Motility Dysfunction Research Articles

Novel rare variation of CCDC40 plays a role in the development of idiopathic scoliosis possibly via dysfunction of cilia motility.

Motile cilia dysfunction was reported to lead to scoliosis-like phenotypes in zebrafish models. There is still a lack of population-based study supporting the role of cilia motility associated genes in the etiology of idiopathic scoliosis (IS). To investigate the molecular mechanism underlying the relationship between cilia motility associated genes and the development of adolescent idiopathic scoliosis (AIS). Population-based genetic study METHODS: A cohort of 56 female AIS patients and 30 age-matched non-scoliotic controls were included for tissue expression analysis. 28 patients with lower CCDC40 expression were selected for the exon sequencing. The novel variation was replicated in an independent cohort of 1326 AIS patients and 954 healthy controls. Exogenous versions of WT or mutant human CCDC40 mRNAs were expressed in zebrafish and the phenotype of body axis curvature was observed RESULTS: CCDC40 was found significantly down-expressed in AIS patients as compared with the non-scoliotic controls. A novel coding variant rs185157579 (c.1459G>A) was found significantly associated with AIS, with the mutant allele A adding to the risk of AIS by 2.44 folds. Zebrafish embryo injected with CCDC40 mRNAs containing mutant c.1459G>A presented significantly higher incidence of scoliosis-like phenotype than the wild group. The mutation c.1459G>A in the exon 10 of CCDC40 may lead to body axis curvature of zebrafish by impacting mRNA expression. The underlying molecular mechanism is worthy of further investigation. Our findings shed a new light on the etiopathogenesis of AIS. The downstream signaling of CCDC40 may be candidate for potential drug targets to prevent the development of AIS. Moreover, the novel variation can be used as a genetic marker of polygenic risk score predicting the risk of AIS.

Circadian rhythm disruption modulates enteric neural precursor cells differentiation leading to gastrointestinal motility dysfunction via the NR1D1/NF-κB axis

ObjectivesCircadian rhythm disruption (CRD) is implicated with numerous gastrointestinal motility diseases, with the enteric nervous system (ENS) taking main responsibility for the coordination of gastrointestinal motility. The purpose of this study is to explore the role of circadian rhythms in ENS remodeling and to further elucidate the underlying mechanisms.MethodsFirst, we established a jet-lagged mice model by advancing the light/dark phase shift by six hours every three days for eight weeks. Subsequent changes in gastrointestinal motility and the ENS were then assessed. Additionally, a triple-transgenic mouse strain (Nestin-creERT2 × Ngfr-DreERT2: DTRGFP) was utilized to track the effects of CRD on the differentiation of enteric neural precursor cells (ENPCs). RNA sequencing was also performed to elucidate the underlying mechanism.ResultsCompared to the control group, CRD significantly accelerated gastrointestinal motility, evidenced by faster intestinal peristalsis (P < 0.01), increased fecal output (P < 0.01), and elevated fecal water content (P < 0.05), as well as enhanced electrical field stimulation induced contractions (P < 0.05). These effects were associated with an increase in the number of glial cells and nitrergic neurons in the colonic myenteric plexus. Additionally, ENPCs in the colon showed a heightened differentiation into glial cells and nitrergic neurons. Notably, the NR1D1/nuclear factor-kappaB (NF-κB) axis played a crucial role in the CRD-mediated changes in ENPCs differentiation. Supplementation with NR1D1 agonist or NF-κB antagonist was able to restore gastrointestinal motility and normalize the ENS in jet-lagged mice.ConclusionsCRD regulates the differentiation of ENPCs through the NR1D1/NF-κB axis, resulting in dysfunction of the ENS and impaired gastrointestinal motility in mice.

