• Criteria for preliminary risk assessment of brownfield site: An international survey of experts

      Mahammedi, Charf; Mahdjoubi, Lamine; Booth, Colin; Bowman, Russell; Butt, Talib E. (Springer, 2022-07-04)
      Comprehensive risk assessment of brownfield sites requires a broad range of knowledge and multi-disciplinary expertise. Whilst the identification of criteria requirements for preliminary risk assessment has received some attention, there appears to be no studies that have specifically examined professional perspectives relating to these requirements. Yet, variations in professional practitioners’ assessments may have significant consequences for the assessment of risks, and how the criteria are imparted to stakeholders. This study aims to identify the criteria requirements for preliminary risk assessment, using the pollutant linkage model (Source–Pathway–Receptor), and explores cross-disciplinary professional perspectives related to these requirements. To this end, this study commenced with a systematic review to identify various criteria streams required for the preliminary risk assessment of brownfield sites. Thereafter, a questionnaire survey was design and shared with brownfield site professionals. Quantitative analysis of the survey responses (n = 76) reveals disciplines have markedly different priorities relating to the same hazard. For instance, geophysicists, geochemists, and hydrologists do not raise concerns regarding ground movement that can result from the removal of storage and tanks, whilst the same hazard was considered as having a high importance by other professions (such as geologists and geotechnical engineers). This example, amongst others revealed in the study, underpins potential issues and implications for various stakeholders compiling and/or using preliminary risk assessment criteria. This study clarifies both the key criteria requirements for the preliminary risk assessment of brownfield sites, as well as the importance of recognising how variation in professionals’ perceptions plays in the risk assessment process. Although, specialist knowledge is essential for brownfield site investigation, so is the maintaining a broad-based view of other experts coming from different backgrounds, as this renders holistic risk assessment insights.
    • Piperacillin/tazobactam-resistant, cephalosporin-susceptible Escherichia coli bloodstream infections are driven by multiple acquisition of resistance across diverse sequence types

      Edwards, T; Heinz, E; van Aartsen, J; Howard, A; Roberts, Paul; Corless, C; Fraser, AJ; Williams, CT; Bulgasim, I; Cuevas, LE; et al. (Microbiology Society, 2022-04-11)
      Resistance to piperacillin/tazobactam (TZP) in Escherichia coli has predominantly been associated with mechanisms that confer resistance to third-generation cephalosporins. Recent reports have identified E. coli strains with phenotypic resistance to piperacillin/tazobactam but susceptibility to third-generation cephalosporins (TZP-R/3GC-S). In this study we sought to determine the genetic diversity of this phenotype in E. coli (n=58) isolated between 2014–2017 at a single tertiary hospital in Liverpool, UK, as well as the associated resistance mechanisms. We compare our findings to a UK-wide collection of invasive E. coli isolates (n=1509) with publicly available phenotypic and genotypic data. These data sets included the TZP-R/3GC-S phenotype (n=68), and piperacillin/tazobactam and third-generation cephalosporin-susceptible (TZP-S/3GC-S, n=1271) phenotypes. The TZP-R/3GC-S phenotype was displayed in a broad range of sequence types, which was mirrored in the same phenotype from the UK-wide collection, and the overall diversity of invasive E. coli isolates. The TZP-R/3GC-S isolates contained a diverse range of plasmids, indicating multiple acquisition events of TZP resistance mechanisms rather than clonal expansion of a particular plasmid or sequence type. The putative resistance mechanisms were equally diverse, including hyperproduction of TEM-1, either via strong promoters or gene amplification, carriage of inhibitor-resistant β-lactamases, and an S133G blaCTX-M-15 mutation detected for the first time in clinical isolates. Several of these mechanisms were present at a lower abundance in the TZP-S/3GC-S isolates from the UK-wide collection, but without the associated phenotypic resistance to TZP. Eleven (19%) of the isolates had no putative mechanism identified from the genomic data. Our findings highlight the complexity of this cryptic phenotype and the need for continued phenotypic monitoring, as well as further investigation to improve detection and predic-tion of the TZP-R/3GC-S phenotype from genomic data.
    • The physiological and phenotypic response of Salvia aethiopis L. to herbicides

