Neurogastroenterology & Motility

Cover image for Vol. 28 Issue 2

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Magnus Simren, Gary Mawe and Jim Galligan, Associate Editor(s): Kirsteen Browning and Arjan Bredenoord

Impact Factor: 3.587

ISI Journal Citation Reports © Ranking: 2014: 25/76 (Gastroenterology & Hepatology); 44/192 (Clinical Neurology); 86/252 (Neurosciences)

Online ISSN: 1365-2982


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  1. Original Articles

    1. The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum

      D. Gallego, O. Ortega, C. Arenas, I. López, E. Mans and P. Clavé

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12788

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      We characterized the effects of levosulpiride, a 5HT4 agonist/D2 antagonist, on the main in vitro motility patterns in the human stomach and jejunum using organ bath. Prokinetic effects of the drug are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.

    2. Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation

      M. A. Mouchli, M. Camilleri, T. Lee, G. Parthasarathy, P. Vijayvargiya, M. Halland, A. Acosta and A. E. Bharucha

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12786

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      We retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

    3. Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave

      L. A. Bradshaw, L. K. Cheng, E. Chung, C. B. Obioha, J. C. Erickson, B. L. Gorman, S. Somarajan and W. O. Richards

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12780

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      The non-invasive magnetogastrogram shows a reduction in gastric slow wave propagation velocity and altered propagation patterns in patients with diabetic gastroparesis when compared with healthy control subjects. Temporal slow wave parameters typically measured in the electrogastrogram are not altered by gastroparesis.

    4. Characterization and correction of pressure drift in the ManoScan high-resolution manometry system: In vitro and in vivo

      K. Lamvik, E. Guiu Hernandez, R. Jones and M.-L. Huckabee

      Article first published online: 3 FEB 2016 | DOI: 10.1111/nmo.12770

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      The aim of this study was to provide critical in-depth analyses of ManoScan high-resolution manometry pressure drift in vitro and in vivo. Results indicate that the substantial drift in the ManoScan HRM system is highly variable and not corrected via the standard operating instructions.

    5. You have full text access to this OnlineOpen article
      Impairment of gastric accommodation induced by water-avoidance stress is mediated by 5-HT2B receptors

      H. Miwa, J. Koseki, T. Oshima, T. Hattori, Y. Kase, T. Kondo, H. Fukui, T. Tomita, Y. Ohda and J. Watari

      Article first published online: 2 FEB 2016 | DOI: 10.1111/nmo.12775

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      Water-avoidance stress significantly inhibited liquid meal-induced gastric accommodation; this inhibition was reversed by 5-HT2B receptor antagonist. This result suggests that stress-induced impairment of gastric accommodation is mediated by the activation of 5-HT2B receptors.

    6. Pressure topography metrics for high-resolution pharyngeal-esophageal manofluorography—a normative study of younger and older adults

      N. Nativ-Zeltzer, J. A. Logemann, S. G. Zecker and P. J. Kahrilas

      Article first published online: 28 JAN 2016 | DOI: 10.1111/nmo.12769

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      This study aimed to define normative values for novel pressure topography metrics of high-resolution pharyngeal-esophageal manometry with videofluoroscopy and examined the effects of age, gender and bolus properties on these measures. Results showed that older individuals exhibited more vigorous contractility in the pharynx than did younger subjects in all but the effortful swallows, perhaps reflecting a compensatory response to other age-related physiological changes.

    7. Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence

      J. Evers, L. Devane, E. V. Carrington, S. M. Scott, C. H. Knowles, P. R. O'Connell and J. F. X. Jones

      Article first published online: 28 JAN 2016 | DOI: 10.1111/nmo.12762

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      The study presented investigated the effect of sacral neuromodulation on anal canal somatosensory evoked potentials in a rodent model of fecal incontinence. Sacral neuromodulation restored anal evoked potentials diminished by pudendal nerve injury and stimulation at 2 Hz (optimum in healthy rats) was more effective than 14 Hz (therapeutic frequency). Sacral neruromodulation also increase expression of PSA-NCAM, a marker for synaptic plasticity, in the somatosensory cortex.

