Phase diagram and critical properties of a two-dimensional associating lattice gas.

We revisit the associating lattice gas (ALG) introduced by Henriques et al. [Phys. Rev. E 71, 031504 (2005)PLEEE81539-375510.1103/PhysRevE.71.031504] in its symmetric version. In this model, defined on the triangular lattice, interaction between molecules occupying nearest-neighbor sites depends on their relative orientation, mimicking the formation of hydrogen bonds in network-forming fluids. Although all previous studies of this model agree that it has a disordered fluid (DF), a low-density liquid (LDL), and a high-density liquid (HDL) phase, quite different forms have been reported for its phase diagram. Here, we present a thorough investigation of its phase behavior using both transfer matrix calculations and Monte Carlo (MC) simulations, along with finite-size scaling extrapolations. Results in striking agreement are found using these methods. The critical point associated with the DF-HDL transition at full occupancy, identified by Furlan et al. [Phys. Rev. E 100, 022109 (2019)2470-004510.1103/PhysRevE.100.022109] is shown to be one terminus of a critical line separating these phases. In opposition to previous simulation studies, we find that the transition between the DF and LDL phases is always discontinuous, similar to the LDL-HDL transition. The associated coexistence lines meet at the point where the DF-HDL critical line ends, making it a critical-end-point. Overall, the form of the phase diagram observed in our simulations is very similar to that found in the exact solution of the model on a Husimi lattice. Our results confirm that, despite the existence of some waterlike anomalies in this model, it is unable to reproduce key features of the phase behavior of liquid water.

Curriculum for neurogastroenterology and motility training: A report from the joint ANMS-ESNM task force.

Although neurogastroenterology and motility (NGM) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency-based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society (ANMS) and the European Society of Neurogastroenterology and Motility (ESNM) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM, consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro-esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy (surgery, endoscopic intervention, medications, other therapy), and transition of pediatric patients into adult practice. A 3-tiered training curriculum covering these domains is proposed here and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected of all gastroenterology trainees and practicing gastroenterologists. Tier 2 knowledge and training is appropriate for trainees who anticipate NGM disorder management and NGM function test interpretation being an important part of their careers, which may require competency assessment and credentialing of test interpretation skills. Tier 3 knowledge and training is undertaken by trainees interested in a dedicated NGM career and may be restricted to specific domains within the broad NGM field. The joint ANMS and ESNM task force anticipates that the NGM curriculum will streamline NGM training in North America and Europe and will lead to better identification of centers of excellence where Tier 2 and Tier 3 training can be accomplished.

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.

BACKGROUND: 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. METHODS: 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. KEY RESULTS: 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. CONCLUSIONS & INFERENCES: 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.

Safety and efficacy of the vibrating capsule, an innovative non-pharmacological treatment modality for chronic constipation.

BACKGROUND: Constipation is a common disorder. Because the prevalence is high and the satisfaction level with currently available treatment is low, there is an unmet need for innovative treatment. We assessed the safety and efficacy of the Vibrant Capsule, a non-pharmacological device that is assumed to induce a normal peristaltic wave in the large intestine to alleviate constipation. METHODS: Two animal safety studies and a safety study on healthy volunteers were conducted, followed by a prospective, non-randomized, open-label, single group assignment, safety and efficacy study. The latter was conducted among 26 patients who ingested the capsule twice weekly for a study period of 7.5 weeks, after a run-in period of 2 weeks without usual treatment for constipation. KEY RESULTS: In the studies on animals and healthy volunteers, there were no adverse events. Twenty-eight patients began the clinical trial and 26 completed it (25 women). The mean age was 47.0 ± 12.6 years (range: 19-65). The two dropouts, who completed the safety phase, and the 26 who completed the entire study expelled the capsule without difficulty. Twelve participants reported 27 adverse events, none serious, and all transient. There was a significant increase of 1.60 ± 1.09 in the mean number of bowel movements/week from 2.19 ± 0.67 to 3.79 ± 1.31 (p < 0.001). This increase was seen in 23 of the 26 patients (88.5%). The mean number of spontaneous bowel movements for the study group increased in each treatment week compared to baseline. CONCLUSIONS & INFERENCES: The Vibrant Capsule is safe and potentially effective in the treatment of constipation, justifying randomized controlled studies.

The role of pain modulators in esophageal disorders - no pain no gain.

