Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett's oesophagus patients.

INTRODUCTION: Epithelial-mesenchymal plasticity (EMP), the process through which epithelial cells acquire mesenchymal features, is needed for wound repair but also might contribute to cancer initiation. Earlier, in vitro studies showed that Barrett's cells exposed to acidic bile salt solutions (ABS) develop EMP. Now, we have (1) induced reflux oesophagitis in Barrett's oesophagus (BO) patients by stopping proton pump inhibitors (PPIs), (2) assessed their biopsies for EMP and (3) explored molecular pathways underlying reflux-induced EMP in BO cells and spheroids. METHODS: 15 BO patients had endoscopy with biopsies of Barrett's metaplasia while on PPIs, and 1 and 2 weeks after stopping PPIs; RNA-seq data were assessed for enrichments in hypoxia-inducible factors (HIFs), angiogenesis and EMP pathways. In BO biopsies, cell lines and spheroids, EMP features (motility) and markers (vascular endothelial growth factor (VEGF), ZEB1, miR-200a&b) were evaluated by morphology, migration assays, immunostaining and qPCR; HIF-1α was knocked down with siRNA or shRNA. RESULTS: At 1 and/or 2 weeks off PPIs, BO biopsies exhibited EMP features and markers, with significant enrichment for HIF-1α, angiogenesis and EMP pathways. In BO cells, ABS induced HIF-1α activation, which decreased miR-200a&b while increasing VEGF, ZEB1 and motility; HIF-1α knockdown blocked these effects. After ABS treatment, BO spheroids exhibited migratory protrusions showing nuclear HIF-1α, increased VEGF and decreased miR-200a&b. CONCLUSIONS: In BO patients, reflux oesophagitis induces EMP changes associated with increased HIF-1α signalling in Barrett's metaplasia. In Barrett's cells, ABS trigger EMP via HIF-1α signalling. Thus, HIF-1α appears to play a key role in mediating reflux-induced EMP that might contribute to cancer in BO. TRIAL REGISTRATION NUMBER: NCT02579460.

An Endoscopic Scoring System for Achalasia: The CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of two years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic CARS score for the prediction of achalasia. METHODS: Part 1: Twenty endoscopic videos were taken from patients undergoing endoscopy for dysphagia or reflux. A survey with videos and endoscopic criteria options was distributed to 6 esophagologists and 6 general gastroenterologists. Inter-rater reliability (IRR) was measured and logistic regression was used to evaluate predictive performance. Three rounds of review were conducted to select the final score of four components. PART 2: A retrospective review was conducted for consecutive patients who had comprehensive esophageal testing. Each patient had a CARS endoscopic score calculated based on findings reported at endoscopy. RESULTS: From a video review and analysis of score components, IRR ranged from 0.23 to 0.57 for score components. The final CARS score was selected based on the following four components: Contents, Anatomy, Resistance, and Stasis. In a mixed effects model, the mean score across raters was higher for achalasia compared to non-achalasia subjects (4.44 vs. 0.87, p = < 0.01). In part 2 of the study, achalasia patients had a higher mean CARS score compared to those with no / ineffective motility disorder (mean 4.1 vs 1.3, p = < 0.01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in clinical setting. The CARS score performed well in predicting achalasia.

The broad impact of functional lumen imaging probe panometry in addition to high-resolution manometry in an esophageal clinical practice.

High-resolution manometry (HRM) with the Chicago Classification (CC) is the standard paradigm to define esophageal motility disorders. Functional lumen imaging probe (FLIP) panometry utilizes impedance planimetry to characterize esophageal compliance and secondary peristalsis. The aim of this study was to explore the clinical impact of FLIP panometry in addition to HRM. A retrospective chart review was performed on FLIP panometry cases utilizing the 322N catheter. Cases with prior foregut surgeries or botulinum injection within 6 months of FLIP panometry were excluded. EGJ-diameter and distensibility index (DI) and secondary contraction patterns at increasing balloon volumes were recorded. An EGJ-DI of ≥2.8 mm2/mm Hg at 60 mL was considered as a normal EGJ distensibility. CC diagnosis, Eckhardt score, Brief Esophageal Dysphagia Questionnaire, and clinical outcomes were obtained for each FLIP case. A total of 186 cases were included. Absent contractility and achalasia types 1 and 2 showed predominantly absent secondary contraction patterns, while type 3 had a variety of secondary contractile patterns on FLIP panometry. Among 77 cases with EGJ outflow obstruction (EGJOO), 60% had a low EGJ-DI. Among those with no motility disorder or ineffective esophageal motility on HRM, 27% had a low DI and 47% had sustained contractions on FLIP, raising concern for an esophageal dysmotility process along the achalasia and/or spastic spectrum. FLIP panometry often confirmed findings on HRM in achalasia and absent contractility. FLIP panometry is useful in characterizing EGJOO cases. Spastic features on FLIP panometry may raise concern for a motility disorder on the spastic spectrum not captured by HRM. Further studies are needed on FLIP panometry to determine how to proceed with discrepancy with HRM and explore diagnoses beyond the CC.

