Neurogastroenterology & Motility

Cover image for Vol. 28 Issue 12

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: 3.31

ISI Journal Citation Reports © Ranking: 2015: 26/79 (Gastroenterology & Hepatology); 57/193 (Clinical Neurology); 92/256 (Neurosciences)

Online ISSN: 1365-2982

VIEW

  1. 1 - 73
  1. Hot Topic

    1. Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: a cross-comparison with migraine and healthy adults

      D.-M. Ellingsen, R. G. Garcia, J. Lee, R. L. Lin, J. Kim, A. H. Thurler, S. Castel, L. Dimisko, B. R. Rosen, N. Hadjikhani, B. Kuo and V. Napadow

      Version of Record online: 1 DEC 2016 | DOI: 10.1111/nmo.13004

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      Cyclic Vomiting Syndrome (CVS) and Episodic Migraine (MIG) may share pathophysiology, but no studies have yet compared these conditions. We found that the mid-posterior insula, a key region for viscero-sensation, shows diminished brain functional connectivity with the Sensorimotor Network in both CVS and MIG, but increased connectivity to the Salience Network for CVS only, compared to age- and sex-matched healthy controls. The results point to both CVS-unique and potentially shared pathophysiology between CVS and episodic migraine.

  2. Original Articles

    1. Anorectal manometry: should it be performed in a seated position?

      G.-j. Wu, F. Xu, L. Lin, P. J. Pasricha and J. D. Z. Chen

      Version of Record online: 1 DEC 2016 | DOI: 10.1111/nmo.12997

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      This study aimed to establish the validity and importance of performing anorectal manometry (ARM) in the physiological seated position instead of frequently used left lateral position. For this, we compared the differences in ARM parameters between water-perfused and solid-state sensors and between lateral and seated positions. The results showed that ARM performed in a seated position using solid-state sensors seems most accurate in assessing rectal pressure, and rectoanal pressure gradient (RAPG) measured under these conditions is predictive of balloon expulsion.

    2. Luminal contents from the gut of colicky infants induce visceral hypersensitivity in mice

      H. Eutamène, C. L. Garcia-Rodenas, S. Yvon, E. d'Aldebert, F. Foata, B. Berger, J. Sauser, V. Theodorou, G. Bergonzelli and E. Mas

      Version of Record online: 1 DEC 2016 | DOI: 10.1111/nmo.12994

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      The infant colic pathophysiology is poorly understood. In this study, luminal contents from colicky infants triggered visceral hyperalgesia in an animal model known to mimic IBS colonic hypersensitivity. Visceral hypersensitivity could be an important etiological factor involved in the prototypical colic crying behavior.

    3. Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's disease and chronic constipation

      F. Giancola, F. Torresan, R. Repossi, F. Bianco, R. Latorre, A. Ioannou, M. Guarino, U. Volta, P. Clavenzani, M. Mazzoni, R. Chiocchetti, F. Bazzoli, R. A. Travagli, C. Sternini and R. De Giorgio

      Version of Record online: 27 NOV 2016 | DOI: 10.1111/nmo.12995

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      Chronic constipation is usually a severe gastrointestinal dysfunction in patients with Parkinson's disease, but its pathogenesis remains poorly understood. This study evaluated functionally distinct submucosal neurons in relation to colonic motility and anorectal function in PD patients with constipation (PD/CC) vs both CC and controls.

      Colonic motor and rectal sensory functions resulted impaired in most parkinsonian constipated patients. Compared with controls, they display a decreased number of submucosal secretomotor neurons containing VIP immunoreactivity accompanied by a reduced mRNA expression of VIP and VIP receptors.

    4. Patients with Barrett's esophagus are hypersensitive to acid but hyposensitive to other stimuli compared with healthy controls

      C. Lottrup, A. L. Krarup, H. Gregersen, P. Ejstrud and A. M. Drewes

      Version of Record online: 27 NOV 2016 | DOI: 10.1111/nmo.12992

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      We assessed esophageal sensitivity including mechanical, heat, electrical, and acid stimulation in 23 patients with Barrett's esophagus and 12 controls using the multimodal probe. Patients showed hypersensitivity to acid, but hyposensitivity to other stimuli, asymptomatic patients were generally hyposensitive compared to symptomatic patients, and acid sensitivity overall increased with lower mucosal baseline impedance. We suggest that impaired mucosal sensitivity as measured by the proxy baseline impedance explains the acid hypersensitivity and hypothesize central pain modulation to cause the hyposensitivity to other stimuli.

    5. Gender differences in chronic constipation on anorectal motility

      M. Zakari, J. Nee, W. Hirsch, B. Kuo, A. Lembo and K. Staller

      Version of Record online: 27 NOV 2016 | DOI: 10.1111/nmo.12980

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      This is the largest comprehensive study of men with chronic constipation using HD-ARM. Our data suggest that there are significant physiologic and symptomatic differences between the sexes.

    6. Rectal intussusception: can high resolution three-dimensional ano-rectal manometry compete with conventional defecography?

      A. Benezech, M. Cappiello, K. Baumstarck, J.-C. Grimaud, M. Bouvier and V. Vitton

      Version of Record online: 27 NOV 2016 | DOI: 10.1111/nmo.12978

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      Three-dimensional high-resolution anorectal manometry (3DHRAM) provides physiological and morphological data about the perineum. The aim of this study was to define a diagnostic strategy using 3DHRAM to identify rectal intussusceptions (RI). On 3DHRAM, an anterior additional high-pressure area associated with an excessive perineal descent allowed the diagnosis of RI with a positive predictive value and a specificity of 100%. 3DHRAM confirmed its interest in the assessment of pelvic floor disorders and could be part of the diagnostic strategy of RI.

    7. The epidemiology of irritable bowel syndrome: Symptom development over a 3-year period in Denmark. A prospective, population-based cohort study

      L. R. Krogsgaard, A. L. Engsbro, M. P. Jones and P. Bytzer

      Version of Record online: 14 NOV 2016 | DOI: 10.1111/nmo.12986

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      IBS symptom development after 1 year influence symptom development after 3 years, with those fulfilling Rome III criteria for IBS after 1 year to be most likely to report IBS symptoms after 3 years.