    8. Evaluation of the pylorus with concurrent intraluminal pressure and EndoFLIP in patients with nausea and vomiting

      W. J. Snape, M. S. Lin, N. Agarwal and R. E. Shaw

      Article first published online: 27 JAN 2016 | DOI: 10.1111/nmo.12772

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      Basal pyloric pressure is increased in 42% of patients with nausea, vomiting, and delayed gastric emptying. In patients with gastric retention >20%, distensibility is significantly decreased. EndoFLIP is a useful tool for evaluating pyloric function.

    9. A novel pathway for the production of H2S by DAO in rat jejunum

      S. Tang, D. Huang, N. An, D. Chen and D. Zhao

      Article first published online: 27 JAN 2016 | DOI: 10.1111/nmo.12765

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      Hydrogen sulfide is produced from D-cysteine (D-Cys) in rat jejunum. D-Amino acid oxidase (DAO) exists in rat jejunum. D-cysteine evokes a short-circuit current across epithelium of rat jejunum. D-cysteine enhances the Na+-coupled L-alanine transport.

    10. Na+/Ca2+ exchanger-heterozygote knockout mice display increased relaxation in gastric fundus and accelerated gastric transit in vivo

      Y. T. Azuma, S. Hayashi, K. Nishiyama, S. Kita, K. Mukai, H. Nakajima, T. Iwamoto and T. Takeuchi

      Article first published online: 19 JAN 2016 | DOI: 10.1111/nmo.12779

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      When an inhibitor of nitric oxide synthase was added following the EFS, neither NCX1 HET nor NCX2 HET exhibited transient relaxation, similar to WT. Furthermore, when a PACAP antagonist was added following the EFS, sustained relaxation in NCX1 HET and NCX2 HET was not observed, similar to WT.

    11. Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity

      Y. Ritze, A. Schollenberger, M. Hamze Sinno, N. Bühler, M. Böhle, G. Bárdos, H. Sauer, I. Mack, P. Enck, S. Zipfel, T. Meile, A. Königsrainer, M. Kramer and S. C. Bischoff

      Article first published online: 19 JAN 2016 | DOI: 10.1111/nmo.12773

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      Gastrointestinal hormone release and the regulation of appetite and body weight are thought to be dysbalanced in obesity. We asked whether ghrelin, GOAT, leptin, and leptinR expression demonstrates an increased expression in the stomach tissue and blood and also correlates with elevated inflammatory markers in obese compared with non-obese humans. Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation.

    12. Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors

      F. Jardí, J. A. Fernández-Blanco, V. Martínez and P. Vergara

      Article first published online: 14 JAN 2016 | DOI: 10.1111/nmo.12766

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      We explored the remodeling of colonic afferents and the potential role of NTFs in Trichinella spiralis-infected rats. T. spiralis induced a colonic inflammatory-like response accompanied by a transient reduction in neurotrophic factor levels. The expression of transient receptor potential vanilloid subtype 1 (TRPV1) in dorsal root ganglia (DRG) was diminished at acute stages of the infection. Moreover, in infected animals, an enhanced down-regulation of TRPV1 levels in lumbosacral DRGs after stimulation with intracolonic capsaicin was observed.

    13. Esophagogastric junction contractile integral (EGJ-CI) quantifies changes in EGJ barrier function with surgical intervention

      D. Wang, A. Patel, M. Mello, A. Shriver and C. P. Gyawali

      Article first published online: 14 JAN 2016 | DOI: 10.1111/nmo.12757

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      The esophagogastric junction contractile integral (EGJ-CI) is a novel high resolution manometry tool designed similar to the distal contractile integral (DCI) in assessing EGJ barrier function. In this study, we compared EGJ-CI at baseline between achalasia, reflux disease and controls, and postoperative EGJ-CI following surgery in achalasia and reflux disease. We demonstrate that the EGJ-CI accurately reflects surgical intervention and correlates well with individual conventional EGJ metrics. The EGJ-CI has potential to complement or replace existing metrics designed to assess the EGJ barrier.