Effects of Obesity in Male Fertility in Khartoum State

Obesity is a severe medical condition causing health issues and reducing life expectancy, affecting 400 million adults and 1.6 million overweight individuals, is a severe medical condition affecting fertility, with extreme obesity causing fertility issues. This study aimed to investigate the effect of obesity on male fertility in Khartoum state; it is a cross-sectional facility-based study studying All males of Infertile couples who come to the infertility clinic. The study discussed patient demographics, past medical and surgical history, and self-reported male sexual dysfunction in addition to the factors that affect male infertility, Body Mass Index (BMI), and spermatic parameters (motility, morphology, concentration) by seminal analysis. The statistical package SPSS 23.0 was used for analysis. The study revealed that 40 men (20.5) were of age &lt;30 years old, 57 men (29.9%) of age 30 – 40 years old, and 98 men (50.3%) were of age &gt;40 years old. “One hundred five men (53.8%) were from North Sudan”, “58 men (29.7%) were from Eastern Sudan,30 men (15.35%) were from Western Sudan overweight, and 2 men (1.15%) were from Southern Sedan, 56 men (28.7%) have BMI &lt;25,81(41.5%) had BMI 25 -30 and 58(29.8%) have BMI of &gt;30, 110 men (56.4%) have normal sperm counts and 85 (43.6) have abnormal sperm counts, 105 men (53.8%) have normal sperm morphology”. In contrast, 90 (46.2) have abnormal morphology. Eighty-eight men (45.1%) have progressive motility, while 107 men (54.9%) have impaired motility. Fifty-six men (28.8%) of participants have erectile dysfunction, while 139 (71.2%) have not. It concluded that increasing the age of the male partner increases the risk of infertility, and ethnicity has an unclear effect on infertility and still needs further studies to prove it. Obesity rates are increasing among men in Khartoum, impacting seminal parameters like motility and erectile dysfunction, as highlighted in a study.

Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus.

The morpho-quantitative analysis of myenteric plexus neurons in the small and large intestines of 120-day-old male GK rats was investigated. The diabetes was confirmed by high fasting blood glucose levels. The myenteric plexus was evaluated through wholemount immunofluorescence. The morpho-quantitative analyses included evaluating neuronal density (neurons per ganglion) of the total neuronal population, the cholinergic and nitrergic subpopulations, and enteric glial cells per ganglion. The cell body area of 100 neurons per segment per animal was measured. The total neurons and nitrergic subpopulation were unaltered in the GK rats' small and large intestines. The cholinergic subpopulation exhibited decreased density in the three segments of the small intestine and an increased number in the proximal colon of the GK rats. The number of enteric glial cells increased in the ileum of the GK rats, which could indicate enteric gliosis caused by the intestinal inflammatory state. The area of the cell body was increased in the total neuronal population of the jejunum and ileum of the GK rats. Frequency histograms of the cell body area distribution revealed the contribution of cholinergic neurons to larger areas in the jejunum and nitrergic neurons in the ileum. The constipation previously reported in GK rats might be explained by the decrease in the density of cholinergic neurons in the small intestine of this animal model.

Emodin repairs interstitial cells of Cajal damaged by cholelithiasis in the gallbladder.

Hypercholesterolemia induces cholelithiasis and dysfunction of gallbladder motility. Interstitial cells of Cajal (ICCs) contribute to gallbladder motility. Emodin modulates the contractility of the gallbladder muscle; however, the underlying mechanism is unknown. This study aimed to explore the effects of emodin on gallbladder ICCs with cholelithiasis in a guinea pig model. Animals were randomly divided into a healthy control group and three study groups. All study groups received a high-cholesterol diet (HCD) for 8 weeks. Subsequently, they were randomly assigned to either the HCD group or one of the emodin treatment groups lasting 4 or 8weeks. Total cholesterol (TC) and triglycerides (TG) were measured to determine changes in serum lipid levels. Immunohistochemistry was performed to detect the morphology and number of ICCs. TUNEL assays were performed to detect ICC apoptosis. Transmission electron microscopy was employed to observe ICC structure. Western blotting and real-time polymerase chain reaction were used to detect changes in stem cell factor (SCF)/c-kit pathway expression. Serum TC and TG were higher in all study groups. In cases of cholelithiasis, the SCF/c-kit pathway was downregulated, the number of gallbladder ICCs decreased, apoptosis increased, and the ICC network structure was damaged. After emodin treatment, the SCF/c-kit pathway was upregulated, the number of gallbladder ICCs increased, apoptosis decreased, and the ICC network structure recovered. Cholelithiasis downregulates the SCF/c-kit pathway and damages gallbladder ICCs. Emodin upregulates the SCF/c-kit pathway and increases gallbladder ICCs, contributing to recovery from gallbladder motility disorders.\.