    8. Acotiamide improves stress-induced impaired gastric accommodation

      K. Ikeo, T. Oshima, H. Sei, T. Kondo, H. Fukui, J. Watari and H. Miwa

      Version of Record online: 14 NOV 2016 | DOI: 10.1111/nmo.12991

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      Pretreatment with acotiamide significantly improved stress-induced impaired gastric accommodation. Acotiamide prolongs gastric accommodation and improves stress-induced impaired gastric accommodation.

    9. Acute sacral nerve stimulation reduces visceral mechanosensitivity in a cross-organ sensitization model

      L. D. Langlois, E. Le Long, M. Meleine, M. Antor, K. Atmani, P. Dechelotte, A. M. Leroi and G. Gourcerol

      Version of Record online: 7 NOV 2016 | DOI: 10.1111/nmo.12987

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      Sacral nerve stimulation reduced colonic nociception in a rat model of cross-organ sensitization. This effect involved an endogenous opioid pathway.

  3. Position Papers

    1. A fresh look at IBS—opportunities for systems medicine approaches

      A. Albusoda, N. Barki, T. Herregods, J. B. J. Kamphuis, T. B. Karunaratne, M. Lazarou, I. Lee, N. Mazurak, E. Perna, A. Polster, T. Pribic, F. Uhlig, H. Wang and P. Enck

      Version of Record online: 7 NOV 2016 | DOI: 10.1111/nmo.12989

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      NeuroGUT is a EU-funded initial training network (ITN) in neurogastroenterology. Neurogut trainees have attended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and critically evaluated the current knowledge on IBS for their respective research activities. They summarize that there is a gap open that should be filled with systems medicine.

  4. Original Articles

    1. Rotenone and elevated extracellular potassium concentration induce cell-specific fibrillation of α-synuclein in axons of cholinergic enteric neurons in the guinea-pig ileum

      D. F. Sharrad, B. N. Chen, W. P. Gai, N. Vaikath, O. M. El-Agnaf and S. J. H. Brookes

      Version of Record online: 7 NOV 2016 | DOI: 10.1111/nmo.12985

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      Impairment of bioenergetic homeostatic mechanisms and misfolding of a-synuclein are implicated in the pathogenesis of Parkinson's disease. Here, we show that rotenone and elevated extracellular potassium cause cell-specific fibrillation of a-synuclein in cholinergic enteric neurons in the guinea pig ileum. Like the central nervous system, the enteric nervous system shows selective vulnerability to stressors implicated in the pathogenesis of Parkinson's disease.

    2. Low-residue diet fed to rabbits induces histomorphological and biomechanical remodeling of small intestine

      Y. Liu, J. Zhao, D. Liao, L. Bao and H. Gregersen

      Version of Record online: 27 OCT 2016 | DOI: 10.1111/nmo.12983

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      This study demonstrated that low-residue diet in rabbits for one month induces intestinal histomorphometric and biomechanical remodelling, specifically mucosal changes and intestinal softening. The intestine is a complex mechanical organ. It is important to consider food-induced changes to all aspects of intestinal function.

    3. P2X3 receptor-mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD-like stress in the dorsal root ganglia of rats

      Y.-Q. He, X.-Q. Lang, L. Lin, L. Ji, X.-Y. Yuan, Q. Chen, Y.-M. Ran, H.-S. Chen, L. Li, J.-M. Wang, Z.-G. Wang, H. Gregersen, D.-W. Zou, H.-P. Liang and M. Yang

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/nmo.12976

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      Patients with posttraumatic stress disorder share co-morbidity with chronic pain conditions. The purpose was to study the underlying mechanisms of increased pain sensitivity in rats following exposure to posttraumatic stress disorder conditions. Motoric responses to colorectal distention were reduced initially in stress-exposed rats but increased afterwards to higher levels. Stress-exposure initially exhibited reduced dorsal root ganglion P2X3 ionic channel expression, which was followed by increased P2X3 expression. The data indicate an important role of P2X3 signaling in visceral pain.

    4. Tumor necrosis factor alpha derived from classically activated “M1” macrophages reduces interstitial cell of Cajal numbers

      S. T. Eisenman, S. J. Gibbons, P. -J. Verhulst, G. Cipriani, D. Saur and G. Farrugia

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/nmo.12984

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      In diabetic mice, M1 macrophages are associated with delayed gastric emptying, whereas M2 macrophages are associated with normal gastric emptying. TNF-α, a factor present in M1-conditioned medium, reduced Kit-positive ICC numbers and TNF-α neutralizing antibodies blocked the effect of M1 medium. TNF-α derived from M1 macrophages injures ICC in vitro and TNF-α may be important in diseases like diabetic gastroparesis.

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

      S. Ballou and L. Keefer

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/nmo.12982

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      This study characterizes daily impairment in patients with IBS. The majority of respondents reported impairment in at least five domains of daily living. Rates of impairment were highest among participants who met questionnaire-based criteria for psychiatric diagnoses.

    6. Early satiety and postprandial fullness in gastroparesis correlate with gastroparesis severity, gastric emptying, and water load testing

      H. P. Parkman, E. K. Hallinan, W. L. Hasler, G. Farrugia, K. L. Koch, L. Nguyen, W. J. Snape, T. L. Abell, R. W. McCallum, I. Sarosiek, P. J. Pasricha, J. Clarke, L. Miriel, J. Tonascia, F. Hamilton and The NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/nmo.12981

  5. Review Articles

    1. Plasticity of gastrointestinal vagal afferent satiety signals

      A. J. Page and S. J. Kentish

      Version of Record online: 25 OCT 2016 | DOI: 10.1111/nmo.12973

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      Vagal afferents are an important link between the gastrointestinal tract and the central nervous system, relaying information on the quantity and type of food consumed and initiating processes leading to behavioral changes in food intake. Whilst this system is effective in the regulation of food intake it is susceptible to disruption in various disease states including obesity. Understanding the mechanisms responsible for these detrimental effects is essential to establish more effective pharmacotherapies or lifestyle strategies for the treatment of obesity.

