Transient Relaxation Research Articles

Gestational diabetes triggers postpartum cardiac hypertrophy via activation of calcineurin/NFAT signaling

Population-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during both pregnancy and postpartum periods. Hypertrophic Ca2+-dependent calcineurin/NFAT signaling was stimulated two months after giving birth in HIP females but not in the WT. In contrast, the CaMKII/HDAC hypertrophy pathway was active immediately after giving birth and returned to the baseline by two months postpartum in both WT and HIP females. Myocytes from two months postpartum HIP females exhibited slower Ca2+ transient relaxation and higher diastolic Ca2+ levels, which may explain calcineurin activation. No such effects occurred in the WT. These results suggest that a GDM-complicated pregnancy accelerates the development of pathological cardiac remodeling likely through activation of calcineurin/NFAT signaling.

Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter

The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 μM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 μM carbenoxolone (a gap junction inhibitor), pretreatment with 100 μM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl−-free solution. However, pretreatment with 100 μM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 μM VIP (6–28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation.

Investigation of the frequency of application of physiotherapy in infants with gastroesophageal reflux

Introduction: Gastroesophageal reflux (GER) is defined as the reflux of gastric and/or intestinal contents into the esophagus. It is a common phenomenon, seen in 40-65% of infants and is due to transient relaxations of the lower esophageal sphincter.Many infants have daily episodes of GER, of short duration after meals, during sleepeven while awake. Its early diagnosis helps towards early intervention and successful treatment of complications. Furthermore, it contributes to improving the infant’s and the family’s quality of life. Physiotherapy as an adjunctive therapeutic intervention seems to be able to contribute significantly to the improvement of GER in infants. The goal is to improve movement, body posture, cardiorespiratory function and coordination in order to limit the phenomenon. Aim:The main purpose of this study was to investigate whether infants with GER, in addition to dietary and other instructions and any pharmaceutical intervention, also undergo physical therapy treatment to improve their symptoms. Additional objectives were to record the infant’s and the family’s quality of life, and to explore parents’ expectations of a physical therapy program. Patients and methods:Thirty infants with GER participated in the study. The research was conducted in Thessaloniki, Greece, in a regular pediatric gastroenterology clinic. The questionnaire was given to the parents and completed under the supervision of the researcher in case of need for clarification. Results:None of the 30 infants studied was following a physical therapy program. In addition, GER was found to have a great impact on parents’ quality of life, since 80% answered that they were significantly affected, not knowing how to manage the condition. Regarding the need for physical therapy intervention and informing parents, 70% answered that they would like to have information and help from a physical therapist. A percentage of 80% of parents were in favor of a physical therapy program that could contribute to the reductioneven the elimination of their children’s medication. Conclusions:Gastroesophageal reflux affects a large percentage of infants. In severe cases, if not treated in time, it can affect the health of young infants and the families’ quality of life. Most parents seem to trust a physical therapy program to improve their children’s health for the fastest recovery from GER. This research can be a pilot for further studies, in the context of a more holistic intervention by doctors and physical therapists in infants with GER symptoms.

Landscape-Flux Framework for Nonequilibrium Dynamics and Thermodynamics of Open Hamiltonian Systems Coupled to Multiple Heat Baths.

We establish a nonequilibrium dynamic and thermodynamic formalism in the landscape-flux framework for open Hamiltonian systems in contact with multiple heat baths governed by stochastic dynamics. To systematically characterize nonequilibrium steady states, the nonequilibrium trinity construct is developed, which consists of detailed balance breaking, nonequilibrium potential landscape, and irreversible probability flux. We demonstrate that the temperature difference of the heat baths is the physical origin of detailed balance breaking, which generates the nonequilibrium potential landscape characterizing the nonequilibrium statistics and creates the irreversible probability flux signifying time irreversibility, with the latter two aspects closely connected. It is shown that the stochastic dynamics of the system can be formulated in the landscape-flux form, where the reversible force drives the conservative Hamiltonian dynamics, the irreversible force consisting of a landscape gradient force and an irreversible flux force drives the dissipative dynamics, and the stochastic force adds random fluctuations to the dynamics. The possible connection of the nonequilibrium trinity construct to nonequilibrium phase transitions is also suggested. A set of nonequilibrium thermodynamic equations, applicable to both nonequilibrium steady states and transient relaxation processes, is constructed. We find that an additional thermodynamic quantity, named the mixing entropy production rate, enters the nonequilibrium thermodynamic equations. It arises from the interplay between detailed balance breaking and transient relaxation, and it also relies on the conservative dynamics. At the nonequilibrium steady state, the heat flow, entropy flow, and entropy production are demonstrated to be thermodynamic manifestations of the nonequilibrium trinity construct. The general nonequilibrium formalism is applied to a class of solvable systems consisting of coupled harmonic oscillators. A more specific example of two harmonic oscillators coupled to two heat baths is worked out in detail. The example may facilitate connection with experiments.