      Mousavimanesh, Nafisehsadat; Karimmojeni, Hassan; Vaghar, Moslem; Baldwin, Timothy (Elsevier, 2022-08-09)
      Salvia aethiopis is an aromatic species within the Lamiaceae family, used both as a herb and as an ornamental plant, the yield and quality of which, when cultivated on a commercial basis, is frequently affected by weed infestation. Therefore, the application of herbicide is often required for the commercial production of this species. Considering which, for the current study, a pot experiment based upon a completely randomized design, with three replications, was conducted to evaluate the physiological and growth response of S. aethiopis to five commonly used herbicides (bentazon, phenmedipham/desmedipham, metribuzin, oxyfluorfen and oxadiargyl). These herbicides were applied at three concentrations (0.75X, 1X and 1.25X where X is equal to the recommended dose of herbicide). The data obtained from this study, demonstrated that herbicide application led to an increase in crop damage, minimum fluorescence (F0) and malondialdehyde content (MDA) and a concomitant decrease in the maximum quantum efficiency of PSΙΙ (FV/FM), maximum fluorescence (FM), SPAD value, relative water content (RWC), plant height and shoot and root dry weight as compared to the control. However, the level of response/tolerance was dependent upon the specific herbicide and the dose applied. Of the selected herbicides, S.aethiopis has shown to display the most tolerance to bentazon. As such, these data indicate that of the herbicides tested, bentazon should be the preferred herbicide used for broad leafed weed control, during the commercial production of this species.
    • Shelf-life prediction and thermodynamic properties of no added sugar chocolate spread fortified with multiple micronutrients

      Tolve, Roberta; Tchuenbou-Magaia, Fideline Laure; Sportiello, Lucia; Bianchi, Federico; Radecka, Iza; Favati, Fabio (MDPI, 2022-08-06)
      The development of fortified healthy pleasant foods, in which saturated fats are replaced with unsaturated ones, poses a challenge for the food industry due to their susceptibility to oxidative rancidity, which decreases product shelf-life, causes the destruction of health-promoting molecules, and forms potentially toxic compounds. A comparative study applying the Arrhenius model was carried out to investigate the oxidative stability and predict the shelf-life of a newly developed no added sugar chocolate spread formulated with sunflower oil, and fortified with vitamin D, Mg, and Ca checked against two commercially available spreads: No Palm and a well-known commercially available product (RB). The results obtained from the accelerated shelf-life testing for peroxide value (PV) showed relatively higher activation energy (Ea, 14.48 kJ/mol K) for RB, whereas lower Ea (11.31–12.78 kJ/mol K) was obtained for No Palm and all the experimental spread chocolates. Q10 values were comparable (1.202–1.154), indicating a similar catalytic effect of the temperature upon the oxidation rate across all the investigated samples. The positive Gibbs free energies ranged from 75.014 to 83.550 kJ/mol and pointed out that the lipid oxidation reaction in the chocolate spread was an endergonic process. The predicted shelf-life at 293.15 K was 8.57 months (RB), 7 months (No Palm), and 6.8 months for all the experimental spreadable chocolate. However, the higher production of hydroperoxides was observed in chocolate fortified with magnesium-calcium carbonate nanoparticles and stored at 313.15 and 323.15 K, suggesting these particles may enhance lipid oxidation.
    • Clinical outcomes for babies born between 27 – 31 weeks of gestation: Should they be regarded as a single cohort?