Functional luminal imaging probe in the evaluation of esophago-gastric junction outflow obstruction.

PURPOSE OF REVIEW: Esophagogastric junction outflow obstruction (EGJOO) comprises a heterogeneous group of conditions that demonstrate impaired deglutitive relaxation of the esophagogastric junction (EGJ) with intact esophageal peristalsis on high-resolution manometry. Functional luminal imaging probe (FLIP) panometry is a powerful tool that can help to clarify the etiology of this manometric diagnosis. The aim of this review is to summarize the use of FLIP for the evaluation and management of EGJOO. RECENT FINDINGS: FLIP panometry provides measures of esophageal compliance at the EGJ and information on esophageal body contractile responses to balloon distention that have important implications for the management of patients with EGJOO. After excluding anatomic causes of impaired EGJ distensibility, FLIP panometry is useful in differentiating true lower esophageal sphincter dysfunction from manometric artifact. FLIP panometry has been shown to be useful in determining the need for invasive treatment in patients with EGJOO, and in intraoperative tailoring of myotomy procedures. SUMMARY: FLIP panometry is easy to perform during endoscopy and provides useful information for characterizing the EGJOO population. FLIP panometry can be used to guide treatment and improve outcomes in the management of patients with EGJOO.

Survival after out-of-hospital cardiac arrest, Viet Nam: multicentre prospective cohort study.

OBJECTIVE: To investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam. METHODS: We did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis. FINDINGS: Of 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54-9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03-8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33-12.74). CONCLUSION: Improvements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.

Impact of bariatric surgery on gastroesophageal reflux disease and esophageal motility.

PURPOSE OF REVIEW: Obesity is rapidly increasing in prevalence, and bariatric surgery has become a popular treatment option that can improve all-cause mortality in obese individuals. Gastroesophageal reflux disease (GERD) and esophageal motility disorders are common in the obese population, and the effects of bariatric surgery on these conditions differ depending on the type of bariatric surgery performed. RECENT FINDINGS: Laparoscopic adjustable gastric banding has declined in popularity due to its contributions to worsening GERD symptoms and the development of esophageal dysmotility. Although laparoscopic sleeve gastrectomy (LSG) is the most popular type of bariatric surgery, a comprehensive assessment for acid reflux should be performed as LSG has been linked with worsening GERD. Novel methods to address GERD due to LSG include magnetic sphincter augmentation and concomitant fundoplication. Due to the decreased incidence of postoperative GERD and dysmotility compared to other types of bariatric surgeries, Roux-en-Y gastric bypass should be considered for obese patients with GERD and esophageal dysmotility. SUMMARY: Bariatric surgery can affect esophageal motility and contribute to worsening or development of GERD. A thorough workup of gastrointestinal symptoms before bariatric surgery should be performed with consideration for formal testing with high-resolution manometry and pH testing. Based on these results, the choice of bariatric surgery technique should be tailored accordingly to improve clinical outcomes.

Insights into the Electrochemical Polymerization of [Mo3 S13 ]2- Generating Amorphous Molybdenum Sulfide.

Amorphous molybdenum sulfide is an attractive electrode material for Li/Mg batteries and an efficient Pt-free catalyst for the hydrogen evolution reaction in water. By using the electrochemical quartz crystal microbalance (EQCM) analysis, new insights were gained into the electrochemical polymerization of the [Mo3 S13 ]2- cluster, which generates amorphous molybdenum sulfide thin films. In this work, it is shown that, at the anodic potential, a two-electron oxidative elimination of the terminal disulfide ligand within the [Mo3 S13 ]2- cluster induces the polymerization. A reductive elimination of the terminal disulfide ligand also occurs at the cathodic potential, inducing the polymerization. However, in sharp contrast to the anodic polymerization, according to which the film growth is rapid, the cathodic polymerization competes with the electrochemical reductive corrosion of the readily grown film, therefore occurring at a significant lower growth rate.

