Search

Spheroidal cancer cell cultures have been used to enrich cancer stem cells (CSC), which are thought to contribute to important clinical features of tumors. This study aimed to map the regulatory networks driven by circular RNAs (circRNAs) in CSC-enriched colorectal cancer (CRC) spheroid cells. The spheroid cells established from two CRC cell lines acquired stemness properties in pluripotency gene expression and multi-lineage differentiation capacity. Genome-wide sequencing identified 1503 and 636 circRNAs specific to the CRC parental and spheroid cells, respectively. In the CRC spheroids, algorithmic analyses unveiled a core network of mRNAs involved in modulating stemness-associated signaling pathways, driven by a circRNA&ndash, microRNA (miRNA)&ndash, mRNA axis. The two major circRNAs, hsa_circ_0066631 and hsa_circ_0082096, in this network were significantly up-regulated in expression levels in the spheroid cells. The two circRNAs were predicted to target and were experimentally shown to down-regulate miR-140-3p, miR-224, miR-382, miR-548c-3p and miR-579, confirming circRNA sponging of the targeted miRNAs. Furthermore, the affected miRNAs were demonstrated to inhibit degradation of six mRNA targets, viz. ACVR1C/ALK7, FZD3, IL6ST/GP130, SKIL/SNON, SMAD2 and WNT5, in the CRC spheroid cells. These mRNAs encode proteins that are reported to variously regulate the GP130/Stat, Activin/Nodal, TGF-&beta, /SMAD or Wnt/&beta, catenin signaling pathways in controlling various aspects of CSC stemness. Using the CRC spheroid cell model, the novel circRNA&ndash, miRNA&ndash, mRNA axis mapped in this work forms the foundation for the elucidation of the molecular mechanisms of the complex cellular and biochemical processes that determine CSC stemness properties of cancer cells, and possibly for designing therapeutic strategies for CRC treatment by targeting CSC.

This paper presents the development of a mobile Augmented Reality (AR) heart rate murmur simulator that can be used for clinical teaching for medical trainees. Traditional medical training often requires the trainees to have hands on experience with real patients. However, it is not often possible to find certain types of heart murmurs with patients available for training. To overcome this limitation, we have developed a wearable clothing system using mobile audible AR that provides heart murmur simulation for facilitating medical learning experience. In this paper we describe the proposed system, a user evaluation study and directions for future work. Refereed/Peer-reviewed

This demonstration presents the development of a mobile augmented reality (AR) murmur simulator that can be used for clinical teaching for medical trainees. Medical training often requires educators and trainees to work with vast amount of experience-based knowledge, hearing and recognizing murmurs is part of the fundamental training for medical students. In this study, we propose a wearable clothing system that is developed to work with mobile audible AR that provides heart murmurs simulation for facilitating medical learning experience. Refereed/Peer-reviewed

OBJECTIVES: We conducted a systematic review to determine the effectiveness of psychological interventions including psychodrama, cognitive behavioral therapy, relaxation therapy, guided imagery, or hypnosis in the improvement of dyspepsia symptoms in patients with nonulcer dyspepsia (NUD). DESIGN: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL, and PsycLIT, using appropriate subject headings and text words and searching bibliographies of retrieved articles. All randomized controlled trials (RCTs) or quasi-randomized studies were eligible. RESULTS: The four eligible trials all used different psychological interventions including applied relaxation therapy, psychodynamic psychotherapy, cognitive therapy, and hypnotherapy. Trials did not present data in a form that could be synthesized. All reported an improvement in the dyspepsia symptom scores at the end of treatment and at 1 yr in the intervention arm compared with controls. All studies only achieved statistically significant results through adjusting for baseline differences between groups. This reflects the small sample sizes of the trials. There were also problems with assumptions made in the statistical analyses used to achieve statistical significance. The studies highlighted problems with recruitment and compliance. CONCLUSIONS: There was insufficient evidence on the efficacy of psychological therapies in NUD. This emphasizes the need for appropriately powered well-designed trials in this area. (Am J Gastroenterol 2004;99:1817‐1822)