      Ismail, Abdul Qader Tahir; Boyle, Elaine M; Pillay, Thillagavathie; OptiPrem Study Team (Elsevier, 2022-04-22)
      Preterm babies born between 27 and 31 weeks of gestation are understudied and historically, have been grouped as a single cohort. Increased evidence relating to clinical outcomes is shaping models of care for babies born ≤26 weeks of gestation. Similar consideration of births between 27 and 31 weeks of gestation is now warranted. To address this, a clear understanding of the impact of progressive maturation in utero on the clinical care required, and on neonatal and infant outcomes of this group of preterm babies is helpful. In this review we highlight the spectrum of clinical presentations for babies born at 27–31 weeks of gestation. We discuss this with respect to key stages of organ/system development occurring in-utero during this five-week period and reveal a consistent trend of decreasing incidence of mortality and major morbidity with increasing gestational age at birth from 27 to 31 weeks. The clinical care required and the outcomes between babies born at either end of this gestational age range appear to be substantially different. This suggests it may be more appropriate to report outcomes by week of gestation rather than as a group in future research. Preterm health service delivery providers and decision makers need to consider this in planning services for the future, especially in environments where neonatal intensive care resources ought to be optimised for those at greatest need.
    • Managerial thinking in neonatal care: a qualitative study of place of care decision-making for preterm babies born at 27-31 weeks gestation in England

      Cupit, Caroline; Paton, Alexis; Boyle, Elaine M; Pillay, Thillagavathie; Armstrong, Natalie; Department of Health Sciences, University of Leicester, Leicester, UK caroline.cupit@le.ac.uk. (BMJ Publishing Group, 2022-06-27)
      Objectives Preterm babies born between 27 and 31 weeks of gestation in England are usually born and cared for in either a neonatal intensive care unit or a local neonatal unit—with such units forming part of Operational Delivery Networks. As part of a national project seeking to optimise service delivery for this group of babies (OPTI-PREM), we undertook qualitative research to better understand how decisions about place of birth and care are made and operationalised. Design Qualitative analysis of ethnographic observation data in neonatal units and semi-structured interviews with neonatal staff. Setting Six neonatal units across two neonatal networks in England. Two were neonatal intensive care units and four were local neonatal units. Participants Clinical staff (n=15) working in neonatal units, and people present in neonatal units during periods of observation. Results In the context of real-world neonatal practice, with multiple (and rapidly-evolving) uncertainties relating to mothers, babies and unit/network capacity, ‘best place of care’ protocols were only one element of much more complex decision-making processes. Staff often made judgements from a less-than-ideal starting point, and were forced to respond to evolving clinical and organisational factors. In particular, we report that managerial considerations relating to demand and capacity organised decision-making; demand and capacity management was time-consuming and generated various pressures on families, and tensions between staff. Conclusions Researchers and policymakers should take account of the organisational context within which place of care decisions are made. The dominance of demand and capacity management considerations is likely to limit the impact of other improvement interventions, such as initiatives to integrate families into the neonatal care provision. Demand and capacity management is an important element of neonatal care that may be overlooked, but significantly organises how care is delivered.
    • Nutrition and immunity in perinatal hypoxic-ischemic injury

      Gandecha, H; Kaur, A; Sanghera, R; Preece, J; Pillay, Thillagavathie; Department of Neonatology, University Hospitals Leicester NHS Trust, Leicester LE1 5WW, UK. (MDPI, 2022-07-01)
      Perinatal hypoxia ischaemia (PHI), acute and chronic, may be associated with considerable adverse outcomes in the foetus and neonate. The molecular and cellular mechanisms of injury and repair associated with PHI in the perinate are not completely understood. Increasing evidence is mounting for the role of nutrients and bioactive food components in immune development, function and repair in PHI. In this review, we explore current concepts around the neonatal immune response to PHI with a specific emphasis on the impact of nutrition in the mother, foetus and neonate.
    • Exploring the prevalence of medication errors in Kuwaiti hospitals