    14. Supragastric belch may be related to globus symptom – a prospective clinical study

      P. Nevalainen, M. Walamies, O. Kruuna, P. Arkkila and L.-M. Aaltonen

      Article first published online: 6 JAN 2016 | DOI: 10.1111/nmo.12764

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      The aim was to investigate the possible esophageal background of globus symptoms, patients with reflux symptoms served as controls. In this study, globus patients without reflux symptoms did not have acid or non-acid GERD in 24-h MII-pH monitoring. However, globus patients had supragastric belch more often than patients with reflux symptoms.

    15. Stress increases descending inhibition in mouse and human colon

      D. E. Reed, Y. Zhang, M. J. Beyak, S. Lourenssen, M. G. Blennerhassett, W. G. Paterson and S. J. Vanner

      Article first published online: 6 JAN 2016 | DOI: 10.1111/nmo.12755

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      Stress and stress hormones increased descending inhibitory neuromuscular transmission in mice and human colon. This increase was via signaling to myenteric nerves. This could lead to greater in descending relaxation and decreased transit time through the colon and subsequent diarrhea.

  2. Review Articles

    1. Emerging treatments in neurogastroenterology: Acotiamade, a novel treatment option for functional dyspepsia

      M. Matsushita, T. Masaoka and H. Suzuki

      Article first published online: 5 JAN 2016 | DOI: 10.1111/nmo.12756

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      Action site of acotiamide hydrochloride (Z-338) in gut neuromuscular junction.

  3. Original Articles

    1. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity

      J. B. Frøkjær, S. Bergmann, C. Brock, A. Madzak, A. D. Farmer, J. Ellrich and A. M. Drewes

      Article first published online: 4 JAN 2016 | DOI: 10.1111/nmo.12760

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      The aim was to explore the effect of combined electrical and physiological modulation of vagal tone on musculoskeletal pain thresholds and gastroduodenal motility. Cardiac vagal tone, thresholds to bone pain, frequency of antral contractions, and gastroduodenal motility index all increased during active treatment compared to sham.

    2. Effect of genetic background and postinfectious stress on visceral sensitivity in Citrobacter rodentium-infected mice

      S. U. Mondelaers, S. A. Theofanous, M. V. Florens, E. Perna, J. Aguilera-Lizarraga, G. E. Boeckxstaens and M. M. Wouters

      Article first published online: 4 JAN 2016 | DOI: 10.1111/nmo.12759

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      Visceral hypersensitivity (VHS) is a hallmark of (postinfectious) irritable bowel syndrome (PI-IBS) but the underlying mechanisms remain largely unknown. We studied whether immunogenetic background and acute stress in the post-Citrobacter rodentium infectious phase influence the development of VHS and found that Citrobacter rodentium infection induces transient VHS in C57BL/6 and Balb/c mice, which persisted 1 week longer in Balb/c mice. Acute stress in the postinfectious phase did not recreate VHS, irrespective of immunogenetic background.

    3. Effects of pacifier and taste on swallowing, esophageal motility, transit, and respiratory rhythm in human neonates

      T. R. Shubert, S. Sitaram and S. R. Jadcherla

      Article first published online: 4 JAN 2016 | DOI: 10.1111/nmo.12748

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      Pacifier use is widely prevalent globally, despite unknown mechanisms regarding swallowing and airway safety. Upon evaluation with high-resolution impedance manometry, oral stimulus with either pacifier or taste interventions in neonates decreases UES and EGJ basal pressure, but has no effects on pharyngo-esophageal motility, airway interactions, or esophageal bolus transit. A decrease in central parasympathetic-cholinergic excitatory drive is likely responsible for the basal effects.

  4. Review Articles

    1. Enteroendocrine cells: a review of their role in brain–gut communication

      R. Latorre, C. Sternini, R. De Giorgio and B. Greenwood-Van Meerveld

      Article first published online: 21 DEC 2015 | DOI: 10.1111/nmo.12754

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      Enteroendocrine cells sense luminal content and release signaling molecules that can enter the circulation to act as classic hormones on distant targets, act locally on neighboring cells, and on distinct neuronal pathways including enteric and extrinsic neurons. Recent studies have shed light on EEC sensory transmission by showing direct connections between EECs and the nervous system via axon-like processes that form a well-defined neuroepithelial circuits through which EECs can directly communicate with the neurons innervating the GI tract to initiate appropriate functional responses.