Subclinical Ocular Motility Dysfunction and Extraocular Muscle Changes in Inactive Graves' Orbitopathy.

This study aimed to investigate the presence of structural and functional changes in extraocular muscles (EMs) among patients with inactive Graves' orbitopathy (GO) classified according to the Clinical Activity Score (CAS). Sixty-seven patients with Graves' disease (GD) and inactive GO were included. The data collected included clinical parameters, thyroid function, autoantibody levels, EOM morphology via orbital ultrasound (US), and ocular motility. Patients were stratified into Red Filter Test (RFT)-positive or RFT-negative groups based on the presence or absence of latent diplopia during the RFT examination. Thirty-three patients (49.25%) exhibited latent diplopia on the RFT, despite not reporting double vision during standard ocular motility tests. Significant differences were observed between the two groups in terms of age, disease duration, intraocular pressure (IOP) elevation in up-gaze, and medial rectus muscle thickness (p < 0.05). No significant differences were found in thyroid status, TRAb and ATA levels, CASs, exophthalmos, or lateral rectus thickness between the two groups. This study revealed that in inactive GO, subclinical EM dysfunction and morphological changes may be present, which might not be apparent through routine ocular examinations. The RFT is effective in detecting latent diplopia, highlighting its utility in identifying subtle ocular motility issues and subclinical muscle involvement. Comprehensive evaluations combining functional tests like the RFT and imaging are essential for early detection of GO-related abnormalities, enabling tailored and prompt management and improving patient outcomes.

Common laryngopharyngeal reflux: A review

Abstract Clinically, gastroesophageal reflux disease (GERD) or gastroesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease characterized by persistent and regular flow of stomach content up into the esophagus, resulting in symptoms and/or complications. Further, if acid reflux symptoms are more apparent in the larynx or pharynx, then the disorder may be called laryngopharyngeal reflux disorder (LPRD). The reflux of such acid to soft tissues beyond the esophagus will cause damage, which may turn into a relatively serious condition, especially for those with laryngeal reflux. Traditionally, obesity has been known as a primary risk factor for GERD or LPRD and related complications. Many studies have reported the association between obesity, hiatus hernia, and various motility dysfunctions of the upper gastrointestinal tract in patients with LPRD. Somehow obesity predisposes to these conditions, or whether they merely coexist with LPRD remains to be elucidated and dissents exist. Previous studies often recommend longer treatment and higher doses of proton pump inhibitors (PPI) for general gastroesophageal reflux because the presence of gastric acid in the pharynx and larynx can damage the vocal cords. Patients with laryngopharyngeal reflux can feel the symptoms while sitting at rest, and those with GERD feel the symptoms when lying down. The stomach contents, including pepsin and gastric acid, are the culprits that cause major damage to the tissues. Bile salts from the gallbladder further worsen the injury. A high-risk population includes people with obesity and/or obstructive sleep apnea.

Navigating through 65years of insights: lessons learned on functional abdominal pain in children.

In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children-a subject that had confounded clinicians of their time. Surprisingly, even after 65years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65years.Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that someof these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results.

Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.

The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Low-intensity pulsed ultrasound combined with ST36 modulate gastric smooth muscle contractile marker expression via RhoA/Rock and MALAT1/miR-449a/DLL1 signaling in diabetic rats.

Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype was related to the diabetes-induced gastric dysfunction, but the mechanism is not clearly elucidated. This study was aimed at exploring the underlying mechanism of LIPUS stimulation application in diabetic gastroparesis rats. In this study, Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DGP), and LIPUS-treated group (LIPUS). LIPUS irradiation was performed bilaterally at ST36 for 20 min per day for 4 weeks. The gastric emptying rate was measured by ultrasound examination. Contraction ability of GSMCs was assessed by muscle strip experiment. The expression of related proteins or mRNAs including α-SMA, SM22α, MHC, RhoA, Rock2, p-MYPT1, MYPT1, p-MLC, MLC, MALAT1, miR-449a, and DLL1 was detected by different methods such as western blotting, RT-qPCR, immunohistochemistry, and immunofluorescence staining, as appropriate. (a) LIPUS stimulation at ST36 could improve the gastric motility dysfunction of diabetic rats. (b) LIPUS increased RhoA, Rock2, p-MYPT1, and p-MLC expression level. (c) MALAT1 and DLL1 contents were decreased, but the level of miR-449a was increased in the LIPUS group. LIPUS may affect the contractile marker expression of gastric smooth muscle through the RhoA/Rock and MALAT1/miR-449a/DLL1 pathway to ameliorate DGP.

Mapping the rat gastric slow-wave conduction pathway: bridging in vitro and in vivo methods, revealing a loosely coupled region in the distal stomach.

Rhythmic electrical events, termed slow waves, govern the timing and amplitude of phasic contractions of the gastric musculature. Extracellular multielectrode measurement of gastric slow waves can be a biomarker for phenotypes of motility dysfunction. However, a gastric slow-wave conduction pathway for the rat, a common animal model, is unestablished. In this study, the validity of extracellular recording was demonstrated in vitro with simultaneous intracellular and extracellular recordings and by pharmacological inhibition of slow waves. The conduction pathway was determined by in vivo extracellular recordings while considering the effect of motion. Slow-wave characteristics [means (SD)] varied regionally having higher amplitude in the antrum than the distal corpus [1.03 (0.12) mV vs. 0.75 (0.31) mV; n = 7; P = 0.025 paired t test] and faster propagation near the greater curvature than the lesser curvature [1.00 (0.14) mm·s-1 vs. 0.74 (0.14) mm·s-1; n = 9 GC, 7 LC; P = 0.003 unpaired t test]. Notably, in some subjects, separate wavefronts propagated near the lesser and greater curvatures with a loosely coupled region occurring in the area near the distal corpus midline at the interface of the two wavefronts. This region had either the greater or lesser curvature wavefront propagating through it in a time-varying manner. The conduction pattern suggests that slow waves in the rat stomach form annular wavefronts in the antrum and not the corpus. This study has implications for interpretation of the relationship between slow waves, the interstitial cells of Cajal network structure, smooth muscles, and gastric motility.NEW & NOTEWORTHY Mapping of rat gastric slow waves showed regional variations in their organization. In some subjects, separate wavefronts propagated near the lesser and greater curvatures with a loosely coupled region near the midline, between the wavefronts, having a varying slow-wave origin. Furthermore, simultaneous intracellular and extracellular recordings were concordant and independent of movement artifacts, indicating that extracellular recordings can be interpreted in terms of their intracellular counterparts when intracellular recording is not possible.