  6. Original Articles

    1. Baseline impedance measured during high-resolution esophageal impedance manometry reliably discriminates GERD patients

      K. Ravi, D. M. Geno, M. F. Vela, M. D. Crowell and D. A. Katzka

      Version of Record online: 24 OCT 2016 | DOI: 10.1111/nmo.12974

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      Previous studies have demonstrated that baseline impedance measured during ambulatory impedance pH monitoring has reliable diagnostic accuracy for GERD. In this study of 29 patients with at least moderate acid reflux and 26 controls, baseline impedance measured during the initial landmark period of a high-resolution esophageal manometry (HRIM) study demonstrated excellent diagnostic accuracy for GERD, with an AUC of 0.931 on ROC analysis. These findings suggest that HRIM determined baseline impedance may represent an accurate, cost-effective, and less invasive tool for the diagnosis of GERD.

  7. Review Articles

    1. Rumination syndrome: pathophysiology, diagnosis, and treatment

      I. Absah, A. Rishi, N. J. Talley, D. Katzka and M. Halland

      Version of Record online: 20 OCT 2016 | DOI: 10.1111/nmo.12954

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      This review critically appraises recent studies of pathophysiology and therapy for rumination syndrome.

  8. Original Articles

    1. Jackhammer esophagus: Observations on a European cohort

      T. V. K. Herregods, A. J. P. M. Smout, J. L. S. Ooi, D. Sifrim and A. J. Bredenoord

      Version of Record online: 17 OCT 2016 | DOI: 10.1111/nmo.12975

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      The aim of our study was to describe a large cohort of patients with jackhammer esophagus and to investigate whether manometric findings can be associated with the presence of symptoms. Most patients with jackhammer esophagus suffered from dysphagia (67.6%) and/or chest pain (47.1%). The symptom chest pain was not associated with any of the manometric findings, whereas the symptom dysphagia was associated with strong contractions of the lower esophageal sphincter, signs of a possible outflow obstruction, and a very high distal contractile integral.

    2. BDNF modulates intestinal barrier integrity through regulating the expression of tight junction proteins

      Y.-B. Yu, D.-Y. Zhao, Q.-Q. Qi, X. Long, X. Li, F.-X. Chen and X.-L. Zuo

      Version of Record online: 17 OCT 2016 | DOI: 10.1111/nmo.12967

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      Brain-derived neurotrophic factor, a member of neurotrophins family, was originally known for its effects on the development and regeneration of central nervous system. In our study, we showed for the first time that BDNF may play a role in regulating intestinal epithelial barrier via affecting the expression of tight junction proteins.

    3. Effects of varying dietary content of fermentable short-chain carbohydrates on symptoms, fecal microenvironment, and cytokine profiles in patients with irritable bowel syndrome

      T. N. Hustoft, T. Hausken, S. O. Ystad, J. Valeur, K. Brokstad, J. G. Hatlebakk and G. A. Lied

      Version of Record online: 16 OCT 2016 | DOI: 10.1111/nmo.12969

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      The results from this study support the efficacy of a low-FODMAP diet in alleviating IBS symptoms, demonstrate intersubject differences in FOS sensitivity, and support the “FODMAP concept” that global restriction is more efficient than a limited restriction. Our findings also suggest that a low-FODMAP diet induces changes in inflammatory cytokines, microbiota profile, and SCFAs, which may have consequences for gut health.

    4. Benchmarks for the interpretation of esophageal high-resolution manometry

      R. Yadlapati, R. N. Keswani, K. B. Dunbar, A. J. Gawron, C. P. Gyawali, P. J. Kahrilas, P. O. Katz, D. Katzka, S. J. Spechler, R. Tatum and J. E. Pandolfino

      Version of Record online: 13 OCT 2016 | DOI: 10.1111/nmo.12971

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      Currently, there is a gap in competency-based training and assessment for esophageal high-resolution manometry (HRM). Using formal standard setting techniques among a group of esophageal experts, we created an exam for the interpretation of esophageal HRM. In addition, we established minimum competency cut scores for esophageal HRM skills at the trainee, physician interpreter, and master level.

    5. Impact of symptom burden and health-related quality of life (HRQOL) on esophageal motor diagnoses

      C. A. Reddy, A. Patel and C. P. Gyawali

      Version of Record online: 9 OCT 2016 | DOI: 10.1111/nmo.12970

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      The interrelationship between esophageal symptom characteristics, symptom burden, and motor diagnoses (Chicago Classification v 3.0) were further studied by obtaining validated self-report questionnaires in 211 patients undergoing esophageal high-resolution manometry (HRM). Chicago Classification diagnoses (outflow obstruction, major disorders) were associated with the highest symptom burden. Symptom characteristics were best characterized by pathophysiologic categorization of motor disorders into outflow obstruction, hypermotility disorders, and hypomotility disorders. Contraction wave abnormalities in patients without a motor disorder (according to Chicago Classification) had distinct symptom characteristics and symptom burden that aligned best with hypermotility disorders.

  9. Review Articles

    1. An ANMS-NASPGHAN consensus document on anorectal and colonic manometry in children

      L. Rodriguez, M. Sood, C. Di Lorenzo and M. Saps

      Version of Record online: 9 OCT 2016 | DOI: 10.1111/nmo.12944

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      The study of the colon and anorectal function has experienced great technical advances that facilitated the performance of tests and allowed a more detailed characterization of reflexes and motor patterns. As a result, we have achieved a much better understanding of the pathophysiology of children with defecation problems. This review highlights some of the recent advances in pediatric colonic and anorectal motility testing including indications and preparation and how to interpret the results.

  10. Original Articles

    1. Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia

      N. Nakajima, H. Sato, K. Takahashi, G. Hasegawa, K. Mizuno, S. Hashimoto, Y. Sato and S. Terai

      Version of Record online: 3 OCT 2016 | DOI: 10.1111/nmo.12968

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      We aimed to analyze the relation between high-resolution manometry (HRM) findings and histopathology of muscularis externa in esophageal motility disorders. ICCs were preserved in high numbers in type III achalasia compared to other achalasia types. In some patients with JE and NE, eosinophilic infiltration of the esophageal muscle layer was shown, possibly related to the hypercontraction on HRM. Histopathological examination of the muscle layer in esophageal motility disorders may elucidate the pathology.

