Designing for Curiosity in Citizen Science

In this paper we explain why curiosity is important for citizen science, we propose 3 tips for encouraging curiosity, and we present our current project Open 3D

Bile acids and the microbiome: Making sense of this dynamic relationship in their role and management in Crohn's disease

© 2022 The Authors. Published by Hindawi. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1155/2022/8416578Background. Bile acids help maintain the physiological balance of the gut microbiome and the integrity of the intestinal epithelial barrier. Similarly, intestinal bacteria play a major role in bile acid metabolism as they are involved in crucial biotransformation steps in the enterohepatic circulation pathway. Understanding the relationship between bile acid signalling and the gut microbiome in Crohn's disease can help target new and innovative treatment strategies. Aims. This review summarises the relationship between bile acids and the microbiome in Crohn's disease and discusses potential novel therapeutic options. Methods. We performed a literature review on bile acid signalling, its effect on the gut microbiome, and therapeutic applications in Crohn's disease. Results. Current research suggests that there is a strong interplay between the dysregulated microbiota, bile acid metabolism, and the mucosal immune system that can result in a changed immunological function, triggering the inflammatory response in Crohn's disease. Recent studies have demonstrated an association with altering the enterohepatic circulation and activating the farnesoid X receptor signalling pathway with the use of probiotics and faecal microbial transplantation, respectively. Bile acid sequestrants have been shown to have anti-inflammatory, cytoprotective, and anti-apoptotic properties with the potential to alter the intestinal microbial composition, suggesting a possible role in inducing and maintaining Crohn's disease. Conclusions. Active Crohn's disease has been correlated with changes in bacterial concentrations, which may be associated with changes in bile acid modification. Further research should focus on targeting these areas for future therapeutic options.The research department of MJB received project funding from Bowel and Cancer Research for part of this work and from an unrestricted grant from Tillotts Pharma for part of this work.Published versio

Fluorescent Sensing of Chlorophenols in Water Using an Azo Dye Modified β-Cyclodextrin Polymer

A water soluble azo dye modified β-cyclodextrin polymer 4 was synthesized and used as a chemosensor for the detection of chlorinated phenols, model chlorinated by-products (CBPs) of water treatment for drinking purposes. The characterization of the intermediates and the azo dye modified β-CD polymer was done by UV/Vis Spectrophotometry, FT-IR and 1H-NMR spectroscopies. The chlorophenols were capable of quenching the fluorescence of the polymer. The polymer showed greater sensitivity towards 2,4-dichlorophenol, with a sensitivity factor of 0.35 compared to 0.05 and 0.12 for phenol and 4-chlorophenol, respectively. The stability constants (Ks) of the pollutants were also determined by the Benesi-Hildebrand method to be 2.104 × 103 M−1 for 2,4-dichlorophenol and 1.120 × 102 M−1 for 4-chlorophenol

A pilot randomised controlled trial of the feasibility of using body scan and isometric exercises for reducing urge to smoke in a smoking cessation clinic

BACKGROUND: The main cause of relapse in smokers attempting to quit is inability to resist urges to smoke. Pharmacotherapy ameliorates but does not entirely prevent urges to smoke when abstinent, so other methods to resist urges to smoke might be helpful. Exercise is effective, but aerobic exercise is often impractical when urges strike. Two techniques, body scan and isometric exercise, have been shown to reduce urge intensity and nicotine withdrawal symptoms in temporarily abstinent smokers. It is unclear whether they would be used or effective in typical smokers attempting to quit. METHODS: In a pilot trial set in a UK smoking cessation clinic, 20 smokers were randomised to receive emails containing.mp3 files and.pdf illustrations of the instructions for doing the body scan and isometric exercises. Twenty smokers received no other intervention, although all 40 were receiving weekly behavioural support and nicotine replacement therapy. Carbon monoxide confirmed abstinence, nicotine withdrawal symptoms, urges to smoke, and use of the techniques to resist urges were recorded weekly for four weeks after quit day. RESULTS: 60-80% of quitters reported using the isometric exercises each week and 40-70% reported using the body scan to deal with urges. On average, these techniques were rated as 'slightly helpful' for controlling the urges. There were no large or significant differences in withdrawal symptoms or urge intensity between the two groups. The risk ratio and 95% confidence interval for exercises compared with controls for prolonged confirmed abstinence at four weeks was 0.82 (0.44-1.53). 81% of quitters intended to continue using isometric exercises and 25% body scan, while 81% and 50% respectively would recommend using these techniques to others trying to stop. CONCLUSION: Isometric exercises, and to a lesser extent body scan, were popular and perceived as somewhat helpful by quitters. The trial showed that these techniques were used and a larger trial could now be developed to examine the influence of the methods on reducing urges to smoke and increasing abstinence