Unique Clinical Features of Los Angeles Grade D Esophagitis Suggest That Factors Other Than Gastroesophageal Reflux Contribute to its Pathogenesis.

BACKGROUND: The Los Angeles (LA) grade of reflux esophagitis (A to D) is assumed to reflect severity of the underlying gastroesophageal reflux disease (GERD). Thus, LA-D esophagitis patients might be expected to have the most conditions predisposing to GERD (eg, obesity, hiatal hernia), and the highest frequency of GERD symptoms. GOALS: The main goal of this study is to compare clinical features of patients with the most severe (LA-D) and mildest (LA-A) grades of esophagitis. STUDY: For this comparative study, we searched our endoscopy database for patients diagnosed with LA-D or LA-A esophagitis, reviewed their endoscopic images, and reviewed medical records of the first 100 we confirmed to have LA-D or LA-A esophagitis. RESULTS: Compared with LA-A patients, LA-D patients were older (mean age, 65±13.4 vs. 56±13.4 y; P<0.001), had lower body mass index (25.9±5.6 vs. 29.4±5.3; P<0.001), were more frequently hospitalized (70% vs. 3%; P<0.001), and in the intensive care unit (15% vs. 0%; P<0.001), and had significantly more serious cardiopulmonary disorders and gastrointestinal bleeding. Conversely, a GERD history was more common in LA-A than LA-D patients (67% vs. 45%; P=0.002). Hiatal hernia was more frequent in LA-A patients than LA-D patients, but not significantly (48% vs. 36%; P=0.09). CONCLUSIONS: LA-D esophagitis primarily affects hospitalized, older, nonobese patients who often have serious comorbidities, and no history of GERD or hiatal hernia. In contrast, LA-A patients are generally younger, obese outpatients who often have a history of GERD and hiatal hernia without serious comorbidities. These profound differences between LA-A and LA-D patients suggest that factors other than typical GERD contribute to LA-D esophagitis pathogenesis.

How to Approach Lymphocytic Esophagitis.

PURPOSE OF REVIEW: Lymphocytic esophagitis (LE) is an unusual esophageal condition defined by an increased number of lymphocytes in the esophageal epithelium. With few published studies of LE available, it is unclear whether LE is a truly distinct clinical entity or a histological manifestation of other known gastrointestinal disorders. This review summarizes recent studies of lymphocytic esophagitis. RECENT FINDINGS: Studies have suggested that LE may be related to eosinophilic esophagitis (EoE) or a manifestation of gastroesophageal reflux disease (GERD). There is an association between LE and Crohn's disease in children, but not in adults. Patients with LE frequently report symptoms of dysphagia and GERD. Treatment options for LE are limited and involve symptom management similar to treatment of EoE or GERD, including proton pump inhibitors (PPI), swallowed topical steroids, and endoscopic dilation. With no formal definition and a variety of clinical presentations and endoscopic findings, diagnosis and management of symptomatic LE patients is challenging for clinicians.

The prophylactic placement of hemoclips to prevent delayed post-polypectomy bleeding: an unnecessary practice? A case control study.

BACKGROUND: With the recent, widespread availability of endoscopic hemoclips, it has become common clinical practice to apply hemoclips to some non-bleeding polypectomy sites "prophylactically" to prevent delayed post-polypectomy bleeding (PPB). Few published data support this practice, however. AIM: The aim of this study was to compare rates of delayed PPB in matched patients who had polypectomies performed with and without the prophylactic placement of hemoclips. METHODS: We reviewed medical records of patients who had elective colonoscopy at our VA Medical Center between July 2008 and December 2009. We identified patients who had hemoclips applied prophylactically (cases) and compared their rate of delayed PPB within 30 days to that of patients who had polypectomy without hemoclipping (controls). Controls were matched 1:1 to cases based on age and on factors known to contribute to the risk of PPB including polyp size, morphology, technique of polyp removal, number of polyps removed, and use of anticoagulants. RESULTS: We identified 184 patients (cases) who underwent prophylactic hemoclipping and 184 well-matched controls. An average of 3.8 polyps per patient were removed in the case group compared to 3.3 polyps per patient in controls (p = 0.6). Delayed PPB occurred in three patients in the prophylactic hemoclip group and in one patient in the control group (1.6 vs. 0.5 %, p = 0.62). CONCLUSIONS: We found no significant difference in the rate of delayed PPB between patients who had prophylactic hemoclipping of polypectomy sites and a well-matched control group of patients who had polypectomy without prophylactic hemoclipping. These data call into question the expensive practice of prophylactic hemoclipping.

