Effects of real-ambient PM2.5 exposure plus lipopolysaccharide on multiple organ damage in mice.

Background: The toxicological effects of fine particulate matter (PM2.5) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM2.5 plus LPS for 23 weeks in Linfen, a city with a high PM2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM2.5 plus LPS.

Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson's Disease Mouse Model.

The exact etiology of Parkinson's disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis (H. suis) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis-infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis-infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.

Role of the posterior mucosal defense barrier in portal hypertensive gastropathy.

Portal hypertensive gastropathy (PHG) is a complication of cirrhotic or noncirrhotic portal hypertension. PHG is very important in the clinic because it can cause acute or even massive blood loss, and its treatment efficacy and prognosis are poor. Currently, the incidence of PHG in patients with cirrhosis is 20-80%, but its pathogenesis is complicated and poorly understood. Studies have shown that portal hypertension can cause changes in gastric mucosal microcirculation hemodynamics, leading to changes in gastric mucosal histology and function and thereby weakening the mucosal defense barrier. However, no specific drug treatment plans are currently available. This article reviews the current literature to further our understanding of the mechanism underlying PHG and the relationship between PHG and the posterior mucosal defense barrier and to explore new therapeutic targets.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Investigating Helicobacter pylori-related pyloric hypomotility: functional, histological, and molecular alterations.

Multiple theories have been proposed describing the pathogenic mechanisms of Helicobacter pylori (H. pylori)-associated gastric motility disorders. We assessed ex vivo pyloric activity in H. pylori-infected rats, and tried to explore the associated ghrelin hormone alteration and pyloric fibrogenesis. In addition, miR-1 was assessed in pyloric tissue samples, being recently accused of having a role in smooth muscle dysfunction. Ninety adult male Wistar albino rats were assigned into nine groups: 1) control group, 2) sterile broth (vehicle group), 3) amoxicillin control, 4) omeperazole control, 5) clarithromycin control, 6) triple therapy control, 7) H. pylori- group, 8) H. pylori-clarithromycin group, and 9) H. pylori-triple therapy group. Urease enzyme activity was applied as an indicator of H. pylori infection. Ex vivo pyloric contractility was evaluated. Serum ghrelin was assessed, and histological tissue evaluation was performed. Besides, pyloric muscle miR-1 expression was measured. The immunological epithelial to mesenchymal transition (EMT) markers; transforming growth factor ß (TGFß), α-smooth muscle actin (α-SMA), and E-cadherin-3 were also evaluated. By H. pylori infection, a significant (P < 0.001) reduced pyloric contractility index was recorded. The miR-1 expression was decreased (P < 0.001) in the H. pylori-infected group, associated with reduced serum ghrelin, elevated TGFß, and α-SMA levels and reduced E-cadherin levels. Decreased miR-1 and disturbed molecular pattern were improved by treatment. In conclusion, H. pylori infection was associated with reduced miR-1, epithelial to mesenchymal transition, and pyloric hypomotility. The miR-1 may be a target for further studies to assess its possible involvement in H. pylori-associated pyloric dysfunction, which might help in the management of human H. pylori manifestations and complications.NEW & NOTEWORTHY This work is investigating functional, histopathological, and molecular changes underlying Helicobacter pylori hypomotility and is correlating these with miR-1, whose disturbance is supposed to be involved in smooth muscle dysfunction and cell proliferation according to literature. Epithelial to mesenchymal transition and reduced ghrelin hormone may contribute to H. pylori infection-associated hypomotility. H. pylori infection was associated with reduced pyloric miR-1 expression. Targeting miR-1 could be valuable in the clinical management of pyloric hypofunction.

Portal hypertensive vasculopathy - An entity worth remembering with non-neoplastic gastrointestinal lesions.

Portal hypertensive vasculopathy (PHV) represents an increase in the pressure in the portal circulation. This increased pressure leads to changes in the mucosa that can be appreciated endoscopically as well as histopathologically. Lesions can be observed in the entire gastrointestinal tract (GIT) including stomach, duodenum, jejunum and colon. The histological changes are appreciated mainly in the mucosal and submucosal blood vessels. A knowledge of these lesions as well as the changes helps in separating them from other close differentials with specific treatment to be instituted. The pathogenesis of the hemodynamic changes is not well-understood. The underlying factor is increased portal pressure. Studies indicate, that besides increased portal pressure other factors in combination led to the observed changes. Portal hypertensive gastropathy (PHG) is seen in the gastric body and fundus, while varices are noted in the cardia and fundus. Changes may be seen in the small intestine and throughout the colon with anorectal varices. Histopathological changes include dilated, congested and ectatic capillaries and edema in the lamina propria besides a large spectrum of other histopathological changes. Mucosal capillaries with thick irregular wall show absence of red blood cells in the lumen. Thickening of the vessel wall serves as a better marker than the vascular diameter when portal hypertension (PHT) is considered. Long standing cases may show fibrosis in lamina propria. At times, these changes may lead to occult gastrointestinal bleeding. Important differentials need to be ruled out in all the cases as the treatment and the outcome of all differs. Endoscopically or histopathologically if the mucosal changes are observed they should not be overlooked and a detailed work-up must be carried out.