Pain modulators have been primarily used for the management of functional esophageal disorders. Recently, these drugs have also been used for the management of other esophageal disorders, such as non-erosive reflux disease, the hypersensitive esophagus, and heartburn that is not responsive to proton pump inhibitor treatment. Several etiologies have been identified in patients with functional esophageal disorders, and these include esophageal hypersensitivity due to peripheral and/or central sensitisation, altered central processing of peripheral stimuli, altered autonomic activity, and psychological comorbidity such as depression and anxiety. Different antidepressants have been used as pain modulators and have demonstrated a beneficial effect on patients with the aforementioned esophageal disorders. Tricyclic antidepressants are the most commonly used class of drugs in clinical practice. Other antidepressants that have been used, some with more clinical success than others, include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and trazodone. Other medications that have been used as pain modulators in esophageal disorders include adenosine antagonists, serotonin agonists, antiepileptics, and medications that ameliorate peripheral neuropathy. The mechanism by which many of the pain modulators confer their visceral analgesic effect remains to be fully elucidated. Regardless, their role and value in treating esophageal disorders have markedly increased in the last decade.

Assessment of high-sensitivity CRP as a marker of micro-inflammation in irritable bowel syndrome.

BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is symptom-based. Although considered a functional disease, accumulating evidence supports a low-grade gut inflammation as an element of its pathophysiology. Thus, high-sensitivity C-reactive protein (hs-CRP), a marker of micro inflammation, may be elevated in IBS. Our aim was to assess whether hs-CRP is higher in IBS patients compared to healthy controls (HC) and does it differ among the IBS clinical subgroups and correlate with disease severity. METHODS: A diagnostic case control study was conducted in two gastroenterology departments. Eighty-eight IBS patients who were recruited prospectively answered the Rome III diagnostic questionnaire. They all completed the Functional Bowel Disorder Severity Index (FBDSI), dietary, and general health questionnaires. All patients underwent blood sampling for hs-CRP levels. Each IBS patient was matched to four HC by age, gender, and BMI. Blood samples were obtained from the HC at a periodic health survey. KEY RESULTS: The mean hs-CRP level in the IBS group was significantly higher than in HC (1.17±1.26mg L(-1) vs 0.72±0.91mg L(-1) respectively, P=0.001). Hs-CRP levels were highest in patients with diarrhea-predominant IBS and in patients with greater disease severity. A cut-off value of 1.08mg L(-1) had a sensitivity of 60.2% and a specificity of 68% for differentiating IBS from HC. CONCLUSIONS & INFERENCES: Hs-CRP levels are higher in IBS patients than HC, but still in the normal laboratory range. This may reflect the low-grade gut inflammation believed to occur in IBS and support its existence.

Firing patterns and synchronization in nonsynaptic epileptiform activity: the effect of gap junctions modulated by potassium accumulation.

Several lines of evidence point to the modification of firing patterns and of synchronization due to gap junctions (GJs) as having a role in the establishment of epileptiform activity (EA). However, previous studies consider GJs as ohmic resistors, ignoring the effects of intense variations in ionic concentration known to occur during seizures. In addition to GJs, extracellular potassium is regarded as a further important factor involved in seizure initiation and sustainment. To analyze how these two mechanisms act together to shape firing and synchronization, we use a detailed computational model for in vitro high-K(+) and low-Ca(2+) nonsynaptic EA. The model permits us to explore the modulation of electrotonic interactions under ionic concentration changes caused by electrodiffusion in the extracellular space, altered by tortuosity. In addition, we investigate the special case of null GJ current. Increased electrotonic interaction alters bursts and action potential frequencies, favoring synchronization. The particularities of pattern changes depend on the tortuosity and array size. Extracellular potassium accumulation alone modifies firing and synchronization when the GJ coupling is null.

Clinical trial: the effect of Johrei on symptoms of patients with functional chest pain.

