Reflux and dyspeptic symptom patterns in patients with non erosive reflux disease (NERD) subclassified using 24-hour ambulatory intraluminal pH-Impedance

Ample evidence supports that prostate tumor metastasis originates from a rare population of cancer cells, known as cancer stem cells (CSCs). Unfortunately, little is known about the identity of these cells, making it difficult to target the metastatic prostate tumor. Here, for the first time, we report the identification of a rare population of prostate cancer cells that express the Tie-2 protein. We found that this Tie-2High population exists mainly in prostate cancer cell lines that are capable of metastasizing to the bone. These cells not only express a higher level of CSC markers but also demonstrate enhanced resistance to the chemotherapeutic drug Cabazitaxel. In addition, knockdown of the expression of the Tie-2 ligand angiopoietin (Ang-1) led to suppression of CSC markers, suggesting that the Ang-1/Tie-2 signaling pathway functions as an autocrine loop for the maintenance of prostate CSCs. More importantly, we found that Tie-2High prostate cancer cells are more adhesive than the Tie-2Low population to both osteoblasts and endothelial cells. Moreover, only the Tie-2High, but not the Tie-2Low cells developed tumor metastasis in vivo when injected at a low number. Taken together, our data suggest that Tie-2 may play an important role during the development of prostate tumor metastasis

Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux disease

INTRODUCTION: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. AIM: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). METHODS: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. RESULTS: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. CONCLUSION: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux

Variability of sulfate signal in ice core records based on five replicate cores

International audienceCurrent volcanic reconstructions based on ice core analysis have significantly improved over the past few decades by incorporating multiple-core analyses with a high temporal resolution from different parts of the polar regions into a composite common volcanic eruption record. Regional patterns of volcanic deposition are based on composite records, built from cores taken at both poles. However, in many cases only a single record at a given site is used for these reconstructions. This assumes that transport and regional meteorological patterns are the only source of the dispersion of the volcanic products. Here we evaluate the local-scale variability of a sulfate profile in a low-accumulation site (Dome C, Antarctica), in order to assess the representativeness of one core for such a reconstruction. We evaluate the variability with depth, statistical occurrence, and sulfate flux deposition variability of volcanic eruptions detected in five ice cores, drilled 1 m apart from each other. Local-scale variability, essentially attributed to snow drift and surface roughness at Dome C, can lead to a non-exhaustive record of volcanic events when a single core is used as the site reference , with a bulk probability of 30 % of missing volcanic events and close to 65 % uncertainty on one volcanic flux measurement (based on the standard deviation obtained from a five-core comparison). Averaging n records reduces the uncertainty of the deposited flux mean significantly (by a factor 1/ √ n); in the case of five cores, the uncertainty of the mean flux can therefore be reduced to 29 %

Diagnosis and outcome of oesophageal Crohn's disease

BACKGROUND AND AIMS: Crohn's disease (CD) can involve any part of the gastrointestinal tract. We aimed to characterize clinical, endoscopic, histologic features and treatment outcomes of CD patients with oesophageal involvement. METHODS: We collected cases through a retrospective multicentre European Crohn's and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. RESULTS: A total of 40 patients were reported [22 males, mean (±SD, range) age at oesophageal CD diagnosis: 25 (±13.3, 10-71) years and mean time of follow-up: 67 (±68.1, 3-240) months]. Oesophageal involvement was established at CD diagnosis in 26 patients (65%) and during follow-up in 14. CD was exclusively located in the oesophagus in 2 patients. Thirteen patients (32.2%) were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in 5 patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors (PPIs) were administered in 37 patients (92.5%). Three patients underwent endoscopic dilation for symptomatic strictures and none oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients (82.5%) after a mean time of 7 (±5.6, 1-18) months. Follow-up endoscopy was performed in 29/40 patients and 26/29 (89.7%) achieved mucosal healing. CONCLUSION: In this case series the endoscopic and histologic characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing IBD-related therapy occurring in two thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.info:eu-repo/semantics/publishedVersio

Sensitive detection of circulating breast cancer cells by reverse-transcriptase polymerase chain reaction of maspin gene