      Saada, Mohammed; Morrissey, Hana; Ball, Patrick (Innovare Academic Sciences, 2022-07-15)
      Objective: Reducing medication errors in Kuwaiti government hospitals through pharmacovigilance involves the improvement of medication safety culture achieve the desired outcome. The study explored the medication management practices in Kuwaiti hospitals and made recommendations for the improvement of medication safety practices. The aim of the study was to investigate the extent of medication errors in Kuwaiti government hospitals. Methods: Medical records and systems audits, healthcare professionals’ observation study, healthcare professionals survey. Data was collected from paper records, electronic records and systems and the observation study. Data was then analysed quantitatively and qualitatively. Results: The study revealed important results at all five steps of the medication process. The audit revealed nearly half of the errors identified to have occurred during the prescribing stage. Conclusion: The study revealed important results at all five steps of the medication process. The audit revealed nearly half of the errors identified to have occurred during the prescribing stage. The study highlights the need for an IT based, no-blame incident reports to be implemented and utilised in investigating adverse events and medication errors across the multiple sites in the Kuwaiti healthcare setting to guide reduction strategies and further improve standards of medication safety.
    • Microbial poly-γ-glutamic acid (γ-PGA) as an effective tooth enamel protectant

      Parati, Mattia; Clarke, Louisa; Anderson, Paul; Hill, Robert; Khalil, Ibrahim; Tchuenbou-Magaia, Fideline Laure; Stanley, Michele S; McGee, Donal; Mendrek, Barbara; Kowalczuk, Marek; et al. (MDPI, 2022-07-20)
      Poly-γ-glutamic acid (γ-PGA) is a bio-derived water-soluble, edible, non-immunogenic nylon-like polymer with the biochemical characteristics of a polypeptide. This Bacillus-derived material has great potential for a wide range of applications, from bioremediation to tunable drug delivery systems. In the context of oral care, γ-PGA holds great promise in enamel demineralisation prevention. The salivary protein statherin has previously been shown to protect tooth enamel from acid dissolution and act as a reservoir for free calcium ions within oral cavities. Its superb enamel-binding capacity is attributed to the L-glutamic acid residues of this 5380 Da protein. In this study, γ-PGA was successfully synthesised from Bacillus subtilis natto cultivated on supplemented algae media and standard commercial media. The polymers obtained were tested for their potential to inhibit demineralisation of hydroxyapatite (HAp) when exposed to caries simulating acidic conditions. Formulations presenting 0.1, 0.25, 0.5, 0.75, 1, 2, 3 and 4% (w/v) γ-PGA concentration were assessed to determine the optimal conditions. Our data suggests that both the concentration and the molar mass of the γ-PGA were significant in enamel protection (p = 0.028 and p < 0.01 respectively). Ion Selective Electrode, combined with Fourier Transform Infra-Red studies, were employed to quantify enamel protection capacity of γ-PGA. All concentrations tested showed an inhibitory effect on the dissolution rate of calcium ions from hydroxyapatite, with 1% (wt) and 2% (wt) concentrations being the most effective. The impact of the average molar mass (M) on enamel dissolution was also investigated by employing commercial 66 kDa, 166 kDa, 440 kDa and 520 kDa γ-PGA fractions. All γ-PGA solutions adhered to the surface of HAp with evidence that this remained after 60 min of continuous acidic challenge. Inductively Coupled Plasma analysis showed a significant abundance of calcium ions associated with γ-PGA, which suggests that this material could also act as a responsive calcium delivery system. We have concluded that all γ-PGA samples tested (commercial and algae derived) display enamel protection capacity regardless of their concentration or average molar mass. However, we believe that γ-PGA D/L ratios might affect the binding more than its molar mass.
    • Bioconversion process of polyethylene from Waste Tetra Pak® packaging to polyhydroxyalkanoates