    2. Reproducibility of high-definition (3D) manometry and its agreement with high-resolution (2D) manometry in women with fecal incontinence

      S. Chakraborty, K. J. Feuerhak, A. R. Zinsmeister and A. E. Bharucha

      Version of Record online: 2 OCT 2016 | DOI: 10.1111/nmo.12950

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      In this study, we evaluated the intra-individual reproducibility of high definition anorectal manometry (HD-ARM) in women with fecal incontinence and compared pressures measured with HD-ARM and high-resolution manometry (HR-ARM). Anal pressures at rest and during squeeze measured with HD-ARM were reproducible on the same and different days, but those during evacuation were not. Resting and squeeze pressures measured with HD-ARM and HR-ARM were also concordant. These findings support the use of HD-ARM for longitudinal assessments of anal resting and squeeze pressures.

    3. May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat

      R. Abalo, J. A. Uranga, I. Pérez-García, R. de Andrés, R. Girón, G. Vera, A. E. López-Pérez and M. I. Martín-Fontelles

      Version of Record online: 30 SEP 2016 | DOI: 10.1111/nmo.12952

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      In this article, we have characterized the effects of the antineoplastic drug 5-fluorouracil using X-rays and conventional histology in the rat, and have evaluated whether cannabinoids might be useful for treating 5-FU-induced diarrhea. A low dose of the non-selective cannabinoid agonist WIN partially prevented the development of diarrhea, probably through actions on motility, but did not prevent 5-FU-induced mucositis. This is the first experimental study on the effects of cannbinoids on chemotherapy-induced diarrhea.

  11. Review Articles

    1. Chronic intestinal pseudo-obstruction in children and adults: diagnosis and therapeutic options

      G. Di Nardo, C. Di Lorenzo, A. Lauro, V. Stanghellini, N. Thapar, T. B. Karunaratne, U. Volta and R. De Giorgio

      Version of Record online: 29 SEP 2016 | DOI: 10.1111/nmo.12945

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      Chronic intestinal pseudo-obstruction (CIPO) represents the most severe form of gastrointestinal dysmotility with debilitating and potentially lethal consequences. Symptoms can be non-specific, and result in an incorrect or too late diagnosis with consequences in terms of morbidity and even mortality. Thus, the present article aims to provide pediatric and adult gastroenterologists with an up to date review about clinical features, diagnosis, and therapeutic options for CIPO.

  12. Original Articles

    1. Functional gastrointestinal disorders in Greek Children based on ROME III criteria: identifying the child at risk

      I. Bouzios, G. Chouliaras, G. P. Chrousos, E. Roma and V. Gemou-Engesaeth

      Version of Record online: 28 SEP 2016 | DOI: 10.1111/nmo.12951

  13. Review Articles

    1. Sleep disturbances in irritable bowel syndrome: a systematic review

      Q. Tu, M. M. Heitkemper, M. E. Jarrett and D. T. Buchanan

      Version of Record online: 28 SEP 2016 | DOI: 10.1111/nmo.12946

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      Sleep disturbances are well-documented among persons with irritable bowel syndrome (IBS). Some researchers have provided evidence of a positive association between poorer subjective sleep quality and increased severity and frequency in gastrointestinal (GI) symptoms in those with IBS, but findings from studies using objective sleep and activity measures are inconclusive. This systematic review of the literature between 1990 and 2015 evaluates the evidence of sleep disturbances in adults with IBS and their relationship with GI symptoms.

  14. Original Articles

    1. The association between Ehlers-Danlos syndrome—hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study

      A. Fikree, R. Aktar, J. K. Morris, R. Grahame, C. H. Knowles and Q. Aziz

      Version of Record online: 28 SEP 2016 | DOI: 10.1111/nmo.12942

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      Comparison of GI symptoms in students with and without EDS-HT. The most common upper GI symptoms in EDS-HT were abdominal pain (42.6%), postprandial fullness (34.4%), early satiety (31.5%) and bloating (26.4%). However, only postprandial fullness (34.4% vs 15.9%, P=.01) and early satiety (EDS-HT: 31.5% vs 17%, P=.03) were significantly increased when compared with non-EDS-HT students (Table 3).

    2. The motility of esophageal sphincters during liquid and solid bolus swallows: a multicenter normative value study of high-resolution manometry in China

      X.-L. Xiang, A. Wang, L. Tu, M.-Y. Ke, Y.-S. Yang, B. Jiang, L. Lin, N. Dai, S.-S. Zhang, L. Tao, H. Xu, X.-M. Liang, X.-C. Fang, Z.-W. Xia, X. Wang, J.-N. Wu, M.-F. Wang, H.-J. Zhang, Y.-F. Fang, C. Shen, J. Wang, L.-H. Peng, W.-Y. Li, Z.-F. Wang, K. Wang, N. Liu and X.-H. Hou

      Version of Record online: 25 SEP 2016 | DOI: 10.1111/nmo.12914

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      This study demonstrated the motility differences between solid and liquid bolus swallows for both the UES and LES. It confirms the application of HRM with solid swallows. More importantly, this study provides the normative values for both liquid and solid bolus swallows of Sierra Scientific Instruments solid-state HRM system for Chinese population.

    3. Do Jackhammer contractions lead to achalasia? A longitudinal study

      L. Huang, M. Pimentel and A. Rezaie

      Version of Record online: 23 SEP 2016 | DOI: 10.1111/nmo.12953

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      Jackhammer esophagus (JE) is a rare and intermittent hypercontractile esophageal motility disorder. In this retrospective study, we have found that some patients with JE can transition to type III achalasia over time, and that this transformation may be more common in those patients who have impaired lower esophageal sphincter relaxation at initial JE diagnosis.