A single faecal bile acid stool test demonstrates potential efficacy in replacing SeHCAT testing for bile acid diarrhoea in selected patients

© 2022 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https: https://doi.org/10.1038/s41598-022-12003-zThis study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn's disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6-4.2), BAD (3.6; 1.9-7.2) and post-cholecystectomy cohort 3.8 (2.3-6.8) were similar, but all were significantly lower (p  15% (2.6; 1.6-4.2); (p < 0.001 and p < 0.0001, respectively). The sensitivity and specificity using FBA cut-off of 1.6 μmol/g (using ≤ 15% SeHCAT retention as diagnostic of BAD) were 90% and 25% respectively. A single random stool sample may have potential use in diagnosing severe BAD or BAD in Crohn's patients. Larger studies are now needed to confirm the potential efficacy of this test to accurately diagnose BAD in the absence of SeHCAT testing.The research department of MJB received project funding from Bowel and Cancer Research for part of this work; The research department of MJB received project funding from an unrestricted grant from Tillotts Pharma for part of this work.Published versio

Oral and intravenous iron therapy differentially alter the on- and off-tumor microbiota in anemic colorectal cancer patients

© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/cancers13061341Iron deficiency anemia is a common complication of colorectal cancer and may require iron therapy. Oral iron can increase the iron available to gut bacteria and may alter the colonic microbiota. We performed an intervention study to compare oral and intravenous iron therapy on the colonic tumor-associated (on-tumor) and paired non-tumor-associated adjacent (off-tumor) microbiota. Anemic patients with colorectal adenocarcinoma received either oral ferrous sulphate (n = 16) or intravenous ferric carboxymaltose (n = 24). On- and off-tumor biopsies were obtained post-surgery and microbial profiling was performed using 16S ribosomal RNA analysis. Off-tumor α- and β-diversity were significantly different between iron treatment groups. No differences in on-tumor diversity were observed. Off-tumor microbiota of oral iron-treated patients showed higher abundances of the orders Clostridiales, Cytophagales, and Anaeroplasmatales compared to intravenous iron-treated patients. The on-tumor microbiota was enriched with the orders Lactobacillales and Alteromonadales in the oral and intravenous iron groups, respectively. The on- and off-tumor microbiota associated with intravenous iron-treated patients infers increased abundances of enzymes involved in iron sequestration and anti-inflammatory/oncogenic metabolite production, compared to oral iron-treated patients. Collectively, this suggests that intravenous iron may be a more appropriate therapy to limit adverse microbial outcomes compared to oral iron.The Ferinject™ used in the original IVICA trial was donated to all study centers, except Nottingham University Hospitals NHS Trust, by Vifor Pharma (Glattbrugg, Switzerland). The study represents independent research funded by the National Institute for Health Research (NIHR) Research for Patient Benefit (RfPB) program (grant number PB-PG-0110-21041)

The analysis of gut microbiota in patients with bile acid diarrhoea treated with colesevelam