Objectives: To evaluate efficacy and cost effectiveness of Helicobacter pylori eradication treatment in patients with non-ulcer dyspepsia infected with H pylori. Design: Systematic review of randomised controlled trials comparing H pylori eradication with placebo or another drug treatment. Results were incorporated into a Markov model comparing health service costs and benefits of H pylori eradication with antacid treatment over one year. Data sources: Six electronic databases were searched for randomised controlled trials from January 1966 to May 2000. Experts in the field, pharmaceutical companies, and journals were contacted for information on any unpublished trials. Trial reports were reviewed according to predefined eligibility and quality criteria. Main outcome measures: Relative risk reduction for remaining dyspeptic symptoms (the same or worse) at 3-12 months. Cost per dyspepsia-free month estimated from Markov model based on estimated relative risk reduction. Results: Twelve trials were included in the systematic review, nine of which evaluated dyspepsia at 3-12 months in 2541 patients. H pylori eradication treatment was significantly superior to placebo in treating non-ulcer dyspepsia (relative risk reduction 9% (95% confidence interval 4% to 14%)), one case of dyspepsia being cured for every 15 people treated. H pylori eradication cost £56 per dyspepsia-free month during first year after treatment. Conclusion:H pylori eradication may be cost effective treatment for non-ulcer dyspepsia in infected patients but further evidence is needed on decision makers9 willingness to pay for relief of dyspepsia.

Clostridium difficile diarrhea is common in elderly patients and leads to prolonged hospitalization. Patients with severe or recurrent Clostridium difficile diarrhea have poor antitoxin antibody responses. Intravenous immunoglobulin has been advocated in these patients. This study was designed to assess the response of patients with refractory, recurrent, or severe Clostridium difficile diarrhea to intravenous immunoglobulin. Retrospective review (November 2003–January 2005) of 14 patients with severe, refractory, recurrent Clostridium difficile diarrhea treated with intravenous immunoglobulin (Flebogamma®, 150–400 mg/kg) from 264 Clostridium difficile toxin-positive patients. Median age was 79 (range, 54–91) years. Median length of symptoms before intravenous immunoglobulin was 29 (range, 3–90) days. Patients received a median of three (range, 1–5) courses of vancomycin or metronidazole before intravenous immunoglobulin. All had hypoalbuminemia (median, 22 g/l; range, 18–33) and raised C-reactive protein (median, 47 mg/l; range, 25–255) at time of infusion. The median white cell count was 15.3 × 109/liters (range, 4–24). Eight patients had evidence of pancolitis on abdominal imaging, suggesting severe Clostridium difficile diarrhea. All patients tolerated intravenous immunoglobulin without side effects. Nine (64 percent) responded with bowels normalizing in a median of ten (range, 2–26) days; one patient received two doses. One patient had a partial response from two doses but died two months later after a recurrence. The other four patients died of other causes within three weeks of infusion. Intravenous immunoglobulin may be effective for severe, refractory, or recurrent Clostridium difficile diarrhea after failed conventional treatment.

BACKGROUND: Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear. OBJECTIVES: To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia. SEARCH STRATEGY: Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies. SELECTION CRITERIA: All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia. DATA COLLECTION AND ANALYSIS: Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms. MAIN RESULTS: Seven randomised controlled trials were included in the systematic review. Five trials compared proton pump inhibitor dual or triple therapy with a proton pump inhibitor + placebo antibiotics, and evaluated dyspepsia at 6-12 months in 1,385 patients. H pylori eradication was significantly superior to placebo in treating non ulcer dyspepsia (relative risk reduction = 7%; 95% CI = 1% to 12%; p=0.02) and there was no significant heterogeneity between the studies. The number needed to treat to cure one case of dyspepsia = 19 (95% CI = 11 to 132). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia. REVIEWER'S CONCLUSIONS: H pylori eradication may be an effective therapy for H pylori positive non-ulcer dyspepsia. This result is not robust and further evidence on the efficacy of H pylori eradication in non ulcer dyspepsia would be helpful. The effect is modest and economic models would help establish whether this approach is cost-effective. This review will be updated as results from other ongoing trials (Malfertheiner 2000) are made available.