    4. Continuous wavelet analysis of postprandial EGGs suggests sustained gastric slow waves may be slow to develop in infants with colic

      G. W. Reynolds, R. G. Lentle, P. W. M. Janssen and C. M. Hulls

      Version of Record online: 20 SEP 2016 | DOI: 10.1111/nmo.12948

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      Continuous wavelet transforms (CWT) of EGG recordings from breastfed babies were used to test the hypothesis that infant colic is associated with abnormal patterns of gastric motility. Univariate and multivariate comparisons of the characteristics of the principal three frequency ranges 1.4–2.5, 2.5–4.0, and 4.0–15 cpm allowed discrimination between colicky and non-colicky babies. The authors conclude that CWT of EGG signals is sufficiently sensitive to detect abnormal electrophysiological patterns in colicky babies.

  15. Review Articles

    1. Exploring hypotheses and rationale for causes of infantile colic

      M. Camilleri, S.-Y. Park, E. Scarpato and A. Staiano

      Version of Record online: 20 SEP 2016 | DOI: 10.1111/nmo.12943

  16. Original Articles

    1. High-resolution impedance manometry parameters enhance the esophageal motility evaluation in non-obstructive dysphagia patients without a major Chicago Classification motility disorder

      D. A. Carlson, T. Omari, Z. Lin, N. Rommel, K. Starkey, P. J. Kahrilas, J. Tack and J. E. Pandolfino

      Version of Record online: 20 SEP 2016 | DOI: 10.1111/nmo.12941

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      We aimed to perform a collaborative analysis of high-resolution impedance manometry metrics to evaluate patients without non-obstructive dysphagia with a major esophageal motility disorder. The esophageal impedance integral (EII) ratio and bolus flow time demonstrated the strongest symptom correlations and differed between dysphagia patients and asymptomatic controls. The EII ratio also differed between dysphagia and non-dysphagia patient–controls, suggesting it may aid characterization of symptomatic patients with otherwise non-diagnostic manometry.

    2. The importance of a high rectal pressure on strain in constipated patients: implications for biofeedback therapy

      Y. Mazor, R. Hansen, G. Prott, J. Kellow and A. Malcolm

      Version of Record online: 20 SEP 2016 | DOI: 10.1111/nmo.12940

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      In this study, we identify a subgroup of patients with dyssynergic symptoms but without a formal Rome III diagnosis of functional defecation disorders, who are characterized by a high rectal pressure on strain. Although these patients displayed some physiological differences to the patients with lower straining rectal pressure, they suffer similarly. Importantly, we show that these patients can respond favorably to anorectal biofeedback treatment.

    3. The added diagnostic value of postreflux swallow-induced peristaltic wave index and nocturnal baseline impedance in refractory reflux disease studied with on-therapy impedance-pH monitoring

      M. Frazzoni, N. de Bortoli, L. Frazzoni, S. Tolone, M. Furnari, I. Martinucci, V. G. Mirante, S. Marchi, V. Savarino and E. Savarino

      Version of Record online: 12 SEP 2016 | DOI: 10.1111/nmo.12947

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      On-therapy impedance-pH monitoring establishes the relationship between PPI-refractory heartburn and reflux. Post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) were highly efficient in distinguishing PPI-refractory non-erosive reflux disease (NERD) from functional heartburn (FH) and refractory reflux esophagitis (RRE) from healed reflux esophagitis (HRE). Abnormal PSPW index and MNBI characterize reflux-related PPI-refractory heartburn.

    4. Morphometric profile of large intestinal neuronal plexuses in normal perinatal autopsies and Hirschsprung disease

      H. Subramanian, B. A. Badhe, P. C. Toi and K. Sambandan

      Version of Record online: 12 SEP 2016 | DOI: 10.1111/nmo.12939

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      Morphometric assessment of neuronal plexuses with image capture and analysis in 40 normal and 40 Hirschsprung colons was used to derive objective reference values based on clearly defined evaluation techniques.

    5. The feasibility, usability, and clinical utility of traditional paper food and symptom journals for patients with irritable bowel syndrome

      J. K. Zia, C.-F. Chung, J. Schroeder, S. A. Munson, J. A. Kientz, J. Fogarty, E. Bales, J. M. Schenk and M. M. Heitkemper

      Version of Record online: 12 SEP 2016 | DOI: 10.1111/nmo.12935

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      The aim of this study was to evaluate the feasibility, usability, and clinical utility of paper food and gastrointestinal symptom journals as data collection tools for patients with irritable bowel syndrome (IBS). Paper journaling of food and symptoms appears to be a feasible and usable data collection tool for IBS patients. Over half perceive journaling as at least somewhat clinically useful.

    6. Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility

      M. P. Guarino, G. Barbara, A. Cicenia, A. Altomare, M. R. Barbaro, S. Cocca, A. Scirocco, C. Cremon, S. Emerenziani, V. Stanghellini, M. Cicala and C. Severi

      Version of Record online: 12 SEP 2016 | DOI: 10.1111/nmo.12928

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      The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. Supernatants were obtained from biopsies of IBS patients and asymptomatic subjects. IBS supernatants reduced colonic contractility mucosal likely through muscular intracellular oxidative stress damage. Depending on the IBS subtype, further different neuromotor mechanisms are involved.

    7. Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24-hour esophageal impedance/pH monitoring in pediatric patients

      J. E. Fortunato, R. B. D'Agostino Jr. and M. O. Lively

      Version of Record online: 7 SEP 2016 | DOI: 10.1111/nmo.12936

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      Pepsin in saliva is a proposed biomarker for oropharyngeal reflux, which may be present in saliva from subjects with GER. The concentration of salivary pepsin decreases rapidly as a function of time after the reflux event. Therefore, saliva samples must be obtained soon after reflux occurs.

    8. Fecal incontinence in irritable bowel syndrome: Prevalence and associated factors in Swedish and American patients

      M. Simrén, O. S. Palsson, S. Heymen, A. Bajor, H. Törnblom and W. E. Whitehead

      Version of Record online: 31 AUG 2016 | DOI: 10.1111/nmo.12919

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      We studied one US (n=304) and one Swedish IBS cohort (n=168), and fecal incontinence (FI) ≥ one day per month was reported by 19.7% (USA) and 13.7% (Sweden) of IBS patients.FI was associated with loose, frequent stools, urgency, and adverse impact on quality of life, psychological symptoms, and work productivity.