© 2023 The Authors. Published by Frontiers Media. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3389/fmicb.2023.1134105Introduction: Bile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity. Materials and methods: Patients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn’s disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (<15%) were given a trial of treatment with colesevelam. Stool samples were collected pre-treatment, 4-weeks, 8-weeks and 6–12 months post-treatment. Faecal 16S ribosomal RNA gene analysis was undertaken. Results: A total of 257 samples were analysed from 134 patients. α-diversity was significantly reduced in patients with BAD and more specifically, in the idiopathic BAD cohort and in patients with severe disease (SeHCAT <5%); p < 0.05. Colesevelam did not alter bacterial α/β-diversity but patients who clinically responded to treatment had a significantly greater abundance of Fusobacteria and Ruminococcus, both of which aid in the conversion of primary to secondary bile acids. Conclusion: This is the first study to examine treatment effects on the microbiome in BAD, which demonstrated a possible association with colesevelam on the microbiome through bile acid modulation in clinical responders. Larger studies are now needed to establish a causal relationship with colesevelam and the inter-crosstalk between bile acids and the microbiome.The research department of MB received project funding from Bowel and Cancer Research for part of this work. The research department of MB received project funding from an unrestricted grant from Tillotts Pharma for part of this work.Published versio

Validity of hand hygiene compliance measurement by observation: A systematic review

BACKGROUND: Hand hygiene is monitored by direct observation to improve practice, but this approach can potentially cause information, selection, and confounding bias, threatening the validity of findings. The aim of this study was to identify and describe the potential biases in hand hygiene compliance monitoring by direct observation; develop a typology of biases and propose improvements to reduce bias; and increase the validity of compliance measurements. METHODS: This systematic review of hospital-based intervention studies used direct observation to monitor health care workers' hand hygiene compliance. RESULTS: Seventy-one publications were eligible for review. None was free of bias. Selection bias was present in all studies through lack of data collection on the weekends (n = 61, 86%) and at night (n = 46, 65%) and observations undertaken in single-specialty settings (n = 35, 49%). We observed inconsistency of terminology, definitions of hand hygiene opportunity, criteria, tools, and descriptions of the data collection. Frequency of observation, duration, or both were not described or were unclear in 58 (82%) publications. Observers were trained in 56 (79%) studies. Inter-rater reliability was measured in 26 (37%) studies. CONCLUSIONS: Published research of hand hygiene compliance measured by direct observation lacks validity. Hand hygiene should be measured using methods that produce a valid indication of performance and quality. Standardization of methodology would expedite comparison of hand hygiene compliance between clinical settings and organizations

Implementation outcome instruments for use in physical healthcare settings: a systematic review

BACKGROUND: Implementation research aims to facilitate the timely and routine implementation and sustainment of evidence-based interventions and services. A glaring gap in this endeavour is the capability of researchers, healthcare practitioners and managers to quantitatively evaluate implementation efforts using psychometrically sound instruments. To encourage and support the use of precise and accurate implementation outcome measures, this systematic review aimed to identify and appraise studies that assess the measurement properties of quantitative implementation outcome instruments used in physical healthcare settings. METHOD: The following data sources were searched from inception to March 2019, with no language restrictions: MEDLINE, EMBASE, PsycINFO, HMIC, CINAHL and the Cochrane library. Studies that evaluated the measurement properties of implementation outcome instruments in physical healthcare settings were eligible for inclusion. Proctor et al.'s taxonomy of implementation outcomes was used to guide the inclusion of implementation outcomes: acceptability, appropriateness, feasibility, adoption, penetration, implementation cost and sustainability. Methodological quality of the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Psychometric quality of the included instruments was assessed using the Contemporary Psychometrics checklist (ConPsy). Usability was determined by number of items per instrument. RESULTS: Fifty-eight publications reporting on the measurement properties of 55 implementation outcome instruments (65 scales) were identified. The majority of instruments assessed acceptability (n = 33), followed by appropriateness (n = 7), adoption (n = 4), feasibility (n = 4), penetration (n = 4) and sustainability (n = 3) of evidence-based practice. The methodological quality of individual scales was low, with few studies rated as 'excellent' for reliability (6/62) and validity (7/63), and both studies that assessed responsiveness rated as 'poor' (2/2). The psychometric quality of the scales was also low, with 12/65 scales scoring 7 or more out of 22, indicating greater psychometric strength. Six scales (6/65) rated as 'excellent' for usability. CONCLUSION: Investigators assessing implementation outcomes quantitatively should select instruments based on their methodological and psychometric quality to promote consistent and comparable implementation evaluations. Rather than developing ad hoc instruments, we encourage further psychometric testing of instruments with promising methodological and psychometric evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 CRD42017065348