BACKGROUND: Patients with functional chest pain (FCP) represent a therapeutic challenge for practising physicians. AIM: To determine the efficacy of Johrei as compared to wait-list in improving symptoms of FCP patients. METHODS: Patients with chest pain of noncardiac origin for at least 3 months were enrolled into the study. All patients had to have negative upper endoscopy, pH testing and oesophageal manometry prior to randomization. Subsequently, patients were randomized to either Johrei or wait-list control. Patients received 18 Johrei sessions from a Johrei practitioner for 6 weeks. RESULTS: A total of 21 FCP patients enrolled into the Johrei group and 18 into the wait-list group. There was no difference in symptom intensity score between Johrei group and wait-list group at baseline (20.28 vs. 23.06, P = N.S.). However, there was a significant pre- and post-treatment reduction in symptom intensity in the Johrei group (20.28 vs. 7.0, P = 0.0023). There was no significant reduction in symptom intensity score between baseline and at the end of the study in the wait-list group (23.06 vs. 20.69, P = N.S.). CONCLUSION: This pilot study shows that Johrei may have a role in improving FCP symptoms; however, future studies are needed to compare Johrei treatment with sham Johrei or supportive care.

Clinical trial: acupuncture vs. doubling the proton pump inhibitor dose in refractory heartburn.

BACKGROUND: The current standard of care in proton pump inhibitor failure is to double the proton pump inhibitor dose, despite limited therapeutic gain. Aims To determine the efficacy of adding acupuncture vs. doubling the proton pump inhibitor dose in gastro-oesophageal reflux disease patients who failed symptomatically on proton pump inhibitors once daily. METHODS: Thirty patients with classic heartburn symptoms who continued to be symptomatic on standard-dose proton pump inhibitors were enrolled into the study. All participants underwent upper endoscopy while on proton pump inhibitors once daily. Subsequently, patients were randomized to either adding acupuncture to their proton pump inhibitor or doubling the proton pump inhibitor dose over a period of 4 weeks. Acupuncture was delivered twice a week by an expert. RESULTS: The two groups did not differ in demographic parameters. The acupuncture + proton pump inhibitor group demonstrated a significant decrease in the mean daytime heartburn, night-time heartburn and acid regurgitation scores at the end of treatment when compared with baseline, while the double-dose proton pump inhibitor group did not demonstrate a significant change in their clinical endpoints. Mean general health score was only significantly improved in the acupuncture + proton pump inhibitor group. CONCLUSION: Adding acupuncture is more effective than doubling the proton pump inhibitor dose in controlling gastro-oesophageal reflux disease-related symptoms in patients who failed standard-dose proton pump inhibitors.

Assessment of 24-h oesophageal pH monitoring should be divided to awake and asleep rather than upright and supine time periods.

Oesophageal acid exposure analysis is divided to upright and supine, based on the assumption that the supine-awake period is similar to the supine-asleep period. To determine if the principal acid-reflux characteristics of supine-awake are closer to supine-asleep or upright period. Patients with heartburn underwent an upper endoscopy and pH testing. The patients were instructed to carefully document their upright, supine-awake and supine-asleep periods. A total of 64 patients were enrolled into this study (M/F 35/29; mean age 52.4 +/- 13.3). The mean percentage total time pH <4, frequency of acid-reflux events (per h) and number of sensed reflux events was not different between upright and the supine-awake period (P = ns). In contrast, the mean percentage total time pH <4, frequency of acid-reflux events and number of sensed reflux events was significantly higher in both upright and supine-awake periods vs supine-asleep (4.3 +/- 6.9, 1.86 +/- 2.7 and 0.01 +/- 0.05, P < 0.0001, respectively). The principal characteristics of the acid-reflux events in the supine-awake period are closer to the upright period than to the supine-asleep period.

Comparisons of the distribution of oesophageal acid exposure throughout the sleep period among the different gastro-oesophageal reflux disease groups.

BACKGROUND: Nocturnal gastro-oesophageal reflux diseases (GERD) can lead to oesophageal mucosal injury and extra-oesophageal complications. AIM: To compare distribution of oesophageal acid exposure during sleep time among patients with non-erosive reflux disease and abnormal pH test (NERD-positive), erosive oesophagitis (EO) and Barrett's oesophagus (BO). METHODS: Patients underwent endoscopy followed by 24-h oesophageal pH testing. Oesophageal acid exposure was assessed every 2 h of the sleep period (0-2, 2-4, 4-6 and 6-8 h). Each period of 2 h was evaluated for acid reflux parameters. All groups were matched by age, time from last meal and duration of sleep time. RESULTS: Thirty-eight patients were enrolled (NERD-positive, 16; EO, 1.4; and BO, 8). All GERD groups demonstrated higher oesophageal acid exposure in the first vs. second half of the sleep period as determined by percent time pH <4 (BO: 34.7 vs.11.6, EO: 13.5 vs. 6.9, NERD-positive: 8.8 vs. 2.5, all P < 0.01). In general, patients with BO had a significantly higher distribution of oesophageal acid exposure than those with NERD-positive and EO. CONCLUSIONS: Oesophageal acid exposure generally declines throughout the sleep period regardless of GERD group, but BO patients demonstrated the greatest decline during the sleep period.

Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett's esophagus.

Thus far, there has been a paucity of studies that have assessed the value of the different gastroesophageal reflux disease (GERD) symptom characteristics in identifying patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus. To determine if any of the symptom characteristics of GERD correlates with long-segment Barrett's esophagus versus short-segment Barrett's esophagus. Patients seen in our Barrett's clinic were prospectively approached and recruited into the study. All patients underwent an endoscopy, validated GERD symptoms questionnaire and a personal interview. Of the 88 Barrett's esophagus patients enrolled into the study, 47 had short-segment Barrett's esophagus and 41 long-segment Barrett's esophagus. Patients with short-segment Barrett's esophagus reported significantly more daily heartburn symptoms (84.1%) than patients with long-segment Barrett's esophagus (63.2%, P = 0.02). There was a significant difference in reports of severe to very severe dysphagia in patients with long-segment Barrett's esophagus versus those with short-segment Barrett's esophagus (76.9%vs. 38.1%, P = 0.02). Longer duration in years of chest pain was the only symptom characteristic of gastroesophageal reflux disease associated with longer lengths of Barrett's mucosa. Reports of severe or very severe dysphagia were more common in long-segment Barrett's esophagus patients. Only longer duration of chest pain was correlated with longer lengths of Barrett's esophagus.

Non-cardiac chest pain: an update.

Non-cardiac chest pain (NCCP) is very common, affecting up to a quarter of the USA adult population. Recent studies have shown that the disorder has a profound impact on patient's quality of life and is associated with marked increase in utilization of healthcare resources. Non-cardiac chest pain is a heterogeneous disorder with gastrointestinal and non-gastrointestinal causes. After excluding a cardiac cause, most NCCP patients are treated by cardiologists or primary care physicians and only the minority are referred to a gastroenterologist for further work-up. Gastro-oesophageal reflux disease (GORD) is the most common cause for NCCP. The role of oesophageal dysmotility in NCCP has been discounted in recent years. However, visceral hyperalgesia has been shown to play an important role in symptom generation of non-GORD-related NCCP. The main therapeutic interventions in GORD-related NCCP patients are potent antireflux modalities and pain modulators in those with non-GORD-related NCCP.

The effect of a therapeutic trial of high-dose rabeprazole on symptom response of patients with non-cardiac chest pain: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Therapeutic trials with high-dose lansoprazole and omeprazole have been shown to be sensitive clinical tools for diagnosing patients with gastro-oesophageal reflux disease-related non-cardiac chest pain. AIM: To determine the clinical value of a therapeutic trial of high-dose rabeprazole over 7 days in detecting patients with gastro-oesophageal reflux disease-related non-cardiac chest pain. METHODS: Double-blind, randomized, placebo-controlled, crossover study. Patients referred by a cardiologist after a comprehensive cardiac work-up were enrolled into the study. Oesophageal mucosal disease was determined by upper endoscopy and 24-h oesophageal pH monitoring assessed acid exposure. Patients were then randomized to either placebo or rabeprazole 20 mg am and 20 mg pm for 7 days. After a washout period of 1 week, patients crossed over to the other arm of the study for an additional 7 days. Patients completed a daily diary assessing severity and frequency of chest pain throughout the baseline, treatment and wash-out periods. The rabeprazole therapeutic trial was considered as a diagnostic tool, if chest pain scores improved > or =50% from baseline. RESULTS: Of the 35 patients enrolled, 16 (46%) were diagnosed as gastro-oesophageal reflux disease-positive and 19 (54%) as gastro-oesophageal reflux disease-negative. Of the gastro-oesophageal reflux disease-positive patients, 12 of 16 (75%) had a significant symptom improvement on rabeprazole when compared with 3 of 16 (19%) on placebo (P = 0.029). Of the gastro-oesophageal reflux disease-negative group, only two of 19 (11%) improved significantly on the medication and four of 19 (21%) on placebo (P = 0.6599). The calculated sensitivity and specificity of the rabeprazole therapeutic trial was 75% and 90%, respectively. CONCLUSIONS: A rabeprazole therapeutic trial is highly sensitive and specific for diagnosing gastro-oesophageal reflux disease-related non-cardiac chest pain patients.