Neurons and Astrocytes in Ventrolateral Periaqueductal Gray Contribute to Restraint Water Immersion Stress-Induced Gastric Mucosal Damage via the ERK1/2 Signaling Pathway.

BACKGROUND: The restraint water immersion stress (RWIS) model includes both psychological and physical stimulation, which may lead to gastrointestinal disorders and cause gastric mucosal damage. The ventrolateral periaqueductal gray (VLPAG) contributes to gastrointestinal function, but whether it is involved in RWIS-induced gastric mucosal damage has not yet been reported. METHODS: The expression of glial fibrillary acidic protein, neuronal c-Fos, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG after RWIS was assessed using western blotting and immunocytochemical staining methods. Lateral ventricle injection of astrocytic toxin L-a-aminoadipate and treatment with extracellular signal-regulated kinase (ERK)1/2 signaling pathway inhibitor PD98059 were further used to study protein expression and distribution in the VLPAG after RWIS. RESULTS: The expression of c-Fos, glial fibrillary acidic protein, and phosphorylated extracellular signal regulated kinase 1/2 in the VLPAG significantly increased following RWIS and peaked at 1 hour after RWIS. Lateral ventricle injection of the astrocytic toxin L-a-aminoadipate significantly alleviated gastric mucosal injury and decreased the activation of neurons and astrocytes. Treatment with the ERK1/2 signaling pathway inhibitor PD98059 obviously suppressed gastric mucosal damage as well as the RWIS-induced activation of neurons and astrocytes in the VLPAG. CONCLUSIONS: These results suggested that activation of VLPAG neurons and astrocytes induced by RWIS through the ERK1/2 signaling pathway may play a critical role in RWIS-induced gastric mucosa damage.

Clinical associations of functional dyspepsia with gastric dysrhythmia on electrogastrography: A comprehensive systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow-wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity; however, the clinical associations require further evaluation. AIMS: This study aimed to systematically assess the clinical associations of EGG in FD. METHODS: MEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal versus abnormal rhythm (bradygastria, normogastria, and tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling, and the meal responses. RESULTS: 1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD -0.74; 95%CI -1.22 to -0.25) and postprandially (-0.86; 95%CI -1.35 to -0.37) compared with controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33-0.93) and tachygastria (0.45; 95%CI 0.12-0.78%). The power ratio (-0.17; 95%CI -0.83-0.48) and dominant frequency meal-response ratio (0.06; 95%CI -0.08-0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied. CONCLUSION: Abnormal gastric slow-wave rhythms are a consistent abnormality present in FD, as defined by EGG and, therefore, likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.

Effect of electroacupuncture at different acupoints in treating rapid gastric emptying: Zusanli (ST36) plus Zhongwan (CV12) versus Zhongwan (CV12) alone.

OBJECTIVE: To evaluate the effect of electroacupuncture on rapid gastric emptying by comparing the effectiveness of electroacupuncture at both Zusanli (ST36) and Zhongwan (CV12) (He-Mu acupoints) versus electroacupuncture at Zhongwan (CV12) alone. METHODS: Sixty-five patients were randomly divided into two groups; 33 patients in the He-Mu acupoints group received electroacupuncture at both Zusanli (ST36) and Zhongwan (CV12), while 32 patients in the single acupoint group received electroacupuncture only at Zhongwan (CV12). Both groups were treated once daily for 30 min, five times per week for 3 weeks. Before and after the 3-week treatment course, patients underwent gastric emptying scintigraphy and were assessed using the Traditional Chinese Medicine (TCM) symptom scale of gastrointestinal diseases. The two groups were compared regarding the percentages of gastric retention at 30 and 60 min and the TCM symptom scores. RESULTS: After the treatment course, the percentages of gastric retention at 30 and 60 min were significantly improved in both groups compared with the pre-treatment values (P < 0.01). The improvement in the gastric retention was significantly better in the He-Mu acupoints group than the single acupoint group at 30 min (P <0.01) and 60 min (P < 0.05). The TCM symptom score was significantly decreased after the treatment course in both groups (P < 0.01). The improvement in the TCM symptom score was significantly better in the He-Mu acupoints group than the single acupoint group (P < 0.01). The total effective rate was 93.55% (29/31) in the He-Mu acupoints group and 77.42% (24/31) in the single acupoint group. The treatment effect was better in the He-Mu acupoints group than the single acupoint group (P < 0.05). CONCLUSIONS: Electroacupuncture at both Zusanli (ST36) and Zhongwan (CV12) or at Zhongwan (CV12) alone is effective in treating rapid gastric emptying. Furthermore, electroacupuncture at both Zusanli (ST36) and Zhongwan (CV12) is more effective than electroacupuncture at Zhongwan (CV12) alone.