The gastrointestinal tract in hunger and satiety signalling.

BackgroundDifferent peripheral pathways are implicated in the regulation of the food ingestion‐digestion cycle.MethodsNarrative review on gastrointestinal mechanisms involved in satiety and hunger signalling.ResultsCombined mechano‐ and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension‐sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon‐like peptide 1 (GLP‐1), cholecystokinin as well as motilin and ghrelin contributes to gut‐brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP‐1 analogues act on these pathways to influence hunger, satiation and food intake.ConclusionGastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

Spinal Cord Perfusion Pressure Correlates with Anal Sphincter Function in a Cohort of Patients with Acute, Severe Traumatic Spinal Cord Injuries

BackgroundAcute, severe traumatic spinal cord injury often causes fecal incontinence. Currently, there are no treatments to improve anal function after traumatic spinal cord injury. Our study aims to determine whether, after traumatic spinal cord injury, anal function can be improved by interventions in the neuro-intensive care unit to alter the spinal cord perfusion pressure at the injury site.MethodsWe recruited a cohort of patients with acute, severe traumatic spinal cord injuries (American Spinal Injury Association Impairment Scale grades A–C). They underwent surgical fixation within 72 h of the injury and insertion of an intrathecal pressure probe at the injury site to monitor intraspinal pressure and compute spinal cord perfusion pressure as mean arterial pressure minus intraspinal pressure. Injury-site monitoring was performed at the neuro-intensive care unit for up to a week after injury. During monitoring, anorectal manometry was also conducted over a range of spinal cord perfusion pressures.ResultsData were collected from 14 patients with consecutive traumatic spinal cord injury aged 22–67 years. The mean resting anal pressure was 44 cmH2O, which is considerably lower than the average for healthy patients, previously reported at 99 cmH2O. Mean resting anal pressure versus spinal cord perfusion pressure had an inverted U-shaped relation (Ȓ2 = 0.82), with the highest resting anal pressures being at a spinal cord perfusion pressure of approximately 100 mmHg. The recto-anal inhibitory reflex (transient relaxation of the internal anal sphincter during rectal distension), which is important for maintaining fecal continence, was present in 90% of attempts at high (90 mmHg) spinal cord perfusion pressure versus 70% of attempts at low (60 mmHg) spinal cord perfusion pressure (P < 0.05). During cough, the rise in anal pressure from baseline was 51 cmH2O at high (86 mmHg) spinal cord perfusion pressure versus 37 cmH2O at low (62 mmHg) spinal cord perfusion pressure (P < 0.0001). During anal squeeze, higher spinal cord perfusion pressure was associated with longer endurance time and spinal cord perfusion pressure of 70–90 mmHg was associated with stronger squeeze. There were no complications associated with anorectal manometry.ConclusionsOur data indicate that spinal cord injury causes severe disruption of anal sphincter function. Several key components of anal continence (resting anal pressure, recto-anal inhibitory reflex, and anal pressure during cough and squeeze) markedly improve at higher spinal cord perfusion pressure. Maintaining too high of spinal cord perfusion pressure may worsen anal continence.

ASSESSMENT OF THE INTESTINAL MICROBIOTA IN ADULTS WITH EROSIVE ESOPHAGITIS.

