The Bile Acid Synthesis Pathway Is Present and Functional in the Human Ovary

Background: Bile acids, end products of the pathway for cholesterol elimination, are required for dietary lipid and fat-soluble vitamin absorption and maintain the balance between cholesterol synthesis in the liver and cholesterol excretion. They are composed of a steroid structure and are primarily made in the liver by the oxidation of cholesterol. Cholesterol is also highly abundant in the human ovarian follicle, where it is used in the formation of the sex steroids. Methodology/Principal Findings: Here we describe for the first time evidence that all aspects of the bile acid synthesis pathway are present in the human ovarian follicle, including the enzymes in both the classical and alternative pathways, the nuclear receptors known to regulate the pathway, and the end product bile acids. Furthermore, we provide functional evidence that bile acids are produced by the human follicular granulosa cells in response to cholesterol presence in the culture media. Conclusions/Significance: These findings establish a novel pathway present in the human ovarian follicle that has the capacity to compete directly with sex steroid synthesis

MSDmotif: exploring protein sites and motifs

<p>Abstract</p> <p>Background</p> <p>Protein structures have conserved features – motifs, which have a sufficient influence on the protein function. These motifs can be found in sequence as well as in 3D space. Understanding of these fragments is essential for 3D structure prediction, modelling and drug-design. The Protein Data Bank (PDB) is the source of this information however present search tools have limited 3D options to integrate protein sequence with its 3D structure.</p> <p>Results</p> <p>We describe here a web application for querying the PDB for ligands, binding sites, small 3D structural and sequence motifs and the underlying database. Novel algorithms for chemical fragments, 3D motifs, ϕ/ψ sequences, super-secondary structure motifs and for small 3D structural motif associations searches are incorporated. The interface provides functionality for visualization, search criteria creation, sequence and 3D multiple alignment options. MSDmotif is an integrated system where a results page is also a search form. A set of motif statistics is available for analysis. This set includes molecule and motif binding statistics, distribution of motif sequences, occurrence of an amino-acid within a motif, correlation of amino-acids side-chain charges within a motif and Ramachandran plots for each residue. The binding statistics are presented in association with properties that include a ligand fragment library. Access is also provided through the distributed Annotation System (DAS) protocol. An additional entry point facilitates XML requests with XML responses.</p> <p>Conclusion</p> <p>MSDmotif is unique by combining chemical, sequence and 3D data in a single search engine with a range of search and visualisation options. It provides multiple views of data found in the PDB archive for exploring protein structures.</p

Empirical treatment based on "typical" reflux symptoms is inappropriate in a population with a high prevalence of Helicobacter pylori infection

Background: Empirical therapy or early endoscopy have been recommended as acceptable management options for GERD. The objective of this study was to determine whether diagnosis and empirical treatment based on reflux symptoms alone are appropriate as initial management for patients with gastroesophageal reflux. Method: Consecutive patients presenting with weekly reflux symptoms were evaluated with a structured questionnaire followed by endoscopy. Patients with dyspepsia as the predominant symptom, "alarm" symptoms (weight loss, dysphagia, or bleeding), history of peptic ulcer or gastric surgery, or recent nonsteroidal anti-inflammatory drugs intake were excluded. Results: Four hundred sixty patients were studied: 82 (18%) were found to have peptic ulcer disease and 78 (95%) were infected with Helicobacter pylori. Concomitant erosive esophagitis was found in 26 (32%) of these patients with peptic ulcer disease. In the remaining 378 patients, 218 (58%) had erosive esophagitis and 1 had esophageal cancer. Among the 159 patients with no endoscopic lesion, 148 (93%) had relief of symptoms when treated with a proton pump inhibitor. Multivariate analysis showed that male gender (OR: 1.8, p = 0.03), age greater than 60 years (OR: 2.2, p = 0.01) and H pylori infection (OR: 3.6, p = 0.008) were significantly associated with a diagnosis of peptic ulcer disease. Coexisting dyspeptic symptom was not a predictor (p = 0.13) for peptic ulcer disease. Conclusions: In populations with a high prevalence of H pylori infection, a significant proportion of patients with GERD have concomitant peptic ulcer disease. Empirical treatment based on "typical" GERD symptoms alone may not be appropriate. Copyright © 2002 by the American Society for Gastrointestinal Endoscopy.link_to_subscribed_fulltex

An ensemble approach for record matching in data linkage

© 2016 The authors and IOS Press. Objectives: To develop and test an optimal ensemble configuration of two complementary probabilistic data matching techniques namely Fellegi-Sunter (FS) and Jaro-Wrinkler (JW) with the goal of improving record matching accuracy. Methods: Experiments and comparative analyses were carried out to compare matching performance amongst the ensemble configurations combining FS and JW against the two techniques independently. Results: Our results show that an improvement can be achieved when FS technique is applied to the remaining unsure and unmatched records after the JW technique has been applied. Discussion: Whilst all data matching techniques rely on the quality of a diverse set of demographic data, FS technique focuses on the aggregating matching accuracy from a number of useful variables and JW looks closer into matching the data content (spelling in this case) of each field. Hence, these two techniques are shown to be complementary. In addition, the sequence of applying these two techniques is critical. Conclusion: We have demonstrated a useful ensemble approach that has potential to improve data matching accuracy, particularly when the number of demographic variables is limited. This ensemble technique is particularly useful when there are multiple acceptable spellings in the fields, such as names and addresses