Forestomach developmental failure in an 11-month-old Japanese Black steer with severely retarded growth and chronic ruminal tympany.

This study reports findings from the pathological examination of the forestomach of an 11-month-old Japanese Black steer with severely retarded growth (41% of expected weight) and chronic ruminal tympany. The ruminal papillae were weakly formed (0.3-0.5 cm long) and unevenly distributed. The cellulae and cristae reticuli were underdeveloped; the cristae were 0.4-0.7 cm in height and milky white. The keratinized layer in the stratified squamous epithelium was thickened. Ruminal pH was 5.25, and ruminal volatile fatty acid concentration was 11.7 mM. The steer's severely retarded growth was considered to be caused by malnutrition due to developmental and functional failure of the forestomach.

Gastric Motility in Parkinson's Disease is Altered Depending on the Digestive Phase and Does Not Correlate with Patient-Reported Motor Fluctuations.

BACKGROUND: Altered gastric motility is a frequent non-motor symptom of Parkinson's disease (PD). It has been hypothesized that disturbed gastric motility contributes to motor fluctuations in PD due to an erratic gastro-duodenal transport and an unpredictable absorption of drugs. OBJECTIVE: We investigated whether patient-reported fluctuations are associated with parameters of gastric motility visualized by real-time magnetic resonance imaging (MRI) of the stomach. METHODS: We analyzed real-time MRI-scans of the stomach after an overnight fasting period in 16 PD patients and 20 controls. MRI was performed 1) in the fasting state, 2) directly after a test meal, and 3) 4 hours postprandially. Gastric motility indices were calculated and compared between groups. RESULTS: MRI showed an attenuated gastric motility in PD patients compared to controls. The difference was most obvious in the early postprandial phase. Gastric motility was not associated with patient-reported motor fluctuations. Using an iron-containing capsule we were able to retrace retention of drugs in the stomach. CONCLUSION: The results of this study stress the importance of considering the phase of digestion when investigating gastric motility in PD. Despite theoretical considerations, we did not find robust evidence for an association between MRI parameters of gastric motility and patient-reported motor fluctuations. For future studies that aim to investigate gastric motility in PD by MRI, we suggest multiple short-time MRIs to better track the whole gastro-duodenal phase in PD. Such an approach would also allow to retrace the retention of drugs in the stomach as shown by our approach using an iron-containing capsule.

Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis.

Introduction Helicobacter pylori causes, via the influence of several virulence factors, persistent infection of the stomach, which leads to severe complications. Vacuolating cytotoxin A (VacA) is observed in almost all clinical strains of H. pylori; however, only some strains produce the toxigenic and pathogenic VacA, which is influenced by the gene sequence variations. VacA exerts its action by causing cell vacuolation and apoptosis. We performed a PubMed search to review the latest literatures published in English language. Areas covered Articles regarding H. pylori VacA and its genotypes, architecture, internalization, and role in gastric infection and pathogenicity are reviewed. We included the search for recently published literature until January 2020. Expert opinion H. pylori VacA plays a crucial role in severe gastric pathogenicity. In addition, VacA mediated in vivo bacterial survival leads to persistent infection and an enhanced bacterial evasion from the action of antibiotics and the innate host defense system, which leads to drug evasion. VacA as a co-stimulator for the CagA phosphorylation may exert a synergistic effect playing an important role in the CagA-mediated pathogenicity.

Study on intelligent syndrome differentiation neural network model of stomachache in traditional Chinese medicine based on the real world.