      Ekere, Itohowo; Johnston, Brian; Tchuenbou-Magaia, Fideline Laure; Townrow, David; Wojciechowski, Szymon; Marek, Adam; Zawadiak, Jan; Duale, Khadar; Zieba, Magdalena; Sikorska, Wanda; et al. (MDPI, 2022-07-12)
      Presented herein are the results of a novel recycling method for waste Tetra Pak® packaging materials. The polyethylene (PE-T) component of this packaging material, obtained via a separation process using a “solvents method”, was used as a carbon source for the biosynthesis of polyhydroxyalkanoates (PHAs) by the bacterial strain Cupriavidus necator H16. Bacteria were grown for 48–72 h, at 30 °C, in TSB (nitrogen-rich) or BSM (nitrogen-limited) media supplemented with PE-T. Growth was monitored by viable counting. It was demonstrated that C. necator utilised PE-T in both growth media, but was only able to accumulate 40% w/w PHA in TSB supplemented with PE-T. Only 1.5% w/w PHA was accumulated in the TSB control, and no PHA was detected in the BSM control. Extracted biopolymers were characterised by nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, electrospray tandem mass spectrometry (ESI-MS/MS), gel permeation chromatography (GPC), and accelerator mass spectrometry (AMS). The characterisation of PHA by ESI-MS/MS revealed that PHA produced by C. necator in TSB supplemented with PE-T contained 3-hydroxybutyrate, 3-hydroxyvalerate, and 3-hydroxyhexanoate co-monomeric units. AMS analysis also confirmed the presence of 96.73% modern carbon and 3.27% old carbon in PHA derived from Tetra Pak®. Thus, this study demonstrates the feasibility of our proposed recycling method for waste Tetra Pak® packaging materials, alongside its potential for producing value-added PHA, and the ability of 14C analysis in validating this bioconversion process.
    • Transpiration cooling in hypersonic turbulent boundary layer

      Cerminara, Adriano (University of Wolverhampton, 2022-05-25)
      The design of new-generation reliable and efficient hypersonic flight vehicles requires analysis and validation of an effective technique to suppress the intense heat loads that generating on the vehicle surface. The purpose of the present contribution is to study the characteristics of a hypersonic turbulent flow over a porous-injecting wall, representative of a transpiration cooling system, and to analyse the pore-size effect on the coolant performance. Direct numerical simulations (DNS) are carried out for a Mach 5 flow over a flat plate. A porous injection model has been designed which mimics coolant injection from a bed of equally-spaced circular pores. Rapid transition to turbulence is triggered by high-amplitude disturbances imposed on the wall upstream of the porous region. Results show that a turbulent wedge-shaped flow structure generates just downstream of the injection region, which produces a reduction of the surface coolant concentration. The pore size influences flow features and coolant concentration in the laminar region, however has a marginal effect within the turbulent region, where the wall-cooling performance depends predominantly on the fluid dynamics of the turbulent flow. The present work sheds light on the effects of turbulence and pore size on transpiration-cooling characteristics in hypersonic flow, still poorly understood and not in-detail explored in the literature. Results indicate that the turbulent-wedge flow features must be deeper investigated with focus on the coolant redistribution, and that a parametric-study-informed tailored calibration of different porous injection parameters is vital for controlling the flow features to optimise the cooling performance.
    • One for all and all in one: Modified silica kit-based protocol for simultaneous sample-specific extraction of DNA from a variety of source materials

      Schmerer, Wera Margarete (Research Square, 2022-01-10)
      Protocols utilized for the extraction of DNA vary significantly with regards to steps involved and duration of the overall procedure due to material-specific requirements for ensuring the highest possible yield in recovery of DNA. This variation mostly affects aspects of sample preparation and digestion steps required to release the DNA from the sample material. In contexts such as the development of new PCR-based assays - which always includes a test of species-specificity - reference samples from a number of species are utilized, requiring extraction of DNA from a variety of source materials, each with their specific conditions for effective isolation of DNA.The method presented here follows the strategy of synchronizing sample material-specific aspects such as sample preparation and digestion in such a way that one common protocol can be utilized for the actual extraction and purification of the DNA, allowing for an overall more efficient extraction process, while maintaining optimized conditions for DNA recovery.
    • Gum Arabic: past, present and future

      Baldwin, Timothy; Majumdar, D.K.; Govil, J.N.; Singh, V.K. (Studium Press LLC, 2003-01-01)
    • The activity of PHMB and other guanidino containing compounds against acanthamoeba and other ocular pathogens

