the minimal clinically important difference (MCID). Results There were 277 subjects (82% women; age=42±15) at baseline and 90 at 3 months. The NRS correlated cross-sectionally with IBSSS (r=0.60; p<0.0011), FBDSI (r=0.49; p<0.0001), IBS-QOL (r=0.43; p<0.0001), EQ5D (r=0.48; p<0.0001), presenteeism (r=0.39; p<0.0001), absenteeism (r=0.17; p=0.04), and distension (r=0.46; p<0.0001), but not stool frequency or form. The MCID was 2.2 points, correlating with a 29.5% reduction over time. Conclusions An abdominal pain NRS exhibits excellent validity and can be readily interpreted with an MCID in patients with IBS. These data support the use of the NRS in IBS clinical trials. PMID:19751360

Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study

PubMed Central

Lobo, Beatriz; Ramos, Laura; Martínez, Cristina; Guilarte, Mar; González-Castro, Ana M; Alonso-Cotoner, Carmen; Pigrau, Marc; de Torres, Inés; Rodiño-Janeiro, Bruno K; Salvo-Romero, Eloisa; Fortea, Marina; Pardo-Camacho, Cristina; Guagnozzi, Danila; Azpiroz, Fernando

2017-01-01

Background and goal Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit. Study Mucosal MC activation (by ultrastructural changes, tryptase release and gene expression) and innate immune signalling (by protein and gene expression) were quantified in jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without treatment (IBS-D-NT group; n = 25). All IBS-D patients recorded abdominal pain and bowel habits at baseline and in the last 10 days prior to jejunal sampling. Results IBS-D-NT exhibited significant MC activation and over-expression of immune-related genes as compared to HS, whereas in IBS-D-DSCG MC activity and gene expression were similar to HS. Furthermore, DSCG significantly reduced abdominal pain and improved stool consistency. Conclusion Oral DSCG modulates mucosal immune activity and improves gut symptoms in IBS-D patients. Future placebo-controlled clinical trials are needed for confirmation of clinical benefit of DSCG for IBS-D. PMID:29026603

Fecal incontinence in irritable bowel syndrome (IBS): Prevalence and associated factors in Swedish and American patients

PubMed Central

Simrén, Magnus; Palsson, Olafur S.; Heymen, Steve; Bajor, Antal; Törnblom, Hans; Whitehead, William E.

2016-01-01

Background Fecal incontinence (FI) is a prevalent but poorly recognized problem in the general population with profound negative effects on daily life. The prevalence of FI in IBS and its association with clinical, demographic and pathophysiological factors are largely unknown. Methods One US (n=304) and one Swedish (n=168) patient cohort fulfilling Rome III criteria for IBS completed Rome III diagnostic questions on FI and IBS symptoms, and questionnaires on IBS symptom severity, quality of life, anxiety and depression, and work productivity impairment. The patients also underwent assessments of colorectal sensitivity and motility. Key Results FI ≥ one day per month was reported by 19.7% (USA) and 13.7% (Sweden) of IBS patients. These proportions rose to 43.4% and 29.8% if patients with less frequent FI were included. FI prevalence was higher in older age groups, with a clear increase above age 40. IBS patients with FI reported greater overall IBS symptom severity, more frequent and loose stools, and greater urgency. Negative effects of FI on quality of life, psychological distress, and work productivity were demonstrated. No associations were found between colorectal physiology and FI. Conclusions & Inferences FI is common in IBS patients, and similar to previous general population reports, the major risk factors for FI in IBS are older age, rectal urgency, and loose, frequent stools. When IBS patients have comorbid FI, the impact on quality of life, psychological symptoms, and work impairment appears greater. PMID:27581702

Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.

PubMed

Duan, Qiming; Madan, Namrata D; Wu, Jian; Kalisz, Jennifer; Doshi, Krunal Y; Haldar, Saptarsi M; Liu, Lijun; Pierre, Sandrine V

2015-03-01

Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart against IR injury. Class I PI3K activation is required for IPC, but its role in OPC has not been investigated. While PI3K-IB is critical to IPC, studies have suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of ouabain 10 μM and IPC was triggered by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at Ser(473). IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by left ventricular developed pressure and end-diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA activation is required for OPC while PI3K-IB activation is needed for IPC. Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation but not PKCε translocation. However, in contrast to PKCε translocation which is critical to protection, Akt activity was not required for OPC. Further studies shall reveal the identity of the downstream targets of this new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance in patients at risk for myocardial infarction with underlying diseases and/or medication that could differentially affect the integrity of cardiac PI3K-IA and IB pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety profile of LCR35 complete freeze-dried culture in irritable bowel syndrome: a randomized, double-blind study.

PubMed

Dapoigny, Michel; Piche, Thierry; Ducrotte, Philippe; Lunaud, Bernard; Cardot, Jean-Michel; Bernalier-Donadille, Annick

2012-05-07

To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture (LCR35) in patients suffering from irritable bowel syndrome (IBS). A randomized, double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria. Patients were allocated to receive either LCR35 (n = 25) at a minimum daily dose of 6 × 10(8) colony forming units or placebo (n = 25) for 4 wk. At inclusion, after treatment and 2 wk later, patients completed the IBS severity scale. Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion. Changes were compared between groups in the whole population and in IBS subtypes (IBS with predominance of constipation, IBS with predominance of diarrhoea, mixed IBS, unsubtyped IBS). The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment. The gastrointestinal quality of life questionnaire and the hospital anxiety and depression (HAD) scale were also completed. Both groups were balanced for baseline characteristics. In 85% of patients, stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract. In the whole population, improvements in the IBS severity score did not differ significantly between treatments with a 25% decrease after 4-wk treatment, and a 15% decrease from baseline 2 wk later in both groups. In IBS subgroups, statistical analysis could not be performed due to small sample size, but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea: no change in the symptom severity score was seen with the placebo after 4 wk treatment, whereas a clinically relevant decrease occurred with LCR35 (-37% vs -3%). Furthermore, in spite of an increase in symptom intensity, the IBS severity score was maintained below the baseline value 2 wk later with LCR35 (-19% from baseline), whilst a slight 5% increase from baseline was observed with placebo. In the IBS subgroup with predominance of diarrhoea only, a clinically relevant decrease in abdominal pain severity score (-36%) was observed with LCR35, whereas no change occurred with placebo. In mixed IBS patients, the 20% and 30% decreases in the IBS severity score observed after treatment with LCR35 and placebo, respectively, were maintained 2 wk later in both groups. A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation (-41% vs -20%) and unsubtyped IBS patients (-47% vs -17%), with the same value maintained 2 wk later. In both groups, no clinically relevant changes were observed either for the gastrointestinal quality of life index or HAD score. Thus, these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician. This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea. These preliminary results need to be confirmed in larger studies.

A cross-cultural investigation of attachment style, catastrophizing, negative pain beliefs, and symptom severity in irritable bowel syndrome.

PubMed

Gerson, C D; Gerson, M-J; Chang, L; Corazziari, E S; Dumitrascu, D; Ghoshal, U C; Porcelli, P; Schmulson, M; Wang, W-A; Zali, M

2015-04-01

Little information exists regarding whether psychosocial variables in irritable bowel syndrome (IBS) vary by geographic location. Adult attachment is an important psychological concept rooted in childhood relationship experience that has not been previously studied in IBS. Catastrophizing and negative pain beliefs have been described in IBS and may be affected by attachment. In this cross-cultural study, we determined: (i) whether attachment differs between IBS patients and controls, (ii) whether geographic location has a significant effect on attachment style, catastrophizing and negative pain beliefs, and (iii) how all three variables correlate with IBS symptom severity. 463 IBS patients, with moderate to severe symptom scores, and 192 healthy controls completed validated questionnaires about attachment, catastrophizing, negative pain beliefs and IBS-SSS in nine locations, USA (New York, Los Angeles), Mexico, Italy (Rome, Bari), Romania, Iran, India, and China. Attachment anxiety and avoidance scores were significantly higher in IBS patients than in controls (p < 0.001). This was particularly true for the fearful-avoidant attachment category, especially in China and Romania. Path analysis showed that attachment anxiety and avoidance had indirect effects on IBS-SSS through catastrophizing (p < 0.0001) and negative pain beliefs (p = 0.005). All three psychosocial measures varied significantly depending on location. In the IBS population studied, attachment style was significantly different in IBS compared to a control population. Geographic differences in attachment, catastrophizing and negative pain beliefs were documented and their correlation with symptom severity and thus, research of psychosocial variables in IBS should take into account the location of the population studied. © 2015 John Wiley & Sons Ltd.

Potential role of alpha-synuclein and metallothionein in lead-induced inclusion body formation.

PubMed

Zuo, Peijun; Qu, Wei; Cooper, Ryan N; Goyer, Robert A; Diwan, Bhalchandra A; Waalkes, Michael P

2009-09-01

Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain alpha-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation.

Down-regulation of the IbEXP1 gene enhanced storage root development in sweetpotato

PubMed Central

Bae, Jung Myung

2013-01-01

The role of an expansin gene (IbEXP1) in the formation of the storage root (SR) was investigated by expression pattern analysis and characterization of IbEXP1-antisense sweetpotato (Ipomoea batatas cv. Yulmi) plants in an attempt to elucidate the molecular mechanism underlying SR development in sweetpotato. The transcript level of IbEXP1 was high in the fibrous root (FR) and petiole at the FR stage, but decreased significantly at the young storage root (YSR) stage. IbEXP1-antisense plants cultured in vitro produced FRs which were both thicker and shorter than those of wild-type (WT) plants. Elongation growth of the epidermal cells was significantly reduced, and metaxylem and cambium cell proliferation was markedly enhanced in the FRs of IbEXP1-antisense plants, resulting in an earlier thickening growth in these plants relative to WT plants. There was a marked reduction in the lignification of the central stele of the FRs of the IbEXP1-antisense plants, suggesting that the FRs of the mutant plants possessed a higher potential than those of WT plants to develop into SRs. IbEXP1-antisense plants cultured in soil produced a larger number of SRs and, consequently, total SR weight per IbEXP1-antisense plant was greater than that per WT plant. These results demonstrate that SR development was accelerated in IbEXP1-antisense plants and suggest that IbEXP1 plays a negative role in the formation of SR by suppressing the proliferation of metaxylem and cambium cells to inhibit the initial thickening growth of SRs. IbEXP1 is the first sweetpotato gene whose role in SR development has been directly identified in soil-grown transgenic sweetpotato plants. PMID:22945944

A study of the methodological and clinical validity of the combined lactulose hydrogen breath test with scintigraphic oro-cecal transit test for diagnosing small intestinal bacterial overgrowth in IBS patients.

PubMed

Zhao, J; Zheng, X; Chu, H; Zhao, J; Cong, Y; Fried, M; Fox, M; Dai, N

2014-06-01

Small intestinal bacterial overgrowth (SIBO) may be a cause of irritable bowel syndrome (IBS); however, current investigations have important limitations. We aimed to identify clinically relevant diagnostic criteria for SIBO based on lactulose hydrogen breath test (LHBT) alone and combined with scintigraphic measurement of oro-cecal transit (SOCT). Results of LHBT/SOCT investigation from 89 IBS patients and 13 healthy volunteers were included in a systematic analysis of six published criteria for SIBO diagnosis. Clinical relevance of competing criteria was determined by assessing (i) prevalence of SIBO in IBS patients and healthy volunteers (ii) if SIBO diagnosis predicted improvement in IBS symptoms in a prospective, pilot therapeutic trial of a non-absorbable antibiotic (rifaximin 600 mg b.d.) in IBS patients. Reproducibility of SIBO diagnosis by combined LHBT/SOCT was near perfect. A ≥5 ppm H2 increase prior to appearance of cecal contrast was detected in more IBS patients than healthy volunteers (35/89 vs 1/13; p = 0.026), but not for other diagnostic criteria. IBS patients with SIBO, compared to those without SIBO, reported significantly greater improvement in abdominal symptoms following rifaximin therapy (p < 0.002 overall IBS symptom severity). This improvement was most marked in D-IBS patients in whom all symptoms improved, including stool frequency and consistency (all p < 0.004). Combined LHBT/SOCT testing using a H2 5 ppm cutoff may identify a subgroup of IBS patients with SIBO. Pilot data examining the clinical response to rifaximin suggest that this subset of IBS patients may benefit more than those with a normal test. © 2014 John Wiley & Sons Ltd.

Reduced Responses of Submucous Neurons from Irritable Bowel Syndrome Patients to a Cocktail Containing Histamine, Serotonin, TNFα, and Tryptase (IBS-Cocktail)

PubMed Central

Ostertag, Daniela; Buhner, Sabine; Michel, Klaus; Pehl, Christian; Kurjak, Manfred; Götzberger, Manuela; Schulte-Frohlinde, Ewert; Frieling, Thomas; Enck, Paul; Phillip, Josef; Schemann, Michael

2015-01-01

Background and Aims: Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). Methods: Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Results: Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. Conclusion: We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients. PMID:26733780

Reduced Responses of Submucous Neurons from Irritable Bowel Syndrome Patients to a Cocktail Containing Histamine, Serotonin, TNFα, and Tryptase (IBS-Cocktail).

PubMed

Ostertag, Daniela; Buhner, Sabine; Michel, Klaus; Pehl, Christian; Kurjak, Manfred; Götzberger, Manuela; Schulte-Frohlinde, Ewert; Frieling, Thomas; Enck, Paul; Phillip, Josef; Schemann, Michael

2015-01-01

Malfunctions of enteric neurons are believed to play an important role in the pathophysiology of irritable bowel syndrome (IBS). Our aim was to investigate whether neuronal activity in biopsies from IBS patients is altered in comparison to healthy controls (HC). Activity of human submucous neurons in response to electrical nerve stimulation and local application of nicotine or a mixture of histamine, serotonin, tryptase, and TNF-α (IBS-cocktail) was recorded in biopsies from 17 HC and 35 IBS patients with the calcium-sensitive-dye Fluo-4 AM. The concentrations of the mediators resembeled those found in biopsy supernatants or blood. Neuronal activity in guinea-pig submucous neurons was studied with the voltage-sensitive-dye di-8-ANEPPS. Activity in submucous ganglia in response to nicotine or electrical nerve stimulation was not different between HC and IBS patients (P = 0.097 or P = 0.448). However, the neuronal response after application of the IBS-cocktail was significantly decreased (P = 0.039) independent of whether diarrhea (n = 12), constipation (n = 5) or bloating (n = 5) was the predominant symptom. In agreement with this we found that responses of submucous ganglia conditioned by overnight incubation with IBS mucosal biopsy supernatant to spritz application of this supernatant was significantly reduced (P = 0.019) when compared to incubation with HC supernatant. We demonstrated for the first time reduced neuronal responses in mucosal IBS biopsies to an IBS mediator cocktail. While excitability to classical stimuli of enteric neurons was comparable to HC, the activation by the IBS-cocktail was decreased. This was very likely due to desensitization to mediators constantly released by mucosal and immune cells in the gut wall of IBS patients.

A-type voltage-gated K+ currents influence firing properties of isolectin B4-positive but not isolectin B4-negative primary sensory neurons.

PubMed

Vydyanathan, Amaresh; Wu, Zi-Zhen; Chen, Shao-Rui; Pan, Hui-Lin

2005-06-01

Voltage-gated K+ channels (Kv) in primary sensory neurons are important for regulation of neuronal excitability. The dorsal root ganglion (DRG) neurons are heterogeneous, and the types of native Kv currents in different groups of nociceptive DRG neurons are not fully known. In this study, we determined the difference in the A-type Kv current and its influence on the firing properties between isolectin B4 (IB4)-positive and -negative DRG neurons. Whole cell voltage- and current-clamp recordings were performed on acutely dissociated small DRG neurons of rats. The total Kv current density was significantly higher in IB+-positive than that in IB(4)-negative neurons. Also, 4-aminopyridine (4-AP) produced a significantly greater reduction in Kv currents in IB4-positive than in IB4-negative neurons. In contrast, IB4-negative neurons exhibited a larger proportion of tetraethylammonium-sensitive Kv currents. Furthermore, IB4-positive neurons showed a longer latency of firing and required a significantly larger amount of current injection to evoke action potentials. 4-AP significantly decreased the latency of firing and increased the firing frequency in IB4-positive but not in IB4-negative neurons. Additionally, IB4-positive neurons are immunoreactive to Kv1.4 but not to Kv1.1 and Kv1.2 subunits. Collectively, this study provides new information that 4-AP-sensitive A-type Kv currents are mainly present in IB4-positive DRG neurons and preferentially dampen the initiation of action potentials of this subpopulation of nociceptors. The difference in the density of A-type Kv currents contributes to the distinct electrophysiological properties of IB4-positive and -negative DRG neurons.

Health-related quality of life of irritable bowel syndrome patients in different cultural settings

PubMed Central

Faresjö, Åshild; Anastasiou, Foteini; Lionis, Christos; Johansson, Saga; Wallander, Mari-Ann; Faresjö, Tomas

2006-01-01

Background Persons with Irritable bowel syndrome (IBS) are seriously affected in their everyday life. The effect across different cultural settings of IBS on their quality of life has been little studied. The aim was to compare health-related quality of life (HRQOL) of individuals suffering from IBS in two different cultural settings; Crete, Greece and Linköping, Sweden. Methods This study is a sex and age-matched case-control study, with n = 30 Cretan IBS cases and n = 90 Swedish IBS cases and a Swedish control group (n = 300) randomly selected from the general population. Health-related quality of life, measured by SF-36 and demographics, life style indicators and co-morbidity, was measured. Results Cretan IBS cases reported lower HRQOL on most dimensions of SF-36 in comparison to the Swedish IBS cases. Significant differences were found for the dimensions mental health (p < 0.0001) and general health (p = 0.05) even after adjustments for educational level and co-morbidity. Women from Crete with IBS scored especially low on the dimensions general health (p = 0.009) and mental health (p < 0.0001) in comparison with Swedish women with IBS. The IBS cases, from both sites, reported significantly lower scores on all HRQOL dimensions in comparison with the Swedish control group. Conclusion The results from this study tentatively support that the claim that similar individuals having the same disease, e.g. IBS, but living in different cultural environments could perceive their disease differently and that the disease might affect their everyday life and quality of life in a different way. The Cretan population, and especially women, are more seriously affected mentally by their disease than Swedish IBS cases. Coping with IBS in everyday life might be more problematic in the Cretan environment than in the Swedish setting. PMID:16566821

Microbiota, gastrointestinal infections, low-grade inflammation, and antibiotic therapy in irritable bowel syndrome: an evidence-based review.

PubMed

Schmulson, M; Bielsa, M V; Carmona-Sánchez, R; Hernández, A; López-Colombo, A; López Vidal, Y; Peláez-Luna, M; Remes-Troche, J M; Tamayo, J L; Valdovinos, M A

2014-01-01

Post-infectious irritable bowel syndrome (PI-IBS) prevalence, small intestinal bacterial overgrowth (SIBO), altered microbiota, low-grade inflammation, and antibiotic therapy in IBS are all controversial issues. To conduct an evidence-based review of these factors. A review of the literature was carried out up to July 2012, with the inclusion of additional articles as far as August 2013, all of which were analyzed through the Oxford Centre for Evidence-Based Medicine (OCEBM) system. 1.There is greater SIBO probability in IBS when breath tests are performed, but prevalence varies widely (2-84%). 2.The gut microbiota in individuals with IBS is different from that in healthy subjects, but a common characteristic present in all the patients has not been established. 3.The incidence and prevalence of PI-IBS varies from 9-10% and 3-17%, respectively, and the latter decreases over time. Bacterial etiology is the most frequent but post-viral and parasitic cases have been reported. 4.A sub-group of patients has increased enterochromaffin cells, intraepithelial lymphocytes, and mast cells in the intestinal mucosa, but no differences between PI-IBS and non-PI-IBS have been determined. 5.Methanogenic microbiota has been associated with IBS with constipation. 6.Rifaximin at doses of 400mg TID/10days or 550mg TID/14days is effective treatment for the majority of overall symptoms and abdominal bloating in IBS. Retreatment effectiveness appears to be similar to that of the first cycle. Further studies are required to determine the nature of the gut microbiota in IBS and the differences in low-grade inflammation between PI-IBS and non-PI-IBS. Rifaximin has shown itself to be effective treatment for IBS, regardless of prior factors. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

[Parasitosis and irritable bowel syndrome].

PubMed

Ibarra, Catalina; Herrera, Valentina; Pérez de Arce, Edith; Gil, Luis Carlos; Madrid, Ana María; Valenzuela, Lucía; Beltrán, Caroll J

2016-06-01

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract characterised by multi-factorial aetiology. In IBS physiopathology are involved diverse factors between them biological, psychosocial, and environmental components which affect the immune activation status of gut mucosa. Among these factors is recognized the intestinal parasitosis. Post-infection IBS (PI-IBS) is recognised as a subgroup of functional disorders whose symptoms onset appear after a symptomatic intestinal infection caused by microbial agents. There are few studies regarding of relationship between IBS and intestinal parasitosis in Chile. However, is has been well described a positive association between IBS and Blastocystis hominis infections, one of prevalent parasites in Chile. In other countries, is also described a relationship between IBS and amebiasis and giardiasis. Both, characterized by a common mode of transmission through water as well as contaminated food. Because the high prevalence of parasitosis in our country it is necessary to expand the association studies to clarify the strength of the parasites ethiology in IBS.

Irritable bowel syndrome and food interaction.

PubMed

Cuomo, Rosario; Andreozzi, Paolo; Zito, Francesco Paolo; Passananti, Valentina; De Carlo, Giovanni; Sarnelli, Giovanni

2014-07-21

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders in Western countries. Despite the high prevalence of this disorders, the therapeutic management of these patients is often unsatisfactory. A number of factors have been suggested to be involved in the pathogenesis of IBS, including impaired motility and sensitivity, increased permeability, changes in the gut microbiome and alterations in the brain-gut axis. Also food seems to play a critical role: the most of IBS patients report the onset or the exacerbation of their symptoms after the meals. Recently, an increasing attention has been paid to the role of food in IBS. In this review we summarize the most recent evidences about the role of diet on IBS symptoms. A diet restricted in fermentable, poorly absorbed carbohydrates and sugar alcohols has beneficial effects on IBS symptoms. More studies are needed to improve our knowledge about the relationship between food and IBS. However, in the foreseeable future, dietary strategies will represent one of the key tools in the therapeutic management of patients with IBS.

Immersed boundary methods for simulating fluid-structure interaction

NASA Astrophysics Data System (ADS)

Sotiropoulos, Fotis; Yang, Xiaolei

2014-02-01

Fluid-structure interaction (FSI) problems commonly encountered in engineering and biological applications involve geometrically complex flexible or rigid bodies undergoing large deformations. Immersed boundary (IB) methods have emerged as a powerful simulation tool for tackling such flows due to their inherent ability to handle arbitrarily complex bodies without the need for expensive and cumbersome dynamic re-meshing strategies. Depending on the approach such methods adopt to satisfy boundary conditions on solid surfaces they can be broadly classified as diffused and sharp interface methods. In this review, we present an overview of the fundamentals of both classes of methods with emphasis on solution algorithms for simulating FSI problems. We summarize and juxtapose different IB approaches for imposing boundary conditions, efficient iterative algorithms for solving the incompressible Navier-Stokes equations in the presence of dynamic immersed boundaries, and strong and loose coupling FSI strategies. We also present recent results from the application of such methods to study a wide range of problems, including vortex-induced vibrations, aquatic swimming, insect flying, human walking and renewable energy. Limitations of such methods and the need for future research to mitigate them are also discussed.

Prevalence of irritable bowel syndrome in young adult Malaysians: a survey among medical students.

PubMed

Tan, Yan-Mei; Goh, Khean L; Muhidayah, Raja; Ooi, Chee L; Salem, Omar

2003-12-01

Irritable bowel syndrome (IBS) is a common functional bowel disease in the West. Information on the prevalence of IBS in the Asian population is relatively scanty. The aims of the present study were to determine the prevalence of IBS and to assess the symptom subgroups based on the predominant bowel habit in a young adult population of Asian origin. Basic demographic data and symptoms of IBS using the Rome I criteria were sought using a questionnaire administered to all apparently healthy students in a medical school. Other questions asked related to alcohol intake, smoking, chili consumption, dietary fiber intake, and to psychological and psychosomatic symptoms of anxiety, depression, insomnia, headache, and backache. The health-care seeking behavior of the subjects was also analyzed. Of the 610 questionnaires administered, 533 complete responses were received (response rate of 87.4%). The responders comprised 229 men (43.0%) and 304 (57.0%) women with a mean age of 22 +/- 1.8 years. The ethnic distribution was Malays 278 (52.2%), Chinese 179 (33.6%), Indians 46 (8.6%), and others 30 (5.6%). Eighty-four (15.8%) reported symptoms consistent with the diagnosis of IBS, predominantly women. Sixty-five (77.4%) and six (7.1%) were of the constipation-predominant and diarrhea-predominant IBS subgroups, respectively. Thirteen (15.5%) subjects fell into the non-specific IBS subgroup. The self-reported psychological and psychosomatic symptoms of anxiety (P = 0.02), depression (P = 0.002), insomnia (P = 0.006), headache (P = 0.04), and backache (P = 0.006) were encountered more frequently in the subjects with IBS. Only 13.1% of the IBS group had consulted their health-care practitioner, and 20.2% reported self-medication. Symptoms supportive of the diagnosis of IBS were common among young Malaysians, with a prevalence rate of 15.8%. There were significantly more women with IBS than men. Within the IBS population, the majority (77.4%) was of the constipation-predominant IBS subgroup. A significantly higher prevalence of psychological and psychosomatic symptoms was found in individuals with IBS. Only a minority sought medical advice for their symptoms.

A study of International Baccalaureate science teachers' choices in curriculum and instruction

NASA Astrophysics Data System (ADS)

Jauss, Lanett S.

This study was designed to investigate the choices International Baccalaureate (IB) science teachers make in curriculum and instruction. Data was gathered via a survey completed by IB science teachers who had attended either an April, 2007 workshop in Reston, Virginia or a January, 2008 IB roundtable discussion in Kansas City, Missouri. Surveys solicited the different choices IB science teachers make for options, Internal Assessment (IA) activities, Theory of Knowledge (TOK) emphasis, and demographics. Teachers' reasons for their option choices were also analyzed. Statistical analysis was performed using SPSS descriptive statistics, Pearson's product-moment correlations, and linear regression. It was found that IB science teachers' most frequent reasons for their option choices were related to ease, interest, background, and available resources. IB science teachers used a variety of IA activities, with hands-on activities and worksheets being most frequent. IB science teachers did not emphasize inquiry, although they did include some aspects of it among their choices. IB science teachers preferred to use activities they design or those designed by other teachers. Years of teaching experience, both total and IB, were correlated to the level of use of some TOK tenets.

Nerve growth factor and diarrhea-predominant irritable bowel syndrome (IBS-D): a potential therapeutic target?

PubMed

Xu, Xiao-juan; Liu, Liang; Yao, Shu-kun

2016-01-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort associated with abnormal bowel habits. Diarrhea-predominant IBS (IBS-D) is a major subtype of IBS, the predominant manifestations of which are abdominal pain and diarrhea. The pathogenesis of IBS-D remained unknown until recently. The effects of psychosocial stress, central hypervigilance, neuroendocrine abnormality, disturbed gastrointestinal motility, mucosal immune activation, intestinal barrier dysfunction, visceral hypersensitivity (VH), altered gut flora, and genetic susceptibility may be involved in its development. Recently, increased attention has been placed on the neural-immune-endocrine network mechanism in IBS-D, especially the role of various neuroendocrine mediators. As a member of the neurotrophin family, nerve growth factor (NGF) has diverse biological effects, and participates in the pathogenesis of many diseases. Basic studies have demonstrated that NGF is associated with inflammatory- and stress-related VH, as well as stress-related intestinal barrier dysfunction. The aim of this study is to summarize recent literature and discuss the role of NGF in the pathophysiology of IBS-D, especially in VH and intestinal barrier dysfunction, as well as its potential as a therapeutic target in IBS-D.

Management of irritable bowel syndrome in primary care: the results of an exploratory randomised controlled trial of mebeverine, methylcellulose, placebo and a self-management website.

PubMed

Everitt, Hazel; Moss-Morris, Rona; Sibelli, Alice; Tapp, Laura; Coleman, Nicholas; Yardley, Lucy; Smith, Peter; Little, Paul

2013-04-21

Many patients with IBS suffer on-going symptoms. The evidence base is poor for IBS drugs but they are widely prescribed and advised in Guidelines. Cognitive Behavioural Therapy (CBT) can be helpful, but availability is poor in the NHS. We developed a web-based CBT self-management programme (Regul8) in partnership with patients and trialled it and common IBS medications in an exploratory factorial RCT to test trial procedures and provide information for a larger trial. Patients, 16 to 60 years, with IBS symptoms fulfilling Rome III criteria were recruited via GP practices and randomised to over-encapsulated mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 website conditions: Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website. 135 patients recruited from 26 GP practices. Mean IBS SSS score 241.9 (sd 87.7), IBS-QOL 64 (sd 20) at baseline. 91% follow-up at 12 weeks. Mean IBS SSS decreased by 35 points from baseline to 12 weeks. There was no significant difference in IBS SSS or IBS-QOL score between medication or website groups at 12 weeks, or in medication groups at 6 weeks, or IBS-QOL in website groups at 6 weeks. However, IBS SSS at 6 weeks was lower in the No website group than the website groups (IBS SSS no website =162.8 (95% CI 137.4-188.3), website 197.0 (172.4 - 221.7), Website + telephone support 208.0 (183.1-233.0) p = 0.037). This exploratory study demonstrates feasibility and high follow-up rates and provides information for a larger trial. Primary outcomes (IBS SS and IBS QOL) did not reach significance at 6 or 12 weeks, apart from IBS SSS being lower in the no-website group at 6 weeks - this disappeared by 12 weeks. Improved Enablement suggests patients with access to the Regul8 website felt better able to cope with their symptoms than the non-website group. Improved SGA score in the Regul8 groups may indicate some overall improvement not captured on other measures. ClinicalTrials.gov Identifier (NCT number): NCT00934973.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

PubMed Central

Varjú, Péter; Farkas, Nelli; Hegyi, Péter; Garami, András; Szabó, Imre; Illés, Anita; Solymár, Margit; Vincze, Áron; Balaskó, Márta; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Huszár, Orsolya; Pécsi, Dániel

2017-01-01

Background Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. Objectives We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). Methods A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Statistical methods Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. Results The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. Conclusions This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet. PMID:28806407

A School-Based Study of Irritable Bowel Syndrome in Medical Students in Beijing, China: Prevalence and Some Related Factors

PubMed Central

Liu, Yang; Liu, Liang; Yang, Yi; He, Yuxi; Zhang, Yanli; Wang, Miao; Chen, Shuo; Yao, Shukun

2014-01-01

Purpose. To investigate the prevalence and some related factors about irritable bowel syndrome (IBS) in medical students. Methods. A cross-sectional study was carried out from February 2014 to Jun 2014 in Beijing University of Chinese Medicine, Beijing, China. All participants were asked to completed self-administered questionnaires. Results. Seven hundred and sixty-seven medical students (23.26 ± 2.88 years, 25.6% males) completed the survey. The prevalence of IBS was 33.3%, with a high prevalence in women (36.1%). Among the IBS patients, 112 cases were IBS-M (43.9%) and 77.6% had moderately severe IBS. There were no statistical differences between control group and IBS patients in anxiety and depression scores (P > 0.05). The total score of Pittsburgh sleep quality index (PSQI) was significantly higher for medical students with IBS and 35.5% of IBS patients had severe sleep disorder; the scores of child trauma questionnaire (CTQ) and student-life stress inventory (SLSI) were also higher in IBS patients. Sex and sleep disorder were independently associated with IBS (OR, 1.914, 95%CI, 1.281–2.860; OR, 1.143, 95%CI, 1.074–1.216). Conclusion. Our study has many valuable findings and they may provide valuable suggestions for the necessary intervention and treatment measures towards medical students. PMID:25371668

Clostridium perfringens Iota-Toxin: Mapping of Receptor Binding and Ia Docking Domains on Ib

PubMed Central

Marvaud, Jean-Christophe; Smith, Theresa; Hale, Martha L.; Popoff, Michel R.; Smith, Leonard A.; Stiles, Bradley G.

2001-01-01

Clostridium perfringens iota-toxin is a binary toxin consisting of iota a (Ia), an ADP-ribosyltransferase that modifies actin, and iota b (Ib), which binds to a cell surface protein and translocates Ia into a target cell. Fusion proteins of recombinant Ib and truncated variants were tested for binding to Vero cells and docking with Ia via fluorescence-activated cytometry and cytotoxicity experiments. C-terminal residues (656 to 665) of Ib were critical for cell surface binding, and truncated Ib variants containing ≥200 amino acids of the C terminus were effective Ib competitors and prevented iota cytotoxicity. The N-terminal domain (residues 1 to 106) of Ib was important for Ia docking, yet this region was not an effective competitor of iota cytotoxicity. Further studies showed that Ib lacking just the N-terminal 27 residues did not facilitate Ia entry into a target cell and subsequent cytotoxicity. Five monoclonal antibodies against Ib were also tested with each truncated Ib variant for epitope and structural mapping by surface plasmon resonance and an enzyme-linked immunosorbent assay. Each antibody bound to a linear epitope within the N terminus (residues 28 to 66) or the C terminus (residues 632 to 655). Antibodies that target the C terminus neutralized in vitro cytotoxicity and delayed the lethal effects of iota-toxin in mice. PMID:11254604

Increased production of BDNF in colonic epithelial cells induced by fecal supernatants from diarrheic IBS patients.