Potential role of short-chain fatty acids in irritable bowel syndrome in overweight and obese individuals

Due to increasing prevalence of functional diseases of the colon in obese patients, the mechanisms by which the intestinal microbiota affects the development of symptoms of irritable bowel syndrome (IBS) in the setting of metabolic activity of adipose tissue should be investigated. The quantitative and qualitative changes in the pool of synthesized short-chain fatty acids, which have a multidirectional impact on the colonic motility is one of the key mechanisms by which the intestinal microbiota affects the occurrence and features of the course of irritable bowel syndrome. But as regards the issue of whether individual short-chain fatty acids have an impact on the severity of abdominal pain and characteristics of colonic motility dysfunction, it remains a subject of discussions. The study of the mechanisms of impact of short-chain fatty acids on the development and progression of obesity deserves special attention. Increased serum and faecal short-chain fatty acid levels in obese patients can either be a result of changes in the intestinal microflora composition associated with special eating habits and lifestyle, or have an independent effect on the development of obesity in individuals due to intestinal microflora composition disorders that have been already developed. Due to special features of the course of irritable bowel syndrome associated with overweight and obesity, studying the intestinal microbiota composition and the short-chain fatty acids produced by it in this cohort of IBS patients is of particular interest. This publication has been prepared to describe and systematize the possible mechanisms of impact of short-chain fatty acids on the development of abdominal pain and impaired colonic motility in IBS patients with overweight and obesity. The literature search was conducted in the databases Embase, PubMed and Google Scholar using the keywords “irritable bowel syndrome”, “obesity”, “short-chain fatty acids”, “gut microbiota”.

Thyroid disorders and gastrointestinal dysmotility: an old association.

Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.

Morphometric Changes of the Myenteric Plexus in the Colon of the Mice-D-Galactose Ageing Model

Ageing-related diseases are paramount for understanding the socioeconomic impact of the postmodern society. Neuronal degeneration is a known phenomenon in ageing. The D-galactose model of accelerated ageing is widely used in age-associated neuronal cell death because of the oxidative stress it induces, which correlates to reduced cognitive performance and robustly detectable neuronal shrinkage in the CNS. This study aims at demonstrating the morphological changes of neurons of the myenteric plexus in mice treated with D-galactose. D-galactose was given orally with drinking water, resulting in an average dose of 500 mg/kg daily for six weeks. In the D-galactose accelerated ageing model, a significant size reduction of the neuronal perikarya of the myenteric plexus was observed all along the large intestine. The average soma area at the caecum in the control group was 305 µm2, which was reduced by almost 20% in the ageing model. In contrast, at the level of the proximal colon in the D-galactose ageing model, the average area of the neuronal soma was 280 µm2, a reduction of 30%. The most significant reduction has been observed at the level of the distal colon, where the neuronal soma was reduced by 40%. There is a significant reduction of the area of the neuronal bodies in the myenteric plexus among different parts of the mice's large intestine in the accelerated ageing model. It can be inferred that D-galactose-induced morphological changes in the myenteric plexus may be related to the increased gastrointestinal motility dysfunction with ageing.

Electroacupuncture alleviates intestinal inflammation via a distinct neuro-immune signal pathway in the treatment of postoperative ileus

BackgroundThe induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. MethodsAfter intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24 h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. ResultsEA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. ConclusionsEA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.

Vasoactive Intestinal Peptide Receptor, CRTH2, Antagonist Treatment Improves Eosinophil and Mast Cell-Mediated Esophageal Remodeling and Motility Dysfunction in Eosinophilic Esophagitis.

Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE.

Understanding Visual Disorders through Correlation of Clinical and Radiologic Findings.

Patients presenting with visual disturbances often require a neuroimaging approach. The spectrum of visual disturbances includes three main categories: vision impairment, ocular motility dysfunction, and abnormal pupillary response. Decreased vision is usually due to an eye abnormality. However, it can also be related to other disorders affecting the visual pathway, from the retina to the occipital lobe. Ocular motility dysfunction may follow disorders of the cranial nerves responsible for eye movements (ie, oculomotor, trochlear, and abducens nerves); may be due to any abnormality that directly affects the extraocular muscles, such as tumor or inflammation; or may result from any orbital disease that can alter the anatomy or function of these muscles, leading to diplopia and strabismus. Given that pupillary response depends on the normal function of the sympathetic and parasympathetic pathways, an abnormality affecting these neuronal systems manifests, respectively, as pupillary miosis or mydriasis, with other related symptoms. In some cases, neuroimaging studies must complement the clinical ophthalmologic examination to better assess the anatomic and pathologic conditions that could explain the symptoms. US has a major role in the assessment of diseases of the eye and anterior orbit. CT is usually the first-line imaging modality because of its attainability, especially in trauma settings. MRI offers further information for inflammatory and tumoral cases. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Retraction: PKC-delta and PKD activate MAPK signal pathway in mechano-transcription of colonic smooth muscle cells.