    9. Propofol inhibits carbachol-induced chloride secretion by directly targeting the basolateral K+ channel in rat ileum epithelium

      S.-H. Tang, H.-Y. Wang, H. Sun, N. An, L. Xiao, Q. Sun and D.-B. Zhao

      Version of Record online: 30 AUG 2016 | DOI: 10.1111/nmo.12934

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      The aim of this study was to investigate the effects of propofol on carbachol (CCh)-evoked short-circuit currents (Isc). The results show that propofol inhibits CCh-induced intestinal secretion by directly targeting basolateral K+ channels.

    10. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis

      S. Sun, Z. Cui, M. Zhou, R. Li, H. Li, S. Zhang, Y. Ba and G. Cheng

      Version of Record online: 30 AUG 2016 | DOI: 10.1111/nmo.12926

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      In the light of the results of our meta-analysis, PPI therapy is associated with a 70% increased risk of cardiovascular events in patients with GERD. Omeprazole could significantly increase the risk of cardiovascular events. Thus, we believe that doctors should be advised to carefully consider the use of PPIs in clinical situations, and try to choose the best treatment option for each patient.

    11. Colonic content: effect of diet, meals, and defecation

      R. A. Bendezú, M. Mego, E. Monclus, X. Merino, A. Accarino, J. R. Malagelada, I. Navazo and F. Azpiroz

      Version of Record online: 21 AUG 2016 | DOI: 10.1111/nmo.12930

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      Ingestion of unabsorbable residues and defecation produce profound changes in colonic content. The rapid turnover of colonic biomass (about 1/3 daily) indicates a high adaptation potential of microbiota to the intraluminal environment.

    12. Increased yield pressure in the anal canal during sacral nerve stimulation: a pilot study with the functional lumen imaging probe

      S. Haas, D. Liao, H. Gregersen, L. Lundby, S. Laurberg and K. Krogh

      Version of Record online: 21 AUG 2016 | DOI: 10.1111/nmo.12929

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      Spatio-temporal diameter map of the anal canal from a single subject. The changing colors from blue to red illustrate increasing diameter.

    13. Impact of prenatal and postnatal exposure to the pesticide chlorpyrifos on the contraction of rat ileal muscle strips: involvement of an inducible nitric oxide synthase-dependent pathway

      W. Darwiche, S. Delanaud, S. Dupont, H. Ghamlouch, W. Ramadan, W. Joumaa, V. Bach and J. Gay-Quéheillard

      Version of Record online: 21 AUG 2016 | DOI: 10.1111/nmo.12918

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      The present study showed that the exposure to chlorpyrifos (CPF), a widely used insecticide, from the first day of gestation to early adulthood, in a rat model, is associated with low EFS-induced ileal contraction, elevated iNOS expression, partial inhibition of AChE activity, and low ileal muscle thickness.

    14. Prolonged measurement improves the assessment of the barrier function of the esophago-gastric junction by high-resolution manometry

      D. Jasper, N. Freitas-Queiroz, M. Hollenstein, B. Misselwitz, P. Layer, T. Navarro-Rodriguez, M. Fox and J. Keller

      Version of Record online: 14 AUG 2016 | DOI: 10.1111/nmo.12925

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      Total-esophagogastric junction contractile integral (EGJ-CI), a new metric summarizing EGJ contractility over the entire length of standard HRM, was tested in 65 healthy controls and 452 GERD patients and proved to be superior over conventional metrics and other HRM metrics for prediction of pathological reflux. In particular, the negative predictive value approached 90% if total-EGJ-CI was within the upper two-thirds of the normal range. These findings suggest that GERD is highly unlikely if the EGJ can maintain normal contractility over several minutes.

    15. Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients

      A. Zifan, Y. Jiang and R. K. Mittal

      Version of Record online: 10 AUG 2016 | DOI: 10.1111/nmo.12917

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      The goal of our study was to perform a detailed time and spectral domain analysis of the esophageal mucosal blood perfusion (EMBP) waveform from of NE patients and controls to determine the optimal EMBP biomarkers that combined with suitable statistical learning models may produce robust discrimination between the two groups.

    16. Stigmatization toward irritable bowel syndrome and inflammatory bowel disease in an online cohort

      T. H. Taft, A. Bedell, J. Naftaly and L. Keefer

      Version of Record online: 8 AUG 2016 | DOI: 10.1111/nmo.12921

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      Stigma toward chronic illness is a pervasive public health issue. This is the first study to evaluate stigmatizing beliefs toward IBS and IBD.

    17. A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population

      F. Bonfiglio, P. G. Hysi, W. Ek, V. Karhunen, N. V. Rivera, M. Männikkö, H. Nordenstedt, M. Zucchelli, F. Bresso, F. Williams, H. Tornblom, P. K. Magnusson, N. L. Pedersen, J. Ronkainen, P. T. Schmidt and M. D'Amato

      Version of Record online: 3 AUG 2016 | DOI: 10.1111/nmo.12923

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      We report a meta-analysis of GERD GWA studies from three independent population-based cohorts identifying 30 independent suggestive signals of association, showing concordant risk directions and functional effects on gene expression.

    18. Spatiotemporal characteristics of the pharyngeal event-related potential in healthy subjects and older patients with oropharyngeal dysfunction

      L. Rofes, O. Ortega, N. Vilardell, L. Mundet and P. Clavé

      Version of Record online: 2 AUG 2016 | DOI: 10.1111/nmo.12916

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      Appropriate oropharyngeal sensory feedback is essential for safe and efficient swallowing. Non-dysphagic older patients present impaired cortical activation compared with young healthy volunteers in response to pharyngeal electrical stimulus. Older patients with dysphagia also present disturbances in the pharyngo-cortical connection together with a disrupted pattern of cortical activation. Swallowing therapy in older people with dysphagia should include strategies aiming to stimulate the pharyngeal sensory afferents to promote recovery of the swallowing function.

    19. Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry

      S. Roman, R. Holloway, J. Keller, F. Herbella, F. Zerbib, Y. Xiao, L. Bernard, A. J. Bredenoord, S. Bruley des Varannes, M. Chen, M. Fox, P. J. Kahrilas, R. K. Mittal, R. Penagini, E. Savarino, D. Sifrim, J. Wu, E. Decullier, J. E. Pandolfino and F. Mion

      Version of Record online: 31 JUL 2016 | DOI: 10.1111/nmo.12920

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      A consensus definition of transient lower espohageal sphincter relaxation (TLESR) using high resolution manometry is proposed. TLESR is defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with crural definition inhibition. Reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis are alternate diagnostic criteria.