The intestinal microbiota influences the appropriate function of the gastrointestinal tract. Intestinal dysbiosis may be associated with a higher risk of esophageal lesions, mainly due to changes in gastroesophageal motility patterns, elevation of intra-abdominal pressure, and increased frequency of transient relaxation of the lower esophageal sphincter. The aim of this study was to evaluate the intestinal microbiota in individuals with erosive esophagitis and in healthy individuals using metagenomics. A total of 22 fecal samples from adults aged between 18 and 60 years were included. Eleven individuals had esophagitis (eight men and three women) and 11 were healthy controls (10 men and one woman). The individuals were instructed to collect and store fecal material into a tube containing guanidine solution. The DNA of the microbiota was extracted from each fecal samples and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion Torrent PGM platform and the data were analyzed using the QIIME™ software version 1.8. Statistical analyses were performed using the Mann-Whitney non-parametric test and the ANOSIM non-parametric method based on distance matrix. The alpha-diversity and beta-diversity indices were similar between the two groups, without statistically significant differences. There was no statistically significant difference in the phylum level. However, a statistically significant difference was observed in the abundance of the family Clostridiaceae (0.3% vs 2.0%, P=0.032) and in the genus Faecaliumbacterium (10.5% vs 4.5%, P=0.045) between healthy controls and esophagitis patients. The findings suggest that reduced abundance of the genus Faecaliumbacterium and greater abundance of the family Clostridiaceae may be risk factors for the development of erosive esophagitis. Intervention in the composition of the intestinal microbiota should be considered as an adjunct to current therapeutic strategies for this clinical condition.

Hydrogen Bonds between Ions of Opposite and Like Charge in Hydroxyl-Functionalized Ionic Liquids: an Exhaustive Examination of the Interplay between Global and Local Motions and Intermolecular Hydrogen Bond Lifetimes and Kinetics.

Hydroxyl-functionalized ionic liquids (ILs) represent a new interesting class of ILs where hydrogen bonds (HBs) play an important role: here, "typical" HBs between cations and anions (ca) are competing with "atypical" HBs connecting pairs of cations (cc). We study the equilibrium and kinetics of (cc) and (ca) HBs in 1-(n-hydroxyalkyl)-pyridinium bis(trifluoromethlysulfonyl)imide [HOCnPy][NTf2] ILs by means of molecular dynamics simulations. (cc) HBs are found to be between 0.96 and 3.76 kJ mol-1 stronger than their (ca) counterparts, depending on the alkyl chain length. HB lifetimes and kinetics are analyzed by means of HB population and reactive flux correlation functions. Essentially, four different HB lifetimes have to be considered, spanning about 3 orders of magnitude, each valid in its own right and each associated with different aspects of HB breaking and HB reformation. The long-time limiting behavior of the HB population correlation function is controlled by diffusion of the ions and can be quantitatively described by analytical expressions. The short-time HB behavior is tied to the localized dynamics of the hydroxyl group exploring its local solvation environment. A minimalist kinetic two-domain model is introduced to realistically describe the time evolution of the HB population correlation function for both (ca) and (cc) HBs over 5 orders of magnitude. By employing the reactive flux method, we determine the kinetics of HB breaking, unaffected by diffusion processes. We determine both, the ultrafast upper boundary and the average rate of HB breaking, allowing recrossing-events during the transient relaxation time period. For sufficiently long alkyl chains, all those computed HB lifetimes indicate a higher kinetic stability of (cc) HBs over (ca) HBs; for short chains, it is vice-versa.

Towards ultrafast cooling through transient phonon currents: A closed-form solution

We develop a closed-form formula to calculate the transient thermal currents flowing through an arbitrary nanoscale phonon device in response to a sudden thermal switch. Our theory provides a solution to the problem in the far-from-equilibrium nonlinear response regime beyond the wide-band-like approximation and Drude regularization. We present calculations in a one-dimensional monatomic chain with Lorentzian-like thermal baths and show that the transient phonon currents are significantly larger than the long-time-limit steady-state phonon current. From the formula's clear mathematical structure, we also show that the transient oscillation periodicity and relaxation time are determined by the poles of the retarded phonon Green's function. In addition, higher temperatures of the thermal baths and stronger coupling between the baths and the central monatomic chain result in higher transient thermal currents. Our results suggest that ultrafast cooling of nanodevices through transient phonon currents is a promising route.