PubMed

Wang, Peng; Chen, Fei-Xue; Du, Chao; Li, Chang-Qing; Yu, Yan-Bo; Zuo, Xiu-Li; Li, Yan-Qing

2015-05-22

Colonic brain-derived neurotrophic factor (BDNF) plays an essential role in pathogenesis of abdominal pain in diarrhea-predominant irritable bowel syndrome (IBS-D), but regulation on its expression remains unclear. We investigated the role of fecal supernatants (FSN) from IBS-D patients on regulating BDNF expression in colonic epithelial cells of human and mice. Using human Caco-2 cells, we found that IBS-D FSN significantly increased BDNF mRNA and protein levels compared to control FSN, which were remarkably suppressed by the serine protease inhibitor. To further explore the potential mechanisms, we investigated the impact of protease-activated receptor-2 (PAR-2) on BDNF expression. We found a significant increase in PAR-2 expression in Caco-2 after IBS-D FSN stimulation. Knockdown of PAR-2 significantly inhibited IBS-D FSN-induced upregulation of BDNF. Moreover, we found that phosphorylation of p38 MAPK, not NF-κB p65, contributed to PAR-2-mediated BDNF overexpression. To confirm these results, we intracolonically infused IBS-D or control FSN in mice and found that IBS-D FSN significantly elevated colonic BDNF and visceral hypersensitivity in mice, which were both suppressed by the inhibitor of serine protease or antagonist of PAR-2. Together, our data indicate that activation of PAR-2 signaling by IBS-D FSN promotes expression of colonic BDNF, thereby contributing to IBS-like visceral hypersensitivity.

Development and pilot testing of an integrated, web-based self-management program for irritable bowel syndrome (IBS).

PubMed

Dorn, S D; Palsson, O S; Woldeghebriel, M; Fowler, B; McCoy, R; Weinberger, M; Drossman, D A

2015-01-01

Although essential, many medical practices are unable to adequately support irritable bowel syndrome (IBS) patient self-management. Web-based programs can help overcome these barriers. We developed, assessed, and refined an integrated IBS self-management program (IBS Self-care). We then conducted a 12-week pilot test to assess program utilization, evaluate its association with patients' self-efficacy and quality of life, and collect qualitative feedback to improve the program. 40 subjects with generally mild IBS were recruited via the Internet to participate in a 12-week pilot study. Subjects found the website easy to use (93%) and personally relevant (95%), and 90% would recommend it to a friend. Self-rated IBS knowledge increased from an average of 47.1 on a 100-point VAS scale (SD 22.1) at baseline to 77.4 (SD: 12.4) at week 12 (p < 0.0001). There were no significant changes in patient self-efficacy (Patient Activation Measure) or quality of life (IBS -Quality of Life Scale). The IBS Self-Care program was well received by users who after 12 weeks reported improved knowledge about IBS, but no significant changes in self-efficacy or quality of life. If applied to the right population, this low cost solution can overcome some of the deficiencies of medical care and empower individuals to better manage their own IBS. © 2014 John Wiley & Sons Ltd.

New insights in IBS-like disorders: Pandora's box has been opened; a review.

PubMed

Borghini, Raffaele; Donato, Giuseppe; Alvaro, Domenico; Picarelli, Antonio

2017-01-01

The most complained gastrointestinal symptoms are chronic diarrhea, bloating and abdominal pain. Once malignancies and inflammatory bowel diseases are excluded, irritable bowel syndrome (IBS) and the so called "IBS-like disorders" should be taken into account. The relationship between IBS as defined by Rome IV criteria and these clinical conditions is sometimes obscure, since many IBS patients identify food as a possible trigger for their symptoms. Here, we discuss IBS and the most common IBS-like disorders (celiac disease, non-celiac gluten sensitivity, fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), lactose intolerance, small intestinal bacterial overgrowth (SIBO), α-amylase/trypsin inhibitor (ATIs), nickel allergic contact mucositis), focusing on epidemiologic, clinical, diagnostic and therapeutic aspects. Given the lack of specificity of symptoms, clinical investigation will be facilitated by awareness of these disorders as well as new specific diagnostic tools.

[Alternative treatments in irritable bowel syndrome].

PubMed

Hagège, H

2009-02-01

Managing irritable bowel syndrome (IBS) is difficult and often a source of dissatisfaction for the patient, explaining the increasingly frequent recourse to alternative treatments. These highly varied treatments are often associated. They can be classed into four categories: reflexology methods, interventions on the psyche, biological therapies, and treatments using certain forms of energy. Although some studies show interesting results, currently there are not sufficient scientific arguments to recommend one or another of these alternative treatments. Multicenter controlled studies are needed to better evaluate the strategies that appear to be cost-effective.

A variant of green fluorescent protein exclusively deposited to active intracellular inclusion bodies

PubMed Central

2014-01-01

Background Inclusion bodies (IBs) were generally considered to be inactive protein deposits and did not hold any attractive values in biotechnological applications. Recently, some IBs of recombinant proteins were confirmed to show their functional properties such as enzyme activities, fluorescence, etc. Such biologically active IBs are not commonly formed, but they have great potentials in the fields of biocatalysis, material science and nanotechnology. Results In this study, we characterized the IBs of DL4, a deletion variant of green fluorescent protein which forms active intracellular aggregates. The DL4 proteins expressed in Escherichia coli were exclusively deposited to IBs, and the IBs were estimated to be mostly composed of active proteins. The spectral properties and quantum yield of the DL4 variant in the active IBs were almost same with those of its native protein. Refolding and stability studies revealed that the deletion mutation in DL4 didn’t affect the folding efficiency of the protein, but destabilized its structure. Analyses specific for amyloid-like structures informed that the inner architecture of DL4 IBs might be amorphous rather than well-organized. The diameter of fluorescent DL4 IBs could be decreased up to 100–200 nm by reducing the expression time of the protein in vivo. Conclusions To our knowledge, DL4 is the first GFP variant that folds correctly but aggregates exclusively in vivo without any self-aggregating/assembling tags. The fluorescent DL4 IBs have potentials to be used as fluorescent biomaterials. This study also suggests that biologically active IBs can be achieved through engineering a target protein itself. PMID:24885571

Negative Aspects of Close Relationships are More Strongly Associated than Supportive Personal Relationships with Illness Burden of Irritable Bowel Syndrome

PubMed Central

Lackner, Jeffrey M.; Gudleski, Gregory D.; Firth, Rebecca; Keefer, Laurie A.; Brenner, Darren M.; Guy, Katie; Simonetti, Camille; Radziwon, Christopher; Quinton, Sarah; Krasner, Susan S.; Katz, Leonard; Garbarino, Guido; Iacobucci, Gary; Sitrin, Michael D.

2013-01-01

OBJECTIVE This study assessed the relative magnitude of associations between IBS outcomes and different aspects of social relationships (social support, negative interactions). METHOD Subjects included 235 Rome III diagnosed IBS patients (M age = 41 yrs, F=78%) without comorbid GI disease. Subjects completed a testing battery that included the Interpersonal Support Evaluation List (Social support or SS), Negative Interaction (NI) Scale, IBS Symptom Severity Scale (IBS-SSS), IBS-QOL, BSI Depression, STAI Trait Anxiety, SOMS-7 (somatization), Perceived Stress Scale, and a medical comorbidity checklist. RESULTS After controlling for demographic variables, both SS and NI were significantly correlated with all of the clinical variables (SS r’s = .20 to .36; NI r’s = .17 to .53, respectively; ps < .05) save for IBS symptom severity (IBS-SSS). NI, but not SS, was positively correlated with IBS-SSS. After performing r-to-z transformations on the correlation coefficients and then comparing z-scores, the correlation between, perceived stress, and NI was significantly stronger than with SS. There was no significant difference between the strength of correlations between NI and SS for depression, somatization, trait anxiety, and IBSQOL. A hierarchical linear regression identified both SS and NI as significant predictors of IBS-QOL. CONCLUSIONS Different aspects of social relationships -- support and negative interactions -- are associated with multiple aspects of IBS experience (e.g. stress, QOL impairment). Negative social relationships marked by conflict and adverse exchanges are more consistently and strongly related to IBS outcomes than social support. PMID:23731746

General practitioners' perceptions of irritable bowel syndrome: a Q-methodological study.

PubMed

Bradley, Stephen; Alderson, Sarah; Ford, Alexander C; Foy, Robbie

2018-01-16

Irritable bowel syndrome (IBS) is a common disorder that imposes a significant burden upon societies, health care and quality of life, worldwide. While a diverse range of patient viewpoints on IBS have been explored, the opinions of the GPs they ideally need to develop therapeutic partnerships with are less well defined. To explore how GPs perceive IBS, using Q-methodology, which allows quantitative interpretation of qualitative data. A Q-methodological study of GPs in Leeds, UK. Thirty-three GPs completed an online Q-sort in which they ranked their level of agreement with 66 statements. Factor analysis of the Q-sorts was performed to determine the accounts that predominated in understandings of IBS. Ten of the GPs were interviewed in person and responses to the statements recorded to help explain the accounts. Analysis yielded one predominant account shared by all GPs-that IBS was a largely psychological disorder. This account overshadowed a debate represented by a minority, polarized between those who viewed IBS as almost exclusively psychological, versus those who believed IBS had an organic basis, with a psychological component. The overwhelming similarity in responses indicates that all GPs shared a common perspective on IBS. Interviews suggested degrees of uncertainty and discomfort around the aetiology of IBS. There was overwhelming agreement in the way GPs perceived IBS. This contrasts with the range of patient accounts of IBS and may explain why both GPs and their patients face difficult negotiations in achieving therapeutic relationships. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fecal and Mucosa-Associated Intestinal Microbiota in Patients with Diarrhea-Predominant Irritable Bowel Syndrome.

PubMed

Maharshak, Nitsan; Ringel, Yehuda; Katibian, David; Lundqvist, Ashley; Sartor, R Balfour; Carroll, Ian M; Ringel-Kulka, Tamar

2018-05-17

Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC). To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC. The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline. The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche. Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.

Irritable bowel syndrome is concentrated in people with higher educations in Iran: an inequality analysis.

PubMed

Mansouri, Asieh; Rarani, Mostafa Amini; Fallahi, Mosayeb; Alvandi, Iman

2017-01-01

Like any other health-related disorder, irritable bowel syndrome (IBS) has a differential distribution with respect to socioeconomic factors. This study aimed to estimate and decompose educational inequalities in the prevalence of IBS. Sampling was performed using a multi-stage random cluster sampling approach. The data of 1,850 residents of Kish Island aged 15 years or older were included, and the determinants of IBS were identified using a generalized estimating equation regression model. The concentration index of educational inequality in cases of IBS was estimated and decomposed as the specific inequality index. The prevalence of IBS in this study was 21.57% (95% confidence interval [CI], 19.69 to 23.44%). The concentration index of IBS was 0.20 (95% CI, 0.14 to 0.26). A multivariable regression model revealed that age, sex, level of education, marital status, anxiety, and poor general health were significant determinants of IBS. In the decomposition analysis, level of education (89.91%), age (-11.99%), and marital status (9.11%) were the three main contributors to IBS inequality. Anxiety and poor general health were the next two contributors to IBS inequality, and were responsible for more than 12% of the total observed inequality. The main contributors of IBS inequality were education level, age, and marital status. Given the high percentage of anxious individuals among highly educated, young, single, and divorced people, we can conclude that all contributors to IBS inequality may be partially influenced by psychological factors. Therefore, programs that promote the development of mental health to alleviate the abovementioned inequality in this population are highly warranted.

The economic consequences of irritable bowel syndrome: a US employer perspective.

PubMed

Leong, Stephanie A; Barghout, Victoria; Birnbaum, Howard G; Thibeault, Crystal E; Ben-Hamadi, Rym; Frech, Feride; Ofman, Joshua J

2003-04-28

The objective of this study was to measure the direct costs of treating irritable bowel syndrome (IBS) and the indirect costs in the workplace. This was accomplished through retrospective analysis of administrative claims data from a national Fortune 100 manufacturer, which includes all medical, pharmaceutical, and disability claims for the company's employees, spouses/dependents, and retirees. Patients with IBS were identified as individuals, aged 18 to 64 years, who received a primary code for IBS or a secondary code for IBS and a primary code for constipation or abdominal pain between January 1, 1996, and December 31, 1998. Of these patients with IBS, 93.7% were matched based on age, sex, employment status, and ZIP code to a control population of beneficiaries. Direct and indirect costs for patients with IBS were compared with those of matched controls. The average total cost (direct plus indirect) per patient with IBS was 4527 dollars in 1998 compared with 3276 dollars for a control beneficiary (P<.001). The average physician visit costs were 524 dollars and 345 dollars for patients with IBS and controls, respectively (P<.001). The average outpatient care costs to the employer were 1258 dollars and 742 dollars for patients with IBS and controls, respectively (P<.001). Medically related work absenteeism cost the employer 901 dollars on average per employee treated for IBS compared with 528 dollars on average per employee without IBS (P<.001). Irritable bowel syndrome is a significant financial burden on the employer that arises from an increase in direct and indirect costs compared with the control group.

Infant botulism in Andalusia (Southern Spain).

PubMed

López-Laso, Eduardo; Roncero-Sánchez-Cano, Inés; Arce-Portillo, Elena; Ley-Martos, Myriam; Aguirre-Rodríguez, Javier; García-Ron, Adrián; Mora-Navarro, David; Méndez-García, Mario; Camino-León, Rafael

2014-05-01

Infant botulism (IB) is caused by the intestinal colonization by Clostridium botulinum in the first year of life and its subsequent production of neurotoxins. Traditionally, IB has been associated to honey consumption. IB cases tend to cluster in geographic regions. In Europe, IB is a rare disorder. From 1976 through 2006, 65 cases were identified in 13 European countries. In Spain, in the last 15 years, most of the cases have been reported in one region, Andalusia (Southern Spain). A specific treatment for IB type A and type B (BabyBIG) is available outside of the United States since 2005. and aims: We performed a retrospective review of IB cases detected in Andalusia since 1997 and compare them with the cases of IB reported in Europe. We identified 11 confirmed cases of IB in Andalusia since 1997, and 14 cases in Spain. Nine out of 11 cases were detected since 2007; none of these infants had been exposed to honey consumption. One case in 1997 and another in 2000 were associated to honey. Two cases were treated with BabyBIG in 2007. In the period 2006-2012 the cases of IB reported in Europe were 54. We identified a considerable increase in the incidence of IB since 2006. A tendency to a reduction in the number of cases of IB linked to honey consumption has also been identified. An increase in the exposure to these bacteria from the environment could be presumed. Clinicians should maintain a high index of suspicion for this treatable disorder. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Heartburn and other related symptoms are independent of body mass index in irritable bowel syndrome.

PubMed

Schmulson, M; Pulido, D; Escobar, C; Farfán-Labone, B; Gutiérrez-Reyes, G; López-Alvarenga, J C

2010-04-01

increasing body mass index (BMI) is a risk factor for GERD but little is known about this association in the irritable bowel syndrome (IBS). to determine the presence of heartburn and other related symptoms in relation with BMI in IBS. volunteers (n = 483) answered the Rome II-Modular Questionnaire, and were divided into IBS and non-IBS (controls) groups. The frequency of heartburn, chest pain, epigastric pain, nausea, vomiting and belching was compared between the groups in the study sample and within three BMI categories. the IBS (23.7%) and controls (76.3%) were similar in gender (females: 68.1%), age (32.2 +/- 12.7 years), and BMI (25.4 +/- 4.4). Raw associations analysis showed that heartburn: OR: 1.62 (95%CI: 1.04-2.53), chest pain: 1.77 (1.13-2.77), epigastric pain: 1.75 (1.03-2.98) and nausea: 2.45 (1.10-5.32) were more frequent in IBS vs. controls. Meanwhile, according to BMI, in those with obesity, heartburn was more frequent in IBS and among those with overweight, epigastric pain and nausea were also more frequent in IBS. However, in an adjusted log linear model, no significant interaction was found between BMI and any other studied symptom and heartburn was found to be independent of IBS: 1,4 (0.9, 4.7). Finally, a logistic regression model found no interaction between BMI and the presence of heartburn or IBS. while heartburn and other reflux-related symptoms are more frequent in IBS than in controls, these associations are independent of BMI.

Chronic Constipation and Constipation-Predominant IBS: Separate and Distinct Disorders or a Spectrum of Disease?

PubMed

Siah, Kewin T H; Wong, Reuben K; Whitehead, William E

2016-03-01

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum.

MLCK-mediated intestinal permeability promotes immune activation and visceral hypersensitivity in PI-IBS mice.

PubMed

Long, Y; Du, L; Kim, J J; Chen, B; Zhu, Y; Zhang, Y; Yao, S; He, H; Zheng, X; Huang, Z; Dai, N

2018-04-11

Alterations in intestinal permeability regulated by tight junctions (TJs) are associated with immune activation and visceral hypersensitivity in irritable bowel syndrome (IBS). Myosin light chain kinase (MLCK) is an important mediator of epithelial TJ. The aim of this study is to investigate the role of MLCK in the pathogenesis of IBS using a post infectious IBS (PI-IBS) mouse model. Trichinella spiralis-infected PI-IBS mouse model was used. Urine lactulose/mannitol ratio was measured to assess intestinal epithelial permeability. Western blotting was used to evaluate intestinal TJ protein (zonula occludens-1) and MLCK-associated protein expressions. Immune profile was assessed by measuring Th (T helper) 1/Th2 cytokine expression. Visceral sensitivity was determined by abdominal withdrawal reflex in response to colorectal distension. Eight weeks after inoculation with T. spiralis, PI-IBS mice developed decreased pain and volume thresholds during colorectal distention, increased urine lactulose/mannitol ratio, elevated colonic Th1/Th2 cytokine ratio, and decreased zonula occludens-1 expression compared to the control mice. MLCK expression was dramatically elevated in the colonic mucosa of PI-IBS mice compared to the control mice, alongside increased pMLC/MLC and decreased MLCP expression. Administration of MLCK inhibitor and TJ blocker both reversed the increased intestinal permeability, visceral hypersensitivity, and Th1-dominant immune profile in PI-IBS mice. MLCK is a pivotal step in inducing increased intestinal permeability promoting low-grade intestinal immune activation and visceral hypersensitivity in PI-IBS mice. MLCK inhibitor may provide a potential therapeutic option in the treatment of IBS. © 2018 John Wiley & Sons Ltd.

The impact of physical complaints, social environment, and psychological functioning on IBS patients' health perceptions: looking beyond GI symptom severity.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Thakur, Elyse R; Stewart, Travis J; Iacobucci, Gary J; Spiegel, Brennan Mr

2014-02-01

In the absence of a reliable biomarker, clinical decisions for a functional gastrointestinal (GI) disorder like irritable bowel syndrome (IBS) depend on asking patients to appraise and communicate their health status. Self-ratings of health (SRH) have proven a powerful and consistent predictor of health outcomes, but little is known about how they relate to those relevant to IBS (e.g., quality of life (QOL), IBS symptom severity). This study examined what psychosocial factors, if any, predict SRH among a cohort of more severe IBS patients. Subjects included 234 Rome III-positive IBS patients (mean age=41 years, female=78%) without comorbid organic GI disease. Subjects were administered a test battery that included the IBS Symptom Severity Scale, Screening for Somatoform Symptoms, IBS Medical Comorbidity Inventory, SF-12 Vitality Scale, Perceived Stress Scale, Beck Depression Inventory, Trait Anxiety Inventory, and Negative Interactions Scale. Partial correlations identified somatization, depression, fatigue, stress, anxiety, and medical comorbidities as variables with the strongest correlations with SRH (r values=0.36-0.41, P values <0.05). IBS symptom severity was weakly associated with SRH (r=0.18, P<0.05). The final regression model explained 41.3% of the variance in SRH scores (F=8.49, P<0.001) with significant predictors including fatigue, medical comorbidities, somatization, and negative social interactions. SRH are associated with psychological (anxiety, stress, depression), social (negative interactions), and extraintestinal somatic factors (fatigue, somatization, medical comorbidities). The severity of IBS symptoms appears to have a relatively modest role in how IBS patients describe their health in general.

Chronic Constipation and Constipation-Predominant IBS: Separate and Distinct Disorders or a Spectrum of Disease?

PubMed Central

Siah, Kewin T. H.; Wong, Reuben K.

2016-01-01

Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum. PMID:27231446

Psychometric assessment of the IBS-D Daily Symptom Diary and Symptom Event Log.

PubMed

Rosa, Kathleen; Delgado-Herrera, Leticia; Zeiher, Bernie; Banderas, Benjamin; Arbuckle, Rob; Spears, Glen; Hudgens, Stacie

2016-12-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients' lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, "Event Log") according to US regulatory recommendations. A US-based observational field study was conducted to understand cross-sectional psychometric properties of the IBS-D Daily Symptom Diary and Event Log. Analyses included item descriptive statistics, item-to-item correlations, reliability, and construct validity. The IBS-D Daily Symptom Diary and Event Log had no items with excessive missing data. With the exception of two items ("frequency of gas" and "accidents"), moderate to high inter-item correlations were observed among all items of the IBS-D Daily Symptom Diary and Event Log (day 1 range 0.67-0.90). Item scores demonstrated reliability, with the exception of the "frequency of gas" and "accidents" items of the Diary and "incomplete evacuation" item of the Event Log. The pattern of correlations of the IBS-D Daily Symptom Diary and Event Log item scores with generic and disease-specific measures was as expected, moderate for similar constructs and low for dissimilar constructs, supporting construct validity. Known-groups methods showed statistically significant differences and monotonic trends in each of the IBS-D Daily Symptom Diary item scores among groups defined by patients' IBS-D severity ratings ("none"/"mild," "moderate," or "severe"/"very severe"), supporting construct validity. Initial psychometric results support the reliability and validity of the items of the IBS-D Daily Symptom Diary and Event Log.

The IB Diploma and UK University Degree Qualifications

ERIC Educational Resources Information Center

Frank-Gemmill, Gerda

2013-01-01

In recent years the International Baccalaureate (IB) Diploma has become widely accepted as a university-entry qualification in the UK, but there has been little quantitative research into the achievements of IB students at degree level. This study investigates IB students from one selective independent school who entered UK universities between…

▼ Eluxadoline for IBS-D.

PubMed

2017-08-01

Irritable bowel syndrome (IBS) is a chronic relapsing gastrointestinal problem characterised by intestinal pain and associated alterations of defecation and/or bowel habit (constipation: IBS-C or diarrhoea: IBS-D). 1,2 Opioid receptors in the gut have a role in gastrointestinal motility, secretion and sensation. 3 Τ Eluxadoline (Truberzi-Allergan) is a locally acting, mixed opioid receptor agonist/antagonist licensed for the treatment of IBS-D in adults. 4 Here, we consider the evidence for eluxadoline and how it fts with current management strategies for IBS-D. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

AR-NcoR Interaction as a Therapeutic Target for Prostate Cancer Prevention and Treatment

DTIC Science & Technology

2005-10-01

mutant AR, VP16-NCoRc, ARE4-luciferase reporter, and control pRL-CMV ( Renilla ) reporter. They were then treated for 24 hrs with 10 nM DHT, 10 nM RU486...or no hormone. Firefly versus Renilla luciferase activities were measure from triplicate samples. Relative light units (RLU) reflect normalized...firefly/ Renilla (+SD). NCoR binding to the RU486 liganded AR is mediated by the C-terminal N1 CoRNR box in NCoR. As NCoR deletion mutants indicated

Experimental Evaluation of Camouflage Effectiveness in the Thermal Infrared (Experimentele Evaluatie van de Effectiviteit van Camouflage in het Thermische Infrarood)

DTIC Science & Technology

1993-03-01

shape distortion. For recognitio , , however, camouflage rnr’f.ure" have to adjiist the tLugek signoawuie in more detail to the background clutter...ous trees, 4m height at ±100m range 4 ag.. _!tural field (seasonal plant growing) 5 ba~e soil (ploughed rough surface) 1) concrete -, face 7 Water...surlace (small pond, Im depth) 8 Up- and down hill slopes (bare seil and grass covered). North and South facing At regular intervals, the physical

Meditation over medication for irritable bowel syndrome? On exercise and alternative treatments for irritable bowel syndrome.

PubMed

Asare, Fredrick; Störsrud, Stine; Simrén, Magnus

2012-08-01

Complimentary alternative treatment regimens are widely used in irritable bowel syndrome (IBS), but the evidence supporting their use varies. For psychological treatment options, such as cognitive behavioral therapy, mindfulness, gut-directed hypnotherapy, and psychodynamic therapy, the evidence supporting their use in IBS patients is strong, but the availability limits their use in clinical practice. Dietary interventions are commonly included in the management of IBS patients, but these are primarily based on studies assessing physiological function in relation to dietary components, and to a lesser degree upon research examining the role of dietary components in the therapeutic management of IBS. Several probiotic products improve a range of symptoms in IBS patients. Physical activity is of benefit for health in general and recent data implicates its usefulness also for IBS patients. Acupuncture does not seem to have an effect beyond placebo in IBS. A beneficial effect of some herbal treatments has been reported.

Scholarship of Teaching International Business: Challenges and Opportunities

ERIC Educational Resources Information Center

Aggarwal, Raj; Goodell, John W.

2011-01-01

International business (IB) is an important topic for business schools as business is global, but much business school teaching of IB still seems inadequate. IB education can be challenging but also presents many opportunities. We need to build our knowledge base of effective IB teaching methods and procedures. Such knowledge can not only be used…

Clostridium perfringens Iota Toxin: Binding Studies and Characterization of Cell Surface Receptor by Fluorescence-Activated Cytometry

PubMed Central

Stiles, Bradley G.; Hale, Martha L.; Marvaud, Jean-Christophe; Popoff, Michel R.

2000-01-01

The binding characteristics of iota toxin, a binary enterotoxin produced by Clostridium perfringens type E, were studied by fluorescence-activated cytometry. The proteolytically activated binding component of iota toxin, iota b (Ib), bound to various cell types when incubated at 4, 25, or 37°C for 10 min. The binding of Ib was inhibited by antisera against C. perfringens type E or Clostridium spiroforme culture supernatants, but not C. perfringens types C or D. Pretreatment of Vero cells with glycosidases or lectins did not affect Ib interactions, while pronase effectively prevented Ib binding to the cell surface. The Ib protomer (Ibp) bound to the cell surface, but trypsinization of Ibp was necessary for docking of the ADP-ribosylating component, iota a (Ia). Ia attached to cell-bound Ib within 10 min at 37°C, but surface levels of Ia decreased 90% after 30 min and were undetectable by 60 min. Detectable surface levels of Ib also diminished over time, and Western blot analysis suggested internalization or embedment of Ib into the membrane. PMID:10816501

Clostridium perfringens iota toxin: binding studies and characterization of cell surface receptor by fluorescence-activated cytometry.

PubMed

Stiles, B G; Hale, M L; Marvaud, J C; Popoff, M R

2000-06-01

The binding characteristics of iota toxin, a binary enterotoxin produced by Clostridium perfringens type E, were studied by fluorescence-activated cytometry. The proteolytically activated binding component of iota toxin, iota b (Ib), bound to various cell types when incubated at 4, 25, or 37 degrees C for 10 min. The binding of Ib was inhibited by antisera against C. perfringens type E or Clostridium spiroforme culture supernatants, but not C. perfringens types C or D. Pretreatment of Vero cells with glycosidases or lectins did not affect Ib interactions, while pronase effectively prevented Ib binding to the cell surface. The Ib protomer (Ibp) bound to the cell surface, but trypsinization of Ibp was necessary for docking of the ADP-ribosylating component, iota a (Ia). Ia attached to cell-bound Ib within 10 min at 37 degrees C, but surface levels of Ia decreased 90% after 30 min and were undetectable by 60 min. Detectable surface levels of Ib also diminished over time, and Western blot analysis suggested internalization or embedment of Ib into the membrane.

Does a low FODMAP diet help IBS?

PubMed

2015-08-01

Irritable bowel syndrome (IBS) is a common condition that can have a significant impact on a person's quality of life. The cause of IBS is unknown but several mechanisms have been proposed including visceral hypersensitivity, central sensitisation, abnormal gut motility and altered gut microbiota. IBS is challenging to manage and many patients report insufficient symptomatic relief from treatment. Approximately 60% of patients identify food as a trigger for their symptoms, and there has been interest in exclusion diets for managing IBS. Dietary adaptation is a common self-management strategy for patients with IBS, with many self-diagnosing intolerance to specific foods. This may lead to patients adopting over-restrictive or inappropriate diets. In recent years, a diet low in poorly absorbed short-chain carbohydrates, known collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), has been advocated for the treatment of IBS. Here, we discuss the background to the FODMAP diet and review the evidence supporting its use for people with IBS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Irritable Bowel Syndrome Symptoms and Health Related Quality of Life in Female Veterans

PubMed Central

Graham, David P.; Savas, Lara; White, Donna; El-Serag, Rola; Laday-Smith, Shirley; Tan, Gabriel; El-Serag, Hashem B.

2010-01-01

SUMMARY Background The status and determinants of health-related quality of life (HRQOL) in female veterans with and without irritable bowel syndrome (IBS) is unknown. Aim To compare HRQOL in female veterans with and without IBS symptoms and examine the contribution of post-traumatic stress disorder (PTSD), depression, and anxiety to HRQOL. Methods A cross-sectional study of 339 female veterans. Self-report questionnaires were used to evaluate IBS symptoms, PTSD, depression, anxiety, and HRQOL. Results Symptoms consistent with IBS were present in 33.5% of participants. Female veterans with IBS symptoms had significant reductions in physical component score (PCS) and 5 of 8 Health Related Quality of Life subscales, and on 7 of 8 Irritable Bowel Syndrome Quality Of Life subscales, than female veterans without IBS symptoms. Compared to the US general female population, female veterans had significantly lower Health Related Quality of Life PCS and mental component scores (MCS) irrespective of IBS symptom status. Differences in the MCS score was most explained by depression; while the PCS score was most explained anxiety. Conclusions IBS symptoms in female veterans are associated with considerable reduction in HRQOL. However, female veterans regardless of IBS symptom status have lower HRQOL compared to the general US female population. PMID:19814746

Short-term effects of mineral particle sizes on cellular degradation activity after implantation of injectable calcium phosphate biomaterials and the consequences for bone substitution.

PubMed

Gauthier, O; Bouler, J M; Weiss, P; Bosco, J; Aguado, E; Daculsi, G

1999-08-01

This in vivo study investigated the influence of two calcium phosphate particle sizes (40-80 microm and 200-500 microm) on the cellular degradation activity associated with the bone substitution process of two injectable bone substitutes (IBS). The tested biomaterials were obtained by associating a biphasic calcium phosphate (BCP) ceramic mineral phase and a 3% aqueous solution of a cellulosic polymer (hydroxypropylmethylcellulose). Both were injected into osseous defects at the distal end of rabbit femurs for 2- and 3-week periods. Quantitative results for tartrate-resistant acid phosphatase (TRAP) cellular activity, new bone formation, and ceramic resorption were studied for statistical purposes. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than IBS 200-500, regardless of implantation time. BCP degradation was quite marked during the first 2 weeks for IBS 40-80, and bone colonization occurred more extensively for IBS 40-80 than for IBS 200-500. The resorption-bone substitution process occurred earlier and faster for IBS 40-80 than IBS 200-500. Both tested IBS displayed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Differences in calcium phosphate particle sizes influenced cellular degradation activity and ceramic resorption but were compatible with efficient bone substitution.

Constructive thinking, rational intelligence and irritable bowel syndrome.

PubMed

Rey, Enrique; Moreno Ortega, Marta; Garcia Alonso, Monica-Olga; Diaz-Rubio, Manuel

2009-07-07

To evaluate rational and experiential intelligence in irritable bowel syndrome (IBS) sufferers. We recruited 100 subjects with IBS as per Rome II criteria (50 consulters and 50 non-consulters) and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire (including symptom characteristics and medical consultation) and the following tests: rational-intelligence (Wechsler Adult Intelligence Scale, 3rd edition); experiential-intelligence (Constructive Thinking Inventory); personality (NEO personality inventory); psychopathology (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social readjustment rating scale). Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. No differences were found between IBS cases and controls in terms of IQ (102.0 +/- 10.8 vs 102.8 +/- 12.6), but IBS sufferers scored significantly lower in global constructive thinking (43.7 +/- 9.4 vs 49.6 +/- 9.7). In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 (0.87-0.97)], without significant OR for total IQ. IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS.

Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

PubMed

Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

2017-09-15

Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

Asian motility studies in irritable bowel syndrome.

PubMed

Lee, Oh Young

2010-04-01

Altered motility remains one of the important pathophysiologic factors in patients with irritable bowel syndrome (IBS) who commonly complain of abdominal pain and stool changes such as diarrhea and constipation. The prevalence of IBS has increased among Asian populations these days. Gastrointestinal (GI) physiology may vary between Asian and Western populations because of differences in diets, socio-cultural backgrounds, and genetic factors. The characteristics and differences of GI dysmotility in Asian IBS patients were reviewed. MEDLINE search work was performed including following terms, 'IBS,' 'motility,' 'transit time,' 'esophageal motility,' 'gastric motility,' 'small intestinal motility,' 'colonic motility,' 'anorectal function,' and 'gallbladder motility' and over 100 articles were categorized under 'esophagus,' 'stomach,' 'small intestine,' 'colon,' 'anorectum,' 'gallbladder,' 'transit,' 'motor pattern,' and 'effect of stressors.' Delayed gastric emptying, slow tansit in constipation predominant IBS patients, rapid transit in diarrhea predominant IBS patients, accelerated motility responses to various stressors such as meals, mental stress, or corticotrophin releasing hormones, and altered rectal compliance and altered rectal accomodation were reported in many Asian studies regarding IBS. Many conflicting results were found among these studies and there are still controversies to conclude these as unique features of Asian IBS patients. Multinational and multicenter studies are needed to be performed vigorously in order to elaborate characteristics as well as differences of altered motililty in Asian patients with IBS.