Feasibility and tolerability of transnasal/per-oral placement of the wireless pH capsule vs. traditional 24-h oesophageal pH monitoring--a randomized trial.

BACKGROUND: The wireless pH is a new technique to monitor oesophageal acid exposure. AIM: To compare the feasibility and tolerability of the wireless pH capsule vs. the traditional pH probe. METHODS: Consecutive patients referred for a pH test were enrolled into the study. Patients were randomized to traditional pH probe, or wireless pH capsule. Patients recorded their activities, food consumption, symptoms, satisfaction with the test and completed a quality of life questionnaire. RESULTS: Of the 50 patients recruited, 25 patients underwent placement of the traditional pH probe, and 25 the wireless pH capsule. Patients with the wireless pH capsule had less nose pain, runny nose, throat pain, throat discomfort and headache as compared with those with the traditional pH probe (P = 0.047, P = 0.001, P = 0.032, P = 0.001, P = 0.009, respectively). Patients in the wireless pH capsule group had more chest discomfort during the pH test (P = 0.037). Patients in the wireless pH capsule group perceived the test as interfering less with their overall daily activities, eating and sleep (P =0.001, P = 0.003, P = 0.025, respectively), and had overall satisfaction with the test (P = 0.023). CONCLUSIONS: Transnasal/per-oral placement of the wireless pH capsule is significantly better tolerated then the traditional pH probe.

Avalanche exponents and corrections to scaling for a stochastic sandpile.

We study distributions of dissipative and nondissipative avalanches in Manna's stochastic sandpile, in one and two dimensions. Our results lead to the following conclusions: (1) avalanche distributions, in general, do not follow simple power laws, but rather have the form P(s) approximately s(-tau(s))(ln s)(gamma)f(s/s(c)), with f a cutoff function; (2) the exponents for sizes of dissipative avalanches in two dimensions differ markedly from the corresponding values for the Bak-Tang-Wiesenfeld (BTW) model, implying that the BTW and Manna models belong to distinct universality classes; (3) dissipative avalanche distributions obey finite-size scaling, unlike in the BTW model.

Critical behavior of a one-dimensional fixed-energy stochastic sandpile.

We study a one-dimensional fixed-energy version (that is, with no input or loss of particles) of Manna's stochastic sandpile model. The system has a continuous transition to an absorbing state at a critical value of the particle density, and exhibits the hallmarks of an absorbing-state phase transition, including finite-size scaling. Critical exponents are obtained from extensive simulations, which treat stationary and transient properties, and an associated interface representation. These exponents characterize the universality class of an absorbing-state phase transition with a static conserved density in one dimension; they differ from those expected at a linear-interface depinning transition in a medium with point disorder, and from those of directed percolation.

Continuously variable survival exponent for random walks with movable partial reflectors.

We study a one-dimensional lattice random walk with an absorbing boundary at the origin and a movable partial reflector. On encountering the reflector at site x, the walker is reflected (with probability r) to x-1 and the reflector is simultaneously pushed to x+1. Iteration of the transition matrix, and asymptotic analysis of the probability generating function show that the critical exponent delta governing the survival probability varies continuously between 1/2 and 1 as r varies between 0 and 1. Our study suggests a mechanism for nonuniversal kinetic critical behavior, observed in models with an infinite number of absorbing configurations.

First- and second-order phase transitions in a driven lattice gas with nearest-neighbor exclusion.

A lattice gas with infinite repulsion between particles separated by < or = 1 lattice spacing, and nearest-neighbor hopping dynamics, is subject to a drive favoring movement along one axis of the square lattice. The equilibrium (zero drive) transition to a phase with sublattice ordering, known to be continuous, shifts to lower density, and becomes discontinuous for large bias. In the ordered nonequilibrium steady state, both the particle and order-parameter densities are nonuniform, with a large fraction of the particles occupying a jammed strip oriented along the drive. The drive thus induces separation into high- and low-density regions in a system with purely repulsive interactions. Increasing the drive can provoke a transition to the ordered phase, and thereby, a sharp reduction in current.