      Ratnayake, Dharanga; Ansah, Michael; Al Ani, Enas; Heaselgrave, Wayne (MDPI, 2022-07-08)
      In recent years, a rise in the number of contact lens users in the UK and worldwide coincided with an increased incidence of microbial keratitis. The aim of this study was to investigate the antimicrobial activities of polyhexamethylene guanidine (PHMG), polyaminopropyl biguanide (PAPB), and guazatine in comparison to the common contact lens disinfectant constituent, polyhexamethylene biguanide (PHMB). The study investigated these compounds against a broad range of organisms, including Acanthamoeba castellanii, Acanthamoeba polyphaga, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. This study demonstrated that PHMG, PAPB, and guazatine are equal in activity to PHMB against Acanthamoeba trophozoites and cysts. PHMG and PAPB are also equal in activity to PHMB against S. aureus and P. aeruginosa, whereas PHMG shows significantly better activity than PHMB against C. albicans (p < 0.001). To our knowledge, this is the first study to demonstrate the effectiveness of PHMB, PHMG, PAPB, and guazatine against Acanthamoeba and other ocular pathogens. As alternatives to PHMB, these compounds warrant further investigation for inclusion in contact lens solutions and for the treatment of keratitis.
    • SARS-CoV-2 vaccination for patients with inflammatory bowel disease: a British Society of Gastroenterology Inflammatory Bowel Disease section and IBD Clinical Research Group position statement

      Alexander, JL; Moran, GW; Gaya, DR; Raine, T; Hart, A; Kennedy, NA; Lindsay, JO; MacDonald, J; Segal, JP; Sebastian, S; et al. (Elsevier, 2021-01-25)
      SARS-CoV-2 has caused a global health crisis and mass vaccination programmes provide the best opportunity for controlling transmission and protecting populations. Despite the impressive clinical trial results of the BNT162b2 (Pfizer/BioNTech), ChAdOx1 nCoV-19 (Oxford/AstraZeneca), and mRNA-1273 (Moderna) vaccines, important unanswered questions remain, especially in patients with pre-existing conditions. In this position statement endorsed by the British Society of Gastroenterology Inflammatory Bowel Disease (IBD) section and IBD Clinical Research Group, we consider SARS-CoV-2 vaccination strategy in patients with IBD. The risks of SARS-CoV-2 vaccination are anticipated to be very low, and we strongly support SARS-CoV-2 vaccination in patients with IBD. Based on data from previous studies with other vaccines, there are conceptual concerns that protective immune responses to SARS-CoV-2 vaccination may be diminished in some patients with IBD, such as those taking anti-TNF drugs. However, the benefits of vaccination, even in patients treated with anti-TNF drugs, are likely to outweigh these theoretical concerns. Key areas for further research are discussed, including vaccine hesitancy and its effect in the IBD community, the effect of immunosuppression on vaccine efficacy, and the search for predictive biomarkers of vaccine success.
    • Improving 30-day mortality following percutaneous endoscopic gastrostomy tube placement in England from 2007 to 2019: a retrospective national cohort analysis of 87,862 patients