Novel Therapies in IBS-D Treatment.

PubMed

Nee, Judy; Zakari, Mohammed; Lembo, Anthony J

2015-12-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain and change in bowel habits. IBS diarrhea predominant (IBS-D), which is arguably the most common subset of IBS, is also associated with rectal urgency, increased frequency, abdominal bloating, and loose to watery stools. Current treatments for diarrhea include mu-opioid agonists (i.e., loperamide, lomotil) and bile acid sequestrants (i.e., cholestyramine) while treatments for abdominal pain include antispasmodics (i.e., hyoscyamine, dicyclomine) and tricyclic antidepressants (i.e., amitriptyline). There are currently 3 FDA-approved treatments for IBS-D, which have been shown to improve both abdominal pain and diarrhea. Alosetron was initially approved by FDA 2000; however, its use is now limited to women with severe IBS-D symptoms refractory to other treatment. Eluxadoline, a mixed mu-opioid agonist, and rifaximin, a broad spectrum gut specific antibiotic, were both FDA approved in 2015. Eluxadoline has been shown to relieve abdominal pain and stool consistency in appropriate candidates. While large trials already showed the efficacy of rifaximin in treating non-constipated IBS for bloating, stool consistency, and abdominal pain, the recent TARGET 3 trial demonstrates that retreatment is also effective. While these new treatments significantly expand options for patients suffering from IBS-D, there is likely to remain a need for additional safe and effective therapies.

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio)

PubMed Central

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-01-01

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp. PMID:27649163

Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

PubMed

Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

2016-09-16

Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.

sPLA2 IB induces human podocyte apoptosis via the M-type phospholipase A2 receptor

PubMed Central

Pan, Yangbin; Wan, Jianxin; Liu, Yipeng; Yang, Qian; Liang, Wei; Singhal, Pravin C.; Saleem, Moin A.; Ding, Guohua

2014-01-01

The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with the PLA2R, sPLA2 IB induced podocyte apoptosis in a time- and concentration-dependent manner. sPLA2 IB-induced podocyte PLA2R upregulation was not only associated with increased ERK1/2 and cPLA2α phosphorylation but also displayed enhanced apoptosis. In contrast, PLA2R-silenced human podocytes displayed attenuated apoptosis. sPLA2 IB enhanced podocyte arachidonic acid (AA) content in a dose-dependent manner. These data indicate that sPLA2 IB has the potential to induce human podocyte apoptosis via binding to the PLA2R. The sPLA2 IB-PLA2R interaction stimulated podocyte apoptosis through activating ERK1/2 and cPLA2α and through increasing the podocyte AA content. PMID:25335547

Anticipation of public speaking and sleep and the hypothalamic-pituitary-adrenal axis in women with irritable bowel syndrome.

PubMed

Heitkemper, M M; Cain, K C; Deechakawan, W; Poppe, A; Jun, S-E; Burr, R L; Jarrett, M E

2012-07-01

Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 min from 08:00 PM until awakening. As the subjects had different sleep onsets, each subject's results were synchronized to the first onset of stage 2 sleep. Compared the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS. © 2012 Blackwell Publishing Ltd.

Anticipation of Public Speaking and Sleep and the Hypothalamic-Pituitary-Adrenal Axis in Women with Irritable Bowel Syndrome

PubMed Central

Heitkemper, Margaret M; Cain, Kevin C; Deechakawan, Wimon; Poppe, Anne; Jun, Sang-Eun; Burr, Robert L; Jarrett, Monica E

2013-01-01

Background Evidence suggests that subgroups of patients with irritable bowel syndrome (IBS) are hyper-responsive to a variety of laboratory stress conditions. Methods This study compared sleep quality and night time plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels in response to anticipation of public speaking between 43 women with IBS and 24 healthy control women. In addition, comparisons were made between subgroups within the IBS sample based on predominant stool patterns, 22 IBS-constipation and 21 IBS-diarrhea. Subjects slept three nights in a sleep laboratory, and on the third night serial blood samples were drawn every 20 minutes from 8 PM until awakening. Because subjects had different sleep onsets, each subject’s results were synchronized to the first onset of stage 2 sleep. Key Results Compared to the healthy control group, women with IBS had significantly worse sleep efficiency, and higher cortisol but not ACTH levels over the night. However, there were no IBS bowel pattern subgroup differences. Among IBS subjects, cortisol levels early in the night were higher than found in our previous study with a similar protocol but without the threat of public speaking. These results suggest that a social stressor, such as public speaking prior to bedtime, increases cortisol but not ACTH levels suggesting HPA dysregulation in women with IBS. Conclusions & Inferences This response to a social stressor contributes to our understanding of the relationship of stress to symptom expression in IBS. PMID:22471712

Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial.

PubMed

Johannesson, Elisabet; Simrén, Magnus; Strid, Hans; Bajor, Antal; Sadik, Riadh

2011-05-01

Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS. We randomized 102 patients to a physical activity group and a control group. Patients of the physical activity group were instructed by a physiotherapist to increase their physical activity, and those of the control group were instructed to maintain their lifestyle. The primary end point was to assess the change in the IBS Severity Scoring System (IBS-SSS). A total of 38 (73.7% women, median age 38.5 (19-65) years) patients in the control group and 37 (75.7% women, median age 36 (18-65) years) patients in the physical activity group completed the study. There was a significant difference in the improvement in the IBS-SSS score between the physical activity group and the control group (-51 (-130 and 49) vs. -5 (-101 and 118), P=0.003). The proportion of patients with increased IBS symptom severity during the study was significantly larger in the control group than in the physical activity group. Increased physical activity improves GI symptoms in IBS. Physically active patients with IBS will face less symptom deterioration compared with physically inactive patients. Physical activity should be used as a primary treatment modality in IBS.

Pseudohypoparathyroidism type Ib associated with novel duplications in the GNAS locus.

PubMed

Perez-Nanclares, Gustavo; Velayos, Teresa; Vela, Amaya; Muñoz-Torres, Manuel; Castaño, Luis

2015-01-01

Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy. Patients with PHP-Ib suffer of defects in the methylation pattern of the complex GNAS locus. PHP-Ib can be either sporadic or inherited in an autosomal dominant pattern. Whereas familial PHP-Ib is well characterized at the molecular level, the genetic cause of sporadic PHP-Ib cases remains elusive, although some molecular mechanisms have been associated with this subtype. The aim of the study was to investigate the molecular and imprinting defects in the GNAS locus in two unrelated patients with PHP-Ib. We have analyzed the GNAS locus by direct sequencing, Methylation-Specific Multiplex Ligation-dependent Probe Amplification, microsatellites, Quantitative Multiplex PCR of Short Fluorescent fragments and array-Comparative Genomic Hybridization studies in order to characterize two unrelated families with clinical features of PHP-Ib. We identified two duplications in the GNAS region in two patients with PHP-Ib: one of them, comprising ∼ 320 kb, occurred 'de novo' in the patient, whereas the other one, of ∼ 179 kb in length, was inherited from the maternal allele. In both cases, no other known genetic cause was observed. In this article, we describe the to-our-knowledge biggest duplications reported so far in the GNAS region. Both are associated to PHP-Ib, one of them occurring 'de novo' and the other one being maternally inherited.

Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.

PubMed

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-10-15

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3-57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

Is Childhood Abuse or Neglect Associated with Symptom Reports and Physiological Measures in Women with Irritable Bowel Syndrome?

PubMed Central

Heitkemper, Margaret M.; Cain, Kevin C.; Burr, Robert L.; Jun, Sang-Eun; Jarrett, Monica E.

2013-01-01

Purpose Early childhood traumatic experiences (e.g., abuse or neglect) may contribute to sleep disturbances as well as other indicators of arousal found in patients with irritable bowel syndrome (IBS). This study compared women with IBS positive for a history of childhood abuse and/or neglect to IBS women without this history, on daily gastrointestinal (GI), sleep, somatic, and psychological symptom distress, polysomnographic sleep, urine catecholamines and cortisol, and nocturnal heart rate variability (HRV). Methods Adult women with IBS recruited from the community were divided into 21 IBS with abuse/neglect and 19 IBS without abuse/neglect based on responses to the Childhood Trauma Questionnaire (physical, emotional, sexual abuse or neglect). Women were interviewed, maintained a 30-day symptom diary, and slept in a sleep laboratory. Polysomnographic and nocturnal heart rate variability data were obtained. First voided urine samples were assayed for cortisol and catecholamine levels. Results Women with IBS positive for abuse/neglect history were older than women without this history. Among GI symptoms, only heartburn and nausea were significantly higher in women with IBS with abuse/neglect. Sleep, somatic and psychological symptoms were significantly higher in women in the IBS with abuse/neglect group. With the exception of percent time in REM sleep, there were few differences in sleep stage variables and urine hormone levels. Mean heart rate interval and the Ln SDNN values were lower in those who experienced childhood abuse/neglect. Conclusion Women with IBS who self report childhood abuse/neglect are more likely to report disturbed sleep, somatic symptoms, and psychological distress. Women with IBS should be screened for adverse childhood events including abuse/neglect. PMID:21196423

Irritable bowel syndrome: A clinical review

PubMed Central

Soares, Rosa LS

2014-01-01

Irritable bowel syndrome (IBS) remains a clinical challenge in the 21st century. It’s the most commonly diagnosed gastrointestinal condition and also the most common reason for referral to gastroenterology clinics. Its can affect up to one in five people at some point in their lives, and has a significantly impact of life quality and health care utilization. The prevalence varies according to country and criteria used to define IBS. Various mechanisms and theories have been proposed about its etiology, but the biopsychosocial model is the most currently accepted for IBS. The complex of symptoms would be the result of the interaction between psychological, behavioral, psychosocial and environmental factors. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria III is the current gold-standard for the diagnoses of IBS. Secure positive evidence of IBS by means of specific disease marker is currently not possible and cannot be currently recommended for routine diagnosis. There is still no clinical evidence to recommend the use of biomarkers in blood to diagnose IBS. However, a number of different changes in IBS patients were demonstrated in recent years, some of which can be used in the future as a diagnostic support. IBS has no definitive treatment but could be controlled by non-pharmacologic management eliminating of some exacerbating factors such certain drugs, stressor conditions and changes in dietary habits.The traditional pharmacologic management of IBS has been symptom based and several drugs have been used. However, the cornerstone of its therapy is a solid patient physician relationship. This review will provide a summary of pathophysiology, diagnostic criteria and current and emerging therapies for IBS. PMID:25232249

The Comparison of WHOQOL-BREF with Disease Specific Heath Related Quality of Life Questionnaire in Irritable Bowel Syndrome.

PubMed

Jamali, Raika; Biglari, Mohammad

2015-11-01

Irritable Bowel Syndrome (IBS) is one of the most common gastrointestinal disorders particularly affecting the quality of life (QOL). Evaluating QOL in IBS patients is a valuable method of defining a psychobiological pattern of disease. Various disease specific and general instruments are now available to measure health-related QOL (HRQOL) in IBS patients. Though, no comparison has been made between these tools especially in non-western countries. We aimed to compare QOL measures between two specific and general QOL questionnaires in a sample of Iranian IBS patients. A total of 250 IBS patients were diagnosed based on Rome III criteria (mean age 29.6 ± 9.6 years). HRQOL was assessed using disease specific quality of life for IBS (IBS-QOL) and generic World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaires. Patients also completed Speilberger`s "State/Trait Anxiety Inventory" and "Beck Depression Inventory-II" for the evaluation of anxiety and depression symptoms. The severity of symptoms was independently associated with HRQOL in patients using WHOQOL-BREF and IBS-QOL (r = -0.48 and -0.39 respectively, P < 0.001). In linear regression analysis, a strong correlation was observed between the HRQOL scores of IBS-QOL and the WHOQOL-BREF questionnaires (standard β = 0.86 (95%CI: 1.15 - 1.44), P value < 0.001). Controlling for anxiety and depression symptoms did not influence the strength of observed correlation. The WHOQOL-BREF is a psychometrically sound, rapid and convenient instrument whose HRQOL measure is as valid and accurate as the disease-specific IBS-QOL questionnaire. It seems reasonable to use the WHOQOL-BREF alongside the IBS-QOL.

Effect of vitamin D on gastrointestinal symptoms and health-related quality of life in irritable bowel syndrome patients: a randomized double-blind clinical trial.

PubMed

Abbasnezhad, A; Amani, R; Hajiani, E; Alavinejad, P; Cheraghian, B; Ghadiri, A

2016-10-01

Low-grade mucosal inflammation and immune activation are involved in the pathogenesis of irritable bowel syndrome (IBS). Furthermore, IBS symptoms are associated with a significantly higher prevalence of psychological distress, which in itself results into an impaired quality of life (QoL). Vitamin D could ameliorate the symptoms of patients suffering from IBS through its beneficial effects on psychological factors and inflammation. A total of 90 IBS patients participated in this double-blind, randomized, placebo-controlled study. Participants were randomly selected to receive either 50 000 IU vitamin D3 or a placebo fortnightly for a period of 6 months. Patients reported their IBS symptoms at the baseline and monthly during intervention periods. The IBS severity score system (IBSSS) and IBS-specific QoL questionnaires were used at the baseline and postintervention. Over the 6-month intervention period, a significantly greater improvement in IBS symptoms such as abdominal pain and distention, flatulence, rumbling, and overall gastrointestinal (GI) symptoms (except dissatisfaction with bowel habits) was observed in the patients receiving vitamin D as compared to the placebo group. The IBSSS and the IBS-QoL scores in the vitamin D group significantly improved compared to the placebo group postintervention (mean IBSSS score change: -53.82 ± 23.3 vs -16.85 ± 25.01, p < 0.001, respectively; mean IBS-QoL score change: 14.26 ± 3 vs 11 ± 2.34, p < 0.001, respectively). Vitamin D seems to be an effective and safe option to improve QoL and symptoms of IBS. ClinicalTrials.gov (NCT02579902). © 2016 John Wiley & Sons Ltd.

Involvement of shared mucosal-associated microbiota in the duodenum and rectum in diarrhea-predominant irritable bowel syndrome.

PubMed

Li, Gangping; Yang, Min; Jin, Yu; Li, Ying; Qian, Wei; Xiong, Hanhua; Song, Jun; Hou, Xiaohua

2018-06-01

Most studies of diarrhea-predominant irritable bowel syndrome (IBS-D) focused on microbiota dysbiosis in a single segment of the intestine such as the colon. However, the intestine as a whole is involved in IBS-D and knowledge about the role of microbiota shared by the duodenum and rectum in IBS-D is limited. Here, we investigated the characteristics of mucosal microbiota shared by the duodenum and rectum in IBS-D patients. We collected duodenal and rectal mucosal samples from 33 adult IBS-D patients and 15 healthy control (HC) subjects. The 454 pyrosequencing method and multiple bioinformatics analyses were used to examine bacterial 16S rRNA. Clinical data including symptoms and Bristol Stool Form were analyzed. Mucosal microbiota in duodenal samples differed from rectal samples in HC, while less difference was shown in IBS-D. More numbers in terms of shared operational taxonomic units and genera found in IBS-D compared with HC. The frequency of genera in the duodenum and rectum of HC differed from that of IBS-D. We identified 24 genera shared in the duodenum and rectum, which both changed dramatically in IBS-D. Among these 24 genera, half had similar trends in frequency differences, and the other half had opposite trends. The frequency of Faecalibacterium and Hyphomicrobium were associated with clinical data of IBS-D patients. Shared mucosal-associated microbiota in the duodenum and rectum appear to contribute to the etiology and pathophysiology of whole intestine of IBS-D and to be potential therapeutic targets. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort

PubMed Central

Sabate, Jean-Marc; Bouchoucha, Michel; Torres, Marion J.; Allès, Benjamin; Hercberg, Serge; Benamouzig, Robert; Julia, Chantal

2017-01-01

Background There is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS. Objective This cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study. Methods Subjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression. Results The included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37–4.91]), IBS mixed (aOR 2.97 95%CI [1.20–7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01–7.59]). Conclusions This study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS. PMID:28841661

Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort.

PubMed

Buscail, Camille; Sabate, Jean-Marc; Bouchoucha, Michel; Torres, Marion J; Allès, Benjamin; Hercberg, Serge; Benamouzig, Robert; Julia, Chantal

2017-01-01

There is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS. This cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study. Subjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression. The included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37-4.91]), IBS mixed (aOR 2.97 95%CI [1.20-7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01-7.59]). This study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS.

Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome.

PubMed

Chua, Chian Sem; Bai, Chyi-Huey; Shiao, Chen-Yu; Hsu, Chien-Yeh; Cheng, Chiao-Wen; Yang, Kuo-Ching; Chiu, Hung-Wen; Hsu, Jung-Lung

2017-01-01

Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

Evaluating the efficacy of mixture of Boswellia carterii, Zingiber officinale, and Achillea millefolium on severity of symptoms, anxiety, and depression in irritable bowel syndrome patients

PubMed Central

Kazemian, Afarin; Toghiani, Ali; Shafiei, Katayoun; Afshar, Hamid; Rafiei, Rahmatollah; Memari, Mahnaz; Adibi, Peyman

2017-01-01

Background: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorders (FGIDs) that affects in different aspects of life and patients experienced depression and anxiety more than others. There are several herbal medicines with positive effects in these patients. The aim of this study is to evaluate the effects of mixture of Boswellia carterii, Zingiber officinale, and Achillea Millefolium on severity of symptoms, anxiety, and depression in IBS patients. Materials and Methods: This clinical trial study was done in sixty IBS patients (with mild-to-moderate symptoms) divided into two case and control groups. Patients were assessed at the beginning, 1 month, and 3 months after by IBS-severity scoring system (IBS-SSS) and Hospital Anxiety and Depression Scale. IBS-SSS is used for quality of life evaluation too. Results: Sixty IBS patients (with mild to moderate symptoms) with a mean age of 38.75 ± 11.74 participated that 55.4% of cases and 72.8% of controls were men. The most prevalent type of IBS was the mixed type of IBS. The mean score of abdominal pain severity and frequency, bloating score, and depression and anxiety score were decreased in patients administered herbal medication, but changes in these variables in controls were not statistically significant. The changes in quality of life score between cases and controls were significant in men (P = 0.01) although it was not significant in women. Conclusion: A mixture of B. Carterii, Z. officinale, and A. millefolium is effective in eliminating IBS symptoms and its related depression and anxiety and using herbal medicine in IBS treatment is suggested. PMID:29259631

Irritable bowel syndrome is concentrated in people with higher educations in Iran: an inequality analysis

PubMed Central

2017-01-01

OBJECTIVES Like any other health-related disorder, irritable bowel syndrome (IBS) has a differential distribution with respect to socioeconomic factors. This study aimed to estimate and decompose educational inequalities in the prevalence of IBS. METHODS Sampling was performed using a multi-stage random cluster sampling approach. The data of 1,850 residents of Kish Island aged 15 years or older were included, and the determinants of IBS were identified using a generalized estimating equation regression model. The concentration index of educational inequality in cases of IBS was estimated and decomposed as the specific inequality index. RESULTS The prevalence of IBS in this study was 21.57% (95% confidence interval [CI], 19.69 to 23.44%). The concentration index of IBS was 0.20 (95% CI, 0.14 to 0.26). A multivariable regression model revealed that age, sex, level of education, marital status, anxiety, and poor general health were significant determinants of IBS. In the decomposition analysis, level of education (89.91%), age (−11.99%), and marital status (9.11%) were the three main contributors to IBS inequality. Anxiety and poor general health were the next two contributors to IBS inequality, and were responsible for more than 12% of the total observed inequality. CONCLUSIONS The main contributors of IBS inequality were education level, age, and marital status. Given the high percentage of anxious individuals among highly educated, young, single, and divorced people, we can conclude that all contributors to IBS inequality may be partially influenced by psychological factors. Therefore, programs that promote the development of mental health to alleviate the abovementioned inequality in this population are highly warranted. PMID:28171714

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up.

PubMed

Andresen, Viola; Löwe, Bernd; Broicher, Wiebke; Riegel, Björn; Fraedrich, Katharina; von Wulffen, Moritz; Gappmayer, Kerrin; Wegscheider, Karl; Treszl, András; Rose, Matthias; Layer, Peter; Lohse, Ansgar W

2016-02-01

In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation.

Effect of acupuncture and its influence on visceral hypersensitivity in IBS-D patients: Study protocol for a randomized controlled trial.

PubMed

Pei, Lixia; Chen, Hao; Guo, Jing; Chen, Lu; Wu, Xiaoliang; Xu, Wanli; Weng, Shengjie; Yang, EunMee; Hammer, Trine; Sun, Jianhua

2018-05-01

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder associated with visceral hypersensitivity. Increased expression of colonic TRPV1 and decreased expression of microRNA-199 are implicated in the pathogenesis of visceral hypersensitivity in IBS-D patients. Acupuncture is one of the frequently used complementary and alternative therapies for the treatment of IBS. The existing clinical studies mostly use IBS-SSS or other subjective scales, so there is a lack of objective biochemical evidence regarding the effect of acupuncture on IBS. Therefore, we designed this study to investigate whether acupuncture alleviate visceral hypersensitivity by influencing the expression of TRPV1 and microRNA-199. This study is a randomized, sham-controlled trial involving 40 patients and 10 healthy volunteers. A total of 40 eligible patients with IBS-D will be randomly assigned to a traditional acupuncture group or sham acupuncture group in a 1:1 ratio. Patients will receive 3 acupuncture treatment sessions per week for 12 consecutive weeks, for a total of 36 sessions during the study. The primary outcome measure is the IBS-Symptom Severity Score (IBS-SSS). Secondary outcomes are Visceral Pain Scale and levels of TRPV1 and microRNA-199 in colonic tissues. Healthy volunteers will not receive any clinical intervention. The safety of interventions will be assessed at every visit. The purpose of this trial is to evaluate the efficacy of acupuncture for IBS-D through IBS-SSS and Visceral Pain Scale. Furthermore, we want to explore the intervention mechanism of acupuncture in improving visceral hypersensitivity by analyzing the colonic TRPV1 and microRNA-199. This trial is registered with Chinese Clinical Trials Register, ChiCTR-IOR- 17010860(http://www.chictr.org.cn/showproj.aspx?proj=18445).

Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 improve quality-of-life and IBS symptoms: a double-blind, randomised, placebo-controlled study.

PubMed

Preston, K; Krumian, R; Hattner, J; de Montigny, D; Stewart, M; Gaddam, S

2018-06-11

A combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 was compared to placebo for relief of symptoms of irritable bowel syndrome (IBS). A total of 113 subjects at 3 clinical sites were randomised in a 2:1 ratio and followed for 12 weeks. Subjects ingested either 2 capsules of active study product, containing 50×10 9 cfu of live organisms, or 2 placebo capsules daily. Endpoints included improvement in abdominal pain, days of pain, distention, stool consistency and frequency, quality of life (QOL), and adequate relief (AR) of IBS symptoms. IBS subtypes constipation (IBS-C), diarrhoea (IBS-D), and mixed (IBS-M) were evaluated separately; the effect of gender was also examined. For all efficacy endpoints improvement of 30% or more vs placebo was considered clinically significant. With the exception of pain intensity and AR, the endpoints demonstrated a therapeutic advantage of active over placebo for IBS symptoms in at least some subject subgroups. The IBS-D and female subgroups showed the largest and most consistent effects. Stool frequency and consistency were evaluated in the IBS-C and IBS-D subgroups, and improvement of active vs placebo was noted in both. QOL improvement was seen overall and in specific domains. Adverse events (AEs) were limited to 7 subjects; all were of mild or moderate intensity except one, severe cramping. Four AEs in the same subject in the placebo group were judged to be related to study product; these resolved by the end of study. There were no serious AEs.

Cytokine Response after Stimulation with Key Commensal Bacteria Differ in Post-Infectious Irritable Bowel Syndrome (PI-IBS) Patients Compared to Healthy Controls.

PubMed

Sundin, Johanna; Rangel, Ignacio; Repsilber, Dirk; Brummer, Robert-Jan

2015-01-01

Microbial dysbiosis and prolonged immune activation resulting in low-grade inflammation and intestinal barrier dysfunction have been suggested to be underlying causes of post-infectious irritable bowel syndrome (PI-IBS). The aim of this study was to evaluate the difference in cytokine response between mucosal specimens of PI-IBS patients and healthy controls (HC) after ex vivo stimulation with key anaerobic bacteria. Colonic biopsies from 11 PI-IBS patients and 10 HC were stimulated ex vivo with the commensal bacteria Bacteroides ovatus, Ruminococcus gnavus, Akkermansia muciniphila, Subdoligranulum variabile and Eubacterium limosum, respectively. The cytokine release (IL-1β, IL-2, IL-8, IL-10, IL-13, IL-17, TNF-α and IFN-γ) in stimulation supernatants was analyzed using the LUMINEX assay. Comparison of cytokine release between PI-IBS patients and healthy controls was performed taking both unstimulated and bacterially stimulated mucosal specimens into account. IL-13 release from mucosal specimens without bacterial stimulation was significantly lower in PI-IBS patients compared to HC (p < 0.05). After stimulation with Subdoligranulum variabile, IL-1β release from PI-IBS patients was significantly increased compared to HC (p < 0.05). Stimulation with Eubacterium limosum resulted in a significantly decreased IL-10 release in HC compared to PI-IBS patients (p < 0.05) and a tendency to decreased IL-13 release in HC compared to PI-IBS patients (p = 0.07). PI-IBS patients differ from HC with regard to cytokine release ex vivo after stimulation with selected commensal bacteria. Hence, our results support that the pathogenesis of PI-IBS comprises an altered immune response against commensal gut microbes.

Tight junctions and IBS--the link between epithelial permeability, low-grade inflammation, and symptom generation?

PubMed

Piche, T

2014-03-01

In this issue of Neurogastroenterology and Motility, Dr Ewa Wilcz-Villega and colleagues report low expression of E-cadherin, a tight junction protein involved in the regulation of paracellular permeability, in the colonic mucosa of patients with the irritable bowel syndrome (IBS) with predominance of diarrhea (IBS-D) or alternating symptoms (IBS-A). These findings constitute an improvement in our knowledge of epithelial barrier disruption associated with IBS. There is mounting evidence to indicate that a compromised epithelial barrier is associated with low-grade immune activation and intestinal dysfunction in at least a proportion of IBS patients. During the last 10 years of research, much interest has focused on the increase in the number of different types of immune cells in the gut mucosa of IBS patients including: mast cells, T lymphocytes, and other local cells such as enteroendocrine cells. The inflammatory mediators released by these cells or other luminal factors could be at the origin of altered epithelial barrier functions and enteric nervous system signaling, which lead to gut hypersensitivity. A current conceptual framework states that clinical symptoms of IBS could be associated with structural and functional abnormalities of the mucosal barrier, highlighting the crucial importance of elucidating the contributory role of epithelial barrier defects in the pathogenesis of IBS. More importantly, disruption of the epithelial barrier could also participate in the generation of persistent abdominal pain and discomfort mimicking IBS in patients with inflammatory bowel diseases considered in remission. This mini review gives a brief summary of clinical and experimental evidence concerning the mechanisms underlying epithelial barrier defects in IBS. © 2014 John Wiley & Sons Ltd.

The clinical potential of ramosetron in the treatment of irritable bowel syndrome with diarrhea (IBS-D).

PubMed

Min, Yang Won; Rhee, Poong-Lyul

2015-05-01

Irritable bowel syndrome (IBS) is a highly prevalent functional bowel disorder. Serotonin (5-HT) is known to play a physiological and pathophysiological role in the regulation of gastrointestinal function. In experimental studies, 5-HT3 receptor antagonists have been reported to slow colon transit, to blunt gastrocolonic reflex, and to reduce rectal sensitivity. Alosetron and cilansetron, potent and selective 5-HT3 receptor antagonists, have proven efficacy in the treatment of IBS with diarrhea (IBS-D). However, alosetron was voluntarily withdrawn due to postmarketing reports of ischemic colitis and complications of constipation, and cilansetron was never marketed. Currently alosetron is available under a risk management program for women with severe IBS-D. Ramosetron is another potent and selective 5-HT3 receptor antagonist, which has been marketed in Japan, South Korea, and Taiwan. In animal studies, ramosetron reduced defecation induced by corticotrophin-releasing hormone and had inhibitory effects on colonic nociception. In two randomized controlled studies including 957 patients with IBS-D, ramosetron increased monthly responder rates of patient-reported global assessment of IBS symptom relief compared with placebo. Ramosetron was also as effective as mebeverine in male patients with IBS-D. In a recent randomized controlled trial with 343 male patients with IBS-D, ramosetron has proved effective in improving stool consistency, relieving abdominal pain/discomfort, and improving health-related quality of life. Regarding safety, ramosetron is associated with a lower incidence of constipation compared with other 5-HT3 receptor antagonists and has not been associated with ischemic colitis. Although further large prospective studies are needed to assess whether ramosetron is effective for female patients with IBS-D and to evaluate its long-term safety, ramosetron appears to be one of the most promising agents for patients with IBS-D.

Fear of GI symptoms has an important impact on quality of life in patients with moderate-to-severe IBS.

PubMed

Lackner, Jeffrey M; Gudleski, Gregory D; Ma, Chang-Xing; Dewanwala, Akriti; Naliboff, Bruce

2014-11-01

Because irritable bowel syndrome (IBS) is a functional medical condition for which there is no curative therapy, treatment goals emphasize relieving gastrointestinal (GI) symptoms and optimizing the quality of life (QOL). This study sought to characterize the magnitude of the associations between QOL impairment, fear of IBS symptoms, and confounding variables. Subjects included 234 Rome III-diagnosed IBS patients (mean age, 41 years, 79%, female) without comorbid organic GI disease who were referred to two specialty care clinics of an National Institutes of Health trial for IBS. Subjects completed a testing battery that included the IBS-specific QOL (IBS-QOL), SF-12 (generic QOL), the UCLA GI Symptom Severity Scale, the Visceral Sensitivity Index, Trait Anxiety Inventory, and Brief Symptom Inventory. Multiple linear regression was used to develop a model for predicting QOL. Data supported an overall model that included sociodemographic, clinical (e.g., current severity of GI symptoms), and psychosocial (e.g., fear of GI symptoms, distress, neuroticism) variables, accounting for 48.7% of the variance in IBS-QOL (F=15.1, P <0.01). GI symptom fear was the most robust predictor of IBS-QOL (β=-0.45 P <0.01), accounting for 14.4% of the total variance. Patients' fear that GI symptoms have aversive consequences, is a predictor of QOL impairment that cannot be fully explained by the severity of their GI symptoms, overall emotional well-being, neurotic personality style, or other clinical features of IBS. An understanding of the unique impact that GI symptom fears have on QOL can inform treatment planning and help gastroenterologists to better manage more severe IBS patients seen in tertiary care clinics.

A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrhea-predominant IBS.

PubMed

Hod, K; Sperber, A D; Ron, Y; Boaz, M; Dickman, R; Berliner, S; Halpern, Z; Maharshak, N; Dekel, R

2017-07-01

Micro-inflammation is considered an element in the pathogenesis of irritable bowel syndrome (IBS). High-sensitivity C reactive protein (hs-CRP) was previously shown to be higher in IBS compared to healthy controls, albeit within the normal range. Since probiotics may suppress micro-inflammation in the gut, we tested if they reduce symptoms and inflammatory markers (hs-CRP and fecal calprotectin (FC) in diarrhea-predominant IBS (IBS-D). The aim of this study was to assess the clinical and laboratory effects of BIO-25, a multispecies probiotic, in women with IBS-D. A double-blind, placebo-controlled study. Following a 2-week run-in, eligible women were assigned at random to a probiotic capsule or an indistinguishable placebo, twice daily for 8 weeks. IBS symptoms and stool consistency were rated daily by Visual Analogue Scales (VAS) and the Bristol Stool Scale (BSS). High-sensitivity C reactive protein was tested at baseline, 4 and 8 weeks. FC was tested at baseline and 8 weeks. One hundred and seventy-two IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n=54) or placebo (n=53) group. All symptoms improved in both groups with no significant difference between them in symptom improvement, hs-CRP or FC levels. An 8-week treatment with BIO-25 improved symptoms in women with IBS-D, but was not superior to placebo. This rigorously designed and executed study supports the findings of other studies that did not demonstrate superiority of probiotics over placebo in IBS. High quality clinical studies are necessary to examine the efficacy of other specific probiotics in IBS-D patients since data are still conflicting. © 2017 John Wiley & Sons Ltd.

Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS.

PubMed

Törnblom, Hans; Van Oudenhove, Lukas; Tack, Jan; Simrén, Magnus

2014-09-01

Rectal sensory and motor interactions in patients with IBS have not been studied in detail. The aim of this study was to evaluate fasting and postprandial rectal sensorimotor characteristics and their interactions in IBS compared with healthy controls. We included 274 patients with IBS and 34 controls. All subjects underwent a rectal barostat study before and 60 min after a standardised liquid meal (800 kcal; 60% fat). Sensory thresholds, intensity of sensations, viscerosomatic referral and compliance were measured. During 15 min before the first distension sequence and until 50 min after meal intake, rectal balloon volumes were registered in 5 min intervals at operating pressure to quantify rectal tone. Mixed models were used to analyse the rectal tone response over time. Rectal sensory thresholds and compliance were decreased and viscerosomatic referral areas increased in patients with IBS compared with controls. Meal intake increased rectal sensitivity, compliance and referral areas in patients and controls and the same proportions of patients were hypersensitive to distension before and after meal intake. There was a higher basal rectal tone in IBS and a significantly different rectal tone response after meal intake in patients with IBS compared with controls and, interestingly, also in IBS with rectal hypersensitivity (defined in the preprandial state), compared with normosensitive patients. Meal intake affects rectal sensorimotor function in IBS and health. Importantly, the rectal tone responses to a high-caloric meal are different between patients with IBS and controls, as well as between hypersensitive and normosensitive patients with IBS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Evaluating the efficacy of mixture of Boswellia carterii, Zingiber officinale, and Achillea millefolium on severity of symptoms, anxiety, and depression in irritable bowel syndrome patients.