Low-dose imipramine for refractory functional dyspepsia: a randomised, double-blind, placebo-controlled trial

Background: Guidelines recommend the use of neuromodulators in patients with functional dyspepsia not responding to proton pump inhibitors (PPIs) and prokinetics; however, there is a lack of data from randomised controlled trials supporting their use. We aimed to assess the safety and efficacy of imipramine, a tricyclic antidepressant (TCA), in treatment-refractory functional dyspepsia. Methods: In this single-centre, double-blind, randomised controlled trial, we enrolled consecutive patients with Rome II functional dyspepsia aged 18–80 years. Eligible patients were Helicobacter pylori-negative, had a normal upper gastrointestinal endoscopy and abdominal ultrasound, and remained symptomatic after open-label treatment with 8 weeks of esomeprazole and 4 weeks of domperidone. Patients completed questionnaires assessing dyspepsia symptoms, mood, and insomnia, and were then randomly assigned (1:1) via a computer-generated list of random numbers to receive imipramine (at a dose of 25 mg once nightly for the first 2 weeks, and then 50 mg thereafter) or placebo for 12 weeks. The primary endpoint was overall satisfactory relief of global dyspepsia symptoms at 12 weeks, via patient-reported assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00164775, and is completed. Findings: Between Sept 11, 2005, and Aug 20, 2010, 107 patients with treatment-refractory functional dyspepsia were randomly assigned to receive imipramine (n=55) or placebo (n=52). Relief of global dyspepsia symptoms at 12 weeks occurred in 35 (63·6%, 95% CI 50·4–75·1) of 55 patients on imipramine compared with 19 (36·5%, 95% CI 24·8–50·1) of 52 on placebo (p=0·0051). Ten (18%) patients on imipramine discontinued the study due to adverse events (three dry mouth, two constipation, two drowsiness, and one each insomnia, palpitations, and blurred vision), compared with four (8%) on placebo (one dry mouth and constipation, and one each palpitations, worsening of gastro-oesophageal reflux, and limb paraesthesia). There were no serious adverse events. Interpretation: Low-dose imipramine should be considered as a possible therapy for patients with functional dyspepsia refractory to both PPIs and prokinetics, although patients should be cautioned about the adverse event profile. Funding: None

Effect of Helicobacter pylori eradication on treatment of gastro-oesophageal reflux disease: A double blind, placebo controlled, randomised trial

Background: The role of Helicobacter pylori eradication in the management of gastro-oesophageal reflux disease (GORD) is controversial. We hypothesised that H pylori eradication leads to worsened control of reflux disease. Methods: Consecutive patients with weekly reflux symptoms were prospectively recruited for endoscopy and symptom evaluation. Patients were enrolled if they had H pylori infection and required long term acid suppressants. Eligible patients were randomly assigned to omeprazole triple therapy (HpE group) or omeprazole with placebo antibiotics (Hp+ group) for one week. Omeprazole 20 mg daily was given for eight weeks for healing of oesophagitis and symptom relief. This was followed by a maintenance dose of 10 mg daily for up to 12 months. The primary study end point was the probability of treatment failure within 12 months, which was defined as either incomplete resolution of symptoms or oesophagitis at the initial treatment phase, or relapse of symptoms and oesophagitis during the maintenance phase. Predictors of treatment failure were determined by Cox's proportional hazards model. Results: A total of 236 GORD patients were screened and 113 (47.9%) were positive for H pylori; 104 (92%) patients were included in the intention to treat analysis (53 in the HpE group and 51 in the Hp+ group). Thirty one patients (30%) had erosive oesophagitis at baseline. H pylori was eradicated in 98% of the HpE group and in 3.9% of the Hp+ group. Overall, 15 patients (28.3%) in the HpE group and eight patients (15.7%) in the Hp+ group had treatment failure. The 12 month probability of treatment failure was 43.2% (95% confidence interval (CI) 29.9-56.5%) in the HpE group and 21.1% (95% CI 9.9-32.3%) in the Hp+ group (log rank test, p = 0.043). In the Cox proportional hazards model, after adjustment for the covariates age, sex, erosive oesophagitis, hiatus hernia, degree of gastritis, and severity of symptoms at baseline, H pylori eradication was the only predictor of treatment failure (adjusted hazard ratio 2.47 (95% CI 1.05-5.85)). Conclusion: H pylori eradication leads to more resilient GORD.link_to_subscribed_fulltex

Effects of Acupuncture on the Recovery Outcomes of Stroke Survivors with Shoulder Pain: A Systematic Review