Background Studies have also shown that NUD patients have higher scores of anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and tendency to be more pessimistic when compared with the community controls. However, the role of psychological interventions in NUD remains uncertain. Objectives This review aims to determine the effectiveness of psychological interventions including psychotherapy, psychodrama, cognitive behavioral therapy, relaxation therapy and hypnosis in the improvement of either individual or global dyspepsia symptom scores and quality of life scores patients with NUD. Search strategy Trials were located through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using very broad subject headings and text words. Bibliographies of retrieved articles were also searched and experts in the field were contacted. Selection criteria All randomised controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness of psychological interventions (including psychotherapy, psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia (NUD) were identified. Data collection and analysis Data collected included individual, global dyspepsia symptom scores and quality of life (QoL) scores. Main results We identified only four trials, each using different psychological interventions and three presenting results in a manner, that did not allow synthesis of the data to form a meta-analysis. All trials suggest that psychological interventions benefit dyspepsia symptoms and this effect persists for one year. However, all trials use statistical techniques that adjusted for baseline differences between groups. This should not be necessary for a randomised trial that is adequately powered suggesting that the sample size of these papers was too small. Unadjusted data was not statistically significant. The other problem of psychological intervention include low recruitment and high drop out rate which has been shown to be greater in patients receiving group therapy. Reviewer's conclusions There is currently insufficient evidence from this review to confirm the efficacy of psychological intervention in NUD. There is also no evidence on the combined effects of pharmacological and psychological therapy. Nevertheless, if there are any benefits of psychological therapies, they are likely to persist long-term and NUD is a chronic relapsing and remitting disorder. Psychological therapies may therefore be offered to patients with severe symptoms that have not responded to pharmacological therapies.

Helicobacter pylori (H pylori) is the main cause of peptic ulcer disease. The role of H pylori in non-ulcer dyspepsia is less clear.To determine the effect of H pylori eradication on dyspepsia symptoms and quality of life scores in patients with non-ulcer dyspepsia.Trials were identified through electronic searches of the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and SIGLE, using appropriate subject headings and keywords, searching bibliographies of retrieved articles, and through contacts with experts in the fields of dyspepsia and with pharmaceutical companies.All parallel group randomised controlled trials (RCTs) comparing drugs to eradicate H pylori with placebo or other drugs known not to eradicate H pylori for patients with non-ulcer dyspepsia.Data were collected on individual and global dyspeptic symptom scores, quality of life measures and adverse effects. Dyspepsia outcomes were dichotomised into minimal/resolved versus same/worse symptoms.Seven randomised controlled trials were included in the systematic review. Five trials compared proton pump inhibitor dual or triple therapy with a proton pump inhibitor + placebo antibiotics, and evaluated dyspepsia at 6-12 months in 1,385 patients. H pylori eradication was significantly superior to placebo in treating non ulcer dyspepsia (relative risk reduction = 7%; 95% CI = 1% to 12%; p=0.02) and there was no significant heterogeneity between the studies. The number needed to treat to cure one case of dyspepsia = 19 (95% CI = 11 to 132). A further two trials compared Bismuth based H pylori eradication with an alternative pharmacological agent. These trials were smaller and had a shorter follow-up but suggested H pylori eradication was more effective than either H2 receptor antagonists or sucralfate in treating non-ulcer dyspepsia.H pylori eradication may be an effective therapy for H pylori positive non-ulcer dyspepsia. This result is not robust and further evidence on the efficacy of H pylori eradication in non ulcer dyspepsia would be helpful. The effect is modest and economic models would help establish whether this approach is cost-effective. This review will be updated as results from other ongoing trials (Malfertheiner 2000) are made available.