PubMed

Kazemian, Afarin; Toghiani, Ali; Shafiei, Katayoun; Afshar, Hamid; Rafiei, Rahmatollah; Memari, Mahnaz; Adibi, Peyman

2017-01-01

Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorders (FGIDs) that affects in different aspects of life and patients experienced depression and anxiety more than others. There are several herbal medicines with positive effects in these patients. The aim of this study is to evaluate the effects of mixture of Boswellia carterii , Zingiber officinale , and Achillea Millefolium on severity of symptoms, anxiety, and depression in IBS patients. This clinical trial study was done in sixty IBS patients (with mild-to-moderate symptoms) divided into two case and control groups. Patients were assessed at the beginning, 1 month, and 3 months after by IBS-severity scoring system (IBS-SSS) and Hospital Anxiety and Depression Scale. IBS-SSS is used for quality of life evaluation too. Sixty IBS patients (with mild to moderate symptoms) with a mean age of 38.75 ± 11.74 participated that 55.4% of cases and 72.8% of controls were men. The most prevalent type of IBS was the mixed type of IBS. The mean score of abdominal pain severity and frequency, bloating score, and depression and anxiety score were decreased in patients administered herbal medication, but changes in these variables in controls were not statistically significant. The changes in quality of life score between cases and controls were significant in men ( P = 0.01) although it was not significant in women. A mixture of B. Carterii , Z. officinale , and A. millefolium is effective in eliminating IBS symptoms and its related depression and anxiety and using herbal medicine in IBS treatment is suggested.

LINE1 family member is negative regulator of HLA-G expression.

PubMed

Ikeno, Masashi; Suzuki, Nobutaka; Kamiya, Megumi; Takahashi, Yuji; Kudoh, Jun; Okazaki, Tsuneko

2012-11-01

Class Ia molecules of human leucocyte antigen (HLA-A, -B and -C) are widely expressed and play a central role in the immune system by presenting peptides derived from the lumen of the endoplasmic reticulum. In contrast, class Ib molecules such as HLA-G serve novel functions. The distribution of HLA-G is mostly limited to foetal trophoblastic tissues and some tumour tissues. The mechanism required for the tissue-specific regulation of the HLA-G gene has not been well understood. Here, we investigated the genomic regulation of HLA-G by manipulating one copy of a genomic DNA fragment on a human artificial chromosome. We identified a potential negative regulator of gene expression in a sequence upstream of HLA-G that overlapped with the long interspersed element (LINE1); silencing of HLA-G involved a DNA secondary structure generated in LINE1. The presence of a LINE1 gene silencer may explain the limited expression of HLA-G compared with other class I genes.

Occurrences and Characterization of Antibiotic-Resistant Bacteria and Genetic Determinants of Hospital Wastewater in a Tropical Country.

PubMed

Le, Thai-Hoang; Ng, Charmaine; Chen, Hongjie; Yi, Xin Zhu; Koh, Tse Hsien; Barkham, Timothy Mark Sebastian; Zhou, Zhi; Gin, Karina Yew-Hoong

2016-12-01

Wastewater discharged from clinical isolation and general wards at two hospitals in Singapore was examined to determine the emerging trends of antibiotic resistance (AR). We quantified the concentrations of 12 antibiotic compounds by analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS), antibiotic-resistant bacteria (ARB), the class 1 integrase gene (intI1), and 16 antibiotic resistance genes (ARGs) that confer resistance to 10 different clinically relevant antibiotics. A subset of 119 antibiotic-resistant isolates were phylogenetically classified and tested for the presence of ARGs encoding resistance to β-lactam antibiotics (bla NDM , bla KPC , bla SHV , bla CTX-M ), amikacin [aac(6')-Ib], co-trimoxazole (sul1, sul2, dfrA), ciprofloxacin (qnrA, qnrB), and the intI1 gene. Among these resistant isolates, 80.7% were detected with intI1 and 66.4% were found to carry at least 1 of the tested ARGs. Among 3 sampled locations, the clinical isolation ward had the highest concentrations of ARB and the highest levels of ARGs linked to resistance to β-lactam (bla KPC ), co-trimoxazole (sul1, sul2, dfrA), amikacin [aac(6')-Ib], ciprofloxacin (qnrA), and intI1 We found strong positive correlations (P < 0.05) between concentrations of bacteria resistant to meropenem, ceftazidime, amikacin, co-trimoxazole, and ciprofloxacin and abundances of bla KPC , aac(6')-Ib, sul1, sul2, dfrA, qnrA, and intI1 genes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

An insight into the active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani

PubMed Central

Das, Aditi; Mandal, Chhabinath; Dasgupta, Arindam; Sengupta, Tanushri; Majumder, Hemanta K.

2002-01-01

DNA topoisomerases are ubiquitous enzymes that govern the topological interconversions of DNA thereby playing a key role in many aspects of nucleic acid metabolism. Recently determined crystal structures of topoisomerase fragments, representing nearly all the known subclasses, have been solved. The type IB enzymes are structurally distinct from other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. A putative topoisomerase I open reading frame from the kinetoplastid Leishmania donovani was reported which shared a substantial degree of homology with type IB topoisomerases but having a variable C-terminus. Here we present a molecular model of the above parasite gene product, using the human topoisomerase I crystal structure in complex with a 22 bp oligonucleotide as a template. Our studies indicate that the overall structure of the parasite protein is similar to the human enzyme; however, major differences occur in the C-terminal loop, which harbors a serine in place of the usual catalytic tyrosine. Most other structural themes common to type IB topoisomerases, including secondary structural folds, hinged clamps that open and close to bind DNA, nucleophilic attack on the scissile DNA strand and formation of a ternary complex with the topoisomerase I inhibitor camptothecin could be visualized in our homology model. The validity of serine acting as the nucleophile in the case of the parasite protein model was corroborated with our biochemical mapping of the active site with topoisomerase I enzyme purified from L.donovani promastigotes. PMID:11809893

Defining the Relationship Between Phenotypic and Genotypic Resistance Profiles of Multidrug-Resistant Enterobacterial Clinical Isolates.

PubMed

Galal, Lamis; Abdel Aziz, Neveen A; Hassan, Walaa M

2018-05-11

Fluoroquinolones and aminoglycosides offer effective therapy for extended-spectrum beta-lactamase (ESBL)-producing enterobacterial infections, but their usefulness is threatened by increasing resistant strains. This study was conducted to demonstrate the phenotypic outcomes of the coexistence of genetic determinants mediating resistance to extended-spectrum cephalosporins and quinolones in enterobacterial isolates collected from patients with health-care-associated infections in Egypt. ESBL phenotype was determined using double-disk synergy test (DDST). The PCR technique was used to detect the presence of the genes mediating quinolone resistance (qnr and aac(6')-Ib-cr) and coexistence with ESBL genes. We also examined the association between the genetic makeup of the isolates and their resistance profiles including effect on MIC results. Phenotypically ESBLs were detected in 60-82% of the enterobacterial isolates. ESBL, qnr and aac(6')-Ib-cr genes were detected with the following percentages in Citrobacter isolates (69%, 69%, and 43%, respectively), E.coli isolates (65%, 70%, and 45%, respectively), Enterobacter isolates (56%, 67%, and 33%, respectively), and finally Klebsiella isolates (42%, 66%, and 25%, respectively). The coexistence of these multiresistant genetic elements significantly increased the MIC values of the tested antibiotics from different classes. We suggest using blaTEM, blaCTX-M-15, qnr, and aac(6')-Ib-cr genes for better and faster prediction of suitable antibiotic therapy with effective doses against ESBL-producing isolates harboring plasmid-mediated quinolone resistance (PMQR) determinants. Amikacin, meropenem, gentamicin, and imipenem seem to be better choices of treatment for such life-threatening infections, because of their remaining highest activity.

Colonic immune cells in irritable bowel syndrome: A systematic review and meta-analysis.

PubMed

Bashashati, M; Moossavi, S; Cremon, C; Barbaro, M R; Moraveji, S; Talmon, G; Rezaei, N; Hughes, P A; Bian, Z X; Choi, C H; Lee, O Y; Coëffier, M; Chang, L; Ohman, L; Schmulson, M J; McCallum, R W; Simren, M; Sharkey, K A; Barbara, G

2018-01-01

Increases in mucosal immune cells have frequently been observed in irritable bowel syndrome (IBS) patients. However, this finding is not completely consistent between studies, possibly due to a combination of methodological variability, population differences and small sample sizes. We performed a meta-analysis of case-control studies that compared immune cell counts in colonic biopsies of IBS patients and controls. PubMed and Embase were searched in February 2017. Results were pooled using standardized mean difference (SMD) and were considered significant when zero was not within the 95% confidence interval (CI). Heterogeneity was assessed based on I 2 statistics where I 2  ≤ 50% and I 2  > 50% indicated fixed and random effect models, respectively. Twenty-two studies on 706 IBS patients and 401 controls were included. Mast cells were increased in the rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = .02) and descending colon (SMD: 1.69 [95% CI: 0.65-2.73]; P = .001) of IBS patients. Increased mast cells were observed in both constipation (IBS-C) and diarrhea predominant IBS (IBS-D). CD3 + T cells were increased in the rectosigmoid (SMD: 0.53 [95% CI: 0.21-0.85]; P = .001) and the descending colon of the IBS patients (SMD: 0.79, 95% CI [0.28-1.30]; P = .002). This was possibly in relation to higher CD4 + T cells in IBS (SMD: 0.33 [95% CI: 0.01-0.65]; P = .04) as there were no differences in CD8 + T cells. Mast cells and CD3 + T cells are increased in colonic biopsies of patients with IBS vs non-inflamed controls. These changes are segmental and sometimes IBS-subtype dependent. The diagnostic value of the quantification of colonic mucosal cells in IBS requires further investigation. © 2017 John Wiley & Sons Ltd.

Risk of Psychiatric Disorders following Irritable Bowel Syndrome: A Nationwide Population-Based Cohort Study.

PubMed

Lee, Yao-Tung; Hu, Li-Yu; Shen, Cheng-Che; Huang, Min-Wei; Tsai, Shih-Jen; Yang, Albert C; Hu, Chang-Kuo; Perng, Chin-Lin; Huang, Yi-Shin; Hung, Jeng-Hsiu

2015-01-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal (GI) disorder observed in patients who visit general practitioners for GI-related complaints. A high prevalence of psychiatric comorbidities, particularly anxiety and depressive disorders, has been reported in patients with IBS. However, a clear temporal relationship between IBS and psychiatric disorders has not been well established. We explored the relationship between IBS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. We selected patients who were diagnosed with IBS caused by gastroenteritis, according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort was formed of patients without IBS who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for both cohorts, based on psychiatrist diagnoses. The IBS cohort consisted of 4689 patients, and the comparison cohort comprised 18756 matched control patients without IBS. The risks of depressive disorder (HR = 2.71, 95% confidence interval [CI] = 2.30-3.19), anxiety disorder (HR = 2.89, 95% CI = 2.42-3.46), sleep disorder (HR = 2.47, 95% CI = 2.02-3.02), and bipolar disorder (HR = 2.44, 95% CI = 1.34-4.46) were higher in the IBS cohort than in the comparison cohort. In addition, the incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0-1, 1-5, ≥5 y). IBS may increase the risk of subsequent depressive disorder, anxiety disorder, sleep disorder, and bipolar disorder. The risk ratios are highest for these disorders within 1 year of IBS diagnosis, but the risk remains statistically significant for more than 5 years. Clinicians should pay particular attention to psychiatric comorbidities in IBS patients.

Childhood bladder and bowel dysfunction predicts irritable bowel syndrome phenotype in adult interstitial cystitis/bladder pain syndrome patients.

PubMed

Doiron, R Christopher; Kogan, Barry A; Tolls, Victoria; Irvine-Bird, Karen; Nickel, J Curtis

2017-08-01

Many clinicians have suggested that a history of bladder and bowel dysfunction (BBD) in childhood predisposes to the development of interstitial cystitis/bladder pain syndrome (IC/BPS) or irritable bowel syndrome (IBS) in adulthood. We hypothesized that BBD symptoms in childhood would predict the IBS-associated phenotype in adult IC/BPS patients. Consecutive female patients (n=190) with a diagnosis of IC/BPS were administered a modified form of a clinical BBD questionnaire (BBDQ) to capture childhood BBD-like symptoms, as well as Interstitial Cystitis Symptoms Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency (PUF) questionnaires and UPOINT categorization. Patients were stratified to IBS-positive or IBS-negative according to clinical assessment of IBS-like symptoms. The 127 patients (67%) identified with IBS-like symptoms recalled significantly higher BBDQ scores than the 63 patients (33%) who were IBS-negative (2.8 vs. 2.3; p=0.05). The IBS-positive patients also reported a higher number of UPOINT domains than their non-IBS counterparts (3.8 vs. 2.9; p=0.0001), while their PUF total scores were significantly higher (13.6 vs. 12.3; p=0.04). IBS-positive patients more often recalled that in childhood they did not have a daily bowel movement (BM) (p=0.04) and had "to push for a BM" (p=0.009). In childhood, they "urinated only once or twice per day" (p=0.03) and recalled "painful urination" more than those without IBS (p=0.03). There were no significant differences between the groups in answers to the other five questions of the BBDQ. Our symptom recollection survey was able to predict the IBS phenotype of IC/BPS based on a childhood BBDQ. Further prospective studies are needed to further evaluate these novel findings.

Reports of "satisfactory relief" by IBS patients receiving usual medical care are confounded by baseline symptom severity and do not accurately reflect symptom improvement.

PubMed

Whitehead, William E; Palsson, Olafur S; Levy, Rona L; Feld, Andrew D; VonKorff, Michael; Turner, Marsha

2006-05-01

Treatment trials for irritable bowel syndrome (IBS) usually define a responder as a patient who reports satisfactory relief or adequate relief of symptoms at the end of the trial. However, these measures have not been adequately validated. (1) Compare a binary satisfactory relief measure to alternative ways of defining a treatment responder. (2) Determine whether baseline IBS symptom severity or psychological distress influence the sensitivity of these outcome measures. A total of 350 patients (81% females, average age 50 yr) who had a medical diagnosis of IBS and satisfied Rome II criteria, were recruited from Group Health Cooperative of Puget Sound. At baseline the Irritable Bowel Severity Scale (IBSS) was used to assess symptom severity and to classify patients as mild, moderate, or severe. Psychological distress and IBS-specific quality of life (IBS-QOL) were also assessed. After 6 months treatment with standard medical care, IBSS and IBS-QOL were reassessed, and patients were asked whether they had experienced satisfactory relief and whether they were somewhat or markedly better. Initial severity of IBS significantly affected the proportion who reported satisfactory relief (mild, 72%; moderate, 53%; severe, 44%) and the proportion who were somewhat or markedly better (mild, 62%; moderate, 44%; severe, 38%), but did not affect the proportion with a 50% reduction in symptoms (mild, 26%; moderate, 25%; severe, 23%). Although mild patients were the most likely to report satisfactory relief, they showed no average decrease in symptom severity or improvement in IBS-QOL. Conversely, severe patients, who were the least likely to report satisfactory relief, had the largest reductions in IBS symptom severity and the largest improvements in IBS-QOL. Psychological distress had no significant effect on the responder rate after adjusting for IBS symptom severity. These data from a descriptive study suggest that satisfactory relief is confounded with initial IBS symptom severity and is poorly correlated with the amount of symptom improvement. Confirmation of these findings in a clinical trial is needed.

Irritable bowel syndrome: prevalence, risk factors in an adult Lebanese population.

PubMed

Chatila, Rajaa; Merhi, Mahmoud; Hariri, Essa; Sabbah, Nada; Deeb, Mary E

2017-12-02

Very few studies report on the prevalence of irritable bowel syndrome (IBS) and its correlates in the Middle East. This study investigated Irritable Bowel Syndrome (IBS) prevalence in a sample of Lebanese adult individuals and associated demographic and behavioral lifestyle factors. This is an observational population-based study. The target population is working Lebanese adults, eighteen-to-sixty five years old. The sample was selected from a convenience population of bank employees in different geographical areas in Lebanon. The study participants completed an anonymous self-administered questionnaire, to collect data on their socio-demographic, behavioral and life style characteristics, and diagnostic questions following Rome III criteria to assess IBS occurrence. The difference in IBS prevalence by socio-demographic characteristics, smoking, alcohol consumption, and physical activity was assessed by using the Chi-square test. Logistic regression adjusted odds ratios were used to investigate the association between risk factors and IBS. Data was collected from 553 individuals and consisted of 52.8% females (mean age 35.9 years, SD = 11.9) and 47.2% males (mean age = 36.1 years, SD = 10.3). The prevalence of IBS in the study population according to Rome III criteria was 20.1%. The bivariate analysis indicated that being younger than 30 years old, a female, an ever water pipe smoker, an ever alcohol consumer are significantly associated with a higher prevalence of IBS. Educational level, cigarettes smoking and physical exercise were not significantly associated with IBS occurrence. The logistic regression adjusted odds ratio showed that females were 1.67 times more likely to have IBS than males (P˂ 0.05). The participants aged less than 30 years old were at a higher risk of having IBS (P˂ 0.01). Those who ever smoked waterpipe were 1.63 times more likely to have IBS than those who never smoked waterpipe (P˂ 0.05). Those who were ever alcohol drinkers were twice as likely to have IBS than never-drinkers (P˂ 0.01). New data on the high prevalence of IBS in an adult population in Lebanon has been reported. This is also the first study to investigate and show an association of waterpipe smoking and IBS. Further longitudinal studies are warranted to determine whether this association is causal.

Prevalence of Irritable Bowel Syndrome (IBS), Migraine and Co-Existing IBS-Migraine in Medical Students.

PubMed

Perveen, Irin; Parvin, Rukhsana; Saha, Madhusudan; Bari, Md Shafiqul; Huda, Md Nazmul; Ghosh, Mridul Kanti

2016-11-01

Irritable Bowel Syndrome (IBS) and migraine frequently co-exist. Stress is a major contributing factor for both. Our medical students are subjected to stress related to the implicit responsibility of courses. But the prevalence of IBS, migraine and co-existing migraine in medical students is not known. To estimate the prevalence of migraine, IBS and co-existing IBS and migraine among medical students. A Cross-Sectional Survey. Self-reported questionnaire based study, was conducted in which migraine was defined according to International Headache Society (IHS) criteria while IBS by both Asian criteria and Rome III criteria. Both preclinical (n=142) and clinical students (n=151) of four medical colleges (government and private) of Dhaka and Sylhet district participated in the study. Statistical Analysis: Student's t-test and chi-square test were used to compare the distributions of continuous data and categorical data respectively with significance level set at 0.05 or less. Among the 293 students (mean age 21.09 ± 2.24 years) volunteered in the study (Males= 177), 14 (4.8%, 11 males, 3 females, p = 0.175) met the criteria for IBS with comparable prevalence among preclinical and clinical (4.2% vs. 5.3%, p = 0.787) students from both private and government institutions (2.1% vs. 7.2%, p = 0.055). IBS-D was the most prevalent subtype (n = 8, M = 6) and abdominal pain relieved by defecation (n = 11), was the most prevalent symptom. Fifty percent (n = 7) of IBS patients considered their bowel habit as normal. Among the 221 (75.4%) students with headache, only 51 (17.4%, 20 males and 31 females, p = 0.001) were diagnosed of migraine, with comparable prevalence among preclinical and clinical students (16.2% vs. 18.5%, p = 0.645). Only 17 (33%) subjects with migraine had accompanying aura. Common triggers were stress (n = 43), lack of sleep (n = 42), and daily life events. Twelve (23.5%) subjects with migraine had migraine-associated frequent disability. Only two female students with IBS-D (14.3%) had concomitant IBS and migraine. IBS and concomitant migraine - IBS prevalence was found to be low in our medical students, but migraine prevalence corresponds to other countries as well as in medical students.

Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Tang, Yurong; Xiong, Wenjie; Shen, Xiaoxue; Jiang, Ling; Lin, Lin

2017-01-01

Aim We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D). Methods We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software. Results We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43–1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]). Conclusions Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events. PMID:28291778

Economic burden of irritable bowel syndrome with constipation: a retrospective analysis of health care costs in a commercially insured population.

PubMed

Doshi, Jalpa A; Cai, Qian; Buono, Jessica L; Spalding, William M; Sarocco, Phil; Tan, Hiangkiat; Stephenson, Judith J; Carson, Robyn T

2014-04-01

The prevalence of irritable bowel syndrome with constipation (IBS-C) is estimated to be between 4.3% and 5.2% among adults in the United States. Little is known about the health care resource utilization and costs associated with IBS-C. To (a) evaluate the annual total all-cause, gastrointestinal (GI)-related, and IBS-C-related health care costs among IBS-C patients seeking medical care in a commercially insured population and (b) estimate the incremental all-cause health care costs among IBS-C patients relative to matched controls. Patients aged ≥ 18 years with continuous medical and pharmacy benefit eligibility in 2010 were identified from the HealthCore Integrated Research Database, which consists of administrative claims from 14 geographically dispersed U.S. health plans representing 45 million lives. IBS-C patients were defined as those with ≥ 1 medical claim with an ICD-9-CM diagnosis code in any position for IBS (ICD-9-CM 564.1x) and either ≥ 2 medical claims for constipation (ICD-9-CM 564.0x) on different service dates or ≥ 1 medical claim for constipation plus ≥ 1 pharmacy claim for a constipation-related prescription on different dates of service during the study period. Controls were defined as patients without any medical claims for IBS, constipation, abdominal pain, or bloating or pharmacy claims for constipation-related prescriptions. Controls were randomly selected and matched with IBS-C patients in a 1:1 ratio based on age (± 4 years), gender, health plan region, and health plan type. Patients with diagnoses or prescriptions suggesting mixed IBS, IBS with diarrhea, chronic diarrhea, or drug-induced constipation were excluded. Total health care costs in 2010 U.S. dollars were defined as the sum of health plan and patient paid costs for prescriptions and medical services, including inpatient visits, emergency room (ER) visits, physician office visits, and other outpatient services. The total cost approach was used to assess total all-cause or disease-specific health care costs for patients with IBS-C, while the incremental cost approach was used to examine the excess all-cause costs of IBS-C by comparing IBS-C patients with matched controls. Generalized linear models with bootstrapping were used to assess the incremental all-cause costs attributable solely to IBS-C after adjusting for demographics, Elixhauser Comorbidity Index (ECI) score, and other general and GI-related comorbidities not included in the ECI score. A total of 7,652 patients (n = 3,826 each in the IBS-C and control cohorts) were included in the analysis. The mean (± SD) age was 48 (± 17) years, and 83.6% were female. The mean annual all-cause health care costs for IBS-C patients were $11,182, with over half (53.7%) of the costs attributable to outpatient services, including physician office visits and other outpatient services (13.1% and 40.6%, respectively). Remaining total all-cause costs were attributable to hospitalizations (21.8%), prescriptions (19.1%), and ER visits (5.4%). GI-related costs ($4,456) comprised 39.8% of total all-cause costs, while IBS-C-related costs ($1,335) accounted for 11.9% and were primarily driven by costs of other outpatient services (50.3%). After adjusting for demographics and comorbidities, the incremental annual all-cause health care costs associated with IBS-C were $3,856 ($8,621 for IBS-C patients vs. $4,765 for controls, P less than 0.01) per patient per year, of which 78.1% of the incremental costs were due to medical services, and 21.9% were due to prescription fills. IBS-C imposes a substantial economic burden in terms of direct health care costs in a commercially insured population. Compared with matched controls, IBS-C patients incurred significantly higher total annual all-cause health care costs even after controlling for general and GI-related comorbidities. Incremental all-cause costs associated with IBS-C were mainly driven by costs related to more frequent use of medical services as opposed to prescriptions.

75 FR 13765 - Draft Guidance for Industry on Irritable Bowel Syndrome-Clinical Evaluation of Products for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

...] Draft Guidance for Industry on Irritable Bowel Syndrome--Clinical Evaluation of Products for Treatment... topics regarding irritable bowel syndrome (IBS) sign and symptom assessment for IBS with diarrhea (IBS-D... IBS. DATES: Although you can comment on any guidance at any time (see 21 CFR 10.115(g)(5)), to ensure...

Gastrointestinal (GI) permeability is associated with trait anxiety in children with functional abdominal pain (FAP) and Irritable Bowel Syndrome (IBS)

USDA-ARS?s Scientific Manuscript database

FAP and IBS affect 10-15% of school age children and bear many physiological similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress and increased GI permeability later in life...

Does a Student's Personality Influence Global Attentiveness and Internationalism in an International Business Course?

ERIC Educational Resources Information Center

Chen, Jiun-Shiu; Stevens, Jeffery; Cox, Susie S.; Tudor, Thomas R.

2016-01-01

Learning outcomes for international business (IB) courses are designed to do more than simply impart IB knowledge. However, past studies have had mixed results on the impact of learning in IB courses. This study examines whether a student's personality may affect learning outcomes. The results suggest that after completing an IB course, students…

Teacher and Student Perceptions of the International Baccalaureate Program: A First Year Perspective

ERIC Educational Resources Information Center

Culross, Rita R.; Tarver, Emily T.

2007-01-01

This study examined the perceptions of teachers and students during the first year of implementation of the International Baccalaureate (IB) Diploma Program at a high school. The research team interviewed all IB teachers and students regarding their decision to teach/enroll in IB; how IB differed from teaching/taking regular courses; and other…

Saturn Apollo Program

NASA Image and Video Library

1965-01-01

Marshall Space Flight Center (MSFC) workers lower S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Center's Dynamic Test Stand on January 12, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle. Developed by the MSFC as an interim vehicle in MSFC's "building block" approach to Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine large boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

Saturn Apollo Program

NASA Image and Video Library

1965-04-01

S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), undergoes a full-duration static firing in Saturn IB static test stand at the Marshall Space Flight Center (MSFC) on April 13, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds. Between April 1965 and July 1968, MSFC performed thirty-two static tests on twelve different S-IB stages.

Prevalence of Irritable Bowel Syndrome–like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease

PubMed Central

Tomita, Toshihiko; Kato, Yu; Takimoto, Mayu; Yamasaki, Takahisa; Kondo, Takashi; Kono, Tomoaki; Tozawa, Katsuyuki; Yokoyama, Yoko; Ikehara, Hisatomo; Ohda, Yoshio; Oshima, Tadayuki; Fukui, Hirokazu; Tanaka, Shigemi; Shima, Masayuki; Watari, Jiro; Miwa, Hiroto

2016-01-01

Background/Aims Few studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD. Methods IBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated. Results IBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant. Conclusions The prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients. PMID:27193973

Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association or reflection of occult inflammation?

PubMed

Keohane, John; O'Mahony, Caitlin; O'Mahony, Liam; O'Mahony, Siobhan; Quigley, Eamonn M; Shanahan, Fergus

2010-08-01

Do gastrointestinal symptoms in patients with inflammatory bowel disease (IBD) in apparent remission reflect the coexistence of irritable bowel syndrome (IBS) or subclinical inflammation? The aims of this study were as follows: (i) to prospectively determine the prevalence of IBS symptoms in IBD patients in remission; and (ii) to determine whether IBS symptoms correlate with levels of fecal calprotectin. Remission was defined by physician assessment: Crohn's disease (CD) activity index

ASSESSING THE SLEEP QUALITY AND DEPRESSION-ANXIETY-STRESS IN IRRITABLE BOWEL SYNDROME PATIENTS.

PubMed

Baniasadi, Nadieh; Dehesh, Mohammad Moein; Mohebbi, Elham; Hayatbakhsh Abbasi, Mahdy; Oghabian, Zohreh

2017-01-01

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders with chronic abdominal pain and altered bowel habit without any organic reason. Sleep disorders may be associated to IBS. We aimed to assess sleep disturbances and depression-anxiety-stress in IBS patients. In this analytical cross sectional study from November 2013 to May 2014, A total of 123 IBS patients were recruited by simple random sampling. IBS was diagnosed using ROME-III criteria. Demographic and basic data were driven from all patients then Pittsburg Sleep Quality Index questionnaire was utilized to estimate sleep quality and DASS (depression anxiety stress scale) questionnaire was filled out for depression, anxiety and stress. The mean age of patients was 29±9, where 48 cases (39%) were male. Twelve cases (10%) had a background disease. Types of IBS in patients were included 38% diarrhea, 42% constipation and 20% mixed. From all IBS patients 87 (71%) cases had depression, 97 (79%) patients stress, 94 (76%) patients had anxiety. Seventy-six (62%) cases of IBS patients had poor sleep quality. Simultaneously employing predictors demonstrate that gender, background disease, and type of IBS did not statistically significant. On the other hand, depression (P=0.034, OR=2.35), anxiety (P=0.011, OR=3.022), and stress (P=0.029, OR=2.77) were significantly effect on sleep quality in poor sleepers. Many of IBS patients is suffering from poor sleep quality. It seems that sleep disorder should be considered and treated in this patients.

Exclusion of the GNAS Locus in PHP-Ib Patients With Broad GNAS Methylation Changes: Evidence for an Autosomal Recessive Form of PHP-Ib?

PubMed Central

Fernández-Rebollo, Eduardo; de Nanclares, Guiomar Pérez; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald

2013-01-01

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. PMID:21523828

Prevalence of organic disease at colonoscopy in patients with symptoms compatible with irritable bowel syndrome: cross-sectional survey.

PubMed

Patel, Purav; Bercik, Premysl; Morgan, David G; Bolino, Carolina; Pintos-Sanchez, Maria Ines; Moayyedi, Paul; Ford, Alexander C

2015-07-01

Guidelines for the management of irritable bowel syndrome (IBS) encourage a positive diagnosis, but some evidence suggests organic disease may be missed unless investigations are performed. We examined yield of colonoscopy in a cohort of secondary care patients meeting criteria for IBS. Demographic data, symptoms and findings at colonoscopy were recorded prospectively in consecutive, unselected adults with gastrointestinal (GI) symptoms compatible with IBS according to the Rome III criteria. Prevalence of organic GI disease was compared between those meeting criteria for IBS, according to the presence or absence of co-existent alarm features, and by IBS subtype. A total of 559 patients met Rome III criteria for IBS, of whom 423 reported ≥1 alarm feature and 136 none. There was a significantly higher prevalence of organic GI disease among those reporting alarm features (117 [27.7%]), compared with those without (21 [15.4%]) (p = 0.002). In the latter group of 136 patients, Crohn's disease was the commonest finding (10 [7.4%] subjects), followed by coeliac disease (4 [2.9%] subjects), and microscopic colitis (3 [2.2%] subjects). Regardless of presence or absence of alarm features, patients with constipation-predominant IBS were less likely to exhibit organic GI disease than those with diarrhea-predominant or mixed IBS (12.7% vs. 32.1% and 23.8%, p = 0.006). One in six patients with symptoms compatible with IBS without alarm features in this selected group exhibited organic GI disease following investigation. Assessment of alarm features in a comprehensive history is vital to reduce diagnostic uncertainty that can surround IBS.

Survey of clinical practice for irritable bowel syndrome in East asian countries.

PubMed

Fukudo, Shin; Hahm, Ki-Baik; Zhu, Qi; Sollano, Jose D; Rani, Abdul A; Syam, Ari F; Kachintorn, Udom; Suzuki, Hidekazu; Kamiya, Takeshi; Joh, Takashi; Uchiyama, Kazuhiko; Naito, Yuji; Takahashi, Shin'ichi; Kinoshita, Yoshikazu; Ueno, Fumiaki; Yamagami, Hirokazu; Chan, Francis K L; Fock, Kwong M; Arakawa, Tetsuo

2015-01-01

Sociocultural factors are important because their different effects on the features of irritable bowel syndrome (IBS) between countries will provide clues towards solving this problem. The aims of this study were to depict the clinical realities of IBS in East Asian countries and test the hypothesis that the diagnosis and treatment of IBS differ between countries. Study participants were 251 physicians involved in the clinical practice of IBS at major institutions in Japan, South Korea, China, the Philippines, Indonesia and Singapore. The questionnaire contained 45 questions focused on the clinical practice of IBS. Subjects in Japan, South Korea, China, Indonesia, the Philippines and Singapore accounted for 55.4, 17.9, 8.8, 8.0, 6.4 and 3.6% of the study cohort, respectively. Amongst East Asian physicians, the most important symptom was considered to be abdominal pain by 33.4%, whilst 24.3% regarded alternating diarrhea and constipation to be the most important symptoms. Total colonoscopy and histopathology use showed no difference among countries. Prescriptions given for mild (p < 0.0001), moderate (p < 0.0001), severe (p < 0.0001), intractable (p = 0.002), diarrheal (p < 0.0001) and constipating (p < 0.0001) patients with IBS significantly differed between the countries. Except for several minor points, IBS specialists showed no significant difference in their diagnosis and treatment of IBS when compared to nonspecialists. This survey provided data on the clinical treatment of IBS among East Asian countries. The results supported the hypothesis that the diagnosis and treatment of IBS differs between countries. © 2015 S. Karger AG, Basel.

The microbiome of the oral mucosa in irritable bowel syndrome

PubMed Central

Fourie, Nicolaas H.; Wang, Dan; Abey, Sarah K.; Sherwin, LeeAnne B.; Joseph, Paule V.; Rahim-Williams, Bridgett; Ferguson, Eric G.; Henderson, Wendy A.