    20. You have full text access to this OnlineOpen article
      Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study

      F. Azpiroz, C. Dubray, A. Bernalier-Donadille, J.-M. Cardot, A. Accarino, J. Serra, A. Wagner, F. Respondek and M. Dapoigny

      Version of Record online: 31 JUL 2016 | DOI: 10.1111/nmo.12911

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      Our aim was to evaluate the effects of short-chain fructooligosaccharides (scFOS) on rectal sensitivity, fecal microbiota, and symptoms in patients with irritable bowel syndrome. Rectal sensitivity improved with scFOS and placebo alike; however, scFOS, but not placebo, significantly increased fecal Bifidobacteria and reduced anxiety score.

    21. Sulfate-reducing bacteria slow intestinal transit in a bismuth-reversible fashion in mice

      N. L. Ritz, D. M. Lin, M. R. Wilson, L. L. Barton and H. C. Lin

      Version of Record online: 31 JUL 2016 | DOI: 10.1111/nmo.12907

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      Desulfovibrio vulgaris, common colonic sulfate-reducing bacteria (SRB), slow small intestinal transit in mice. This slowing effect was not seen when the bacteria are heat-killed suggesting that the slowing effect is dependent on metabolic activity of live SRB.

    22. Esophageal dysfunction in different stages of Parkinson's disease

      I. Suttrup, J. Suttrup, S. Suntrup-Krueger, M.-L. Siemer, J. Bauer, C. Hamacher, S. Oelenberg, D. Domagk, R. Dziewas and T. Warnecke

      Version of Record online: 31 JUL 2016 | DOI: 10.1111/nmo.12915

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      In patients with Parkinson's disease, esophageal motor impairment seems to be a widespread affection occurring during all stages of the disease. Using high-resolution manometry, for the first time, a detailed description of occurrence and patterns of esophageal impairment was possible. Our findings indicate an early involvement of alpha-synucleinopathy in the enteric nervous system of the tubular esophagus.

    23. Esophagogastric junction distensibility identifies achalasia subgroup with manometrically normal esophagogastric junction relaxation

      F. A. Ponds, A. J. Bredenoord, B. F. Kessing and A. J. P. M. Smout

      Version of Record online: 25 JUL 2016 | DOI: 10.1111/nmo.12908

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      Achalasia is diagnosed by HRM showing aperistalsis and incomplete relaxation of the EGJ, determined by an IRP >15 mm Hg. A subgroup of patients with clinical and radiological features of achalasia has an IRP <15 mm Hg, but their EGJ distensibility is impaired similar to classical achalasia patients, and achalasia treatment is effective. The study shows that the diagnosis of achalasia should still be considered in patients with an IRP <15 mm Hg and treated as such.

    24. You have full text access to this OnlineOpen article
      GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine

      K. Pokusaeva, C. Johnson, B. Luk, G. Uribe, Y. Fu, N. Oezguen, R. K. Matsunami, M. Lugo, A. Major, Y. Mori-Akiyama, E. B. Hollister, S. M. Dann, X. Z. Shi, D. A. Engler, T. Savidge and J. Versalovic

      Version of Record online: 25 JUL 2016 | DOI: 10.1111/nmo.12904

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      Increasing evidence suggests that gut bacteria contribute to abdominal pain perception by modulating the microbiome-gut-brain axis. Here, we demonstrate that commensal Bifidobacterium dentium produces GABA via enzymatic decarboxylation of glutamate by GadB. Daily oral administration of this specific Bifidobacterium (but not a gadB deficient) strain modulated sensory neuron activity in a rat fecal retention model of visceral hypersensitivity.

    25. Improving biofeedback for the treatment of fecal incontinence in women: implementation of a standardized multi-site manometric biofeedback protocol

      A. D. Markland, J. E. Jelovsek, W. E. Whitehead, D. K. Newman, U. U. Andy, K. Dyer, I. Harm-Ernandes, S. Cichowski, J. McCormick, C. Rardin, G. Sutkin, A. Shaffer, S. Meikle and on behalf of the Pelvic Floor Disorders Network

      Version of Record online: 24 JUL 2016 | DOI: 10.1111/nmo.12906

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      Our goal was to develop novel biofeedback protocols to improve standardization of clinical care for fecal incontinence in a multicenter clinical trial. Separate biofeedback protocols addressed the most common causes for fecal incontinence: strength exercises, sensory perception, and urge resistance. Centralized training along with the use of standardized patient models was an effective method for teaching the biofeedback protocols. Auditing of the biofeedback visits revealed high adherence to the biofeedback protocols.

    26. Integrated low-intensity biofeedback therapy in fecal incontinence: evidence that “good” in-home anal sphincter exercise practice makes perfect

      D. H. Vasant, K. Solanki, S. Balakrishnan and N. V. Radhakrishnan

      Version of Record online: 20 JUL 2016 | DOI: 10.1111/nmo.12912

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      Despite low-intensity BFT, comparable outcomes to data from tertiary centers were achieved. Our data emphasize the importance of technique and in-home practice of anal sphincter exercises.

    27. Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms in the Greek population

      K. Triantafyllou, A. Kourikou, M. Gazouli, G. P. Karamanolis and G. D. Dimitriadis

      Version of Record online: 19 JUL 2016 | DOI: 10.1111/nmo.12913

    28. Cough reflex attenuation and swallowing dysfunction in sub-acute post-stroke patients: prevalence, risk factors, and clinical outcome

      N. Vilardell, L. Rofes, W. V. Nascimento, D. Muriana, E. Palomeras and P. Clavé

      Version of Record online: 18 JUL 2016 | DOI: 10.1111/nmo.12910

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      We found that the prevalence of OD was much higher than impairments in the CRT response. Neurotopographical and clinical stroke factors attenuated the CRT response but no specific risk factors for impaired CRT response were found. However, age, TACI, poor functional status and malnutrition risk were associated with OD suggesting that the swallow response receives a stronger cortical control than the cough reflex. No differences in the outcome of PSP were detected considering their CRT response whereas OD and impaired safety of swallow strongly increased institutionalization, respiratory infection and mortality 12 months after stroke, the poorest outcome being for PSP with both dysfunctions.