Characterization of esophageal motor activity, gastroesophageal reflux, and evaluation of prokinetic effectiveness in mechanically ventilated critically ill patients: a high-resolution impedance manometry study

BackgroundMotility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide.MethodsWe prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; < 100 mL/24 h, n = 8) or high gastric volume (HGV; > 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h.ResultsThe findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group.ConclusionAll critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status.Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966.

Usefulness of The Reflux Symptom Index in the Management of Laryngopharyngeal Reflux

Introduction Laryngopharyngeal Reflux (LPR) is highly prevalent in the general population and its impact on health systems is growing dramatically by the day. The contents of the stomach flowing back into the oesophagus, pharynx and larynx because of a transient relaxation of the lower oesophageal sphincter leads to a spectrum of symptoms diagnosed as LPR and Gastroesophageal Reflux Disease (GERD). The aim was to study in detail the symptoms of LPR and to ascertain if and how they hamper the routine of an individual by using the Reflux Symptom Index (RSI). Materials and Methods The Reflux Symptom Index (RSI) is a self-administered nine-item outcomes instrument for LPR. Ninety-one patients with clinically diagnosed LPR were taken up for this study and were issued the RSI (translated into the local language for better results) before and after treatment. Data was assessed at the end of 3 months and 6 months. Results The tabulated data showed significant improvement in the symptomatic index after treatment. Conclusion It can thus be concluded that RSI is still highly valid in the follow-up for patients with LPR because it can be easily administered and gives accurate results with excellent validation.

The many flavours of mechanochemistry and its plausible conceptual underpinnings.

Mechanochemistry describes diverse phenomena in which mechanical load affects chemical reactivity. The fuzziness of this definition means that it includes processes as seemingly disparate as motor protein function, organic synthesis in a ball mill, reactions at a propagating crack, chemical actuation, and polymer fragmentation in fast solvent flows and in mastication. In chemistry, the rate of a reaction in a flask does not depend on how fast the flask moves in space. In mechanochemistry, the rate at which a material is deformed affects which and how many bonds break. In other words, in some manifestations of mechanochemistry, macroscopic motion powers otherwise endergonic reactions. In others, spontaneous chemical reactions drive mechanical motion. Neither requires thermal or electrostatic gradients. Distinct manifestations of mechanochemistry are conventionally treated as being conceptually independent, which slows the field in its transformation from being a collection of observations to a rigorous discipline. In this Review, we highlight observations suggesting that the unifying feature of mechanochemical phenomena may be the coupling between inertial motion at the microscale to macroscale and changes in chemical bonding enabled by transient build-up and relaxation of strains, from macroscopic to molecular. This dynamic coupling across multiple length scales and timescales also greatly complicates the conceptual understanding of mechanochemistry.

Current Insights in the Pathophysiology of Gastroesophageal Reflux Disease.

The pathophysiology of Gastroesophageal reflux disease (GERD) is multifactorial determined and remains a matter of discussions between the involved medical subspecialties, mainly gastroenterologists and gastrointestinal surgeons, but also ear-nose-and-throat colleagues and pulmonologists. The purpose of this manuscript is an overview on the different pathophysiologic components of GERD, their influence as well as a certain weighing of their involvement in the disease. The lower esophageal sphincter (LES) represents together with the muscles and ligamentous structures of the diaphragm at the esophageal hiatus the antireflux barrier between esophagus and stomach. The crucial factor in GERD is an increased amount of gastric contents refluxing into the esophagus above the physiologic level. This creates pathologic esophageal acid exposure (EAE) to the mucosa, which may lead to symptoms and damage. The underlying pathophysiologic mechanisms are anatomical components such as LES and diaphragm, and functional components such as LES-incompetence, transient LES relaxations, impaired esophageal motility, gastroduodenal dysfunctions and alterations of the refluxate such as duodeno-gastro-esophageal reflux. The quantitative assessment of these components has been reported in a number of studies demonstrating the importance of LES-incompetence (incidence 80 %) and the role of hiatal hernia (incidence 80 %) in the severity of GERD indicated by excessive esophageal acid exposure and visible damage of the esophageal mucosa. All known pathophysiologic components of GERD can be investigated currently by diagnostic assessment, detecting a LES-incompetence or an increase in transient relaxations, detecting a hiatal hernia with increasing size, detecting increasing exposure to gastric contents in addition to other possible functional associated disorders such as an insufficient esophageal motility and or a delayed gastric emptying, which all can aggravate the disease and the patient's status.