Background: Poststroke shoulder pain limits stroke survivors' physical functioning, impairs their ability to perform daily activities, and compromises their quality of life. The use of acupuncture to manage shoulder pain after a stroke is believed to free the blockage of energy flow and produce analgesic effects, but the evidence is unclear. We therefore conducted a systematic review to summarize the current evidence on the effects of acupuncture on the recovery outcomes of stroke survivors with shoulder pain. Methods: Fourteen English and Chinese databases were searched for data from January 2009 to August 2017. The review included adult participants with a clinical diagnosis of ischemic or hemorrhagic stroke who had developed shoulder pain and had undergone conventional acupuncture, electroacupuncture, fire needle acupuncture, or warm needle acupuncture. The participants in the comparison group received the usual stroke care only. Results: Twenty-nine randomized controlled trials were included. Most studies were assessed as having a substantial risk of bias. Moreover, due to the high heterogeneity of the acupuncture therapies examined, pooling the results in a meta-analysis was not appropriate. A narrative summary of the results is thus presented. The review showed that conventional acupuncture can be associated with benefits in reducing pain and edema and improving upper extremity function and physical function. The effects of conventional acupuncture on improving shoulder range of motion (ROM) are in doubt because this outcome was only examined in two trials. Electroacupuncture might be effective in reducing shoulder pain and improving upper extremity function, and conclusions on the effects of electroacupuncture on edema, shoulder ROM, and physical function cannot be drawn due to the limited number of eligible trials. The evidence to support the use of fire needle or warm needle acupuncture in stroke survivors with shoulder pain is also inconclusive due to the limited number of studies. Conclusion: Although most studies reviewed concluded that conventional and electroacupuncture could be effective for management of shoulder pain after stroke, the very high potential for bias should be considered. Further work in this area is needed that employs standardized acupuncture treatment modalities, endpoint assessments, and blinding of treatments

Helicobacter pylori infection in 1st degree relatives of Chinese gastric cancer patients

Objective. Familial aggregation of gastric cancer has been linked to familial clustering of Helicobacter pylori infection. Patterns and risk factors associated with H. pylori infection were investigated in 1st degree relatives of Chinese gastric cancer patients. Material and methods. Gastric cancer relatives were invited for screening endoscopy. H. pylori infection was diagnosed by endoscopic and serological methods. Results. Among the 270 cancer relatives examined, 161 (59.6%) were found to be infected with H. pylori. The prevalence of infection in cancer relatives was significantly higher than age- and gender-matched dyspeptic control (45.5%, p = 0.0006). The mean age of H. pylori-infected relatives was significantly older than that of non-infected relatives (43.9 versus 38.3 years; p 45 years (OR = 1.8; 95% CI, 1.02-3.3) and a history of gastric cancer in siblings (OR = 1.9; 95% CI, 1.06-3.3) were independent risk factors for H. pylori infection, and that the youngest sibling in the family had a reduced risk (OR = 0.45; 95% CI, 0.24-0.84). Conclusions. This study identifies the patterns and risk factors for H. pylori in gastric cancer relatives, which may shed light on the evolving epidemiology of H. pylori infection in Chinese patients. © 2006 Taylor & Francis.link_to_subscribed_fulltex

Is non-Helicobacter pylori, non-NSAID peptic ulcer a common cause of upper GI bleeding? A prospective study of 977 patients

Non-Helicobacter pylori, non-NSAID ulcer is relatively common in Western countries. Whether it is a significant problem in the Orient is unclear. The aim of this study was to investigate the incidence of non-H pylori, non-NSAID ulcers presenting with GI bleeding. A prospective study was done of 1675 consecutive patients presenting with upper GI bleeding over a period of 12 months. Upper endoscopy was performed with biopsy specimens taken from the antrum and body of the stomach for a biopsy urease test (BUT) and histology for detection of H pylori. Exposure to nonsteroidal anti-inflammatory drugs (NSAID) or aspirin within 4 weeks of hospitalization was carefully scrutinized. A 6-week course of treatment with an H2-receptor antagonist was prescribed for patients who did not use an NSAID and had a negative BUT result. Follow-up endoscopy was performed to confirm H pylori status with a BUT and histology. Positive histology at either initial or follow-up endoscopy was used as the standard for diagnosing H pylori infection. Among 977 patients who were found to have ulcer bleeding, 434 (44%) had exposure to aspirin or an NSAID. Of the 543 non-NSAID users, 431 (79.4%) had a positive BUT and 112 (20.6%) were BUT negative on initial endoscopy. Eighty-nine of 112 patients who were NSAID negative, BUT negative returned for follow-up endoscopy. Forty-nine of 89 (55.1%) were found to have a positive BUT and positive histology at follow-up endoscopy. Only 40 of 977 (4.1%) patients admitted with ulcer bleeding were confirmed to have non-H pylori, non-NSAID ulcers. Non-H pylori, non-NSAID bleeding ulcer is uncommon. A negative BUT is unreliable for exclusion of H pylori infection during the acute phase of ulcer bleeding.link_to_subscribed_fulltex

Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs

Background: Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury. Aim: To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users. Methods: NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 μg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia. Results: A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P = 0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group. Conclusions: Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.link_to_subscribed_fulltex