2016-01-01

abstract Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions. In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity. The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r2 > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS. PMID:26963804

Which psychological factors exacerbate irritable bowel syndrome? Development of a comprehensive model.

PubMed

van Tilburg, Miranda A L; Palsson, Olafur S; Whitehead, William E

2013-06-01

There is evidence that psychological factors affect the onset, severity and duration of irritable bowel syndrome (IBS). However, it is not clear which psychological factors are the most important and how they interact. The aims of the current study are to identify the most important psychological factors predicting IBS symptom severity and to investigate how these psychological variables are related to each other. Study participants were 286 IBS patients who completed a battery of psychological questionnaires including neuroticism, abuse history, life events, anxiety, somatization and catastrophizing. IBS severity measured by the IBS Severity Scale was the dependent variable. Path analysis was performed to determine the associations among the psychological variables, and IBS severity. Although the hypothesized model showed adequate fit, post hoc model modifications were performed to increase prediction. The final model was significant (Chi(2)=2.2; p=0.82; RMSEA<.05) predicting 36% of variance in IBS severity. Catastrophizing (standardized coefficient (β)=0.33; p<.001) and somatization (β=0.20; p<.001) were the only two psychological variables directly associated with IBS severity. Anxiety had an indirect effect on IBS symptoms through catastrophizing (β=0.80; p<.001); as well as somatization (β=0.37; p<.001). Anxiety, in turn, was predicted by neuroticism (β=0.66; p<.001) and stressful life events (β=0.31; p<.001). While cause-and-effect cannot be determined from these cross-sectional data, the outcomes suggest that the most fruitful approach to curb negative effects of psychological factors on IBS is to reduce catastrophizing and somatization. Copyright © 2013 Elsevier Inc. All rights reserved.

Lactulose Breath Test Gas Production in Childhood IBS Is Associated With Intestinal Transit and Bowel Movement Frequency.

PubMed

Chumpitazi, Bruno P; Weidler, Erica M; Shulman, Robert J

2017-04-01

In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-17 years) with pediatric Rome III IBS completed validated psychosocial questionnaires and a 2-week daily diary capturing pain and stooling characteristics. Stool form determined IBS subtype. Subjects then completed a 3-hour lactulose breath test for measurement of total breath hydrogen and methane production. Carmine red was used to determine whole intestinal transit time. A total of 87 children (mean age 13 ± 2.6 [standard deviation] years) were enrolled, of whom 50 (57.5%) were girls. All children produced hydrogen and 51 (58.6%) produced methane. Hydrogen and methane production did not correlate with either abdominal pain frequency/severity or psychosocial distress. Hydrogen and methane production did not differ significantly by IBS subtype. Methane production correlated positively with whole intestinal transit time (r = 0.31, P < 0.005) and inversely with bowel movement frequency (r = -0.245, P < 0.05). Methane production (threshold 3 ppm) as a marker for identifying IBS-C had a sensitivity of 60% and specificity of 42.9%. Lactulose breath test total methane production may serve as a biomarker of whole intestinal transit time and bowel movement frequency in children with IBS. In children with IBS, lactulose breath test hydrogen and methane production did not, however, correlate with abdominal pain, IBS subtype, or psychosocial distress.

Multiparticle Simulation of Intrabeam Scattering for SuperB

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biagini, M.; Boscolo, M.; Demma, T.

In this communication we present the structure of a multiparticle tracking code to investigate intrabeam scattering effects in low emittance colliders. Simulation results obtained with particular reference to the SuperB parameters are compared with those of conventional IBS theories.and with those of a novel semi-analythical model able to predict IBS effect in terms of emittance growths. Intrabeam scattering (IBS) is associated with multiple small angle scattering events leading to emittance growth. In most electron storage rings, the growth rates arising from IBS are usually much longer than damping times due to synchrotron radiation, and its effect is not observed. However,more » IBS growth rates increase with bunch charge density, and for machines such as SuperB, that operate with high bunch charges and very low emittances, the IBS growth rates can be large enough to observe significant emittance increase. Several formalisms have been developed for calculating IBS growth rates in storage rings, notably those by Piwinski, Bjorken and Mtingwa, and their high energy approximations. Calculations show that IBS should be manageable in both SuperB rings. However these analytical models, based on Gaussian bunch distributions, cannot investigate some interesting aspects of IBS such as its impact during the damping process and its effect on the beam distribution. We developed a multiparticle tracking code, based on the Zenkevich-Bolshakov algorithm, to investigate these effects. In this communication we present the structure of the code and some simulation results obtained with particular reference to the SuperB parameters. Simulation results are compared with those of conventional IBS theories.« less

Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy.

PubMed

Ghoshal, Uday C; Shukla, Ratnakar; Ghoshal, Ujjala

2017-03-15

The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.

Prevalence and risk factors for irritable bowel syndrome in recovered and non-recovered borderline patients over 10 years of prospective follow-up.

PubMed

Niesten, Isabella J M; Karan, Esen; Frankenburg, Frances R; Fitzmaurice, Garrett M; Zanarini, Mary C

2014-02-01

This study examined rates of irritable bowel syndrome (IBS) over 10 years of prospective follow-up among recovered and non-recovered patients with borderline personality disorder (BPD). Subsequently, risk factors for IBS were examined in female BPD patients. As part of the McLean Study of Adult Development, 264 BPD patients were assessed at baseline, and their medical conditions and time-varying predictors of IBS were assessed over five waves of follow-up (from 6-year follow-up to 16-year follow-up). Semi-structured interviews were used to assess both our IBS outcome variable and our baseline and time-varying predictor variables. Rates of IBS were not significantly different between recovered and non-recovered borderline patients when men and women were considered together and when men were considered alone. However, a significant difference in IBS rates was found between recovered and non-recovered female BPD patients, with the latter reporting significantly higher rates. The rates of IBS in women with BPD were found to be significantly predicted by a family history of IBS and a childhood history of verbal, emotional and/or physical abuse. Taken together, the results of this study suggest that both biological/social learning factors and childhood adversity may be risk factors for IBS in women with BPD. Copyright © 2013 John Wiley & Sons, Ltd.

Gender differences in irritable bowel syndrome: The interpersonal connection

PubMed Central

Thakur, Elyse R.; Gurtman, Michael B.; Keefer, Laurie; Brenner, Darren M.; Lackner, Jeffrey M.

2015-01-01

Background While IBS affects women more often than men, the reasons are unclear. Research on the female preponderance of IBS has focused on gender differences in sex-linked biological processes; much less attention has been paid to the role of psychosocial factors. Interpersonal difficulties may be one source of stress that may significantly impact women with IBS. Because of the importance that women attach to relationships, we suspected they would be more reactive to interpersonal stress. Methods 283 (M age = 41 yrs., F = 80%), Rome III-diagnosed IBS patients completed a test battery that included the IBS Symptom Severity Scale, McGill Pain Questionnaire, Inventory of Interpersonal Problems (IIP), Interpersonal Support Evaluation List (social support), Negative Interactions Scale, Brief Symptom Inventory (distress), Beck Depression Inventory, Anxiety Sensitivity Inventory, and IBS-Quality of Life as part of baseline assessment of an NIH trial. Key Results Males scored higher on 2 IIP scales reflecting a hostile-dominant interpersonal pattern, and reported less social support. The quality of relationship problems (more interpersonal difficulties, lower support) correlated with IBS symptom severity as measured mainly by gastroenterologists. Conclusions & Inferences Male, not female, IBS patients reported more interpersonal difficulties. Male patients -- a population for whom little is known -- are characterized by hostile-dominant interpersonal problems. This finding has clinical importance, given that relationship problems may influence MDs’ estimation of IBS symptom severity and undermine the physician-patient relationship. PMID:26265427

Fatty acid components in Asian female patients with irritable bowel syndrome

PubMed Central

Chua, Chian Sem; Huang, Shih-Yi; Cheng, Chiao-Wen; Bai, Chyi-Huey; Hsu, Chien-Yeh; Chiu, Hung-Wen; Hsu, Jung-Lung

2017-01-01

Abstract Abdominal pain is one of the key symptoms of irritable bowel syndrome (IBS). Studies have indicated an increase in the incidence of IBS in Asia. However, yet the pathophysiology of this disease remains unknown. Women are more likely to develop the condition than men, especially the constipation-predominant type. Essential fatty acid (EFA) malnutrition is one of several theories discussing the mechanism of IBS. The authors hypothesized that significant EFA deficiency may cause abdominal pain in patients with IBS. However, because patterns in the oral intake of EFAs differ between cultures, the authors narrowed this study to examine the nutritional status of Asian female patients with IBS The authors investigated Asian female patients with IBS and compared them with a group of healthy controls. Thirty patients with IBS and 39 healthy individuals were included in this study. The participants’ age, height, weight, and waist size were recorded. The 24-item Hamilton Depression Rating Scale was documented. Both erythrocyte and plasma fatty acid content were analyzed through gas–liquid chromatography. The authors found that patients with IBS exhibited significantly higher scores for depression, higher proportions of plasma saturated fatty acids and monounsaturated fatty acids, and lower proportions of docosahexaenoic acid and total omega-3 polyunsaturated fatty acids in plasma are associated with IBS in Asian female patients. Further study is indicated to confirm the causality of this association. PMID:29245334

Constructive thinking, rational intelligence and irritable bowel syndrome

PubMed Central

Rey, Enrique; Ortega, Marta Moreno; Alonso, Monica Olga Garcia; Diaz-Rubio, Manuel

2009-01-01

AIM: To evaluate rational and experiential intelligence in irritable bowel syndrome (IBS) sufferers. METHODS: We recruited 100 subjects with IBS as per Rome II criteria (50 consulters and 50 non-consulters) and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire (including symptom characteristics and medical consultation) and the following tests: rational-intelligence (Wechsler Adult Intelligence Scale, 3rd edition); experiential-intelligence (Constructive Thinking Inventory); personality (NEO personality inventory); psychopathology (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social readjustment rating scale). Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. RESULTS: No differences were found between IBS cases and controls in terms of IQ (102.0 ± 10.8 vs 102.8 ± 12.6), but IBS sufferers scored significantly lower in global constructive thinking (43.7 ± 9.4 vs 49.6 ± 9.7). In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 (0.87-0.97)], without significant OR for total IQ. CONCLUSION: IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS. PMID:19575489

Polyhedron-like inclusion body formation by a mutant nucleopolyhedrovirus expressing the granulin gene from a granulovirus.

PubMed

Zhou, C E; Ko, R; Maeda, S

1998-01-20

The polyhedrin gene in Bombyx mori nucleopolyhedrovirus (BmNPV) was replaced with the granulin gene of Trichoplusia ni granulovirus (TnGV). The substitution was verified by Southern hybridization, and expression of granulin by the mutant virus, BmGran, was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by amino acid sequencing of the predominant protein of BmGran inclusion bodies (IBs). Light and electron microscopy examination of BmGran-infected B. mori and BmN cells revealed large, cuboidal, polyhedron-like IBs in the nucleus and cytoplasm, but granules were not seen. IBs contained small, parallel, electron-dense streaks, which defined the geometric pattern of crystallization. Geometric patterns of nuclear IBs were frequently disrupted by occlusion of polyhedron envelope fragments, resulting in IB instability and fracturing. Virions were not embedded in most of the polyhedron-like IBs, but accumulated with polyhedron envelope fragments. Some virions were coated with matrix protein and were partially wrapped by polyhedron envelope. These results suggested that (1) the amino acid sequence of granulin insufficient for determining IB morphology in TnGV-infected cells, and TnGV may have genes, not present in BmNPV, that control granule formation, and (2) interactions among the virion, the IB envelope, and the matrix protein may be important in virion occlusion and IB morphology and stability.

A Novel RNA Polymerase I Transcription Initiation Factor, TIF-IE, Commits rRNA Genes by Interaction with TIF-IB, Not by DNA Binding

PubMed Central

Al-Khouri, Anna Maria; Paule, Marvin R.

2002-01-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE. PMID:11784852

A novel RNA polymerase I transcription initiation factor, TIF-IE, commits rRNA genes by interaction with TIF-IB, not by DNA binding.

PubMed

Al-Khouri, Anna Maria; Paule, Marvin R

2002-02-01

In the small, free-living amoeba Acanthamoeba castellanii, rRNA transcription requires, in addition to RNA polymerase I, a single DNA-binding factor, transcription initiation factor IB (TIF-IB). TIF-IB is a multimeric protein that contains TATA-binding protein (TBP) and four TBP-associated factors that are specific for polymerase I transcription. TIF-IB is required for accurate and promoter-specific initiation of rRNA transcription, recruiting and positioning the polymerase on the start site by protein-protein interaction. In A. castellanii, partially purified TIF-IB can form a persistent complex with the ribosomal DNA (rDNA) promoter while homogeneous TIF-IB cannot. An additional factor, TIF-IE, is required along with homogeneous TIF-IB for the formation of a stable complex on the rDNA core promoter. We show that TIF-IE by itself, however, does not bind to the rDNA promoter and thus differs in its mechanism from the upstream binding factor and upstream activating factor, which carry out similar complex-stabilizing functions in vertebrates and yeast, respectively. In addition to its presence in impure TIF-IB, TIF-IE is found in highly purified fractions of polymerase I, with which it associates. Renaturation of polypeptides excised from sodium dodecyl sulfate-polyacrylamide gels showed that a 141-kDa polypeptide possesses all the known activities of TIF-IE.

Carbon footprint of construction using industrialised building system

NASA Astrophysics Data System (ADS)

Lim, P. Y.; Yahya, K.; Aminudin, E.; Zakaria, R.; Haron, Z.; Mohamad Zin, R.; Redzuan, A. A. H.

2017-11-01

Industrialised Building System (IBS) is more sustainable to the environment as compared to the conventional construction methods. However, the construction industry in Malaysia has low acceptance towards IBS due to the resistance to change and also lack of awareness towards sustainability development. Therefore, it is important to study the amount carbon footprint produced by IBS during its manufacturing and construction stage, and also the amount of carbon footprint produced by one meter square of gross floor area of IBS construction using Life Cycle Assessment (LCA) to ease future research through the comparison of the carbon footprint of IBS with the conventional building system. As a result, a case study on a residential type of construction in the vicinity of Johor Bahru, Malaysia was carried out to obtain the necessary data and result. From the data analysis, the amount of greenhouse gases (GHG) for a residential type IBS construction based on the raw materials and resources involved to manufacture and construct IBS components is 0.127 tonnes fossil CO2Eq per meter square. Raw material that contributed to the most amount of carbon footprint is Ordinary Portland Cement (OPC), followed by steel bars, autoclaved aerated blocks and diesel. The LCA data acquired will be very useful in implementing IBS in the residential type construction. As a result, the awareness towards sustainable construction using IBS can be improved.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

PubMed Central

de Bortoli, Nicola; Martinucci, Irene; Bellini, Massimo; Savarino, Edoardo; Savarino, Vincenzo; Blandizzi, Corrado; Marchi, Santino

2013-01-01

Several studies indicate a significant degree of overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both functional heartburn (FH) and IBS are functional digestive disorders that may occur in the same patients. However, data establishing a solid link between FH and IBS are lacking, mainly because the clinical definition of FH has undergone substantial changes over the years. The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS. In particular, several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH (as defined by the Rome III criteria) from GERD via pathophysiological investigations. Independent of these critical issues, there is preliminary evidence supporting a significant degree of FH-IBS overlap. This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications, particularly to distinguish FH from GERD. This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders. PMID:24124323

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome.

PubMed

de Bortoli, Nicola; Martinucci, Irene; Bellini, Massimo; Savarino, Edoardo; Savarino, Vincenzo; Blandizzi, Corrado; Marchi, Santino

2013-09-21

Several studies indicate a significant degree of overlap between irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD). Likewise, both functional heartburn (FH) and IBS are functional digestive disorders that may occur in the same patients. However, data establishing a solid link between FH and IBS are lacking, mainly because the clinical definition of FH has undergone substantial changes over the years. The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS. In particular, several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH (as defined by the Rome III criteria) from GERD via pathophysiological investigations. Independent of these critical issues, there is preliminary evidence supporting a significant degree of FH-IBS overlap. This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications, particularly to distinguish FH from GERD. This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

The Role of Genetics in IBS

PubMed Central

Saito, Yuri A.

2011-01-01

IBS is a common disorder that has been shown to aggregate in families, to affect multiple generations, but not in a manner consistent with a major Mendelian effect. Relatives of an individual with IBS are two to three times as likely to have IBS, with both genders being affected. The estimated genetic liability ranges between 1–20%, with heritability estimates ranging between 0–57%. Although the role of childhood events such as nasogastric tube placement, poor nutrition, abuse, and other stressors have been clearly associated with IBS, these factors have not been studied in families and are unlikely to completely explain the clustering of bowel dysfunction observed in family studies. Furthermore, the familial clustering of IBS does not appear to be explained by psychological traits, based on family studies as well as candidate gene studies of functional variants associated with other psychiatric disorders. To date, over a hundred genetic variants in over 60 genes from various pathways have been studied in a number of candidate gene studies with several positive associations reported. These findings suggest that there may be distinct, as well as shared, molecular underpinnings for IBS and its subtypes. Much new and confirmatory work remains to be performed to elucidate the role of specific genetic variants in IBS development, as well as the specific ways the genes and environment interact to result in IBS susceptibility. PMID:21333900

Possible Involvement of Avoidant Attachment Style in the Relations Between Adult IBS and Reported Separation Anxiety in Childhood.

PubMed

Ben-Israel, Yuval; Shadach, Eran; Levy, Sigal; Sperber, Ami; Aizenberg, Dov; Niv, Yaron; Dickman, Ram

2016-12-01

Irritable bowel syndrome (IBS) in adults as well as separation anxiety disorder (SAD) and recurrent abdominal pain (RAP) in childhood are associated with anxiety and somatization. Our aim was to examine possible associations between IBS in adulthood and SAD in childhood. Patients with IBS and healthy subjects completed a demographic questionnaire, the Separation Anxiety Symptom Inventory (SASI), the Somatization Subscale of Symptom Checklist-90-R (SCL-90-R), the Attachment Style Questionnaire, and a retrospective self-report questionnaire regarding RAP. Compared with controls, patients with IBS were characterized by an avoidant attachment style and scored higher on the SCL-90-R scale regarding the tendency to somatization (25.35 ± 7.47 versus16.50 ± 4.40, p < 0.001). More patients with IBS (25% versus 7.5%) reported RAP in childhood, but contrary to prediction, also had significantly lower SASI scores. Adults with IBS were characterized by somatization, insecure attachment style and recalled higher rates of RAP and surprisingly less symptoms of SAD in childhood. Based on these results, an etiological model for IBS is suggested, in which an avoidant attachment style and a tendency to somatization play an important role in the development of IBS. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

International Education, Values and Attitudes: A Critical Analysis of the International Baccalaureate (IB) Learner Profile

ERIC Educational Resources Information Center

Wells, John

2011-01-01

This article provides a critical review of the way that the International Baccalaureate (IB) promotes international education and international mindedness through the IB Learner Profile. While discussing theories of values and attitudes, and the teaching of values and theories of value acquisition, the paucity of such topics in IB texts is noted.…

Why Offer the International Baccalaureate Middle Years Programme? A Comparison between Schools in Asia-Pacific and Other Regions

ERIC Educational Resources Information Center

Wright, Ewan; Lee, Moosung; Tang, Hayes; Chak Pong Tsui, Gordon

2016-01-01

The International Baccalaureate (IB) has become a powerful educational brand by developing a reputation for combining progressive approaches with academic rigour. This can be identified by the growing number of schools adopting IB programmes globally and especially in the IB Asia-Pacific region. As part of this trend, the IB Middle Years Programme…

The Academic Impact of Enrollment in International Baccalaureate Diploma Programs: A Case Study of Chicago Public Schools

ERIC Educational Resources Information Center

Saavedra, Anna Rosefsky

2014-01-01

Background: In schools accredited as "IB World Schools" by the International Baccalaureate Organization (IBO), teachers use IB curriculum and pedagogy to teach a range of courses that are intended to prepare IB-enrolled students for college. Over the past 18 years, the number of U.S. schools that implement IB programs has increased…

Bacterial Overgrowth and Irritable Bowel Syndrome: Unifying Hypothesis or a Spurious Consequence of Proton Pump Inhibitors?

PubMed Central

Spiegel, Brennan M.R.; Chey, William D.; Chang, Lin

2010-01-01

Some studies indicate that small intestinal bacterial overgrowth (SIBO), as measured by hydrogen breath tests (HBT), is more prevalent in patients with irritable bowel syndrome (IBS) vs. matched controls without IBS. Although the data are conflicting, this observation has led to the hypothesis that SIBO may be a primary cause of IBS. Yet, it remains unclear whether SIBO is truly fundamental to the pathophysiology of IBS, or is instead a mere epiphenomenon or bystander of something else altogether. We hypothesize that SIBO might be a byproduct of the disproportionate use of proton pump inhibitors (PPIs) in IBS, as follows: (1) IBS patients are more likely than controls to receive PPI therapy; (2) PPI therapy may promote varying forms of SIBO by eliminating gastric acid; and (3) existing studies linking SIBO to IBS have not adjusted for or excluded the use of PPI therapy. When linked together, these premises form the basis for a simple and testable hypothesis: the relationship between SIBO and IBS may be confounded by PPIs. Our article explores these premises, lays out the argument supporting this “PPI hypothesis,” discusses potential implications, and outlines next steps to further investigate this possibility. PMID:19086951

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

PubMed

Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

2008-12-01

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

Combined Interactions with I1-, I2-Imidazoline Binding Sites and α2-Adrenoceptors To Manage Opioid Addiction

PubMed Central

2016-01-01

Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α2-adrenoceptors (α2-ARs) and I1- and I2-imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α2-ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I1-/I2-IBS or I1-/I2-IBS/α2-ARs. The compounds showing the highest affinities for I1-/I2-IBS or I1-/I2-IBS/α2-ARs have been selected for their in vivo evaluation on opiate withdrawal syndrome. Interestingly, 9, displaying I1-/I2-IBS/α2-ARs interaction profile, appears more effective in reducing expression and acquisition of morphine dependence and, therefore, might be considered a promising tool in managing opioid addiction. PMID:27774136

Modeling and characterization of different channels based on human body communication.

PubMed

Jingzhen Li; Zedong Nie; Yuhang Liu; Lei Wang

2017-07-01

Human body communication (HBC), which uses the human body as a transmission medium for electrical signals, provides a prospective communication solution for body sensor networks (BSNs). In this paper, an inhomogeneous model which includes the tissue layers of skin, fat, and muscle is proposed to study the propagation characteristics of different HBC channels. Specifically, the HBC channels, namely, the on-body to on-body (OB-OB)channel, on-body to in-body (OB-IB) channel, in-body to on-body (IB-OB) channel, and in-body to in-body (IB-IB)channel, are studied over different frequencies (from 1MHz to 100MHz) through numerical simulations with finite-difference time-domain (FDTD) method. The results show that the gain of OB-IB channel and IB-OB channel is almost the same. The gain of IB-IB channel is greater than other channels in the frequency range 1MHz to 70MHz. In addition, the gain of all channels is associated with the channel length and communication frequency. The simulations are verified by experimental measurements in a porcine tissue sample. The results show that the simulations are in agreement with the measurements.

Probiotic Fermented Milk Containing Dietary Fiber Has Additive Effects in IBS with Constipation Compared to Plain Probiotic Fermented Milk.

PubMed

Choi, Sung Chul; Kim, Beom Jin; Rhee, Poong-Lyul; Chang, Dong Kyung; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Kim, Soon Im; Han, Young Sil; Sim, Ki Hyeon; Park, Seok Nam

2011-03-01

Although controversial, probiotics and dietary fiber are commonly used for patients with irritable bowel syndrome (IBS). We evaluated the effects of multistrain probiotics on the symptoms of IBS to determine whether the addition of dietary fi ber had an additive effect on constipation-predominant IBS. A total of 142 participants who met the Rome III criteria were recruited and randomized into a control group or a test group. Participants in the control group received multistrain probiotic fermented milk with Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacterium infantis; the participants in the test group received the same probiotic fermented milk mixed with dietary fi ber such as sea tangle extracts, radish extracts and glasswort extracts. The patients were treated for four weeks. Most of the symptoms of IBS, with the exception of fl atulence, stool consistency, and frequency of defecation, signifi cantly improved in both groups. In the analysis of IBS subtypes, especially constipation-predominant IBS, the frequency and duration of defecation and straining at stool were improved more in the test group than in the control group. Dietary fiber had additive benefits for the symptoms of constipation, especially in constipation-predominant IBS.

Therapeutic Potential of Zataria multiflora Boiss in Treatment of Irritable Bowel Syndrome (IBS).

PubMed

Mahboubi, Mohaddese

2018-01-15

Irritable Bowel syndrome (IBS), the most common chronic functional gastrointestinal disorder, is categorized as IBS-C and IBS-D, which are equivalent to Ghoolenj Rihi and Maghs Rihi in Iranian traditional medicine. One of the main applications of Zataria multiflora Boiss in traditional medicine is its efficacy in the gastrointestinal tract with symptoms such as IBS. The aim of this study was to evaluate the efficacy of Zataria multiflora essential oil in management of IBS. We used all the accessible references (electronic and published books, theses, and reports) to write this article. The results of our investigation show that the majority of gas chromatography-mass spectrometry (GC-MS) analyses exhibited carvacrol and thymol as the main components of Zataria multiflora essential oil, and 60 drops oral daily dose of Z. multiflora essential oil (2%) can relieve the symptoms of IBS without any adverse effects. The pharmacological studies confirmed the analgesic, anti-inflammatory, antispasm and antiulcer effects of Z. multiflora essential oils and main components. According to the results of studies, oral Z. multiflora essential oil (2%) is a good candidate for management of IBS, but more studies are required to better understand its efficacies.

Implications of Pharmacogenomics to the Management of IBS.

PubMed

Camilleri, Michael

2018-04-27

The objectives are to review the role of pharmacogenomics in drug metabolism of medications typically used in patients with irritable bowel syndrome (IBS) focusing predominantly on cytochrome P450 metabolism. Other aims are to provide examples of genetic variation of receptors or intermediary pathways that are targets for IBS drugs and to critically appraise the situations where precision medicine is impacting health in IBS. Pharmacogenomics impacts both pharmacokinetics and pharmacodynamics. Although large clinical trials have not incorporated testing for genetic variations that could impact the efficacy of medications in IBS, there are therapeutic advantages to inclusion of pharmacogenomics testing for individual patients, as has been demonstrated particularly in the treatment with central neuromodulators in psychiatry practice. Clinical practice in IBS is moving in the same direction with the aid of commercially available tests focused on drug metabolism. Specific mechanisms leading to pathophysiology of IBS are still poorly characterized, relative to diseases such as cancer and inflammatory bowel disease, and, therefore, pharmacogenomics related to drug pharmacodynamics is still in its infancy and requires extensive future research. With increased attention to pharmacogenomics affecting drug metabolism, it is anticipated that pharmacogenomics will impact care of IBS. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Paternal uniparental isodisomy of the entire chromosome 20 as a molecular cause of pseudohypoparathyroidism type Ib (PHP-Ib).

PubMed

Bastepe, Murat; Altug-Teber, Ozge; Agarwal, Chhavi; Oberfield, Sharon E; Bonin, Michael; Jüppner, Harald

2011-03-01

Pseudohypoparathyoridism type Ib (PHP-Ib) typically defines the presence of end-organ resistance to parathyroid hormone in the absence of Albright's hereditary osteodystrophy. Patients affected by this disorder present with imprinting defects in the complex GNAS locus. Microdeletions within STX16 or GNAS have been identified in familial cases with PHP-Ib, but the molecular cause of the GNAS imprinting defects in sporadic PHP-Ib cases remains poorly defined. We now report a case with sporadic PHP-Ib for whom a SNPlex analysis revealed loss of the maternal GNAS allele. Further analysis of the entire genome with a 100K SNP chip identified a paternal uniparental isodisomy affecting the entire chromosome 20 without evidence for another chromosomal abnormality. Our findings explain the observed GNAS methylation changes and the patient's hormone resistance, and furthermore suggest that chromosome 20 harbors, besides GNAS, no additional imprinted region that contributes to the clinical and laboratory phenotype. Copyright © 2010 Elsevier Inc. All rights reserved.

Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome.

PubMed

Durbán, Ana; Abellán, Juan J; Jiménez-Hernández, Nuria; Salgado, Patricia; Ponce, Marta; Ponce, Julio; Garrigues, Vicente; Latorre, Amparo; Moya, Andrés

2012-04-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in western countries. Previous studies on IBS, mostly based on faecal samples, suggest alterations in the intestinal microbiota. However, no consensus has been reached regarding the association between specific bacteria and IBS. We explore the alterations of intestinal bacterial communities in IBS using massive sequencing of amplified 16S rRNA genes. Mucosal biopsies of the ascending and descending colon and faeces from 16 IBS patients and 9 healthy controls were analysed. Strong inter-individual variation was observed in the composition of the bacterial communities in both patients and controls. These communities showed less diversity in IBS cases. There were larger differences in the microbiota composition between biopsies and faeces than between patients and controls. We found a few over-represented and under-represented taxa in IBS cases with respect to controls. The detected alterations varied by site, with no changes being consistent across sample types. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Irritable Bowel Syndrome: Clinical Manifestations, Dietary Influences, and Management

PubMed Central

Ikechi, Ronald; Fischer, Bradford D.; DeSipio, Joshua; Phadtare, Sangita

2017-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by symptoms of chronic abdominal pain and altered bowel habits in the absence of an overtly identifiable cause. It is the most commonly diagnosed functional gastrointestinal disorder, accounting for about one third of gastroenterology visits. It generally presents as a complex of symptoms, including psychological dysfunction. Hypersensitivity to certain foods, especially foods that contain high amounts of fructose, plays a role in the pathophysiology of IBS. Elevated consumption of high-fructose corn syrup (HFCS) has been discussed in this aspect. The treatment options for IBS are challenging and varied. In addition to dietary restrictions for HFCS-induced IBS, such as low-FODMAP (Fermentable Oligosaccharides, Disaccharide, Monosaccharides, and Polyols) diets, existing drug therapies are administered based on the predominant symptoms and IBS-subtype. Patients with IBS are likely to suffer from issues, such as anxiety, depression, and post-traumatic-stress disorder. Biopsychosocial factors particularly socioeconomic status, sex, and race should, thus, be considered for diagnostic evaluation of patients with IBS. PMID:28445436

Total costs of IBS: employer and managed care perspective.

PubMed

Cash, Brooks; Sullivan, Sean; Barghout, Victoria

2005-04-01

Irritable bowel syndrome (IBS) is a common gastrointestinal motility disorder that typically affects persons of working age and is costly to employers. The financial burden attributable to the direct (use of healthcare resources) and indirect (missed days from work [absenteeism] and loss of productivity while at work [presenteeism]) costs of IBS is similar to that of other common long-term medical disorders, such as asthma, migraine, hypertension, and congestive heart failure. The symptoms of IBS are significantly bothersome and place a substantial burden on the personal and working lives of patients. As with other long-term medical conditions that have a significant impact on productivity, directed efforts by employers can address IBS in the workplace and thereby potentially decrease its impact. In this article, the symptoms of IBS and its impact on patients and on society as a whole are discussed; options are outlined by which employers can help reduce the total costs of IBS, including lost productivity (both absenteeism and presenteeism), in the workplace.

Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin.

PubMed

Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko

2018-05-20

Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca 2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca 2+ . Ib induced the extracellular release of ASMase in the presence of Ca 2+ . ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells.

Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin

PubMed Central

Nagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko

2018-01-01

Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca2+. Ib induced the extracellular release of ASMase in the presence of Ca2+. ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells. PMID:29783772

Inflammation in irritable bowel syndrome: Myth or new treatment target?