Background: Maspin, a recently identified protein related to the family of serpins, is believed to play a role in human breast cancer. In an effort to improve the present methods of detection, we have developed a reverse-transcriptase polymerase chain reaction (RT-PCR) assay for maspin transcript to identify small numbers of mammary carcinoma cells in the peripheral blood and bone marrow of patients with breast cancer. Patients and methods: Five non-neoplastic mammary tissue samples, 13 breast cancer specimens as well as 17 peripheral blood and 4 bone marrow samples from normal subjects were screened for the presence of maspin mRNA by RT-PCR. The same assay was applied to peripheral blood or bone marrow samples obtained from 29 patients with stages I to IV breast cancer. Results: By RT-PCR it was possible to amplify maspin mRNA in all of the primary and metastatic breast cancer specimens, but in none of the normal hemopoietic samples from healthy donors. Thus, detection of maspin transcript in the peripheral blood or marrow of a patient known to have breast cancer is indicative of the presence of mammary carcinoma cells. In reconstitution experiments, maspin RT-PCR reliably detected 10 mammary carcinoma cells in 1 million normal peripheral-blood mononuclear cells (PBMCs). None of the 9 patients with stages I, II, or III breast cancer had maspin transcript in peripheral blood. Of note, 3 of 9 patients with stage TV breast cancer receiving systemic therapy at the time of sample collection, but only I of 11 patients with stage IV not receiving therapy, had detectable maspin transcript in peripheral blood. Moreover, 3 marrow specimens from stage TV patients tested positive by this assay. Conclusions: This pilot study suggests that maspin RT-PCR assay is a sensitive, specific and sufficiently rapid method for detection of small numbers of circulating cells and marrow micrometastases in breast cancer patients. The possibility of applying this assay in the detection of tumor cell contamination of both marrow and stem-cell apheresis harvests of breast cancer patients merits further investigation

Management advice for patients with reflux-like symptoms: an evidence-based consensus

Copyright \ua9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to \u27low-quality\u27 evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings and two rounds of voting was conducted to generate consensus statements based on prespecified criteria (67% voting \u27strongly agree\u27 or \u27agree with minor reservation\u27). After expert discussion and two rounds of voting, 21 consensus statements were generated, and assigned strength of evidence and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) rating. Eleven statements achieved the strongest (100%) agreement: five are related to diet and include identification and avoidance of dietary triggers, limiting alcohol, coffee and carbonated beverages, and advising patients troubled by postprandial symptoms not to overeat; the remaining six statements concern advice around smoking cessation, weight loss, raising the head-of-the-bed, avoiding recumbency after meals, stress reduction and alginate use. The aim of developing the consensus statements is that they may serve as a foundation for tools and advice that can routinely help patients with reflux-like symptoms better understand the causes of their symptoms and manage their individual risk factors and triggers

Stratospheric Ozone Changes From Explosive Tropical Volcanoes: Modeling and Ice Core Constraints

Major tropical volcanic eruptions have emitted large quantities of stratospheric sulphate and are potential sources of stratospheric chlorine although this is less well constrained by observations. This study combines model and ice core analysis to investigate past changes in total column ozone. Historic eruptions are good analogues for future eruptions as stratospheric chlorine levels have been decreasing since the year 2000. We perturb the pre-industrial atmosphere of a chemistry-climate model with high and low emissions of sulphate and chlorine. The sign of the resulting Antarctic ozone change is highly sensitive to the background stratospheric chlorine loading. In the first year, the response is dynamical, with ozone increases over Antarctica. In the high HCl (2 Tg emission) experiment, the injected chlorine is slowly transported to the polar regions with subsequent chemical ozone depletion. These model results are then compared to measurements of the stable nitrogen isotopic ratio, δ15N(NO−3), from a low snow accumulation Antarctic ice core from Dronning Maud Land (recovered in 2016-17). We expect ozone depletion to lead to increased surface ultraviolet (UV) radiation, enhanced air-snow nitrate photo-chemistry and enrichment in δ15N(NO−3) in the ice core. We focus on the possible ozone depletion event that followed the largest volcanic eruption in the past 1000 years, Samalas in 1257. The characteristic sulphate signal from this volcano is present in the ice-core but the variability in δ15N(NO−3) dominates any signal arising from changes in UV from ozone depletion. Prolonged complete ozone removal following this eruption is unlikely to have occurred over Antarctica.National Environment Research Council (NERC) Standard Grant (NE/N011813/1