  5. Technical Notes

    1. Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations

      B. P. Chumpitazi, M. M. Self, D. I. Czyzewski, S. Cejka, P. R. Swank and R. J. Shulman

      Article first published online: 21 DEC 2015 | DOI: 10.1111/nmo.12738

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      Rater reproducibility of the Bristol Stool Form Scale (BSFS), which categorizes stools into one of seven types, is unknown. We found that the BSFS has excellent reliability and agreement when used to rate individual stool type by expert raters. However, BSFS reliability and agreement decreases when determining Rome III stool form categories.

  6. Original Articles

    1. Patterns of esophageal pressure responses to a rapid drink challenge test in patients with esophageal motility disorders

      I. Marin and J. Serra

      Article first published online: 21 DEC 2015 | DOI: 10.1111/nmo.12749

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      Specific motor patterns elicited by a rapid drink challenge test discriminate between different groups of esophageal motility disorders, and detect abnormal motor responses in patients with clinical suspicion of esophageal motility disorders but normal HRM. To characterize specific pressure patterns in diverse esophageal motility disorders and to determine the potential of these patterns in the diagnosis of patients with normal manometry, a 200-mL multiple swallow test was performed in 30 healthy controls and 285 patients with esophageal motility disorders. Three different patterns of responses were characterized, that discriminated: (i) healthy subjects and patients with hypocontractile disorders; (ii) patients with non-obstructive hypercontractile disorders; and (iii) patients with achalasia. Seventeen percent of patients with esophageal symptoms but normal manometry had abnormal responses to the 200-mL challenge test.

    2. GERD phenotypes from pH-impedance monitoring predict symptomatic outcomes on prospective evaluation

      A. Patel, G. S. Sayuk, V. M. Kushnir, W. W. Chan and C. P. Gyawali

      Article first published online: 20 DEC 2015 | DOI: 10.1111/nmo.12745

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      Patients with GERD symptoms can be phenotyped into four distinct categories using a combination of abnormal acid exposure time (AET) and symptom reflux association using symptom association probability (SAP). The phenotypes include strong GERD evidence (abnormal AET, positive SAP), good evidence (abnormal AET, negative SAP), reflux hypersensitivity (normal AET, positive SAP), and equivocal or no GERD evidence (normal AET, negative SAP). By assessing symptom burden (dominant symptom intensity, global symptom severity) at the time of pH impedance monitoring and at follow-up, we demonstrate that these phenotypes can predict varying grades of symptomatic outcome.

    3. The zebrafish mutant lessen: an experimental model for congenital enteric neuropathies

      L. Uyttebroek, I. T. Shepherd, P. Vanden Berghe, G. Hubens, J.-P. Timmermans and L. Van Nassauw

      Article first published online: 20 DEC 2015 | DOI: 10.1111/nmo.12732

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      This study shows that the zebrafish mutant embryo lessen, revealing alterations in intestinal motility, intrinsic innervations and ICC network, is an appropriate model to investigate congenital enteric neuropathies.

    4. Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease

      R. Hotta, L. S. Cheng, H. K. Graham, W. Pan, N. Nagy, J. Belkind-Gerson and A. M. Goldstein

      Article first published online: 20 DEC 2015 | DOI: 10.1111/nmo.12744

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      Successful engraftment and differentiation of isogenic enteric neural progenitor cells transplanted into Hirschsprung mice. red-Tuj1 (neuron), green-GFP.