PubMed Central

Sinagra, Emanuele; Pompei, Giancarlo; Tomasello, Giovanni; Cappello, Francesco; Morreale, Gaetano Cristian; Amvrosiadis, Georgios; Rossi, Francesca; Lo Monte, Attilio Ignazio; Rizzo, Aroldo Gabriele; Raimondo, Dario

2016-01-01

Low-grade intestinal inflammation plays a key role in the pathophysiology of irritable bowel syndrome (IBS), and this role is likely to be multifactorial. The aim of this review was to summarize the evidence on the spectrum of mucosal inflammation in IBS, highlighting the relationship of this inflammation to the pathophysiology of IBS and its connection to clinical practice. We carried out a bibliographic search in Medline and the Cochrane Library for the period of January 1966 to December 2014, focusing on publications describing an interaction between inflammation and IBS. Several evidences demonstrate microscopic and molecular abnormalities in IBS patients. Understanding the mechanisms underlying low-grade inflammation in IBS may help to design clinical trials to test the efficacy and safety of drugs that target this pathophysiologic mechanism. PMID:26900287

Equilibrium and Balanced Growth of a Vegetative Crop

PubMed Central

SEGINER, IDO

2004-01-01

• Model A previously developed dynamic model, NICOLET, designed to predict growth and nitrate content of a lettuce crop, is subjected to (virtual) constant environmental conditions. For every combination of shoot and root environment, the cell sap, here assumed to reside in the ‘vacuole’ compartment, equilibrates at a certain nitrate concentration level. This, in turn, defines the composition of the crop in terms of carbon and nitrogen content in each of the three compartments of the model. Growth under constant environmental conditions is defined as ‘equilibrium’ growth (EG). If, in addition, the source strengths of carbon and nitrogen balance each other, as well as the sink strength of the growing crop, the growth is said to be ‘balanced’ (BG). • Results It is shown that the range of BG approximately coincides with the range of ‘mild’ nitrogen stress, where reduction in nitrogen availability results in a mild reduction of relative growth rate (RGR). Beyond a certain low nitrate concentration in the cell sap, the N‐stress becomes ‘severe’ and the loss of growth increases considerably. • Conclusions The model is able to mimic the five central observations of many constant‐environment growth‐chamber experiments, namely (1) the initial exponential growth and later decline of the RGR, (2) the constant chemical composition, (3) the equality of the RGR and the relative nutrient supply rate (RNR), (4) the proportionality between the N : C ratio and the RNR, and (5) the proportionality between the water content and the reduced N content. Guidelines for the optimal combination of the shoot and root environments are suggested. PMID:14681082

Cadmium inhibits the protein degradation of Sml1 by inhibiting the phosphorylation of Sml1 in Saccharomyces cerevisiae

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baek, In-Joon; Kang, Hyun-Jun; Chang, Miwha

Highlights: Black-Right-Pointing-Pointer Cd inhibits Sml1-p formation. Black-Right-Pointing-Pointer Cd affects cell cycle. Black-Right-Pointing-Pointer Cd inhibits Sml1 ubiquitination. -- Abstract: Cadmium is a toxic metal, and the mechanism of cadmium toxicity in living organisms has been well studied. Here, we used Saccharomyces cerevisiae as a model system to examine the detailed molecular mechanism of cell growth defects caused by cadmium. Using a plate assay of a yeast deletion mutant collection, we found that deletion of SML1, which encodes an inhibitor of Rnr1, resulted in cadmium resistance. Sml1 protein levels increased when cells were treated with cadmium, even though the mRNA levels ofmore » SML1 remained unchanged. Using northern and western blot analyses, we found that cadmium inhibited Sml1 degradation by inhibiting Sml1 phosphorylation. Sml1 protein levels increased when cells were treated with cadmium due to disruption of the dependent protein degradation pathway. Furthermore, cadmium promoted cell cycle progression into the G2 phase. The same result was obtained using cells in which SML1 was overexpressed. Deletion of SML1 delayed cell cycle progression. These results are consistent with Sml1 accumulation and with growth defects caused by cadmium stress. Interestingly, although cadmium treatment led to increase Sml1 levels, intracellular dNTP levels also increased because of Rnr3 upregulation due to cadmium stress. Taken together, these results suggest that cadmium specifically affects the phosphorylation of Sml1 and that Sml1 accumulates in cells.« less

Bacterial Signaling Nucleotides Inhibit Yeast Cell Growth by Impacting Mitochondrial and Other Specifically Eukaryotic Functions

PubMed Central

Vergnano, Marta; Wan, Chris

2017-01-01

ABSTRACT We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP. Mutations compromising mitochondrial function and chromatin remodeling show negative epistatic interactions with all three nucleotides. In contrast, certain mutations that cause defects in chromatin modification and ribosomal protein function show positive epistasis, alleviating growth inhibition by at least two of the three nucleotides. Uniquely, cdiGMP is lethal both to cells growing by respiration on acetate and to obligately fermentative petite mutants. cdiGMP is also synthetically lethal with the ribonucleotide reductase (RNR) inhibitor hydroxyurea. Heterologous expression of the human ppGpp hydrolase Mesh1p prevented the accumulation of ppGpp in the engineered yeast and restored cell growth. Extensive in vivo interactions between bacterial signaling molecules and eukaryotic gene function occur, resulting in outcomes ranging from growth inhibition to death. cdiGMP functions through a mechanism that must be compensated by unhindered RNR activity or by functionally competent mitochondria. Mesh1p may be required for abrogating the damaging effects of ppGpp in human cells subjected to bacterial infection. PMID:28743817

Multisystemic Therapy and Functional Family Therapy Compared on their Effectiveness Using the Propensity Score Method.

PubMed

Eeren, Hester V; Goossens, Lucas M A; Scholte, Ron H J; Busschbach, Jan J V; van der Rijken, Rachel E A

2018-01-09

Multisystemic Therapy (MST) and Functional Family Therapy (FFT) have overlapping target populations and treatment goals. In this study, these interventions were compared on their effectiveness using a quasi-experimental design. Between October, 2009 and June, 2014, outcome data were collected from 697 adolescents (mean age 15.3 (SD 1.48), 61.9% male) assigned to either MST or FFT (422 MST; 275 FFT). Data were gathered during Routine Outcome Monitoring. The primary outcome was externalizing problem behavior (Child Behavior Checklist and Youth Self Report). Secondary outcomes were the proportion of adolescents living at home, engaged in school or work, and who lacked police contact during treatment. Because of the non-random assignment, a propensity score method was used to control for observed pre-treatment differences. Because the risk-need-responsivity (RNR) model guided treatment assignment, effectiveness was also estimated in youth with and without a court order as an indicator of their risk level. Looking at the whole sample, no difference in effect was found with regard to externalizing problems. For adolescents without a court order, effects on externalizing problems were larger after MST. Because many more adolescents with a court order were assigned to MST compared to FFT, the propensity score method could not balance the treatment groups in this subsample. In conclusion, few differences between MST and FFT were found. In line with the RNR model, higher risk adolescents were assigned to the more intensive treatment, namely MST. In the group with lower risk adolescents, this more intensive treatment was more effective in reducing externalizing problems.

A Quasi-Experimental Evaluation of High-Intensity Inpatient Sex Offender Treatment in the Netherlands.

PubMed

Smid, Wineke J; Kamphuis, Jan H; Wever, Edwin C; Van Beek, Daan J

2016-08-01

The current study quasi-experimentally assessed the outcome of high-intensity inpatient sex offender treatment in the Netherlands in terms of sexual and violent (including sexual) recidivism. It was hypothesized that treated sex offenders would show lower recidivism rates than untreated sex offenders of the same risk level. In line with the risk principle of the Risk, Need, Responsivity (RNR) model, we predicted that this would especially hold true for offenders of higher risk levels. The study sample consisted of 25% of all convicted Dutch sex offenders not referred to any form of treatment and discharged from prison between 1996 and 2002, and all convicted Dutch sex offenders referred to inpatient treatment who were discharged between 1996 and 2002. Static-99R risk levels of these 266 offenders were retrospectively assessed and survival curves regarding sexual and violent (including sexual) recidivism were compared between treated and untreated offenders, controlling for level of risk. Mean follow-up was 148.0 months (SD = 29.6) and the base rate of sexual recidivism was 15.0% and 38.4% for violent (including sexual) recidivism. Cox regression survival analyses showed marginally significant lower failure rates regarding sexual recidivism for treated high-risk offenders only, and significantly lower failure rates regarding violent (including sexual recidivism) for treated sex offenders of moderate-high and high-risk levels. No treatment effects for low and low-moderate risk offenders were found. Results underscore the risk principle of the RNR model: Treatment is more effective when its dosage is attuned to risk level. © The Author(s) 2014.

A compromised yeast RNA polymerase II enhances UV sensitivity in the absence of global genome nucleotide excision repair.

PubMed

Wong, J M; Ingles, C J

2001-02-01

Nucleotide excision repair is the major pathway responsible for removing UV-induced DNA damage, and is therefore essential for cell survival following exposure to UV radiation. In this report, we have assessed the contributions of some components of the RNA polymerase II (Pol II) transcription machinery to UV resistance in Saccharomyces cerevisiae. Deletion of the gene encoding the Pol II elongation factor TFIIS (SII) resulted in enhanced UV sensitivity, but only in the absence of global genome repair dependent on the RAD7 and RAD16 genes, a result seen previously with deletions of RAD26 and RAD28, yeast homologs of the human Cockayne syndrome genes CSB and CSA, respectively. A RAD7/16-dependent reduction in survival after UV irradiation was also seen in the presence of mutations in RNA Pol II that confer a defect in its response to SII, as well as with other mutations which reside in regions of the largest subunit of Pol II not involved in SII interactions. Indeed, an increase in UV sensitivity was achieved by simply decreasing the steadystate level of RNA Pol II. Truncation of the C-terminal domain and other RNA Pol II mutations conferred sensitivity to the ribonucleotide reductase inhibitor hydroxyurea and induction of RNR1 and RNR2 mRNAs after UV irradiation was attenuated in these mutant cells. That UV sensitivity can be a consequence of mutations in the RNA Pol II machinery in yeast cells suggests that alterations in transcriptional programs could underlie some of the pathophysiological defects seen in the human disease Cockayne syndrome.

Determination of triapine, a ribonucleotide reductase inhibitor, in human plasma by liquid chromatography tandem mass spectrometry.

PubMed

Feng, Ye; Kunos, Charles A; Xu, Yan

2015-09-01

Triapine is an inhibitor of ribonucleotide reductase (RNR). Studies have shown that triapine significantly decreases the activity of RNR and enhanced the radiation-mediated cytotoxicity in cervical and colon cancer. In this work, we have developed and validated a selective and sensitive LC-MS/MS method for the determination of triapine in human plasma. In this method, 2-[(3-fluoro-2-pyridinyl)methylene] hydrazinecarbothioamide (NSC 266749) was used as the internal standard (IS); plasma samples were prepared by deproteinization with acetonitrile; tripaine and the IS were separated on a Waters Xbridge Shield RP18 column (3.5 µm; 2.1 × 50 mm) using a mobile phase containing 25.0% methanol and 75.0% ammonium bicarbonate buffer (10.0 mM, pH 8.50; v/v); column eluate was monitored by positive turbo-ionspray tandem mass spectrometry; and quantitation of triapine was carried out in multiple-reaction-monitoring mode. The method developed had a linear calibration range of 0.250-50.0 ng/mL with correlation coefficient of 0.999 for triapine in human plasma. The IS-normalized recovery and the IS-normalized matrix factor of triapine were 101-104% and 0.89-1.05, respectively. The accuracy expressed as percentage error and precision expressed as coefficient of variation were ≤±6 and ≤8%, respectively. The validated LC-MS/MS method was applied to the measurement of triapine in patient samples from a phase I clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.

Saturn Apollo Program

NASA Image and Video Library

1965-01-01

S-IB-200D, a dynamic test version of the Saturn IB launch vehicle's first stage (S-IB), makes its way to the Marshall Space Flight Center (MSFC) East Test Area on January 4, 1965. Test Laboratory persornel assembled a complete Saturn IB to test the structural soundness of the launch vehicle in the Dynamic Test Stand. Developed by the MSFC as an interim vehicle in MSFC's "building block" approach to the Saturn rocket development, the Saturn IB utilized Saturn I technology to further develop and refine the larger boosters and the Apollo spacecraft capabilities required for the manned lunar missions.

Rome III survey of irritable bowel syndrome among ethnic Malays

PubMed Central

Lee, Yeong Yeh; Waid, Anuar; Tan, Huck Joo; Chua, Andrew Seng Boon; Whitehead, William E

2012-01-01

AIM: To survey irritable bowel syndrome (IBS) using Rome III criteria among Malays from the north-eastern region of Peninsular Malaysia. METHODS: A previously validated Malay language Rome III IBS diagnostic questionnaire was used in the current study. A prospective sample of 232 Malay subjects (80% power) was initially screened. Using a stratified random sampling strategy, a total of 221 Malay subjects (112 subjects in a “full time job” and 109 subjects in “no full time job”) were recruited. Subjects were visitors (friends and relatives) within the hospital compound and were representative of the local community. Red flags and psychosocial alarm symptoms were also assessed in the current study using previously translated and validated questionnaires. Subjects with IBS were sub-typed into constipation-predominant, diarrhea-predominant, mixed type and un-subtyped. Univariable and multivariable analyses were used to test for association between socioeconomic factors and presence of red flags and psychosocial alarm features among the Malays with IBS. RESULTS: IBS was present in 10.9% (24/221), red flags in 22.2% (49/221) and psychosocial alarm features in 9.0% (20/221). Red flags were more commonly reported in subjects with IBS (83.3%) than psychosocial alarm features (20.8%, P < 0.001). Subjects with IBS were older (mean age 41.4 years vs 36.9 years, P = 0.08), but no difference in gender was noted (P = 0.4). Using univariable analysis, IBS was significantly associated with a tertiary education, high individual income above RM1000, married status, ex-smoker and the presence of red flags (all P < 0.05). In multiple logistic regression analysis, only the presence of red flags was significantly associated with IBS (odds ratio: 0.02, 95%CI: 0.004-0.1, P < 0.001). The commonest IBS sub-type was mixed type (58.3%), followed by constipation-predominant (20.8%), diarrhea-predominant (16.7%) and un-subtyped (4.2%). Four of 13 Malay females (30.8%) with IBS also had menstrual pain. Most subjects with IBS had at least one red flag (70.8%), 12.5% had two red flags and 16.7% with no red flags. The commonest red flag was a bowel habit change in subjects > 50 years old and this was reported by 16.7% of subjects with IBS. CONCLUSION: Using the Rome III criteria, IBS was common among ethnic Malays from the north-eastern region of Peninsular Malaysia. PMID:23197894

Prevalence, Risk Factors, and Outcomes of Irritable Bowel Syndrome After Infectious Enteritis: a Systematic Review and Meta-analysis

PubMed Central

Klem, Fabiane; Wadhwa, Akhilesh; Prokop, Larry; Sundt, Wendy; Farrugia, Gianrico; Camilleri, Michael; Singh, Siddharth; Grover, Madhusudan

2017-01-01

Background & Aims Foodborne illness affects 15% of the United States population each year and is a risk factor for irritable bowel syndrome (IBS). We evaluated risk of, risk factors for, and outcomes of IBS after infectious enteritis Methods We performed a systematic review of electronic databases from 1994 through August 31, 2015 to identify cohort studies of the prevalence of IBS 3 months or more after infectious enteritis. We used random effects meta-analysis to calculate the summary point prevalence of IBS after infectious enteritis, as well as relative risk (compared to individuals without infectious enteritis) and host- and enteritis-related risk factors. Results We identified 45 studies, comprising 21,421 individuals with enteritis, followed for 3 months–10 years for development of IBS. The pooled prevalence of IBS at 12 months after infectious enteritis was 10.1% (95% CI, 7.2–14.1) and at more than 12 months after infectious enteritis was 14.5% (95% CI, 7.7–25.5). Risk of IBS was 4.2-fold higher in patients who had infectious enteritis in the past 12 months than in individuals in those who had not (95% CI, 3.1–5.7); risk of IBS was 2.3-fold higher in individuals who had infectious enteritis longer than 12 months ago than in individuals who had not (95% CI, 1.8–3.0). Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused bacterial infection, 13.8% developed IBS. Risk of IBS was significantly increased in women (odds ratio [OR], 2.2; 95% CI, 1.6–3.1) and with antibiotic exposure (OR, 1.7; 95% CI, 1.2–2.4), anxiety (OR, 2; 95% CI, 1.3–2.9), depression (OR, 1.5; 95% CI, 1.2–1.9), somatization (OR, 4.1; 95% CI, 2.7–6.0), neuroticism (OR, 3.3; 95% CI, 1.6–6.5), and clinical indicators of enteritis severity. There was a considerable level of heterogeneity among studies. Conclusion In a systematic review and meta-analysis, we found more than 10% of patients with infectious enteritis to later develop IBS; risk of IBS was 4-fold higher than in individuals who did not have infectious enteritis, although there was heterogeneity among studies analyzed. Women—particularly those with severe enteritis—are at increased risk for developing IBS, as are individuals with psychological distress and users of antibiotics during the enteritis. PMID:28069350

Evaluation of latent links between irritable bowel syndrome and sleep quality

PubMed Central

Bellini, Massimo; Gemignani, Angelo; Gambaccini, Dario; Toti, Simona; Menicucci, Danilo; Stasi, Cristina; Costa, Francesco; Mumolo, Maria Gloria; Ricchiuti, Angelo; Bedini, Remo; de Bortoli, Nicola; Marchi, Santino

2011-01-01

AIM: To examine the links between quality of sleep and the severity of intestinal symptoms in irritable bowel syndrome (IBS). METHODS: One hundred and forty-two outpatients (110 female, 32 male) who met the Rome III criteria for IBS with no psychiatric comorbidity were consecutively enrolled in this study. Data on age, body mass index (BMI), and a set of life-habit variables were recorded, and IBS symptoms and sleep quality were evaluated using the questionnaires IBS Symptom Severity Score (IBS-SSS) and Pittsburgh Sleep Quality Index (PSQI). The association between severity of IBS and sleep disturbances was evaluated by comparing the global IBS-SSS and PSQI score (Pearson’s correlation and Fisher’s exact test) and then analyzing the individual items of the IBS-SSS and PSQI questionnaires by a unitary bowel-sleep model based on item response theory (IRT). RESULTS: IBS-SSS ranged from mild to severe (120-470). The global PSQI score ranged from 1 to 17 (median 5), and 60 patients were found to be poor sleepers (PSQI > 5). The correlation between the global IBS-SSS and PSQI score indicated a weak association (r = 0.2 and 95% CI: -0.03 to 0.35, P < 0.05), which becomes stronger using our unitary model. Indeed, the IBS and sleep disturbances severities, estimated as latent variables, resulted significantly high intra-subject correlation (posterior mean of r = 0.45 and 95% CI: 0.17 to 0.70, P < 0.05). Moreover, the correlations between patient features (age, sex, BMI, daily coffee and alcohol intake) and IBS and sleep disturbances were also analyzed through our unitary model. Age was a significant regressor, with patients ≤ 50 years old showing more severe bowel disturbances (posterior mean = -0.38, P < 0.05) and less severe sleep disturbances (posterior mean = 0.49, P < 0.05) than older patients. Higher daily coffee intake was correlated with a lower severity of bowel disturbances (posterior mean = -0.31, P < 0.05). Sex (female) and daily alcohol intake (modest) were correlated with less severe sleep disturbances. CONCLUSION: The unitary bowel-sleep model based on IRT revealed a strong positive correlation between the severity of IBS symptoms and sleep disturbances. PMID:22171143

Apples and Oranges: Comparing the Backgrounds and Academic Trajectories of International Baccalaureate (IB) Students to a Matched Comparison Group

ERIC Educational Resources Information Center

May, Henry; Rodriguez, Awilda; Sirinides, Philip M.; Perna, Laura W.; Yee, April; Ransom, Tafaya

2013-01-01

As a critical step in understanding the impacts of IB, the analyses presented in this report examined the selection mechanisms behind IB participation across Florida, the state with the second highest representation of IB programs in the nation. We use longitudinal student and school-level data from 1995 through 2009 from the Florida K-20…

Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial.

PubMed

Cash, Brooks D; Pimentel, Mark; Rao, Satish S C; Weinstock, Leonard; Chang, Lin; Heimanson, Zeev; Lembo, Anthony

2017-09-01

Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D. Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks. A validated 34-item IBS-QOL questionnaire examined patient responses in 8 domains. The 2579 patients receiving open-label rifaximin experienced a mean improvement from baseline in IBS-QOL overall score of 54.9%. Responders to open-label rifaximin ( n = 1074 of 2438 evaluable; 44.1%) had significantly greater improvement from baseline in IBS-QOL overall and all eight subdomain scores, including dysphoria, food avoidance, interference with activity, body image, and sexual function versus nonresponders at 4 weeks posttreatment ( n = 1364; p < 0.001 for all comparisons). A significantly greater percentage of responders to open-label rifaximin achieved the minimally clinically important difference (MCID; ⩾14-point improvement from baseline) in the overall IBS-QOL score versus nonresponders [ n = 561 (52.2%) versus n = 287 (21.0%); p < 0.0001]. Among 636 patients with IBS-D relapse, the MCID in the overall IBS-QOL score was achieved by a significantly greater percentage of patients receiving double-blind rifaximin versus placebo (38.6% versus 29.6%, respectively; p = 0.009). Open-label and blinded retreatment with a short course (2 weeks) of rifaximin improved IBS-QOL in patients with IBS-D [ClinicalTrials.gov identifier: NCT01543178].

Diarrhea-Predominant Irritable Bowel Syndrome Is Associated With Diverticular Disease: A Population-Based Study

PubMed Central

Jung, Hye-kyung; Choung, Rok Seon; Locke, G. Richard; Schleck, Cathy D.; Zinsmeister, Alan R.; Talley, Nicholas J.

2010-01-01

OBJECTIVES A subset of patients with colonic diverticular disease have chronic gastrointestinal symptoms, and some have a clinical diagnosis of irritable bowel syndrome (IBS), but whether IBS and diverticular disease are linked is uncertain. We aimed to evaluate this association in the community. METHODS A population-based, cross-sectional survey was conducted by mailing a valid symptom questionnaire to the eligible residents of Olmsted County, MN, aged 30 –95 years. Colonic diverticular disease (diverticulosis and diverticulitis) was ascertained through a review of the complete medical history of all responders. Subjects with at least one relevant test (colonoscopy, computed tomography (CT) scan, CT colonography, or barium enema) were included. IBS was defined using Rome II criteria. RESULTS Among 2,267 eligible respondents, there were 1,712 subjects who had undergone colon testing (76%): 919 women (54%); mean (±s.d.) age 65 (±11 years). Colonic diverticular disease was identified in 44.4% (95% confidence interval (CI) 42.1–46.8) of the subject. IBS was reported by 8.8% (95% CI 6.9 –11.0) of men and 17.0% (95% CI 14.6 –19.6) of women. After adjusting for age and gender, the presence of IBS was associated with an increased odds for diverticulosis (odds ratio (OR) = 1.8, 95% CI 1.3 – 2.4) but not diverticulitis (OR = 1.7, 95% CI 0.9 –3.2). In those 65 years of age or older, the presence of IBS was associated with a ninefold higher odds for diverticulosis (OR = 9.4, 95% CI 5.8–15.1). Relative to the non-IBS subgroup, diarrhea-predominant IBS and mixed IBS were significantly associated with an increased odds for diverticular disease (OR = 1.9, 95% CI 1.1–3.2; OR = 2.6, 95% CI 1.0 –6.4, respectively). CONCLUSIONS There is a significantly increased odds for colonic diverticulosis in subjects with IBS (relative to those without IBS). These results suggest that IBS and colonic diverticular disease may be connected. PMID:19861955

Using read codes to identify patients with irritable bowel syndrome in general practice: a database study

PubMed Central

2013-01-01

Background Estimates of the prevalence of irritable bowel syndrome (IBS) vary widely, and a large proportion of patients report having consulted their general practitioner (GP). In patients with new onset gastrointestinal symptoms in primary care it might be possible to predict those at risk of persistent symptoms. However, one of the difficulties is identifying patients within primary care. GPs use a variety of Read Codes to describe patients presenting with IBS. Furthermore, in a qualitative study, exploring GPs’ attitudes and approaches to defining patients with IBS, GPs appeared reluctant to add the IBS Read Code to the patient record until more serious conditions were ruled out. Consequently, symptom codes such as 'abdominal pain’, 'diarrhoea’ or 'constipation’ are used. The aim of the current study was to investigate the prevalence of recorded consultations for IBS and to explore the symptom profile of patients with IBS using data from the Salford Integrated Record (SIR). Methods This was a database study using the SIR, a local patient sharing record system integrating primary, community and secondary care information. Records were obtained for a cohort of patients with gastrointestinal disorders from January 2002 to December 2011. Prevalence rates, symptom recording, medication prescribing and referral patterns were compared for three patient groups (IBS, abdominal pain (AP) and Inflammatory Bowel Disease (IBD)). Results The prevalence of IBS (age standardised rate: 616 per year per 100,000 population) was much lower than expected compared with that reported in the literature. The majority of patients (69%) had no gastrointestinal symptoms recorded in the year prior to their IBS. However a proportion of these (22%) were likely to have been prescribed NICE guideline recommended medications for IBS in that year. The findings for AP and IBD were similar. Conclusions Using Read Codes to identify patients with IBS may lead to a large underestimate of the community prevalence. The IBS diagnostic Read Code was rarely applied in practice. There are similarities with many other medically unexplained symptoms which are typically difficult to diagnose in clinical practice. PMID:24295337

Using read codes to identify patients with irritable bowel syndrome in general practice: a database study.

PubMed

Harkness, Elaine F; Grant, Laura; O'Brien, Sarah J; Chew-Graham, Carolyn A; Thompson, David G

2013-12-02

Estimates of the prevalence of irritable bowel syndrome (IBS) vary widely, and a large proportion of patients report having consulted their general practitioner (GP). In patients with new onset gastrointestinal symptoms in primary care it might be possible to predict those at risk of persistent symptoms. However, one of the difficulties is identifying patients within primary care. GPs use a variety of Read Codes to describe patients presenting with IBS. Furthermore, in a qualitative study, exploring GPs' attitudes and approaches to defining patients with IBS, GPs appeared reluctant to add the IBS Read Code to the patient record until more serious conditions were ruled out. Consequently, symptom codes such as 'abdominal pain', 'diarrhoea' or 'constipation' are used. The aim of the current study was to investigate the prevalence of recorded consultations for IBS and to explore the symptom profile of patients with IBS using data from the Salford Integrated Record (SIR). This was a database study using the SIR, a local patient sharing record system integrating primary, community and secondary care information. Records were obtained for a cohort of patients with gastrointestinal disorders from January 2002 to December 2011. Prevalence rates, symptom recording, medication prescribing and referral patterns were compared for three patient groups (IBS, abdominal pain (AP) and Inflammatory Bowel Disease (IBD)). The prevalence of IBS (age standardised rate: 616 per year per 100,000 population) was much lower than expected compared with that reported in the literature. The majority of patients (69%) had no gastrointestinal symptoms recorded in the year prior to their IBS. However a proportion of these (22%) were likely to have been prescribed NICE guideline recommended medications for IBS in that year. The findings for AP and IBD were similar. Using Read Codes to identify patients with IBS may lead to a large underestimate of the community prevalence. The IBS diagnostic Read Code was rarely applied in practice. There are similarities with many other medically unexplained symptoms which are typically difficult to diagnose in clinical practice.

Role of ictal baseline shifts and ictal high-frequency oscillations in stereo-electroencephalography analysis of mesial temporal lobe seizures.

PubMed

Wu, Shasha; Kunhi Veedu, Hari Prasad; Lhatoo, Samden D; Koubeissi, Mohamad Z; Miller, Jonathan P; Lüders, Hans O

2014-05-01

To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

PubMed Central

Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric A.; Fricchione, Gregory L.; Benson, Herbert; Libermann, Towia A.; Korzenik, Joshua; Denninger, John W.

2015-01-01

Introduction Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. Trial Registration ClinicalTrials.Gov NCT02136745 PMID:25927528

Better Understanding and Recognition of the Disconnects, Experiences, and Needs of Patients with Irritable Bowel Syndrome with Constipation (BURDEN IBS-C) Study: Results of an Online Questionnaire.

PubMed

Quigley, Eamonn M M; Horn, John; Kissous-Hunt, Michele; Crozier, Robert A; Harris, Lucinda A

2018-06-26

The BURDEN IBS-C study was conducted to better understand the experiences, attitudes, and unmet needs of sufferers of irritable bowel syndrome with constipation (IBS-C) in comparison to the perceptions and challenges of healthcare providers (HCPs) who treat IBS-C patients. This was an author-developed, online questionnaire using KnowledgePanel ® to survey individuals with IBS-C (N = 1311). HCPs participated in a complementary online questionnaire and were recruited separately (N = 331). The study was fielded from June 29, 2016, to January 30, 2017. Most patients had used (86%) and/or were using (76%) over-the-counter treatments for their IBS-C, with 12% currently on prescription therapy. At the time this study was conducted, 66% and 63% were not satisfied/completely satisfied with over-the-counter or prescription treatment, respectively, citing inadequate efficacy (55%) and side effects (39%), most commonly diarrhea, as common reasons for dissatisfaction. IBS-C respondents most commonly reported feeling frustrated (43%) and stressed (28%) regarding IBS-C, though 39% were accepting of IBS-C as part of daily life. HCPs were aligned with patients in thinking that patients were frustrated (76%) and stressed (65%) but HCPs were less likely to recognize that patients had become accepting of their IBS-C (13%). Most HCPs (79%) were not satisfied/completely satisfied with the prescription treatments available at the time this study was conducted. Inadequate response rates to current therapies (55%) and treatment adherence/compliance issues (58%) were the most frequent challenges encountered by HCPs. IBS-C respondents reported that their symptoms impacted productivity and personal activity, on average, 4 and 3 days/month, respectively. These results suggest that current management pathways may not be adequately addressing the symptoms and needs of individuals with IBS-C, most notably side effects and lack of efficacy. Patients and HCPs expressed dissatisfaction with over-the-counter and prescription treatments available at the time this study was conducted. Additional treatment options and improved dialogue would be beneficial to HCPs and patients. Synergy Pharmaceuticals Inc.

Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.

PubMed

Bajor, Antal; Törnblom, Hans; Rudling, Mats; Ung, Kjell-Arne; Simrén, Magnus

2015-01-01

Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8). Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Treatment patterns, symptom reduction, quality of life, and resource use associated with lubiprostone in irritable bowel syndrome constipation subtype.

PubMed

Solem, Caitlyn T; Patel, Haridarshan; Mehta, Sonam; Mody, Reema; Macahilig, Cynthia; Gao, Xin

2016-05-01

Objectives Real-world patient outcomes data is scarce concerning the high disease burden of IBS-C. The aim of this study was to compare patient-reported symptom control, health-related quality of life (HRQoL), resource utilization, and treatment satisfaction of lubiprostone vs non-lubiprostone treatment for irritable bowel syndrome-constipation (IBS-C). Research design and methods An observational, retrospective US chart review and computer-assisted telephone patient survey was conducted March to August 2013 recruiting women over 18 years old with physician-confirmed IBS-C who had initiated new treatment from inadequate relief of previous treatments and who had been on the new treatment ≥3 months. Multiple IBS-C treatments were permitted. IBS-C severity, time since diagnosis, age, and race were controlled using inverse probability of treatment weighting. Weighted outcomes were compared using t-tests (continuous outcomes) and chi-squared tests (categorical outcomes). Main outcomes measures Instruments included Patient Assessment of Constipation Symptoms (PAC-SYM) and IBS quality of life (IBS-QoL). A single item assessed current treatment satisfaction. Results Of 162 patients (mean age 45.9 [SD 15.3] years old, 71% white, 61.1% with moderate IBS-C), 76 switched to lubiprostone and 86 to non-lubiprostone. Groups were similar in clinical and demographic characteristics and previous 30 day IBS-C treatment. After weighting, all PAC-SYM scores were lower for lubiprostone (P < 0.05). All IBS-QoL subscales were higher for lubiprostone including overall, dysphoria, social reaction, sexual, and relationship scores (P < 0.05.) More lubiprostone patients reported positive treatment satisfaction (92.3% vs 71.0%, P < 0.001). Conclusions In IBS-C patients with inadequate response to previous therapies, lubiprostone improved patient-reported symptom control, treatment satisfaction, and HRQoL. Key limitations include lack of measurement of patient-reported outcomes at treatment start and potential data gaps in chart documentation.

The prevalence of abnormal celiac antibodies and celiac disease in patients with suspected irritable bowel syndrome: a prospective multi-center US study

PubMed Central

Cash, Brooks D.; Rubenstein, Joel H.; Young, Patrick E.; Gentry, Andrew; Nojkov, Borko; Lee, Dong; Andrews, A. Hirsohi; Dobhan, Richard; Chey, William D.

2011-01-01

Background & Aims Guidelines recommend that patients with symptoms of non-constipated inflammatory bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies and biopsy confirmed CD among patients with NC-IBS in a large US population. Methods In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and non-specific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. Results Of patients with NC-IBS, 7.3% had abnormal results in tests for CD-associated antibodies, compared to 4.8% of controls (adjusted odds ratio=1.49; 95% confidence interval, 0.76–2.90. P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>0.99). Conclusions Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, indicating that gluten sensitivity might mediate IBS symptoms; further studies are needed. PMID:21762658

Post-infectious irritable bowel syndrome (PI-IBS) after infection with Shiga-like toxin-producing Escherichia coli (STEC) O104:H4: A cohort study with prospective follow-up

PubMed Central

Löwe, Bernd; Broicher, Wiebke; Riegel, Björn; Fraedrich, Katharina; von Wulffen, Moritz; Gappmayer, Kerrin; Wegscheider, Karl; Treszl, András; Rose, Matthias; Layer, Peter; Lohse, Ansgar W

2015-01-01

Background In May/June 2011, the new Shiga-like toxin-producing Escherichia coli (STEC) strain O104:H4 caused the severest outbreak ever recorded of hemorrhagic enterocolitis in 3842 patients in Germany. Objectives As bacterial enterocolitis is an established risk factor of subsequent irritable bowel syndrome (IBS), we aimed to estimate prevalence and incidence of post-infectious (PI)-IBS after six and 12 months in a cohort of STEC O104:H4 patients and to prospectively identify associated somatic and psychometric risk factors. Methods A total of 389 patients were studied prospectively at baseline and at six and 12 months after STEC infection using STEC disease-related questionnaires and validated instruments for IBS (Rome III) and psychological factors. Frequencies and logistic regression models using multiple imputations were applied to assess predictor variables. Results Prevalence of IBS increased from 9.8% prior to STEC infection to 23.6% at six and 25.3% at 12 months after STEC infection. In patients without IBS symptoms prior to STEC infection, incidence of new IBS was 16.9%. Logistic regression models indicated higher somatization and anxiety scores as risk factors for, and mesalazine treatment during, STEC infection as the only significant protective factor against IBS. No other factor analyzed, including disease severity, showed an association. Conclusions PI-IBS rates following this unusually severe STEC outbreak were similar to what has been observed after other infectious gastroenteritis outbreaks. Our findings suggest that mesalazine may have reduced the risk of subsequent PI-IBS. As altered mucosal immune activity is a pivotal pathogenic factor in PI-IBS, our observation of a potential protective effect of mesalazine might be explained by its known modulatory action on mucosal immunity, and may warrant further investigation. PMID:26966532

Co-occurrence of IBS and symptoms of anxiety or depression, among Norwegian twins, is influenced by both heredity and intrauterine growth.