Stomachache is not only disease name of Traditional Chinese medicine (TCM) but also the clinical symptom. It is a common and multiple diseases. TCM has its particular advantage in clinical treatment of stomachache. Syndrome differentiation is an important concept in TCM practice. The therapeutic process is virtually a nonlinear mapping process from clinical symptom to syndrome diagnosis with processing and seeking rules from mass data. Artificial neutral network has strong learning ability for nonlinear relationship. Artificial neutral network has been widely used to TCM area where the multiple factors, multilevel, nonlinear problem accompanied by a large number of optimization exist.We present an original experimental method to apply the improved third-order convergence LM algorithm to intelligent syndrome differentiation for the first time, and compare the predicted ability of Levenberg-Marquardt (LM) algorithm and the improved third-order convergence LM algorithm in syndrome differentiation.In this study, 2436 cases of stomachache electronic medical data from hospital information system, and then the real world data were normalized and standardized. Afterwards, LM algorithm and the improved third-order convergence LM algorithm were used to build the Back Propagation (BP) neural network model for intelligent syndrome differentiation of stomachache on Matlab, respectively. Finally, the differentiation performance of the 2 models was tested and analyzed.The testing results showed that the improved third-order convergence LM algorithm model has better average prediction and diagnosis accuracy, especially in predicting "liver-stomach disharmony" and "stomach yang deficiency", is above 95%.By effectively using the self-learning and auto-update ability of the BP neural network, the intelligent syndrome differentiation model of TCM can fully approach the real side of syndrome differentiation, and shows excellent predicted ability of syndrome differentiation.

Genome-wide identification and characterization of novel long non-coding RNA in Ruminal tissue affected with sub-acute Ruminal acidosis from Holstein cattle.

Sub-acute ruminal acidosis is a type of metabolic disorder in which affected cattle show a considerable depression of rumen pH. This leads to a dramatic decline in productivity and consequent loss of income for many dairy farms. The objective of the present study is to identify and characterize novel long non-coding RNAs (lncRNAs) in Holstein cattle affected by sub-acute ruminal acidosis. Two replicates from six animals were sequenced that bioinformatically analyzed. Results showed 6679 novel lncRNAs among which 12 intergenic lncRNAs showed differential expression (p value ≤0.05). GO and KEGG analysis revealed that calcium signaling and G protein couple-receptor pathways may be involved in regulating metabolic processes during sub-acute ruminal acidosis. Furthermore, other biological processes including transmembrane transport, adult behavior, neuroactive ligand-receptor interaction, GABAergic synapse, cholinergic synapse were significantly enriched. The present data suggest that these differentially expressed lncRNAs may play regulatory roles in modulating biological processes associated with sub-acute ruminal acidosis in cattle rumen.

Clinical features and disturbances of gastrointestinal transit in patients with rapid gastric emptying.

AIMS: Some patients with upper gastrointestinal symptoms have rapid gastric emptying (GE). We aimed to compare patients with normal and rapid GE and to identify phenotypes among patients with rapid GE. METHODS: Among 2798 patients who underwent GE scintigraphy, we compared patients with normal and rapid GE and separately, patients with rapid GE at 1 hour (GE1), 2 hours (GE2), or both (GE12). RESULTS: In 2798 patients, GE was normal (74%), delayed (18%), or rapid (8%). Among 211 patients with rapid GE, patterns were rapid GE1 (48%), 2 hours (17%), or 1 and 2 hours (35%); 42 (20%) had diseases that explain rapid GE. A combination of upper and lower gastrointestinal symptoms (54%) was more common that isolated upper (17%) or lower (28%) gastrointestinal symptoms (P < .001). Constipation was more prevalent in patients with rapid GE 2 (72%) than rapid GE 1 (47%) or rapid GE12 hours (67%) (P < .05). Among 179 diabetes mellitus (DM) patients, 15% had rapid GE, which was not associated with the DM phenotype. By multivariable analysis, insulin therapy (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.15-0.88), and weight loss (OR, 0.10; 95% CI, 0.01-0.78) were associated with a lower risk of rapid than normal GE in DM. CONCLUSIONS: Eight percent of patients undergoing scintigraphy had rapid GE, which is most frequently associated with upper and lower gastrointestinal symptoms; constipation is common. Insulin therapy and weight loss were associated with a lower risk of rapid than normal GE in DM patients.

Nuclear magnetic resonance (NMR)-based metabolome profile evaluation in dairy cows with and without displaced abomasum.