Dielectric polarization effect and transient relaxation in FAPbBr3 films before and after PMMA passivation.

In organic-inorganic hybrid ionic lead halide perovskites with a naturally arranged layered structure, the dielectric polarization effect caused by the dielectric mismatch between the organic and inorganic layers takes effect in their optical responses. But this effect has received little attention. Here we used infrared transient spectroscopy to study FAPbBr3 perovskite polycrystalline films before and after PMMA film passivation and found that there is a dielectric polarization effect at the interface between the organic cation layer and the inorganic lattice layer inside the perovskite lattice, and also at the interface between the PMMA film and perovskite film. Due to the dielectric polarization effect and the spatial confinement of the surface electronic (or polaron) state, the luminescence intensity of the passivated perovskite film is significantly enhanced, and the exciton lifetime is greatly increased. Dielectric polarization enhances their efficient transient absorption (TA) and leads to the intramolecular vibration frequency red-shifts, which exhibited the combined relaxation kinetics of the large polaron with dielectric polarization in the perovskite film. Dielectric polarization between the internal lattice and the nanocrystal surface of the perovskite film shows different relaxation processes. The polarization-dependent TA spectrum reveals that the dielectric polarization field causes light-induced anisotropy by changing the chemical bond configurations. These direct TA experimental observations help us to understand the influence of the dielectric polarization effect on the electronic state in various organic-inorganic nanocomposite perovskites.

Current Advancement on the Dynamic Mechanism of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a common clinical disease associated with upper gastrointestinal motility disorders. Recently, with improvements in living standards and changes in lifestyle and dietary habits, the incidence of GERD has been increasing yearly. However, the mechanism of GERD has not been fully elucidated due to its complex pathogenesis, and this had led to unsatisfactory therapeutic outcomes. Currently, the occurrence and development of GERD involve multiple factors. Its pathogenesis is mainly thought to be related to factors, such as lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, crural diaphragmatic dysfunction, hiatus hernia, and impaired esophageal clearance. Therefore, explaining the pathogenesis of GERD more clearly and systematically, exploring potential and effective therapeutic targets, and choosing the best treatment methods have gradually become the focus of scholars' attention. Herein, we reviewed current advancements in the dynamic mechanism of GERD to better counsel patients on possible treatment options.

Usefulness of the reflux symptom index in laryngopharyngeal reflux

Introduction: Laryngopharyngeal reflux (LPR) is highly prevalent in the general population and its impact on health systems is growing dramatically by the day. The term reflux means back flow. The contents of the stomach flowing back into the esophagus, pharynx, and larynx because of a transient relaxation of the lower esophageal sphincter cause of a spectrum of symptoms diagnosed with LPR and gastroesophageal reflux disease. Aims and Objectives: To study in detail the symptoms caused in LPR and to ascertain if and how they hamper the routine of an individual by using the reflux symptom index (RSI). Materials and Methods: The RSI is a self-administered nine-item outcomes instrument for LPR. Ninety-one patients with clinically diagnosed LPR were taken up for this study and were issued the RSI (translated into the local language for better results) before and after treatment. Data were assessed at the end of 3 months and 6 months. Observations and Results: The tabulated data showed significant improvement in the symptomatic index after treatment. Conclusion: It can thus be concluded that RSI is still highly valid in the follow-up for patients with LPR because of it can be easily administered and gives excellent validation for accurate results.

Refractory Gastro-oesophageal Reflux Disease and Laryngopharyngeal Reflux - Use the Bottom up Approach

Most gastro-oesophageal reflux events are triggered by transient lower oesophageal sphincter relaxations (TLOSRs). Acid-related reflux disease with typical heartburn and reflux oesophagitis generally responds well to acid suppression with proton pump inhibitors (PPI), but treating non-acid and mixed gaseous reflux has proven more challenging.

The bitter tastant denatonium benzoate has no influence on the number of transient lower esophageal sphincter relaxations in health.