    29. A study with pharyngeal and esophageal 24-hour pH–impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors

      C. Dulery, A. Lechot, S. Roman, P.-L. Bastier, D. Stoll, L. de Gabory and F. Zerbib

      Version of Record online: 18 JUL 2016 | DOI: 10.1111/nmo.12909

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      The role of gastroesophageal reflux in chronic laryngeal symptoms is difficult to establish. This prospective study shows that patients with suspected laryngopharyngeal reflux refractory to therapy do not exhibit abnormal pharyngeal or esophageal pH–impedance reflux. In these patients, laryngopharyngeal reflux is unlikely and has been largely overestimated.

    30. You have full text access to this OnlineOpen article
      Rapid Drink Challenge in high-resolution manometry: an adjunctive test for detection of esophageal motility disorders

      D. Ang, M. Hollenstein, B. Misselwitz, K. Knowles, J. Wright, E. Tucker, R. Sweis and M. Fox

      Version of Record online: 15 JUL 2016 | DOI: 10.1111/nmo.12902

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      Emerging data suggest that a 200-mL Rapid Drink Challenge (RDC) test provides additional information during esophageal high-resolution manometry (HRM). We present normal values for RDC from healthy volunteers and patient controls and establish diagnostic thresholds for esophagogastric junction (EGJ) and peristaltic dysfunction. Rapid Drink Challenge is simple to perform during routine HRM studies and appears to increase diagnostic yield for symptomatic EGJ outflow obstruction and other, clinically relevant, motility disorders.

    31. Anatomical and functional deficiencies of the crural diaphragm in patients with esophagitis

      M. Â. N. e Souza, R. A. Nobre, P. C. Bezerra, A. A. dos Santos and D. Sifrim

      Version of Record online: 14 JUL 2016 | DOI: 10.1111/nmo.12899

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      This study shows that the CD right crus is thinner in esophagitis patients compared to healthy subjects. Additionally, esophagitis patients failed to keep the EGJ-CI and the “EGJ total activity” at high levels as the inspiratory load increased. This phenomenon did not occur in healthy subjects.

    32. Prevalence and risk factors for functional bowel disorders in South China: a population based study using the Rome III criteria

      Y. Long, Z. Huang, Y. Deng, H. Chu, X. Zheng, J. Yang, Y. Zhu, M. Fried, M. Fox and N. Dai

      Version of Record online: 14 JUL 2016 | DOI: 10.1111/nmo.12897

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      FBDs are as common in South China as in western populations. A similar number of men and women report FBDs and IBS. Independent risk factors associated with FBDs included physical and psychosocial stressors.

    33. Fatigue: a distressing symptom for patients with irritable bowel syndrome

      Å. Frändemark, E. Jakobsson Ung, H. Törnblom, M. Simrén and S. Jakobsson

      Version of Record online: 11 JUL 2016 | DOI: 10.1111/nmo.12898

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      Using a multi-methods approach this study describes the impact and manifestations of fatigue in 160 patients with IBS and investigates the relationship between fatigue severity and illness-related and health-promoting factors. Results include the multidimensional impact on life with poor bodily stamina being the most prominent feature. Severe fatigue was accompanied by more severe IBS symptoms, anxiety and depression, and lower sense of coherence.

    34. Pancreatic polypeptide stimulates mouse gastric motor activity through peripheral neural mechanisms

      A. Amato, S. Baldassano, G. F. Caldara and F. Mulè

      Version of Record online: 6 JUL 2016 | DOI: 10.1111/nmo.12901

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      It is unclear if pancreatic polypeptide (PP) reduces food intake by influencing the gastric motor function and it is not known yet whether PP can act directly on the stomach.

      1. The results of the current paper show that PP is able to act peripherally in mouse stomach and to stimulate gastric motility through neural release of acetylcholine and tachykinins acting on NK2 receptors.
      2. The PP peripheral action does not appear to represent a satiation signal.
    35. Lactobacillus rhamnosus strain JB-1 reverses restraint stress-induced gut dysmotility

      C. West, R. Y. Wu, A. Wong, A. M. Stanisz, R. Yan, K. K. Min, M. Pasyk, K.-A. McVey Neufeld, M. I. Karamat, J. A. Foster, J. Bienenstock, P. Forsythe and W. A. Kunze

      Version of Record online: 6 JUL 2016 | DOI: 10.1111/nmo.12903

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      Environmental stress promotes gut dysmotility characterized by increased colonic and reduced small intestine propagating contractile cluster activity. We measured propulsive motility in mouse jejunum and colon ex vivo after restraint stress. Luminal Lactobacillus rhamnosus JB-1 restored stress-induced motility changes within minutes of application. Beneficial microbes may be useful clinically to treat stress-induced gut dysmotility via rapid drug-like actions on the enteric nervous system.

  17. Hot Topic

    1. You have full text access to this OnlineOpen article
      In vivo transplantation of fetal human gut-derived enteric neural crest cells

      J. E. Cooper, D. Natarajan, C. J. McCann, S. Choudhury, H. Godwin, A. J. Burns and N. Thapar

      Version of Record online: 6 JUL 2016 | DOI: 10.1111/nmo.12900

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      This study demonstrates for the first time that human gut-derived ENCCs are capable of colonization of mouse colon, in vivo, forming both neurons and glia. Importantly, human gut-derived ENCCs make functional neuronal connections with the endogenous ENS. These findings increase the prospect of using human ENCC as a cell source for autologous cell replacement therapies to treat enteric neuropathies. ENCCs were isolated from fetal human gut by FACS for p75NTR before propagation in vitro and transplantation in vivo. Transplanted bowel was analyzed after 4 weeks by immunohistochemistry and calcium imaging. Transplanted cells displayed engraftment, spread, extension of projections, differentiation towards neurons and glia as well as functional connectivity with the endogenous ENS.

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