PubMed

Bengtson, May-Bente; Aamodt, Geir; Vatn, Morten H; Harris, Jennifer R

2015-02-05

Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression. A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g. In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g. Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.

Diet in irritable bowel syndrome.

PubMed

El-Salhy, Magdy; Gundersen, Doris

2015-04-14

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder that is characterized by intermittent abdominal pain/discomfort, altered bowel habits and abdominal bloating/distension. This review aimed at presenting the recent developments concerning the role of diet in the pathophysiology and management of IBS. There is no convincing evidence that IBS patients suffer from food allergy/intolerance, and there is no evidence that gluten causes the debated new diagnosis of non-coeliac gluten sensitivity (NCGS). The component in wheat that triggers symptoms in NCGS appears to be the carbohydrates. Patients with NCGS appear to be IBS patients who are self-diagnosed and self-treated with a gluten-free diet. IBS symptoms are triggered by the consumption of the poorly absorbed fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) and insoluble fibre. On reaching the distal small intestine and colon, FODMAPS and insoluble fibre increase the osmotic pressure in the large-intestine lumen and provide a substrate for bacterial fermentation, with consequent gas production, abdominal distension and abdominal pain or discomfort. Poor FODMAPS and insoluble fibres diet reduces the symptom and improve the quality of life in IBS patients. Moreover, it changes favourably the intestinal microbiota and restores the abnormalities in the gastrointestinal endocrine cells. Five gastrointestinal endocrine cell types that produce hormones regulating appetite and food intake are abnormal in IBS patients. Based on these hormonal abnormalities, one would expect that IBS patients to have increased food intake and body weight gain. However, the link between obesity and IBS is not fully studied. Individual dietary guidance for intake of poor FODMAPs and insoluble fibres diet in combination with probiotics intake and regular exercise is to be recommended for IBS patients.

Overlapping irritable bowel syndrome and inflammatory bowel disease: less to this than meets the eye?

PubMed Central

Quigley, Eamonn M. M.

2016-01-01

Though distinct in terms of pathology, natural history and therapeutic approach, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) have some features in common. These include shared symptomatology and largely similar demographics. However, in most instances, clinical presentation, together with laboratory, imaging and endoscopic findings will readily permit the differentiation of active IBD from IBS. More problematic is the situation where a subject with IBD, in apparent remission, continues to complain of symptoms which, in aggregate, satisfy commonly employed criteria for the diagnosis of IBS. Access to methodologies, such the assay for levels of calprotectin in feces, now allows identification of ongoing inflammation in some such individuals and prompts appropriate therapy. More challenging is the IBD patient with persisting symptoms and no detectable evidence of inflammation; is this coincident IBS, IBS triggered by IBD or an even more subtle level of IBD activity unrecognized by available laboratory or imaging methods? Arguments can be advanced for each of these proposals; lacking definitive data, this issue remains unresolved. The occurrence of IBS-type symptoms in the IBD patient, together with some data suggesting a very subtle level of ‘inflammation‘ or ‘immune activation‘ in IBS, raises other questions: is IBS a prodromal form of IBD; and are IBS and IBD part of the spectrum of the same disease? All of the available evidence indicates that the answer to both these questions should be a resounding ‘no’. Indeed, the whole issue of overlap between IBS and IBD should be declared moot given their differing pathophysiologies, contrasting natural histories and divergent treatment paths. The limited symptom repertoire of the gastrointestinal tract may well be fundamental to the apparent confusion that has, of late, bedeviled this area. PMID:26929782

Effects of Demographic Factors, Body Mass Index, Alcohol Drinking and Smoking Habits on Irritable Bowel Syndrome: A Case Control Study

PubMed Central

Farzaneh, N; Ghobaklou, M; Moghimi-Dehkordi, B; Naderi, N; Fadai, F

2013-01-01

Background: Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder. Aims: To identify demographic factors in patients with IBS. Subjects and Methods: One-hundred and fifty three IBS patients seen at Taleghani Hospital Gastroenterology Clinic and met the Rome III criteria and 163 peoples who did not meet IBS criteria were consecutively enrolled. Both groups were asked to complete a self-rating questionnaire containing information, which included questions about age, sex, monthly income, education level, marital status, height, weight, alcohol drinking and smoking habits. Student's t-test, Pearson's Chi-square and logistic regression were used to statistical analysis. Results: The mean (SD) age for IBS patients 36.3 (13.5) years and 33.1 (9.9) years in non-IBS group (P < 0.001). Frequency of IBS defined by Rome III criteria was higher in females and younger individuals. Univariate analysis showed that IBS in males was associated with a lower monthly income and educational level and in females younger age, single, lower monthly income and educational level, body mass index (BMI), and unemployment status. Multivariate logistic regression identified a low level of education in males (Odds ratio [OR] = 3.6, 95% Confidence interval [CI]: 1.4-9.6) and in females, lower education level (OR = 2.4, 95% CI: 1.1-5.2), lower BMI (OR = 0.94, 95% CI: 0.89-0.99), unemployed (OR = 0.31, 95% CI: 0.11-0.85) and smoking (OR = 6.2, 95% CI: 1.03-37.2). Conclusion: We identified demographic factors in IBS patients. Being single and having a lower educational level, income, lower BMI and being unemployed were the most important factors associated with IBS, particularly in females. PMID:24116320

Internet-Delivered Cognitive Behavior Therapy for Adolescents With Irritable Bowel Syndrome: A Randomized Controlled Trial.

PubMed

Bonnert, Marianne; Olén, Ola; Lalouni, Maria; Benninga, Marc A; Bottai, Matteo; Engelbrektsson, Johanna; Hedman, Erik; Lenhard, Fabian; Melin, Bo; Simrén, Magnus; Vigerland, Sarah; Serlachius, Eva; Ljótsson, Brjánn

2017-01-01

Few treatments have been able to effectively manage pediatric irritable bowel syndrome (IBS). Internet-delivered cognitive behavior therapy (Internet-CBT) based on exposure for abdominal symptoms is effective for adult IBS. The objective of this study was to evaluate the efficacy of Internet-CBT based on behavioral exposure for adolescents with IBS. Adolescents with IBS fulfilling the Rome III criteria were randomized to either Internet-CBT or a wait-list control. The Internet-CBT was a 10-week intervention where the main component was exposure to IBS symptoms by reduction of avoidance of abdominal symptoms and instead stepwise provocation of symptoms. The primary outcome was total score on Gastrointestinal Symptoms Rating Scale for IBS (GSRS-IBS). Secondary outcomes included adolescent- and parent-rated quality of life and parent-rated gastrointestinal symptoms. Difference between groups was assessed from pretreatment to posttreatment and the Internet-CBT group was also evaluated at 6 months after treatment completion. A total of 101 adolescents with IBS (13-17 years of age) were included in this study. Dropout rates were low (6%) and all randomized patients were included in intent-to-treat analyses based on mixed effects models. Analyses showed a significant larger pretreatment to posttreatment change on the primary outcome GSRS-IBS (B=-6.42, P=0.006, effect size Cohen's d=0.45, 95% confidence interval (0.12, 0.77)) and on almost all secondary outcomes for the Internet-CBT group compared with the control group. After 6 months, the results were stable or significantly improved. Internet-CBT based on exposure exercises for adolescents with IBS can effectively improve gastrointestinal symptoms and quality of life.

Stimulation of ANP secretion by 2-Cl-IB-MECA through A(3) receptor and CaMKII.

PubMed

Yuan, Kuichang; Bai, Guang Yi; Park, Woo Hyun; Kim, Sung Zoo; Kim, Suhn Hee

2008-12-01

Adenosine is a potent mediator of myocardial protection against hypertrophy via A(1) or A(3) receptors that may be partly related to atrial natriuretic peptide (ANP) release. However, little is known about the possible involvement of the A(3) receptor on ANP release. We studied the effects of the A(3) receptor on atrial functions and its modification in hypertrophied atria. A selective A(3) receptor agonist, 2-chloro-N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (2-CI-IB-MECA), was perfused into isolated, beating rat atria with and without receptor modifiers. 2-CI-IB-MECA dose-dependently increased the ANP secretion, which was blocked by the A(3) receptor antagonist, but the increased atrial contractility and decreased cAMP levels induced by 30muM 2-CI-IB-MECA were not affected. The 100muM 2-(1-hexylnyl)-N-methyladenosine (HEMADO) and N(6)-(3-iodobenzyl) adenosine-5'-N-methyluronamide (IB-MECA), A(3) receptor agonist, also stimulated the ANP secretion without positive inotropy. The potency for the stimulation of ANP secretion was 2-CI-IB-MECA>IB-MECA=HEMADO. The inhibition of the ryanodine receptor or calcium/calmodulin-dependent kinase II (CaMKII) attenuated 2-CI-IB-MECA-induced ANP release, positive inotropy, and translocation of extracellular fluid. However, the inhibition of L-type Ca(2+) channels, sarcoplasmic reticulum Ca(2+)-reuptake, phospholipase C or inositol 1,4,5-triphosphate receptors did not affect these parameters. 2-CI-IB-MECA decreased cAMP level, which was blocked only with an inhibitor of CaMKII or adenylyl cyclase. These results suggest that 2-CI-IB-MECA increases the ANP secretion mainly via A(3) receptor activation and positive inotropy by intracellular Ca(2+) regulation via the ryanodine receptor and CaMKII.

Anti-HCV immunoblot indeterminate results in blood donors: non-specific reactivity or past exposure to HCV?

PubMed

Kiely, P; Styles, C

2017-08-01

The significance of anti-HCV immunoblot (IB) indeterminate results can be difficult to determine. We analysed results for blood donors tested on the MP Diagnostics HCV Blot 3.0 IB assay to determine whether indeterminate results representing past exposure to HCV could be distinguished from those due to non-specific reactivity. Results for all donors tested by IB during the study period (July 2010 to December 2013) were included in this study. Of 131 donors tested by IB, 34 (26.0%) were negative, 38 (29.0%) were indeterminate, and 59 (45.0%) were positive. There was no significant difference in IB band reactivity strength between indeterminate and positive donors. The PRISM HCV chemiluminescent immunoassay (ChLIA) sample to cut-off (s/co) ratio distribution for the indeterminate donors was significantly higher than for those with biological false reactivity (P = 0·037), but significantly lower than for donors who were IB positive/HCV RNA negative (P < 0·001) or IB not tested/HCV RNA positive (P < 0·001). Of donors available for follow-up, 53.1% of the indeterminate group disclosed a putative risk factor for HCV infection compared to 39.4% (P < 0·001) for the IB-negative group, 76.6% (P = 0·065) for the IB-positive group and 83.4% (P < 0·001) for the HCV RNA-positive group. The results of this study indicate that PRISM ChLIA s/co ratios >2·00 with IB indeterminate results predict exposure to HCV, particularly in the presence of putative risk factors for HCV infection. These findings may be applied to optimizing counselling of donors with indeterminate HCV results. © 2017 International Society of Blood Transfusion.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

PubMed

Yamada, Eiji; Inamori, Masahiko; Uchida, Eri; Tanida, Emiko; Izumi, Motoyoshi; Takeshita, Kimiya; Fujii, Tetsuro; Komatsu, Kazuto; Hamanaka, Jun; Maeda, Shin; Kanesaki, Akira; Matsuhashi, Nobuyuki; Nakajima, Atsushi

2014-12-01

No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

The effect of biofeedback therapy on dyssynergic constipation in patients with or without Irritable Bowel Syndrome.

PubMed

Ahadi, Tannaz; Madjlesi, Faezeh; Mahjoubi, Bahar; Mirzaei, Rezvan; Forogh, Bijan; Daliri, Seyedeh Somayeh; Derakhshandeh, Seyed Majid; Behbahani, Roxana Bazaz; Raissi, G Reza

2014-10-01

The Rome II and III diagnostic criteria for dyssynergic defecation recommended the exclusion of irritable bowel syndrome (IBS). This study determined the effect of biofeedback therapy on dyssynergic constipation in patients with or without IBS. This study was a nonrandomized, single blinded, semi experimental study. Dyssynergic defecation patients with and without IBS were asked to undergo biofeedback therapy 8 sessions. The defecation dynamics and balloon expulsion time were evaluated before, at the end and 1 month after the biofeedback therapy. IBS symptoms were graded using a 4-point Likert scale. Mann-Whitney U-test, Wilcoxon test and Friedman test were applied to analyze data using SPSS software package (SPSS Inc., Chicago, IL, USA). After the biofeedback therapy, the IBS symptoms have been decreased significantly (the median of 2 before and 1 after therapy, P < 0.01). The biofeedback therapy significantly decreased the anismus index in IBS group by the mean of 0.75 ± 0.31, 0.28 ± 0.07 and 0.28 ± 0.06 in three phases, respectively. Similar results were found in non-IBS patients (the mean of 0.74 ± 0.32, 0.28 ± 0.08, 0.27 ± 0.08 in three phases, respectively). The symptoms of constipation (sensation of incomplete evacuation, difficult and painful defecation), defecation facilitative manual maneuver frequency, pelvic floor muscles resting amplitude and strain amplitude decreased and squeezing amplitude improved significantly after biofeedback therapy in both groups with and without IBS (P < 0.001). There were not significant differences between patients with and without IBS (P > 0.05) with respect to outcome. No complication was observed in treatment groups. Dyssynergic constipation patients with and without IBS will likely benefit from biofeedback therapy.

The effect of biofeedback therapy on dyssynergic constipation in patients with or without Irritable Bowel Syndrome

PubMed Central

Ahadi, Tannaz; Madjlesi, Faezeh; Mahjoubi, Bahar; Mirzaei, Rezvan; Forogh, Bijan; Daliri, Seyedeh Somayeh; Derakhshandeh, Seyed Majid; Behbahani, Roxana Bazaz; Raissi, G. Reza

2014-01-01

Background: The Rome II and III diagnostic criteria for dyssynergic defecation recommended the exclusion of irritable bowel syndrome (IBS). This study determined the effect of biofeedback therapy on dyssynergic constipation in patients with or without IBS. Materials and Methods: This study was a nonrandomized, single blinded, semi experimental study. Dyssynergic defecation patients with and without IBS were asked to undergo biofeedback therapy 8 sessions. The defecation dynamics and balloon expulsion time were evaluated before, at the end and 1 month after the biofeedback therapy. IBS symptoms were graded using a 4-point Likert scale. Mann–Whitney U-test, Wilcoxon test and Friedman test were applied to analyze data using SPSS software package (SPSS Inc., Chicago, IL, USA). Results: After the biofeedback therapy, the IBS symptoms have been decreased significantly (the median of 2 before and 1 after therapy, P < 0.01). The biofeedback therapy significantly decreased the anismus index in IBS group by the mean of 0.75 ± 0.31, 0.28 ± 0.07 and 0.28 ± 0.06 in three phases, respectively. Similar results were found in non-IBS patients (the mean of 0.74 ± 0.32, 0.28 ± 0.08, 0.27 ± 0.08 in three phases, respectively). The symptoms of constipation (sensation of incomplete evacuation, difficult and painful defecation), defecation facilitative manual maneuver frequency, pelvic floor muscles resting amplitude and strain amplitude decreased and squeezing amplitude improved significantly after biofeedback therapy in both groups with and without IBS (P < 0.001). There were not significant differences between patients with and without IBS (P > 0.05) with respect to outcome. No complication was observed in treatment groups. Conclusion: Dyssynergic constipation patients with and without IBS will likely benefit from biofeedback therapy. PMID:25538778

Adverse childhood experiences are associated with irritable bowel syndrome and gastrointestinal symptom severity.

PubMed

Park, S H; Videlock, E J; Shih, W; Presson, A P; Mayer, E A; Chang, L

2016-08-01

Early adverse life events (EALs) are associated with irritable bowel syndrome (IBS). Exposure to EALs as assessed by the Adverse Childhood Experiences (ACE) questionnaire is associated with greater disease prevalence, but ACE has not been studied in gastrointestinal disorders. Study aims were to: (i) Estimate the prevalence of EALs in the IBS patients using the ACE questionnaire; (ii) Determine correlations between ACE and Early Trauma Inventory Self Report-Short Form (ETI-SR) scores to confirm its validity in IBS; and (iii) Correlate ACE scores with IBS symptom severity. A total of 148 IBS (73% women, mean age = 31 years) and 154 HCs (59% women, mean age = 30 years) completed the ACE and ETI-SR between June 2010 and April 2015. These surveys measured EALs before age 18 in the domains of physical, sexual, and emotional abuse, and general trauma. IBS and abdominal pain severity was measured by a 20-point scale (0 = none, 20 = worst symptoms). The ACE score increased the odds of having IBS (odds ratio [OR] = 2.05, 95% confidence interval [CI]: 1.21-3.48, p = 0.008). Household mental illness (p < 0.001), emotional abuse (p = 0.004), and incarcerated household member (p = 0.019) were significant predictors of IBS. Adverse childhood experiences and ETI-SR scores were strongly correlated (r = 0.59, p < 0.001). ACE, but not ETI-SR, modestly correlated with IBS severity (r = 0.17, p = 0.036) and abdominal pain (r = 0.20, p = 0.015). The ACE questionnaire is a useful instrument to measure EALs in IBS based on its use in large studies, its ability to measure prevalence across different EAL domains, and its correlation with symptom severity. © 2016 John Wiley & Sons Ltd.

BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development

PubMed Central

Li, Lu; Lin, Minkui; Wang, Ying; Cserjesi, Peter; Chen, Zhi; Chen, YiPing

2010-01-01

The BMP signaling plays a pivotal role in the development of craniofacial organs, including the tooth and palate. BmprIa and BmprIb encode two type I BMP receptors that are primarily responsible for BMP signaling transduction. We investigated mesenchymal tissue-specific requirement of BmprIa and its functional redundancy with BmprIb during the development of mouse tooth and palate. BmprIa and BmprIb exhibit partially overlapping and distinct expression patterns in the developing tooth and palatal shelf. Neural crest specific inactivation of BmprIa leads to formation of an unusual type of anterior clefting of the secondary palate, an arrest of tooth development at the bud/early cap stages, and severe hypoplasia of the mandible. Defective tooth and palate development is accompanied by the down-regulation of BMP responsive genes and reduced cell proliferation levels in the palatal and dental mesenchyme. To determine if BmprIb could substitute for BmprIa during tooth and palate development, we expressed a constitutively active form of BmprIb (caBmprIb) in the neural crest cells in which BmprIa was simultaneously inactivated. We found that substitution of BmprIa by caBmprIb in neural rest cells rescues the development of molars and maxillary incisor, but the rescued teeth exhibit a delayed odontoblast and ameloblast differentiation. In contrast, caBmprIb fails to rescue the palatal and mandibular defects including the lack of lower incisors. Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue specific manner during tooth and palate development. PMID:21034733

Exclusion of the GNAS locus in PHP-Ib patients with broad GNAS methylation changes: evidence for an autosomal recessive form of PHP-Ib?

PubMed

Fernández-Rebollo, Eduardo; Pérez de Nanclares, Guiomar; Lecumberri, Beatriz; Turan, Serap; Anda, Emma; Pérez-Nanclares, Gustavo; Feig, Denice; Nik-Zainal, Serena; Bastepe, Murat; Jüppner, Harald

2011-08-01

Most patients with autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib) carry maternally inherited microdeletions upstream of GNAS that are associated with loss of methylation restricted to GNAS exon A/B. Only few AD-PHP-Ib patients carry microdeletions within GNAS that are associated with loss of all maternal methylation imprints. These epigenetic changes are often indistinguishable from those observed in patients affected by an apparently sporadic PHP-Ib form that has not yet been defined genetically. We have now investigated six female patients affected by PHP-Ib (four unrelated and two sisters) with complete or almost complete loss of GNAS methylation, whose healthy children (11 in total) showed no epigenetic changes at this locus. Analysis of several microsatellite markers throughout the 20q13 region made it unlikely that PHP-Ib is caused in these patients by large deletions involving GNAS or by paternal uniparental isodisomy or heterodisomy of chromosome 20 (patUPD20). Microsatellite and single-nucleotide variation (SNV) data revealed that the two affected sisters share their maternally inherited GNAS alleles with unaffected relatives that lack evidence for abnormal GNAS methylation, thus excluding linkage to this locus. Consistent with these findings, healthy children of two unrelated sporadic PHP-Ib patients had inherited different maternal GNAS alleles, also arguing against linkage to this locus. Based on our data, it appears plausible that some forms of PHP-Ib are caused by homozygous or compound heterozygous mutation(s) in an unknown gene involved in establishing or maintaining GNAS methylation. Copyright © 2011 American Society for Bone and Mineral Research.

Impact of parental-rearing styles on irritable bowel syndrome in adolescents: a school-based study.

PubMed

Xing, Zhouxiong; Hou, Xiaohua; Zhou, Kan; Qin, Diyuan; Pan, Wen

2014-03-01

A strong association between family function and irritable bowel syndrome (IBS) has been observed. Parental rearing styles, as a comprehensive mark for family function, may provide new clues to the etiology of IBS. This study aimed to explore which dimensions of parental rearing styles were risk factors or protective factors for IBS in adolescents. Two thousand three hundred twenty adolescents were recruited from one middle school and one high school randomly selected from Jiangan District (an urban district in Wuhan City). Data were collected using two Chinese versions of validated self-report questionnaires including the Rome III diagnostic criteria for pediatric IBS and the Egna Minnen Beträffande Uppfostran: One's Memories of Upbringing for perceived parental rearing styles. Ninety-six subjects diagnosed as pediatric IBS were compared with 1618 controls. The IBS patients reported less both paternal and maternal emotional warmth (all P < 0.01) and more both paternal and maternal punishment, overinterference, rejection, and overprotection (only for father) (all P < 0.01) than the controls. Furthermore, the IBS patients had higher total scores of parental rearing styles (all P < 0.001) than the controls. With univariate logistic regression, standardized regression coefficients and odds ratios of parental rearing variables were calculated. Multivariate logistic regression revealed that paternal rejection (P = 0.001) and maternal overinterference (P = 0.002) were independent risk factors for IBS in adolescents. Parental emotional warmth is a protective factor for IBS in adolescents and parental punishment, overinterference, rejection, and overprotection are risk factors for IBS in adolescents. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

A randomized placebo-controlled clinical trial of a multi-strain probiotic formulation (Bio-Kult®) in the management of diarrhea-predominant irritable bowel syndrome.

PubMed

Ishaque, Shamsuddin M; Khosruzzaman, S M; Ahmed, Dewan Saifuddin; Sah, Mukesh Prasad

2018-05-25

Accumulating evidence supports the view that an imbalance of gut bacteria contributes to IBS, and that increasing the mass of beneficial species may reduce the numbers of pathogenic bacteria and help alleviate symptoms. In this double-blind trial 400 adult patients with moderate-to-severe symptomatic diarrhea-predominant IBS (IBS-D) were randomized to treatment with the multi-strain probiotic Bio-Kult® (14 different bacterial strains) or placebo for 16 weeks. The change in severity and frequency of abdominal pain was the primary outcome measure. Probiotic treatment significantly improved the severity of abdominal pain in patients with IBS-D. A 69% reduction for probiotic versus 47% for placebo (p < 0.001) equates to a 145 point reduction on the IBS-severity scoring system (IBS-SSS). The proportion of patients who rated their symptoms as moderate-to-severe was reduced from 100% at baseline to 14% for the multi-strain probiotic at follow-up (month 5) versus 48% for placebo (p < 0.001). Also, the number of bowel motions per day from month 2 onwards was significantly reduced in the probiotic group compared with the placebo group (p < 0.05). In addition to relieving symptoms, the probiotic markedly improved all dimensions of quality of life in the 34-item IBS-Quality of Life (IBS-QoL) questionnaire. No serious adverse events were reported. The multi-strain probiotic was associated with significant improvement in symptoms in patients with IBS-D and was well-tolerated. These results suggest that probiotics confer a benefit in IBS-D patients which deserves further investigation. [Clinicaltrials.gov NCT03251625 ; retrospectively registered on August 9, 2017].

In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria.

PubMed

Simonetti, Oriana; Cirioni, Oscar; Ghiselli, Roberto; Orlando, Fiorenza; Silvestri, Carmela; Mazzocato, Susanna; Kamysz, Wojciech; Kamysz, Elzbieta; Provinciali, Mauro; Giacometti, Andrea; Guerrieri, Mario; Offidani, Annamaria

2014-05-01

The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections. Copyright © 2014 Elsevier Inc. All rights reserved.

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

PubMed

Lam, Ching; Tan, Wei; Leighton, Matthew; Hastings, Margaret; Lingaya, Melanie; Falcone, Yirga; Zhou, Xiaoying; Xu, Luting; Whorwell, Peter; Walls, Andrew F; Zaitoun, Abed; Montgomery, Alan; Spiller, Robin

2016-01-01

Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. NCT01316718. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being.

PubMed

Jonefjäll, Börje; Öhman, Lena; Simrén, Magnus; Strid, Hans

2016-11-01

Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

Hypnosis for IBS

MedlinePlus

... the treatment options for IBS. Other psychological methods, cognitive therapy in particular, are also effective options. Hypnosis may ... Medications Probiotics and Antibiotics Psychological Treatments Understanding Stress Cognitive Behavioral Therapy Relaxation Techniques for IBS Take Part in Online ...

Take the IBS Test

MedlinePlus

... Committed to Quality in Patient Care TAKE THE IBS TEST Do you have recurrent abdominal pain or ... have a real and treatable medical condition called irritable bowel syndrome (IBS). Your doctor now has new information and ...

Vacuum ultraviolet coatings of Al protected with MgF(2) prepared both by ion-beam sputtering and by evaporation.

PubMed

Fernández-Perea, Mónica; Larruquert, Juan I; Aznárez, José A; Pons, Alicia; Méndez, José A

2007-08-01

Ion-beam sputtering (IBS) and evaporation are the two deposition techniques that have been used to deposit coatings of Al protected with MgF(2) with high reflectance in the vacuum ultraviolet down to 115 nm. Evaporation deposited (ED) Al protected with IBS MgF(2) resulted in a larger (smaller) reflectance below (above) 125 nm than the well-known all-evaporated coatings. A similar comparison is obtained when the Al film is deposited by IBS instead of evaporation. The lower reflectance of the coatings protected with IBS versus ED MgF(2) above 125 nm is because of larger absorption of the former. Both nonprotected IBS Al, as well as IBS Al protected with ED MgF(2), resulted in a band of reflectance loss that was peaked at 127 and 157 nm, respectively. This result was attributed to the excitation of surface plasmons due to the enhancement of surface roughness with large spatial wave vectors in the sputter deposition. This reflectance loss for IBS Al protected with MgF(2) is small at the short (lambda~120 nm) and long (lambda<350 nm) wavelengths investigated. IBS Al protected with ED MgF(2) is thus a promising coating for these two spectral regions. Coatings protected with IBS MgF(2) resulted in a reflectance as high as coatings protected with ED MgF(2) at wavelengths longer than 550 nm, whereas the former had a lower reflectance below this wavelength.

Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

PubMed

Pimentel, M

2016-01-01

The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts

PubMed Central

Gitz, Eelo; Koekman, Cornelis A; van den Heuvel, Dave J.; Deckmyn, Hans; Akkerman, Jan W.; Gerritsen, Hans C.; Urbanus, Rolf T.

2012-01-01

Background Storing platelets for transfusion at room temperature increases the risk of microbial infection and decreases platelet functionality, leading to out-date discard rates of up to 20%. Cold storage may be a better alternative, but this treatment leads to rapid platelet clearance after transfusion, initiated by changes in glycoprotein Ibα, the receptor for von Willebrand factor. Design and Methods: We examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy. Results Cold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-Dglucosamine residues, which sequestered with GM1 gangliosides in lipid rafts. Raft-associated glycoprotein Ibα formed clusters upon binding of 14-3-3ζ adaptor proteins to its cytoplasmic tail, a process accompanied by mitochondrial injury and phosphatidyl serine exposure. Cold storage left glycoprotein Ibα surface expression unchanged and although glycoprotein V decreased, the fall did not affect glycoprotein Ibα clustering. Prevention of glycoprotein Ibα clustering by blockade of deglycosylation and 14-3-3ζ translocation increased the survival of cold-stored platelets to above the levels of platelets stored at room temperature without compromising hemostatic functions. Conclusions We conclude that glycoprotein Ibα translocates to lipid rafts upon cold-induced deglycosylation and forms clusters by associating with 14-3-3ζ. Interference with these steps provides a means to enable cold storage of platelet concentrates in the near future. PMID:22733027

Gender differences in irritable bowel syndrome: the interpersonal connection.

PubMed

Thakur, E R; Gurtman, M B; Keefer, L; Brenner, D M; Lackner, J M

2015-10-01

While irritable bowel syndrome (IBS) affects women more than men, the reasons are unclear. Research on the female preponderance of IBS has focused on gender differences in sex-linked biological processes; much less attention has been paid to the role of psychosocial factors. Interpersonal difficulties may be one source of stress that may significantly impact on women with IBS. Because of the importance that women attach to relationships, we suspected they would be more reactive to interpersonal stress. A total of 283 (M age = 41 years, F = 80%), Rome III-diagnosed IBS patients completed a test battery that included the IBS Symptom Severity Scale, McGill Pain Questionnaire, Inventory of Interpersonal Problems (IIP), interpersonal support evaluation list (social support), Negative Interactions Scale, Brief Symptom Inventory (distress), Beck Depression Inventory, Anxiety Sensitivity Inventory, and IBS-Quality of Life as part of baseline assessment of an NIH trial. Males scored higher on two IIP scales reflecting a hostile-dominant interpersonal pattern, and reported less social support. The quality of relationship problems (more interpersonal difficulties, lower support) correlated with IBS symptom severity as measured mainly by gastroenterologists. Male, not female, IBS patients reported more interpersonal difficulties. Male patients-a population for whom little is known-are characterized by hostile-dominant interpersonal problems. This finding has clinical importance, given that relationship problems may influence MDs' estimation of IBS symptom severity and undermine the physician-patient relationship. © 2015 John Wiley & Sons Ltd.

Investigation of the interactions between 1-butyl-3-methylimidazolium-based ionic liquids and isobutylene using density functional theory.

PubMed

Li, Xiaoning; Guo, Wenli; Wu, Yibo; Li, Wei; Gong, Liangfa; Zhang, Xiaoqian; Li, Shuxin; Shang, Yuwei; Yang, Dan; Wang, Hao

2018-03-06

To identify ionic liquids (ILs) that could be used as solvents in isobutylene (IB) polymerization, the interactions between IB and eight different ILs based on the 1-butyl-3-methylimidazolium cation ([Bmim] + ) were investigated using density functional theory (DFT). The anions in the ILs were chloride, hexafluorophosphate, tetrafluoroborate, bis[(trifluoromethyl)sulfonyl]imide, tetrachloroaluminate ([AlCl 4 ] - ), tetrachloroferrate, acetate, and trifluoroacetate. The interaction geometries were explained by changes in the total energy, intermolecular distances, Hirshfeld charges, and the electrostatic potential surface. The IL solvents were screened by comparing their interaction intensities with IB to the interaction intensities of reference ILs ([AlCl 4 ] - -based ILs) with IB. The microscopic mechanism for IB dissolution was rationalized by invoking a previously reported microscopic mechanism for the dissolution of gases in ILs. Computation results revealed that hydrogen (H) bonding between C2-H on the imidazolium ring and the anions plays a key role in ion pair (IP) formation. The addition of IB leads to slight changes in the dominant interactions of the IP. IB molecules occupied cavities created by small angular rearrangements of the anions, just as CO 2 does when it is dissolved in an IL. The limited total free space in the ILs and the much larger size of IB than CO 2 were found to be responsible for the poor solubility of IB compared with that of CO 2 in the ILs.

Detection of the High-Level Aminoglycoside Resistance Gene aph(2")-Ib in Enterococcus faecium

PubMed Central

Kao, Susan J.; You, Il; Clewell, Don B.; Donabedian, Susan M.; Zervos, Marcus J.; Petrin, Joanne; Shaw, Karen J.; Chow, Joseph W.

2000-01-01

A new high-level gentamicin resistance gene, designated aph(2")-Ib, was cloned from Enterococcus faecium SF11770. The deduced amino acid sequence of the 897-bp open reading frame of aph(2")-Ib shares homology with the aminoglycoside-modifying enzymes AAC(6′)-APH(2"), APH(2")-Ic, and APH(2")-Id. The observed phosphotransferase activity is designated APH(2")-Ib. PMID:10991878

Gastrointestinal (GI) permeability correlates with trait anxiety and urinary norepinephrine/creatinine (CR)ratio in children with functional abdominal pain (FAP)and irritable bowel syndrome (IBS) but not in controls

USDA-ARS?s Scientific Manuscript database

FAP and IBS affect 10–15% of school age children and bear many similarities to irritable bowel syndrome (IBS) in adults (e.g., functional pain, visceral hyperalgesia). Animal models of IBS have suggested a relationship between neonatal stress/anxiety and increased GI permeability later in life. We h...

Saturn Apollo Program

NASA Image and Video Library

1965-03-01

S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), sat in the Marshall Space Flight Center (MSFC) Saturn IB static test stand on March 15, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Effect of prolonged stress on the adrenal hormones of individuals with irritable bowel syndrome.