Retraction: [PKC-delta and PKD activate MAPK signal pathway in mechano-transcription of colonic smooth muscle cells, Z. Yang, K. He, T. Wang, etal. Neurogastroenterology & Motility 2023; e14623 (https://onlinelibrary.wiley.com/doi/full/10.1111/nmo.14623)]. The above article, published online on June 6, 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editor in Chief, Maura Corsetti, and John Wiley & Sons Ltd. The retraction has been agreed due to unattributed overlap between this article and the abstract published in Gastroenterology: Li F, Sarna SK and Shi XP. Roles of PKCs and PKD in Mechanotranscription in Colonic Smooth Muscle Cells: Inhibition of Mechanotranscription as a Potential Treatment for Motility Dysfunction in Obstructive Disorders. In: 2012 Digestive Disease Week Abstract Supplement; May 19-22, San Diego, CA. Abstract 120 (https://www.gastrojournal.org/article/S0016-5085(12)60115-2/pdf).

P499 Anorectal Motility Disorders In Inflammatory Bowel Disease Patients

Abstract Background In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients. Methods We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol Results We studied 30 patients (18 patients with Ulcerative Colitis and 12 patients with Crohn’s Disease, 18 females and 12 males, mean age 40 (±12.85) years. Only 33% (10 patients) had rectal active involvement. Symptoms were reported by 87% (26) patients: anal incontinence (85%), difficult evacuation (35%) and urgency (46%); rectal inflammation was not correlated with the presence of symptoms in our study group (p=0.28). Perianal surgical interventions didn’t represent a risk factor for fecal incontinence (p=0.18), or for dyssinergic defecation (p=0.1). Modified manometric parameters were found in 23 patients (79%). Low resting pressures were registered in 48% of patients; 55% of them presented low squeeze pressures; during push maneuvers, 34% of patients had insufficient rectal propulsive force, presenting low rectal pressures and 59% of them lacked anal canal relaxation. We performed sensibility testing on 18 patients: 9 patients presented criteria for hypersensitivity, hence reduced rectal compliance; 7 patients presented rectal hyposensitivity, while only 2 patients had normal rectal sensation. Recto-anal inhibitory reflex (RAIR) was present only in 28% of the patients, reflecting the dysfunction of the enteric neural system. Conclusion Patients with inflammatory bowel disease (IBD) have significantly higher rates of functional anorectal disease. Therefore, pelvic floor investigation is an essential tool in the investigation and management of IBD patients with ongoing symptoms not thought to be related to an IBD flare.

Exploring the gut microbiota's crucial role in acute pancreatitis and the novel therapeutic potential of derived extracellular vesicles.

During acute pancreatitis, intestinal permeability increases due to intestinal motility dysfunction, microcirculatory disorders, and ischemia-reperfusion injury, and disturbances in the intestinal flora make bacterial translocation easier, which consequently leads to local or systemic complications such as pancreatic and peripancreatic necrotic infections, acute lung injury, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Therefore, adjusting intestinal ecosystem balance may be a promising approach to control local and systemic complications of acute pancreatitis. In this paper, we reviewed the causes and manifestations of intestinal flora disorders during acute pancreatitis and their complications, focused on the reduction of acute pancreatitis and its complications by adjusting the intestinal microbial balance, and innovatively proposed the treatment of acute pancreatitis and its complications by gut microbiota-derived extracellular vesicles.