The millipede family Polydesmidae Leach, 1816 (Diplopoda, Polydesmida) from Vietnam, with a description of a new cavernicolous species.

The millipede family Polydesmidae Leach, 1816 is reviewed in the scope of the Vietnamese fauna. The distribution of the species, Polydesmusvietnamicus Nguyen, 2009 is extended northward to Ha Giang Province. A new cavernicolous polydesmid, Pacidesmustuachuasp. nov., is described from two caves in northwestern Vietnam, representing the first record of the genus from Vietnam. Extensive illustrations and DNA barcodes are provided for both species, a revised key is presented to all 12 species of Pacidesmus Golovatch, 1991, as well as a key to all eight genera of Asian Polydesmidae.

Two new earthworm species of the genus Amynthas Kinberg, 1867 (Annelida, Oligochaeta, Megascolecidae) from the Southeast region, Vietnam.

Two new earthworm species, namely Amynthas rarus sp. nov. and Amynthas tayninhensis sp. nov., are described from Tay Ninh Province, southeastern Vietnam. Amynthas rarus sp. nov. is recognized by having male pores in xix, two pairs of spermathecal pores in 6/7/8, and genital markings paired in vii, viii, 18/19, and 19/20. Amynthas tayninhensis sp. nov. is distinguished by having a pair of spermathecal pores in 5/6, numerous genital markings in transverse lines in 17/18 including three surrounding male pores, and spermatheca with fully developed diverticula. The COI fragments are also provided for those two new species.

The solitary wasp genus Orancistrocerus from Vietnam, with descriptions of two new species (Hymenoptera, Vespidae, Eumeninae).

New data are presented for the potter wasp genus Orancistrocerus van der Vecht (Eumeninae, Odynerini) occurring in Vietnam. Two species are described as new to science: Orancistrocerusthanhnhatsp. nov. and O.thanghensp. nov.Orancistrocerusaterrimuserythropus van der Vecht is synonymized with Orancistrocerusaterrimusaterrimus (de Saussure); the male genitalia of this species are described for the first time. An updated key is presented to all species of the genus.

Cu2MoS4 Nanocatalyst-Based Electrochemical Sensor for Ofloxacin Electro-Oxidation: Delineating the Combined Roles of Crystallinity and Morphology on the Analytical Performance.

In this study, we demonstrate the influence of crystallinity and morphology on the analytical performance of various Cu2MoS4 (CMS) nanocatalysts-based electrochemical sensors for the high-efficiency detection of Ofloxacin (OFX) antibiotic. The electrochemical kinetics parameters including peak current response (ΔIp), peak-to-peak separation (ΔEp), electrochemically active surface area (ECSA), electron-transfer resistance (Rct), were obtained through the electrochemical analyses, which indicate the single-crystalline nature of CMS nanomaterials (NMs) is beneficial for enhanced electron-transfer kinetics. The morphological features and the electrochemical results for OFX detection substantiate that by tuning the tube-like to plate-like structures of the CMS NMs, it might noticeably enhance multiple adsorption sites and more intrinsic active catalytic sites due to the diffusion of analytes into the interstitial spaces between CMS nanoplates. As results, highly single-crystalline and plate-shaped morphology structures of CMS NMs would significantly enhance the electrocatalytic OFX oxidation in terms of onset potential (Eonset), Tafel slope, catalytic rate constant (kcat), and adsorption capacity (Γ). The CMS NMs-based electrochemical sensing platform showed excellent analytical performance toward the OFX detection with two ultra-wide linear detection concentration ranges from 0.25-100 and 100-1000 µM, a low detection limit of 0.058 µM, and an excellent electrochemical sensitivity (0.743 µA µM-1 cm-2).

Frequent discrepancies among diagnostic tests for detecting lower esophageal sphincter-related obstruction.