Background: Displaced abomasum (DA) is a condition of dairy cows that severely impacts animal welfare and causes huge economic losses.Objective: To assess the metabolic status of the disease using metabolomics in serum, urine and liver samples aimed at both water soluble and lipid soluble fractions.Methods: Fifty Holstein multiparous cows with DA (42 left, 8 right) and 20 clinically healthy Holstein multiparous cows were used. Left DA was associated with concomitant ketosis in 19 animals and right in two. NMR-based metabolomics approach and hematological and biochemical analyses were performed. Statistical analysis was carried out on 1H-NMR data after they have been normalized using PQN method.Results: Contrary to generated PCA score plots the OPLS-supervised method revealed differences between healthy animals and diseased ones based on serum water-soluble samples. While water and lipid soluble metabolites decreased in serum samples, fatty acid fractions and cholesterol were increased in liver samples in DA affected cows. The metabolomic and chemical profiles clearly revealed that cows with DA (especially with LDA) were at risk of ketosis and fatty liver. Serum hippuric acid concentration was significantly higher in healthy cows in comparison with LDA, whereas serum glycine concentration was reported higher for healthy when compared to RDA affected animals.Conclusion: A biochemical network and pathway mapping revealed 'valine, leucine and isoleucine biosynthesis' and 'phenylalanine, tyrosine and tryptophan biosynthesis' as the most probable altered metabolic pathway in DA condition. Serum was advocated as the optimal biological matrix for the 1H-NMR analysis.

Bayesian inverse methods for spatiotemporal characterization of gastric electrical activity from cutaneous multi-electrode recordings.

Gastrointestinal (GI) problems give rise to 10 percent of initial patient visits to their physician. Although blockages and infections are easy to diagnose, more than half of GI disorders involve abnormal functioning of the GI tract, where diagnosis entails subjective symptom-based questionnaires or objective but invasive, intermittent procedures in specialized centers. Although common procedures capture motor aspects of gastric function, which do not correlate with symptoms or treatment response, recent findings with invasive electrical recordings show that spatiotemporal patterns of the gastric slow wave are associated with diagnosis, symptoms, and treatment response. We here consider developing non-invasive approaches to extract this information. Using CT scans from human subjects, we simulate normative and disordered gastric surface electrical activity along with associated abdominal activity. We employ Bayesian inference to solve the ill-posed inverse problem of estimating gastric surface activity from cutaneous recordings. We utilize a prior distribution on the spatiotemporal activity pertaining to sparsity in the number of wavefronts on the stomach surface, and smooth evolution of these wavefronts across time. We implement an efficient procedure to construct the Bayes optimal estimate and demonstrate its superiority compared to other commonly used inverse methods, for both normal and disordered gastric activity. Region-specific wave direction information is calculated and consistent with the simulated normative and disordered cases. We apply these methods to cutaneous multi-electrode recordings of two human subjects with the same clinical description of motor function, but different diagnosis of underlying cause. Our method finds statistically significant wave propagation in all stomach regions for both subjects, anterograde activity throughout for the subject with diabetic gastroparesis, and retrograde activity in some regions for the subject with idiopathic gastroparesis. These findings provide a further step towards towards non-invasive phenotyping of gastric function and indicate the long-term potential for enabling population health opportunities with objective GI assessment.

Rapid gastric emptying in diabetes mellitus: Pathophysiology and clinical importance.

Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.

Subjective Hunger, Gastric Upset, and Sleepiness in Response to Altered Meal Timing during Simulated Shiftwork.

Shiftworkers report eating during the night when the body is primed to sleep. This study investigated the impact of altering food timing on subjective responses. Healthy participants (n = 44, 26 male, age Mean ± SD = 25.0 ± 2.9 years, BMI = 23.82 ± 2.59kg/m2) participated in a 7-day simulated shiftwork protocol. Participants were randomly allocated to one of three eating conditions. At 00:30, participants consumed a meal comprising 30% of 24 h energy intake (Meal condition; n = 14, 8 males), a snack comprising 10% of 24 h energy intake (Snack condition; n = 14; 8 males) or did not eat during the night (No Eating condition; n = 16, 10 males). Total 24 h individual energy intake and macronutrient content was constant across conditions. During the night, participants reported hunger, gut reaction, and sleepiness levels at 21:00, 23:30, 2:30, and 5:00. Mixed model analyses revealed that the snack condition reported significantly more hunger than the meal group (p < 0.001) with the no eating at night group reporting the greatest hunger (p < 0.001). There was no difference in desire to eat between meal and snack groups. Participants reported less sleepiness after the snack compared to after the meal (p < 0.001) or when not eating during the night (p < 0.001). Gastric upset did not differ between conditions. A snack during the nightshift could alleviate hunger during the nightshift without causing fullness or increased sleepiness.