    5. Role of sympathetic nervous system in rat model of chronic visceral pain

      D. W. Gil, J. Wang, C. Gu, J. E. Donello, S. Cabrera and E. D. Al-Chaer

      Article first published online: 16 DEC 2015 | DOI: 10.1111/nmo.12742

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      This study examines the role of sympathetic outflow in chronic visceral hypersensitivity using recordings of electromyographic responses to colorectal distension in a rat colon irritation (CI) model with hallmarks of irritable bowel syndrome (IBS). Clonidine — alpha2-adrenergic agonist — and prazosin — alpha1-adrenergic antagonist—reduced the visceral hypersensitivity. Chemical sympathectomy with guanethidine and surgical sympathectomy also resulted in a loss of the chronic visceral hypersensitivity. The results support a role of the sympathetic nervous system in driving the chronic visceral and somatic hypersensitivity seen in CI rats. They further suggest that treatments that decrease sympathetic outflow or block activation of adrenergic receptors on sensory nerves could be beneficial in the treatment of generalized pain syndromes such as IBS. The sympathetic nervous system (SNS) exacerbates pain sensation when central pain inhibition is reduced; this observation is highly relevant to chronic pain disorders.

    6. Genome-wide DNA methylation profiling of peripheral blood mononuclear cells in irritable bowel syndrome

      S. Mahurkar, C. Polytarchou, D. Iliopoulos, C. Pothoulakis, E.A. Mayer and L. Chang

      Article first published online: 16 DEC 2015 | DOI: 10.1111/nmo.12741

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      Because irritable bowel syndrome (IBS) is a stress-sensitive disorder and environmental factors including stress can trigger epigenetic changes, we investigated genome-wide DNA methylation of IBS patients and healthy controls (HCs) using Illumina HM450 array. We identified DMPs in novel candidate genes such as glutathione-S-transferase and SCO-spondin, which could provide new insights into disease mechanisms. However, these preliminary findings warrant confirmation in larger, independent studies.

    7. Do endoflip assessments of anal sphincter distensibility provide more information on patients with fecal incontinence than high-resolution anal manometry?

      G. Gourcerol, S. Granier, V. Bridoux, J. F. Menard, P. Ducrotté and A. M. Leroi

      Article first published online: 15 DEC 2015 | DOI: 10.1111/nmo.12740

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      The EndoFLIP® can be used to measure anal canal distensibility. Fecal incontinence (FI) is associated with high distensibility at rest and during voluntary contraction. The ability of the distensibility index to discriminate between the FI patients and the healthy subjects was significantly better than anal pressures measured by 3D high-resolution manometry (3D-HRM).

    8. G protein-coupled estrogen receptor is involved in modulating colonic motor function via nitric oxide release in C57BL/6 female mice

      Y. Li, J. Xu, F. Jiang, Z. Jiang, C. Liu, L. Li, Y. Luo, R. Lu, Y. Mu, Y. Liu and B. Xue

      Article first published online: 12 DEC 2015 | DOI: 10.1111/nmo.12743

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      GPER is expressed in colonic myenteric neurons and co-localized with nNOS, its activation inhibits colonic propulsion in vivo and the contractile response in circular smooth muscle in vitro. The inhibitory effects of GPER may be mediated by promoting NO release from myenteric nitrergic nerves.

    9. Diaphragmatic breathing for rumination syndrome: efficacy and mechanisms of action

      M. Halland, G. Parthasarathy, A. E. Bharucha and D. A. Katzka

      Article first published online: 10 DEC 2015 | DOI: 10.1111/nmo.12737

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      Regurgitation in rumination syndrome occurs due to development of a flow permissive gastroesophageal pressure gradient resulting from greater gastric pressure and lower EGJ and UES pressure.

    10. Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo-obstruction and healthy controls

      A. Menys, S. Butt, A. Emmanuel, A. A. Plumb, A. Fikree, C. Knowles, D. Atkinson, N. Zarate, S. Halligan and S. A. Taylor

      Article first published online: 10 DEC 2015 | DOI: 10.1111/nmo.12735

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      The stimulatory effects of intravenous neostigmine on global small bowel motility may differ according to disease phenotype.

    11. Water avoidance stress induces visceral hyposensitivity through peripheral corticotropin releasing factor receptor type 2 and central dopamine D2 receptor in rats

      T. Nozu, S. Miyagishi, R. Nozu, K. Takakusaki and T. Okumura

      Article first published online: 10 DEC 2015 | DOI: 10.1111/nmo.12747

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      Water avoidance stress-induced visceral hyposensitivity in rats and this response was mediated through peripheral corticotropin releasing factor receptor type 2 and central dopamine D2 receptor.