BACKGROUND: There are frequent discrepancies among high-resolution manometry (HRM), functional lumen imaging probe (FLIP), and esophagram in identifying lower esophageal sphincter (LES)-related obstruction. We aimed to determine the frequency of those discrepancies and how they influenced clinical treatment/outcomes. METHODS: We identified patients who had all three tests (HRM, FLIP, and esophagram) and endoscopy performed for evaluation of esophageal symptoms in our Center for Esophageal Diseases. Discrepancies among the tests for the presence of LES obstruction were noted, and the performance of individual tests was compared against a consensus opinion rendered by a panel of esophagologists. Binary logistical regression was performed, and ROC curves were generated for prediction of the consensus clinical diagnosis of LES obstruction. KEY RESULTS: A total of 126 patients (mean age 57.9 ± 17.0 years; 67% female) met inclusion criteria. All three tests agreed on the presence or absence of LES obstruction in only 72 (57%) patients [no LES obstruction in 57 (45%), LES obstruction in 15 (12%)]. Thirteen patients (10%) had a change in management based on additional findings on FLIP +/- esophagram not seen on HRM with 69% having symptomatic improvement after LES-directed intervention. FLIP was the strongest predictor of a consensus diagnosis of LES obstruction by logistic regression and ROC (OR 23.36, AUC 0.796), followed by HRM (OR 15.41, AUC 0.764). CONCLUSIONS & INFERENCE: High-resolution manometry, functional lumen imaging probe, and esophagram each have considerable limitations for identifying LES obstruction, and discrepancies among these tests occur frequently. Multimodal testing is often required for adequate evaluation of LES-related obstruction.

Desilification of phytolith exacerbates the release of arsenic from rice straw.

Arsenic (As) turnover in rice paddy agro-ecosystems has received much attention because As can enter the food chain through its accumulation in rice, thereby affecting human health. Returning straw to soil is a common practice to retain nutrients for soil and crops, but it also cycles As within the rice paddy field ecosystems. However, there is still a lack of detailed understanding of the fate of As in rice straw, and how or to what extent it is recycled back into the soil environment. This study aims to elucidate the relationship between the microstructure of rice straw and the release of As during rice straw decomposition. The microstructure of rice straw was found to comprise both organic and silica (phytolith) components. These two constituents are inter-embedded to form a composite-like structure that contains up to 6.48 mg As Kg-1. The 30-day batch experiments revealed that the biochemical release of As simultaneously depends upon the decomposition of the organic component and the desilicification of the silica component. Accompanying the release of As was the release of other elements such as Fe, Al, P and S. These elements can further interact with As to form less mobile compounds. The introduction of either Trichoderma harzianum or Bacillus velezensis was expected to accelerate the decomposition of rice straw, and enhance the silica dissolution, hence contributing to an increase in the As release. Despite these expectations, our observations showed the opposite effects. Microorganisms presumably have facilitated the change in solution chemistry or the inclusion of As into the newly-formed precipitates. The biochemical decomposition process can reduce straw particle size, while the negatively-charge surface will involve microsized straw particles in the electrostatic interaction, thereby favoring the dispersibility state. Therefore, the co-transport of micro-sized straw particles with As under field conditions should not be neglected.

An annotated checklist of centipedes (Chilopoda) of Vietnam.

The centipede fauna of Vietnam is reviewed from the literature. A total of 71 species in 26 genera, 13 families in four orders, Scolopendromorpha, Geophilomorpha, Lithobiomorpha and Scutigeromorpha, has been recorded from Vietnam. Four genera, Tonkinodentus, Alluropus, Anopsobiella and Megalacrus, are monotypic; and twenty-two species and subspecies are known only from Vietnam. Distribution data for each species is provided here to promote further studies on the centipede fauna of Vietnam.

A review of Vietnamese Scolopocryptops Newport, 1844 (Chilopoda: Scolopendromorpha), with a description of S. hoanglieni n. sp. and the updated generic list of species.

The Vietnamese fauna of the genus Scolopocryptops Newport, 1844 was reviewed based on recently collected specimens and material from Zoological Museum of the Moscow Lomonosov State University (ZMMU) and Naturhistorisches Museum Wien (NHMW). As a result of study of 164 specimens from 13 sampling regions, four species have been recognized, of which S. rubiginosus C.L. Koch, 1878 and S. spinicaudus Wood, 1862 already reported from Vietnam, S. hoanglieni described as n. sp., and S. capillipedatus (Takakuwa, 1938) for the first time recorded for this country. S. broelemanni esulcata Attems, 1938 was redescribed and confirmed as a valid. The COI fragments were obtained for the above mentioned species and the K2P genetic divergence between Vietnamese Scolopocryptops species was preliminarily estimated. New data on intraspecific variations of spiracle number in Scolopocryptops, an identification key for East Asian species and the general list of species of Scolopocryptops are provided.