PubMed

Sugaya, Nagisa; Izawa, Shuhei; Saito, Keisuke; Shirotsuki, Kentaro; Nomura, Shinobu; Shimada, Hironori

2015-01-01

The purpose of this study was to investigate the effect of prolonged stress on the salivary adrenal hormones (cortisol, dehydroepiandrosterone [DHEA], DHEA-sulfate [DHEA-S]) of individuals with irritable bowel syndrome (IBS). The participants were female college students, including 10 with IBS and 16 without IBS (control group), who were scheduled for a 2-week teaching practice at a kindergarten. Participants were asked to collect saliva for determining adrenal hormones immediately and 30 min after awakening and before sleep, 2 weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. Regarding cortisol/DHEA ratio, significantly increased levels were found during the first week of the practice, and a significant interaction between group and time was found; the ratio at 30 min after awakening in the IBS group was higher than that in the control group. For the other adrenal hormone indexes, no significant differences due to the presence of IBS were found. Individuals with IBS showed an elevated cortisol/DHEA ratio after awakening compared with individuals without IBS, and the elevated ratio peaked under the prolonged stress. The present study suggests that the cortisol effect is dominant in individuals with IBS under prolonged stress.

Isolation and Abiotic Stress Resistance Analyses of a Catalase Gene from Ipomoea batatas (L.) Lam.

PubMed

Yong, Bin; Wang, Xiaoyan; Xu, Pan; Zheng, Haiyan; Fei, Xueting; Hong, Zixi; Ma, Qinqin; Miao, Yuzhi; Yuan, Xianghua; Jiang, Yusong; Shao, Huanhuan

2017-01-01

As an indicator of the antioxidant capability of plants, catalase can detoxify reactive oxygen species (ROS) generated by environmental stresses. Sweet potato is one of the top six most important crops in the world. However, its catalases remain largely unknown. In this study, a catalase encoding gene, IbCAT2 (accession number: KY615708), was identified and cloned from sweet potato cv. Xushu 18. It contained a 1479 nucleotides' open reading frame (ORF). S-R-L, Q-K-L, and a putative calmodulin binding domain were located at the C-terminus of IbCAT2, which suggests that IbCAT2 could be a peroxisomal catalase. Next-generation sequencing (NGS) based quantitative analyses showed that IbCAT2 was mainly expressed in young leaves and expanding tuberous roots under normal conditions. When exposed to 10% PEG6000 or 200 mmol/L NaCl solutions, IbCAT2 was upregulated rapidly in the first 11 days and then downregulated, although different tissues showed different degree of change. Overexpression of IbCAT2 conferred salt and drought tolerance in Escherichia coli and Saccharomyces cerevisiae . The positive response of IbCAT2 to abiotic stresses suggested that IbCAT2 might play an important role in stress responses.

Endogenous Inhibition of Somatic Pain is Impaired in Girls with Irritable Bowel Syndrome Compared with Healthy Girls

PubMed Central

Williams, Amy E.; Heitkemper, Margaret; Self, Mariella M.; Czyzewski, Danita I.; Shulman, Robert J.

2013-01-01

Endogenous pain-inhibition is often deficient in adults with chronic pain conditions including irritable bowel syndrome (IBS). It is unclear whether deficiencies in pain-inhibition are present in young children with IBS. The present study compared endogenous pain-inhibition, somatic pain threshold, and psychosocial distress in young girls with IBS versus controls. Girls with IBS did not show significant endogenous pain-inhibition of heat pain-threshold during a cold-pressor task in contrast to controls who had significant pain-inhibition. Girls with IBS did not differ from peers on measures of somatic pain but had more symptoms of depression, somatization, and anxiety than controls. When psychological variables were included as covariates the difference in pain-inhibition was no longer significant, although poor achieved power limits interpretation of these results. Higher-order cognitive processes including psychological variables may be contributing to observed pain-inhibition. In girls with IBS, pain-inhibition was positively related to the number of days without a bowel movement. To our knowledge, this is the first study to demonstrate deficiencies of endogenous pain-inhibition in young children with IBS. Findings have implications for better understanding of onset and maintenance of IBS and other chronic pain conditions. PMID:23685184

[Prevalence of irritable bowel syndrome in Veracruz City, Mexico: a community-based survey].

PubMed

Valerio-Ureña, J; Vásquez-Fernández, F; Jiménez-Pineda, A; Cortázar-Benítez, L F; Azamar-Jácome, A A; Duarte-Velázquez, M E; Torres-Medina, V

2010-01-01

Irritable bowel syndrome (IBS) is recognized as the most frequent functional digestive disorder around the world. In Latin America and Mexico there are few studies in order to demonstrate its real prevalence in general population. To determine the prevalence of IBS in general population from Veracruz City Mexico, using the Rome II criteria. Using basic information given by bureau for planning urban services from Veracruz country, a 10% random population sample was obtained. Subjects between 16-80 years old were interviewed using a questionnaire based on Rome II criteria and a visual analogous scale in order to estimate the negative effect of IBS symptoms on daily activities. We interviewed 459 subjects with a median age of 31.2 +/- 13.6 years old detecting 78 subjects (16.9%) with IBS symptoms: 25 males and 53 females (gender prevalence of 11.3% and 22.1%, respectively). 28.2% of them had IBS with diarrhea, 50% had IBS with constipation and 21.8% alternating bowel movements, diarrhea and constipation. Negative effect of IBS symptoms on daily activities was significant. The prevalence of IBS in open population was 16.9% according to Rome II criteria, being higher in those older than 35 years old. Constipation was the predominant pattern. Further studies should evaluate associated factors of these findings.

Isolation and Abiotic Stress Resistance Analyses of a Catalase Gene from Ipomoea batatas (L.) Lam

PubMed Central

Yong, Bin; Wang, Xiaoyan; Xu, Pan; Zheng, Haiyan; Fei, Xueting; Hong, Zixi; Ma, Qinqin; Miao, Yuzhi; Yuan, Xianghua; Jiang, Yusong

2017-01-01

As an indicator of the antioxidant capability of plants, catalase can detoxify reactive oxygen species (ROS) generated by environmental stresses. Sweet potato is one of the top six most important crops in the world. However, its catalases remain largely unknown. In this study, a catalase encoding gene, IbCAT2 (accession number: KY615708), was identified and cloned from sweet potato cv. Xushu 18. It contained a 1479 nucleotides' open reading frame (ORF). S-R-L, Q-K-L, and a putative calmodulin binding domain were located at the C-terminus of IbCAT2, which suggests that IbCAT2 could be a peroxisomal catalase. Next-generation sequencing (NGS) based quantitative analyses showed that IbCAT2 was mainly expressed in young leaves and expanding tuberous roots under normal conditions. When exposed to 10% PEG6000 or 200 mmol/L NaCl solutions, IbCAT2 was upregulated rapidly in the first 11 days and then downregulated, although different tissues showed different degree of change. Overexpression of IbCAT2 conferred salt and drought tolerance in Escherichia coli and Saccharomyces cerevisiae. The positive response of IbCAT2 to abiotic stresses suggested that IbCAT2 might play an important role in stress responses. PMID:28638833

Data for a direct fibrinolytic metalloproteinase, barnettlysin-I from Bothrops barnetti (barnett,s pitviper) snake venom with anti-thrombotic effect

PubMed Central

Sanchez, Eladio Flores; Richardson, Michael; Gremski, Luiza Helena; Veiga, Silvio Sanches; Yarleque, Armando; Niland, Stephan; Lima, Augusto Martins; Estevao-Costa, Maria Inácia; Eble, Johannes Andreas

2016-01-01

Initial association of platelets after vascular injury is mediated by glycoprotein (GP)Ib-IX-V binding to von Willebrand factor (vWf) immobilized on exposed collagens and eventually leads to thrombus formation. This article provides data about a new P-I class snake venom metalloproteinase (SVMP), barnettlysin-I (Bar-I), purified from the venom of Bothrops barnetti. This Data in Brief manuscript complements the main research article by providing additional data of the biochemical characterization of Bar-I 10.1016/j.bbagen.2015.12.021[1]. PMID:27222863

UV chromospheric and circumstellar diagnostic features among F supergiant stars

NASA Technical Reports Server (NTRS)

Stencel, R. E.; Worden, S. P.; Giampapa, M. S.

1981-01-01

A survey of F supergiant stars to evaluate the extension of chromospheric and circumstellar characteristics commonly observed in the slightly cooler G, K, and M supergiant is discussed. An ultraviolet survey was elected since UV features of Mg II and Fe II might persist in revealing outer atmosphere phenomena even among F supergiants. The encompassed spectral types F0 to G0, and luminosity classes Ib, Ia, and Ia-0. In addition, the usefulness of the emission line width-to-luminosity correlation for the G-M stars in both the Ca II and Mg II lines is examined.

Irritable bowel syndrome.

PubMed

Malone, Michael A

2011-09-01

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that leads to crampy pain, gassiness, bloating, and changes in bowel habits in the absence of any currently identifiable organic disorder. Patients with IBS may be classified by their predominant bowel habit: diarrhea-predominant, constipation-predominant, or IBS with alternating bowel movements. IBS is often associated with stress or anxiety. Although IBS can be frustrating and concerning to patients with this disorder, it does not cause permanent harm to the intestines and does not lead to a serious disease such as cancer. Although treatments exist for its symptoms, there is no known cure. Copyright © 2011 Elsevier Inc. All rights reserved.

EXPERIMENTAL STUDIES OF IBS (INTRA-BEAM SCATTERING) IN RHIC AND COMPARISON WITH THEORY.

DOE Office of Scientific and Technical Information (OSTI.GOV)

FEDOTOV, A.V.; FISCHER, W.; TEPIKIAN, S.

A high-energy electron cooling system is presently being developed to overcome emittance growth due to Intra-beam Scattering (IBS) in RHIC. A critical item for choosing appropriate parameters of the cooler is an accurate description of the IBS. The analytic models were verified vs dedicated IBS measurements. Analysis of the 2004 data with the Au ions showed very good agreement for the longitudinal growth rates but significant disagreement with exact IBS models for the transverse growth rates. Experimental measurements were improved for the 2005 run with the Cu ions. Here, we present comparison of the 2005 data with theoretical models.

Celiac disease: Serologic prevalence in patients with irritable bowel syndrome.

PubMed

Mehdi, Zobeiri; Sakineh, Ebrahimi; Mohammad, Farahvash; Mansour, Rezaei; Alireza, Abdollahi

2012-09-01

The prevalence of irritable bowel syndrome (IBS) in the community is 10%-20% and have symptom based diagnostic criteria. Many symptoms of celiac disease (CD) with 1% prevalence in some communities can mimic IBS. Sensitive and specific serologic tests of CD can detect asymptomatic cases. The purpose of this study was to compare the level of anti-tissue-transglutaminase (tTG) IgA in IBS patients and controls group. This case-control study was performed at a University hospital in which 107 patients with IBS who met the Rome II criteria for their diagnosis were compared with 126 healthy age and sex-matched controls. Both groups were investigated for CD by analysis of their serum tTG IgA antibody with human recombinant antigen. Titers were positive containing over 10u/ml and borderline if they were between 4 and 10 u/ml. 86 percent of IBS patients were female. The mean antibody level was 0.837 u/ml in IBS group and 0.933 u/ml in control group without any significant difference. Results of this study may intensify disagreement on the situation of CD in IBS patients.

A purified transcription factor (TIF-IB) binds to essential sequences of the mouse rDNA promoter.

PubMed Central

Clos, J; Buttgereit, D; Grummt, I

1986-01-01

A transcription factor that is specific for mouse rDNA has been partially purified from Ehrlich ascites cells. This factor [designated transcription initiation factor (TIF)-IB] is required for accurate in vitro synthesis of mouse rRNA in addition to RNA polymerase I and another regulatory factor, TIF-IA. TIF-IB activity is present in extracts both from growing and nongrowing cells in comparable amounts. Prebinding competition experiments with wild-type and mutant templates suggest that TIF-IB interacts with the core control element of the rDNA promoter, which is located immediately upstream of the initiation site. The specific binding of TIF-IB to the RNA polymerase I promoter is demonstrated by exonuclease III protection experiments. The 3' border of the sequences protected by TIF-IB is shown to be on the coding strand at position -21 and on the noncoding strand at position -7. The results suggest that direct binding of TIF-IB to sequences in the core promoter element is the mechanism by which this factor imparts promoter selectivity to RNA polymerase I. Images PMID:3456157

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

PubMed Central

Revest, J-M; Kaouane, N; Mondin, M; Le Roux, A; Rougé-Pont, F; Vallée, M; Barik, J; Tronche, F; Desmedt, A; Piazza, P V

2010-01-01

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress. PMID:20368707

SYMPOSIUM REPORT: An Evidence-Based Approach to IBS and CIC: Applying New Advances to Daily Practice

PubMed Central

Chey, William D.

2017-01-01

Many nonpharmacologic and pharmacologic therapies are available to manage irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC). The American College of Gastroenterology (ACG) regularly publishes reviews on IBS and CIC therapies. The most recent of these reviews was published by the ACG Task Force on the Management of Functional Bowel Disorders in 2014. The key objective of this review was to evaluate the efficacy of therapies for IBS or CIC compared with placebo or no treatment in randomized controlled trials. Evidence-based approaches to managing diarrhea-predominant IBS include dietary measures, such as a diet low in gluten and fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs); loperamide; antispasmodics; peppermint oil; probiotics; tricyclic antidepressants; alosetron; eluxadoline, and rifaximin. Evidence-based approaches to managing constipation-predominant IBS and CIC include fiber, stimulant laxatives, polyethylene glycol, selective serotonin reuptake inhibitors, lubiprostone, and guanylate cyclase agonists. With the growing evidence base for IBS and CIC therapies, it has become increasingly important for clinicians to assess the quality of evidence and understand how to apply it to the care of individual patients. PMID:28729815

First evidences of interaction between pyranoanthocyanins and salivary proline-rich proteins.

PubMed

García-Estévez, Ignacio; Cruz, Luís; Oliveira, Joana; Mateus, Nuno; de Freitas, Victor; Soares, Susana

2017-08-01

The contribution of other classes of polyphenol compounds besides tannins to the overall perception of astringency is still poorly understood. So, this work aimed to study the interaction between a family of salivary proline-rich proteins (aPRPs) and representative pyranoanthocyanins in red wines [pyranomalvidin-3-glucoside (vitisin B), pyranomalvidin-3-glucoside-catechol, and pyranomalvidin-3-glucoside-epicatechin] using saturation transfer difference-NMR and MALDI-TOF. For vitisin B K D was of 1.74mM; for pyranomalvidin-3-glucoside-catechol was 1.17mM and for pyranomalvidin-3-glucoside-epicatechin it was 0.87mM. The presence of the flavanol structural unit in the pyranoanthocyanins led to an increase in their interaction with aPRPs. Further, it is also interesting that the values obtained were in the range of K D obtained previously reported for the interaction between the human saliva proline-rich peptides (IB7 14 and IB9 37 ) and procyanidins. Overall, the results obtained suggest that, along with tannins, other polyphenols present in red wine, namely pyranoanthocyanins, could actively contribute to red wine global astringency. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rare isotope accelerator project in Korea and its application to high energy density sciences

NASA Astrophysics Data System (ADS)

Chung, M.; Chung, Y. S.; Kim, S. K.; Lee, B. J.; Hoffmann, D. H. H.

2014-01-01

As a national science project, the Korean government has recently established the Institute for Basic Science (IBS) with the goal of conducting world-class research in basic sciences. One of the core facilities for the IBS will be the rare isotope accelerator which can produce high-intensity rare isotope beams to investigate the fundamental properties of nature, and also to support a broad research program in material sciences, medical and biosciences, and future nuclear energy technologies. The construction of the accelerator is scheduled to be completed by approximately 2017. The design of the accelerator complex is optimized to deliver high average beam current on targets, and to maximize the production of rare isotope beams through the simultaneous use of Isotope Separation On-Line (ISOL) and In-Flight Fragmentation (IFF) methods. The proposed accelerator is, however, not optimal for high energy density science, which usually requires very high peak currents on the target. In this study, we present possible beam-plasma experiments that can be done within the scope of the current accelerator design, and we also investigate possible future extension paths that may enable high energy density science with intense pulsed heavy ion beams.

Active learning for solving the incomplete data problem in facial age classification by the furthest nearest-neighbor criterion.

PubMed

Wang, Jian-Gang; Sung, Eric; Yau, Wei-Yun

2011-07-01

Facial age classification is an approach to classify face images into one of several predefined age groups. One of the difficulties in applying learning techniques to the age classification problem is the large amount of labeled training data required. Acquiring such training data is very costly in terms of age progress, privacy, human time, and effort. Although unlabeled face images can be obtained easily, it would be expensive to manually label them on a large scale and getting the ground truth. The frugal selection of the unlabeled data for labeling to quickly reach high classification performance with minimal labeling efforts is a challenging problem. In this paper, we present an active learning approach based on an online incremental bilateral two-dimension linear discriminant analysis (IB2DLDA) which initially learns from a small pool of labeled data and then iteratively selects the most informative samples from the unlabeled set to increasingly improve the classifier. Specifically, we propose a novel data selection criterion called the furthest nearest-neighbor (FNN) that generalizes the margin-based uncertainty to the multiclass case and which is easy to compute, so that the proposed active learning algorithm can handle a large number of classes and large data sizes efficiently. Empirical experiments on FG-NET and Morph databases together with a large unlabeled data set for age categorization problems show that the proposed approach can achieve results comparable or even outperform a conventionally trained active classifier that requires much more labeling effort. Our IB2DLDA-FNN algorithm can achieve similar results much faster than random selection and with fewer samples for age categorization. It also can achieve comparable results with active SVM but is much faster than active SVM in terms of training because kernel methods are not needed. The results on the face recognition database and palmprint/palm vein database showed that our approach can handle problems with large number of classes. Our contributions in this paper are twofold. First, we proposed the IB2DLDA-FNN, the FNN being our novel idea, as a generic on-line or active learning paradigm. Second, we showed that it can be another viable tool for active learning of facial age range classification.

Combat Modeling Evaluation at the United States Military Academy.

DTIC Science & Technology

1985-06-01

Ti.s to a smil- ique eitew de = Smaleissei by doe S hefer Press. am rnr we ma@"e- even I - "-re is hso use mom a sly ente orders bring dartani, vphae... transported to the VIIA *yet= at MR., a proes* which to almeet complete. 2Me lepertmet of fts- tory will thee be able te evelse the Sharks, md Arfemme...danewa its we modified As mei mmr Ciaur. 6). &W mit thot sooogltoly esm~hts Its supply of inmoitIawl"q eoat is Smoediaboly de . ttopd. IM6 OSOMe WOW. U

Changes in ciprofloxacin resistance levels in Enterobacter aerogenes isolates associated with variable expression of the aac(6')-Ib-cr gene.

PubMed

Ruiz, Elena; Ocampo-Sosa, Alain A; Alcoba-Flórez, Julia; Román, Elena; Arlet, Guillaume; Torres, Carmen; Martínez-Martínez, Luis

2012-02-01

Two closely related Enterobacter aerogenes isolates presented a new identical aac(6')-Ib-cr genetic environment, including IS26. One isolate showed lower MICs of ciprofloxacin, norfloxacin, tobramycin, and amikacin and decreased expression of aac(6')-Ib-cr, which might be related to a 12-bp deletion causing a displacement of the -10 box upstream of the aac(6')-Ib-cr gene.

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

S-IB-211, the flight version of the Saturn IB launch vehicle's first (S-IVB) stage, arrives at Marshall Space Flight Center's (MSFC's) S-IB static test stand. Between December 1967 and April 1968, the stage would undergo seven static test firings. The S-IB, developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility near New Orleans, Louisiana, utilized eight H-1 engines and each produced 200,000 pounds of thrust.

Saturn Apollo Program

NASA Image and Video Library

1965-03-15

Workers at the Marshall Space Flight Center (MSFC) hoist S-IB-1, the first flight version of the Saturn IB launch vehicle's first stage (S-IB stage), into the Saturn IB static test stand on March 15, 1965. Developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility (MAF) in New Orleans, Louisiana, the 90,000-pound booster utilized eight H-1 engines to produce a combined thrust of 1,600,000 pounds.

Saturn Apollo Program

NASA Image and Video Library

1967-10-01

S-IB-211, the flight version of the Saturn IB launch vehicle's (S-IVB) first stage, after installation at the Marshall Space Flight Center's (MSFC's) S-IB static test stand. Between December 1967 and April 1968, the stage would undergo seven static test firings. The S-IB, developed by the MSFC and built by the Chrysler Corporation at the Michoud Assembly Facility near New Orleans, Louisiana, utilized eight H-1 engines and each produced 200,000 pounds of thrust.

Probiotics and irritable bowel syndrome.

PubMed

Dai, Cong; Zheng, Chang-Qing; Jiang, Min; Ma, Xiao-Yu; Jiang, Li-Juan

2013-09-28

Irritable bowel syndrome (IBS) is common gastrointestinal problems. It is characterized by abdominal pain or discomfort, and is associated with changes in stool frequency and/or consistency. The etiopathogenesis of IBS may be multifactorial, as is the pathophysiology, which is attributed to alterations in gastrointestinal motility, visceral hypersensitivity, intestinal microbiota, gut epithelium and immune function, dysfunction of the brain-gut axis or certain psychosocial factors. Current therapeutic strategies are often unsatisfactory. There is now increasing evidence linking alterations in the gastrointestinal microbiota and IBS. Probiotics are living organisms which, when ingested in certain numbers, exert health benefits beyond inherent basic nutrition. Probiotics have numerous positive effects in the gastrointestinal tract. Recently, many studies have suggested that probiotics are effective in the treatment of IBS. The mechanisms of probiotics in IBS are very complex. The purpose of this review is to summarize the evidence and mechanisms for the use of probiotics in the treatment of IBS.

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome

PubMed Central

Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

2014-01-01

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting. PMID:24976697

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

PubMed

Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

2014-06-28

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

IBS for non-gaussian distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fedotov, A.; Sidorin, A.O.; Smirnov, A.V.

In many situations distribution can significantly deviate from Gaussian which requires accurate treatment of IBS. Our original interest in this problem was motivated by the need to have an accurate description of beam evolution due to IBS while distribution is strongly affected by the external electron cooling force. A variety of models with various degrees of approximation were developed and implemented in BETACOOL in the past to address this topic. A more complete treatment based on the friction coefficient and full 3-D diffusion tensor was introduced in BETACOOL at the end of 2007 under the name 'local IBS model'. Suchmore » a model allowed us calculation of IBS for an arbitrary beam distribution. The numerical benchmarking of this local IBS algorithm and its comparison with other models was reported before. In this paper, after briefly describing the model and its limitations, they present its comparison with available experimental data.« less

Health-related quality of life, work productivity, and indirect costs among patients with irritable bowel syndrome with diarrhea.

PubMed

Buono, Jessica L; Carson, Robyn T; Flores, Natalia M

2017-02-14

Irritable bowel syndrome (IBS) affects 10-15% of adults in the US, and is associated with significant impairment in health-related quality of life (HRQoL); however, information specific to the diarrhea subtype (IBS-D) is lacking. We assessed the impact of IBS-D on HRQoL, work productivity, and daily activities, and the associated indirect costs, among a sample of the US population. Respondents (≥18 years) from the 2012 US National Health and Wellness Survey who reported an IBS-D diagnosis by a physician or symptoms consistent with Rome II criteria for IBS-D were identified as having IBS-D. Controls included respondents without IBS-D or inflammatory bowel disease. HRQoL was assessed via the Short Form 36 Health Survey version 2 questionnaire and summarized into Mental and Physical Component Summary (MCS; PCS) scores and a Short Form-6 dimension (SF-6D) utility score. Work and activity impairment were assessed via the Work Productivity and Activity Impairment Questionnaire: General Health version (WPAI:GH), which measures absenteeism, presenteeism, overall work productivity loss, and daily activity impairment. Indirect costs were calculated using unit cost data from the Bureau of Labor Statistics and variables from the WPAI:GH. Generalized linear models were used to examine differences in health outcomes between respondents with IBS-D and controls, controlling for demographic and health characteristics. In total, 66,491 respondents (1102 IBS-D; 65,389 controls) were analyzed. Mean age was 48.7 years; 50% were female. Compared with controls, the IBS-D cohort reported significantly lower HRQoL (mean MCS: 45.16 vs. 49.48; p < 0.001; mean PCS: 47.29 vs. 50.67; p < 0.001; mean SF-6D: 0.677 vs. 0.741; p < 0.001) and greater absenteeism (5.1% vs. 2.9%; p = 0.004), presenteeism (17.9% vs. 11.3%; p < 0.001), overall work productivity loss (20.7% vs. 13.2%; p < 0.001), and activity impairment (29.6% vs. 18.9%; p < 0.001). Respondents with IBS-D also incurred an estimated $2486 more in indirect costs ($7008 vs. $4522; p < 0.001). Compared with controls, IBS-D is associated with significantly lower HRQoL, greater impairments in work and daily activities, and higher indirect costs, imposing a substantial burden on patients and employers. These findings suggest a significant unmet need exists for effective IBS-D treatments.

Prospective evaluation of quality of life after interstitial brachytherapy for localized prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caffo, Orazio; Fellin, Gianni; Bolner, Andrea

2006-09-01

Purpose: Permanent interstitial brachytherapy (IB) has become an increasingly appealing therapeutic option for localized prostate cancer (LPC) among physicians and patients because it involves short hospitalization and treatment and its postulated low degree of toxicity may reduce its impact on the patients' quality of life (QoL). The aim of this prospective study was to assess the impact of IB on the QoL of patients with LPC. Methods and Materials: A validated self-completed questionnaire was administered to the patients before and after IB and then at yearly intervals. The items allowed the identification of seven subscales exploring physical well-being (PHY), physicalmore » autonomy (POW), psychological well-being (PSY), relational life (REL), urinary function (URI), rectal function (REC), and sexual function (SEX). Results: The assessment of the QoL of 147 patients treated between May 2000 and February 2005 revealed no relevant differences in the PHY scale scores 1 month after IB or later, and the same was true of the POW, PSY, and REL scales. Urinary function significantly worsened after IB and returned to pretreatment levels only after 3 years; the impact of the treatment on the URI scale was greater in the patients with good baseline urinary function than in those presenting more urinary symptoms before IB. Rectal and sexual functions were significantly worse only at the post-IB evaluation. Conclusions: The results of the present study confirm that the impact of IB on the patients' QoL is low despite its transient negative effects on some function, and extend existing knowledge concerning QoL after IB.« less

Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report

PubMed Central

Liu, Xiaolin; Silverman, Alan; Kern, Mark; Ward, B. Douglas; Li, Shi-Jiang; Shaker, Reza; Sood, Manu R.

2015-01-01

Background The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (1) brain responses to visceral stimulation in adolescents are similar to those in adults, and (2) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. Methods IBS patients and controls received subliminal and liminal rectal distension during imaging. Stimulus-induced brain activations were determined. Salience network integrity was evaluated by functional connectivity of its seed regions activated by rectal distension in the insular and cingulate cortices. Key Results Compared with controls, IBS patients demonstrated greater activation to rectal distension in neural structures of the homeostatic afferent and emotional arousal networks, especially the anterior cingulate and insular cortices. Greater brain responses to liminal vs. subliminal distension were observed in both groups. Particularly, IBS is uniquely associated with an excessive coupling of the salience network with the DMN and ECN in their key frontal and parietal node areas. Conclusions & Inferences Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms. PMID:26467966

[Irritable bowel syndrome and cardiac right-to-left shunt through a patent foramen ovale].

PubMed

Alarcón-Fernández, Onofre; Alvarez-Fernández, Jesús-Andrés; Baudet, Juan-Salvador; Pérez-Quintero, Raquel; Sánchez-Del Río, Antonio; Borja-Gutiérrez, Elisa; Borque-Barrera, Pilar

2008-05-31

Both irritable bowel syndrome (IBS) and patent foramen ovale (PFO) have a similar prevalence in the general population, affect more commonly women and are related to comorbidities such as migraine. In IBS there are alterations in the metabolism of certain substances like serotonin. In the presence of PFO with a right- to left-shunt (RLS), a percentage of venous blood bypasses the lung filter and may increase these substances in blood. A phone interview was done to determine the presence of IBS in patients previously attended for detection of RLS with transcranial Doppler ultrasound. The presence and grade of RLS was analyzed and compared with subjects without gastrointestinal symptoms (NoGI). Rome II criteria were used to diagnose IBS or other functional gastrointestinal disorder (FGD) and Venice 1999 consensus were used for the diagnosis of RLS. Thirthy-three (18.3%) of 180 interviewed patients had IBS and 62 (34.4%) other FGD. RLS was found in 41% of NoGI patients, 64% of patients with IBS and 68% of patients with other FGD (odds ratio [OR] = 2.56; p < 0.05 for SII, and OR = 3.06; p < 0.01 for other FGD). RLS with a massive pattern was registered in en 27% of NoGI patients, 39% of patients with IBS and 45% of patients with other FGD (OR = 1.73; p = 1 for IBS, and OR = 2.21; p < 0.05 for other FGD). We found a higher prevalence of cardiac RLS through a PFO in patients with IBS and other FGD. A possible etiopathogenic relationship must be considered in future studies.

Patient satisfaction after gut-directed hypnotherapy in irritable bowel syndrome.

PubMed

Lindfors, P; Ljótsson, B; Bjornsson, E; Abrahamsson, H; Simrén, M

2013-02-01

Gut-directed hypnotherapy is an effective treatment option for irritable bowel syndrome (IBS). However, clinical observations suggest that patient satisfaction with hypnotherapy is not always associated with improvement in IBS symptoms. We evaluated 83 patients with IBS treated with gut-directed hypnotherapy (1 h week(-1), 12 weeks). After the treatment period, patients reported their satisfaction with the treatment (ranging from 1 = not at all satisfied, to 5 = very satisfied) and completed questionnaires to assess IBS symptom severity, quality of life, cognitive function, sense of coherence, depression, and anxiety before and after treatment. After hypnotherapy improved IBS symptom severity, quality of life, cognitive function, and anxiety were seen. Thirty patients (36%) were very satisfied with the treatment and 57 (69%) patients scored 4 or 5 on the patient satisfaction scale. Patient satisfaction was associated with less severe IBS symptoms and better quality of life after the treatment. In a multiple linear regression analysis, only the quality of life domain sexual relations was independently associated with patient satisfaction after hypnotherapy, explaining 22% of the variance. Using 25% reduction of IBS symptom severity to define an IBS symptom responder, 52% of the responders were very satisfied with hypnotherapy, but this was also true for 31% in the non-responder group. Patient satisfaction with gut-directed hypnotherapy in IBS is associated with improvement of quality of life and gastrointestinal (GI) symptoms. However, other factors unrelated to GI symptoms also seems to be of importance for patient satisfaction, as a substantial proportion of patients without GI symptom improvement were also very satisfied with this treatment option. © 2012 Blackwell Publishing Ltd.

Prevalence of irritable bowel syndrome in caregivers of patients with chronic diseases.

PubMed

Remes-Troche, J M; Torres-Aguilera, M; Montes-Martínez, V; Jiménez-García, V A; Roesch-Dietlen, F

2015-06-01

Caregivers are an at-risk population for psychic and physical diseases such as irritable bowel syndrome (IBS). However, it is not known whether providing care for the chronically ill patient can be considered a risk factor for developing IBS. In this study, our aim was to evaluate the prevalence of IBS according to the Rome II criteria in a group of caregivers. A cross-sectional study was conducted through an evaluation of caregivers of chronically ill patients. Subjects completed questionnaires including the Rome II Modular Questionnaire, the Hospital Anxiety and Depression Scale, the Zarit Caregiver Burden Interview (ZCBI) (an instrument for evaluating the burden experienced by caregivers), and the irritable bowel syndrome quality of life (IBS-QoL) questionnaire. Ninety-six primary caregivers (mean age was 43.6 ± 13.7 years and 87% were women) were evaluated. The mean length of time providing care was 37.6 months (3-288 months). Forty-seven caregivers (49%) presented with IBS. The caregivers with IBS had higher scores in the global ZCBI score (47 ± 8 vs 28 ± 8, p = 0.001) and on the anxiety and depression scale (p = 0.001) than those that did not have IBS. A total of 72% were diagnosed with caregiver stress syndrome; 42 of them had IBS according to the Rome II questionnaire (60% vs 18%, p = 0.001, relative risk 3.28, 95% CI: 1.4-7.4). Caregivers of chronically ill patients have a high prevalence of IBS, which is associated with depression, anxiety, and poor QoL. © 2015 John Wiley & Sons Ltd.

Role of alimentation in irritable bowel syndrome.

PubMed

Dapoigny, M; Stockbrügger, R W; Azpiroz, F; Collins, S; Coremans, G; Müller-Lissner, S; Oberndorff, A; Pace, F; Smout, A; Vatn, M; Whorwell, P

2003-01-01

Different food items are made responsible for irritable bowel syndrome (IBS) symptoms, but the physiopathology of IBS remains unclear. During a meeting in Nice, France, experts of the European Working Team of the IBiS Club discussed selected data regarding the relationships between alimentation, food items (including fibers) and IBS symptoms. Food allergy remains a difficult diagnosis, but medical and general history, presence of general symptoms such as skin rash, and hypersensitivity tests may help in achieving a positive diagnosis. On the other hand, food intolerance is more confusing because of the subjectivity of the relationship between ingestion of certain foods and the appearance of clinical symptoms. Different food items which are commonly implicated in adverse reactions mimicking IBS were found to be stimulants for the gut, suggesting that patients with predominant diarrhea IBS have to be carefully questioned about consumption of different kinds of food (i.e., coffee, alcohol, chewing gum, soft drinks) and not only on lactose ingestion. Gas production is discussed on the basis of retention of intestinal gas as well as on malabsorption of fermentable substrates. The role of a large amount of this kind of substrate reaching the colon is suggested as a potential mechanism of IBS-type symptoms in overeating patients. Regarding the role of fiber in IBS, the expert group concluded that fibers are not inert substances and that they could trigger pain or bloating in some IBS patients. Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dieteticians may have a positive role in managing such patients. Copyright 2003 S. Karger AG, Basel