    12. Esophageal diverticula are associated with propagating peristalsis: a study utilizing high-resolution manometry

      D. A. Carlson, A. B. Gluskin, B. Mogni, J. Koo, R. Sood, Z. Lin and J. E. Pandolfino

      Article first published online: 8 DEC 2015 | DOI: 10.1111/nmo.12739

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      Retrospective evaluation of 19 patients with esophageal diverticula and high-resolution manometry demonstrated that propagating peristalsis (motility diagnoses of normal motility [42%], EGJ outflow obstruction [26%], and jackhammer esophagus [11%]), but not achalasia (only one patient) was the predominant motility pattern observed. In addition, an abnormal pressure slope was noted during the compartmentalization phase of esophageal bolus transit in the diverticula patients, suggesting that abnormal esophageal wall mechanics may be associated with diverticula.

    13. Acute lumbosacral nerve stimulation does not affect anorectal motor function in a rodent model

      L. A. Devane, J. Evers, M. S. Scott, C. H. Knowles, P. O'Connell and J. F. X. Jones

      Article first published online: 26 NOV 2015 | DOI: 10.1111/nmo.12733

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      In a rodent model, acute sacral nerve stimulation does not affect internal or external anal sphincter motor function or rectoanal reflexes. This lack of action on the motor pathways of continence is in contrast to the known effects of SNS on sensory evoked cortical potentials and suggests that SNS works predominantly by increasing cortical awareness of the pelvic floor.

    14. Colon wall motility: comparison of novel quantitative semi-automatic measurements using cine MRI

      C. L. Hoad, A. Menys, K. Garsed, L. Marciani, V. Hamy, K. Murray, C. Costigan, D. Atkinson, G. Major, R. C. Spiller, S. A. Taylor and P. A. Gowland

      Article first published online: 26 NOV 2015 | DOI: 10.1111/nmo.12727

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      This study reports the development of an objective metric of ascending colon motility derived from cine MRI data using image registration techniques to remove respiratory motion and parameterize bowel movements. The line analysis metric produced the highest correlation coefficient with the observer scoring. Inter- and intra-observer variability was low for this metric.

    15. Lack of endogenous cholecystokinin promotes cholelithogenesis in mice

      H. H. Wang, M. Liu, P. Portincasa, P. Tso and D. Q.-H. Wang

      Article first published online: 25 NOV 2015 | DOI: 10.1111/nmo.12734

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      To elucidate the complex pathophysiological mechanisms determining the biliary characteristics of celiac disease, a mouse model with the lack of endogenous CCK was created. The lack of endogenous CCK enhances cholelithogenesis by accelerating cholesterol crystallization through impairing gallbladder emptying and by providing excess amounts of intestine-derived cholesterol for biliary hypersecretion through reducing small intestinal transit time and increasing intestinal cholesterol absorption.

  7. Review Articles

    1. The joint power of sex and stress to modulate brain–gut–microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome

      M. Pigrau, B. K. Rodiño-Janeiro, M. Casado-Bedmar, B. Lobo, M. Vicario, J. Santos and C. Alonso-Cotoner

      Article first published online: 11 NOV 2015 | DOI: 10.1111/nmo.12717

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      Stress and sex hormones play a relevant role in maintaining microbiome and brain–gut homeostasis. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain–gut–microbiome axis dysfunction and the implications for irritable bowel syndrome.

    2. The voltage-gated sodium channel NaV1.9 in visceral pain

      J. R. F. Hockley, W. J. Winchester and D. C. Bulmer

      Article first published online: 14 OCT 2015 | DOI: 10.1111/nmo.12698

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      Visceral pain and hypersensitivity are symptoms of patients with gastrointestinal diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recent evidence implicates the voltage-gated sodium channel subtype 1.9 (NaV1.9) as a regulator of primary visceral nociceptor sensitivity and as a contributor to sodium current conductance in neurones of the enteric nervous system. Patients with painful and painless phenotypes associated with mutations in NaV1.9 have been identified, which, in some cases, possess complex gastrointestinal disorders. These studies have served to confirm a key role for NaV1.9 in visceral pain and suggest that NaV1.9 may contribute to gastrointestinal disorders.


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