Administration of a bitter compound can alter the intragastric pressure (IGP) after a meal. Additionally, a negative correlation between IGP and the number of transient lower esophageal sphincter relaxations (TLESRs) has been demonstrated. However, the effect of a bitter tastant on the number of TLESRs and subsequent reflux episodes has never been investigated and it is unclear whether bitter food items should be avoided in gastro-esophageal reflux disease. We hypothesize that bitter administration in healthy volunteers (HVs) will lead to an increase in the number of TLESRs. After an overnight fast, 20 female HVs (36years [21-63]) underwent a high-resolution impedance manometry (HRiM) measurement. After placement of the HRiM probe, 0.1ml/kg of a 10mM denatonium benzoate solution (bitter) or an identical volume of water (placebo) was administered directly into the stomach. The number of TLESRs and reflux episodes was quantified 30min before and 2h after consumption of a high caloric meal. There was no significant difference in the number of TLESRs or reflux episodes between the bitter and placebo condition. Additionally, no differences were observed in the nature (gas or liquid) and extent of reflux events. Lower esophageal sphincter pressures dropped significantly in the first postprandial hour to start recovering slowly back to baseline values during the second postprandial hour (p<0.0001), without any difference between both conditions. Administration of the bitter tastant denatonium benzoate has no influence on the number of TLESRs or reflux episodes.

A Cross-Sectional Study to Determine the Prevalence of Gastroesophageal Reflux in Children with Persistent Cough and Wheezing

Background: Gastroesophageal reflux (GER) occurs in more than two-thirds of otherwise healthy infants and is the topic of discussion with pediatricians at one-quarter of all routine 6-month infant visits. GER is considered a normal physiologic process that occurs several times a day in healthy infants, children, and adults. GER is generally associated with transient relaxations of the lower esophageal sphincter independent of swallowing, which permits gastric contents to enter the esophagus. The Objective to find out the prevalence of GER in children with cough and wheezing and its associated factors. Subjects and Methods: A cross-sectional study was done at A tertiary care hospital at the Institute of Naval Medicine, INHS, Mumbai from August 2016 to December 2017. A total of 30 study subjects Aged between the age of one to twelve years with persistent cough and wheezing lasting for more than three months despite treatment were included for the study. Results: The prevalence of gastroesophageal reflux (GER) in our study was 63.3%.The logistic regression analysis showed that Age, Height, Weight, BMI, duration of cough, Duration of asthma were not significantly associated with Gastroesophageal reflux (GER) (p&gt;0.05). Conclusion: GER seems to have a high prevalence in children with chronic cough. However, no definite recommendations can be made regarding the management of such cases from our study.

The gastro-sphincteric pressure gradient: A new parameter to diagnose a rumination episode.

Rumination is defined as the repetitive, effortless regurgitation of recently ingested food into the mouth. These episodes are preceded by a rise in intragastric pressure (IGP) and mainly occur postprandially. IGP peaks >30mmHg have been proposed as a cutoff to differentiate rumination from reflux events. In clinical practice, we observed that this cutoff, which does not consider esophagogastric junction (EGJ) resistance, is not always reached. We studied 27 patients with rumination syndrome [age: 43.6, 59% female] and 28 gastro-esophageal reflux disease patients [age: 45.9, 54% female]. For each rumination episode, reflux event, transient lower esophageal sphincter relaxation (TLESR), or straining without regurgitation, the following parameters were registered: maximal IGP, IGP, and EGJ pressure preceding the respective episodes. We also quantified the gastro-sphincteric pressure gradient (GSPG) prior to the respective episodes. Five reflux episodes were characterized by a maximal IGP >30mmHg. In 28% of the rumination episodes, the IGP peak did not exceed 30mmHg. Median GSPG was positive for rumination episodes and significantly higher compared with TLESRs, reflux episodes, and straining without regurgitation (7 [3-13] vs. 0 [-1-0] vs. 0 [-1-0] vs. -9 [-13--2]; p<0.0001). Applying the proposed cutoff of 30mmHg, 28% of the rumination episodes were missed. We found that the GSPG differentiates between rumination (positive GSPG), TLESRs and reflux events (GSPG around 0), and straining without regurgitation (negative GSPG). We propose a GSPG value ≥2mmHg to distinguish rumination from reflux episodes, TLESRs, and straining without regurgitation.