      Kamran, Umair; Lee, Pui Chi; Coupland, Ben; Abbasi, Abdullah; Steed, Helen; Ispoglou, Sissi; Varyani, Fumi; Trudgill, Nigel (Elsevier, 2022-07-04)
      Background and aims Percutaneous endoscopic gastrostomy (PEG) has been associated with poor case selection and high mortality. We examined indications, 30-day mortality and 7-day complications in a national cohort undergoing PEG insertion. Methods Adults undergoing first PEG insertion from 2007–2019 were identified in Hospital Episode Statistics. The indications and complications were identified using ICD-10 codes. Multivariable logistic regression modelling examined factors associated with mortality. Results 87,682 patients identified; 58% male; median age 69 (IQR 57-79) years. The number of patients with dementia or stroke as PEG indication fell from 2007 to 2019 : dementia - 147 to 28, p<0.001; stroke - 2851 to 1781, p<0.001. Median interval from stroke admission to PEG insertion increased from 21 (IQR 12-36) to 28 (13-45) days, p<0.001. Aspiration pneumonia within 7 days of PEG fell from 10.2% to 8.6%, p 0.04. 30 day mortality fell from 13.2% to 5.3% (p<0.001) and factors associated included: increasing age (≥ 82 years quintile odds ratio 4.44 (95% CI 4.01-4.92)); PEG insertion during emergency admission (2.10 (1.97-2.25)); Charlson comorbidity score ≥ 5 (1.67 (1.53-1.82)); and dementia (1.46 (1.26-1.71)).Female sex (0.81 (0.77-0.85)), least deprived quintile (0.88 (0.81-0.95)), and more recent years of PEG insertion (2019, 0.44 (0.39-0.51)) were negatively associated with mortality. Conclusions 30 day mortality following PEG insertion has fallen 60% over 13 years. Dementia or stroke as a PEG indication fell and the time interval from stroke to PEG insertion increased. These findings may be attributable to improved patient selection and timing for PEG insertion.
    • Correlation of ex vivo and in vivo confocal microscopy imaging of Acanthamoeba

      Alantary, Noor; Heaselgrave, Wayne; Hau, Scott (BMJ Publishing Group, 2022-06-24)
      Background/aims The aim of this study was to correlate the various forms of Acanthamoeba on ex vivo confocal microscopy (EVCM) with in vivo confocal microscopy (IVCM) and findings from cultured positive cases of Acanthamoeba keratitis. Methods Acanthamoeba live, dead and empty cysts, and live trophozoites were prepared in vitro and inoculated into porcine cornea using a sterile 26-gauge needle and examined ex vivo using the Heidelberg Retina Tomograph II/Rostock Corneal Module. IVCM images from 12 cultured positive Acanthamoeba cases, obtained using the same instrument, were compared with EVCM findings. Phase contrast images were also obtained to compare with both EVCM and IVCM findings. The change in cyst morphology with depth was evaluated by imaging the same cysts over a defined cornea depth measurement. Results EVCM morphologies for live cysts included four main types—hyper-reflective central dot with hyper-reflective outer ring, hyper-reflective central dot with hyporeflective outer region, stellate shaped hyper-reflective centre with hyporeflective outer region and hyper-reflective round/polygonal shaped cyst; one main type for dead cysts—hyper-reflective central dot with hyporeflective outer region; two main types for empty cysts— hyper-reflective central dot with hyper-reflective outer ring/hyporeflective outer region; and one main type for trophozoites—large coarse speckled area of heterogeneous hyper-reflective material. Matching IVCM images show good correlation with EVCM. Cyst morphology altered when imaged at different depths. Conclusion EVCM demonstrated the various forms of Acanthamoeba cyst and trophozoites can be used as a reference to identify similar structures on IVCM.
    • Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn's disease: long-term outcomes for 11928 patients in the UK inflammatory bowel disease bioresource

      Steed, Helen; Brookes, Matthew; Stournaras, Evangelos; Qian, Wendi; Pappas, Apostolos; Hong, You Yi; Shawky, Rasha; UK IBD BioResource Investigators; Raine, Tim; Parkes, Miles; et al. (BMJ, 2020-10-01)
      Objective Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD.
    • Inflammatory bowel disease clinical service recovery during the COVID-19 pandemic

      Din, Shahida; Gaya, Daniel; Kammermeier, Jochen; Lamb, Christopher A; Macdonald, Jonathan; Moran, Gordon; Parkes, Gareth; Pollok, Richard; Sebastian, Shaji; Segal, Jonathan; et al. (BMJ, 2021-04-21)
    • Bile acids and the microbiome: Making sense of this dynamic relationship in their role and management in Crohn's disease

      Kumar, Aditi; Al-Hassi, Hafid Omar; Steed, Helen; Phipps, Oliver; Brookes, Matthew; Department of Gastroenterology, The Royal Wolverhampton NHS Trust, New Cross Hospital, Wolverhampton, UK. (Hindawi, 2022-03-22)
      Background. 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.