The effect of conditioning films on the hygienic status of titanium based and antimicrobial surfaces

Biofouling and contamination of surfaces is of critical importance to both the food and medical industries, causing not only huge economic burden, but also increased health risks to consumers and patients. The choice of surfaces which can help mitigate these risks is of critical importance. Antimicrobial surfaces were developed through unbalanced magnetron sputtering was producing titanium nitride and silver surfaces (Ag content = 15.03 % 25.45 %) which were to be assessed alongside surfaces commonly utilised in both medical and food industries; 3042R and 316L stainless steel, titanium, 316Ti, 316TiN. The surfaces were assessed for their physical and chemical properties through the use of SEM, EDX, goniometry, FTIR-DRIFTS, WLP and through comparisons with the pristine surfaces (control), assessment of what changes the addition of the bacterial species Staphylococcus aureus and Escherichia coli, 10 % bovine plasma conditioning film, or both the bacteria and conditioning film made to those parameters. The antimicrobial properties of the surfaces and their propensity to retain the bacterial species was also measured through ZOI, NTV and retention assays, as well as assessment of what effect the addition of the conditioning film upon the surfaces had upon bacterial retention. Results demonstrated the addition of the conditioning film made no significant difference to the physical properties of the surfaces but did affect the chemical properties. Assessment of the antimicrobial properties of the surfaces demonstrated that only the TiN/Ag surfaces were antimicrobial and that the bacterial response was species specific. Retention assays demonstrated that upon the pristine surfaces the E. coli was influenced by the physicochemistry of the surfaces, whilst the S. aureus was influenced by the surface topography. The conditioning film produced a significant reduction in the numbers retain bacteria to the surfaces. In conclusion, the bacteria were more significantly affected by the presence of the conditioning film than the physical parameters of the surfaces. This result was mediated by the affects that the conditioning film had upon the chemical parameters of the surfaces in conjunction with the molecular effects of protein binding to surface adhesins. This work demonstrates that whilst characterisation of the surface parameters is important, this must also be done in the presence of an appropriate conditioning film

The role of pathogen effector proteins in altering host plant transcription

Plant pathogens secrete effector proteins in order to overcome immunity in plants stimulated by common microbial patterns. The genomes of oomycete pathogens including Hyaloperonospora arabidopsidis (Hpa) are predicted to contain a large number of effectors. These experiments focussed on characterising an interaction between predicted Hpa effector HaRxL14 and Arabidopsis protein phosphatase type-2CA (PP2CA), which functions as a co-receptor in response to the phytohormone abscisic acid (ABA). This interaction was previously identified in a yeast two-hybrid screen. Bimolecular fluorescence complementation experiments verified an interaction in the nucleus. Over-expression of the effector in planta enhances susceptibility of Arabidopsis to Hpa, although knocking-out PP2CA in the host did not have a clear effect on infection. Furthermore, a potential role for the interaction in enhancing host signalling associated with ABA was highlighted from microarray analysis of Arabidopsis lines over-expressing the effector. The up-regulation of various ABA-related genes supports previous findings that ABA may disrupt host response to biotrophic pathogens. Furthermore, it was hypothesised that phytohormones including jasmonic acid (JA), ABA, and salicylic acid (SA) could have a role in coordinating host transcription at the level of chromosome conformation. Progress was made towards optimising a method for use with Arabidopsis related to chromosome conformation capture (3C). These experiments began to examine the spatial interactions of JA-induced genes in Arabidopsis. This method could be used to determine if related genes co-localise at specialised transcription factories. These transcription factories have previously been studied in other models including mammals, although their potential role in plants is currently not well understood. Overall, a Hpa effector was shown to interact with host protein PP2CA potentially to up-regulate ABA-related genes. It remains to be established if phytohormones have a role in coordinating transcription through manipulating spatial interactions of genes

PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS/DESIGN PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE

The effect of surface properties on bacterial retention: a study utilising stainless steel and TiN/25.65at.%Ag substrata

The requirement for antimicrobial surfaces to control microorganisms for use in the food industries is increasing. A TiN/25.65at.%Ag coating and a stainless steel (304 2R) surface were characterised for roughness parameters, chemistry and physicochemistry (PC). Microbiological analysis was performed to determine the antimicrobial efficacy and retention of Staphylococcus aureus and Escherichia coli on the surfaces. Zone of inhibition assays were successful against only E. coli on the TiN/25.65at.%Ag coating. A bacterial respiratory assay demonstrated that the TiN/25.65at.%Ag coating was antimicrobial against both bacteria. Retention assays demonstrated that the physicochemistry of the bacteria and surfaces influenced bacterial retention. Multifractal analysis of the retained bacteria demonstrated that the surface properties affected the spread and clustering, but not the density of the bacteria. This work suggests that surface properties influenced specific species: surface interactions and therefore surfaces need to be tailored to specific requirements depending on the environment and microorganisms to be targeted. This work may aid in the production of coatings or surfaces that may provide more hygienic conditions

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial

BACKGROUND: The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient. Therefore, there is a growing need for a reliable, feasible, and cost-effective, noninvasive diagnostic tool for these conditions. LiverMultiScan is one such promising tool that uses multi-parametric magnetic resonance imaging (mpMRI) to characterize liver tissue and to aid in the diagnosis and monitoring of liver diseases of various etiologies. OBJECTIVE: The primary objective of this trial (RADIcAL1) is to evaluate the cost-effectiveness of the introduction of LiverMultiScan as a standardized diagnostic test for liver disease in comparison to standard care for NAFLD, in different EU territories. METHODS: RADIcAL1 is a multi-center randomized control trial with 2 arms conducted in 4 European territories (13 sites, from across Germany, Netherlands, Portugal, and the United Kingdom). In total, 1072 adult patients with suspected fatty liver disease will be randomized to be treated according to the result of the mpMRI in the intervention arm, so that further diagnostic evaluation is recommended only when values for metrics of liver fat or fibro-inflammation are elevated. Patients in the control arm will be treated as per center guidelines for standard of care. The primary outcome for this trial is to compare the difference in the proportion of patients with suspected NAFLD incurring liver-related hospital consultations or liver biopsies between the study arms, from the date of randomization to the end of the study follow-up. Secondary outcomes include patient feedback from a patient satisfaction questionnaire, at baseline and all follow-up visits to the end of the study, and time, from randomization to diagnosis by the physician, as recorded at the final follow-up visit. RESULTS: This trial is currently open for recruitment. The anticipated completion date for the study is December 2020. CONCLUSIONS: This randomized controlled trial will provide the evidence to accelerate decision making regarding the inclusion of mpMRI-based tools in existing NAFLD/NASH clinical care. RADIcAL1 is among the first and largest European health economic studies of imaging technologies for fatty liver disease. Strengths of the trial include a high-quality research design and an in-depth assessment of the implementation of the cost-effectiveness of the mpMRI diagnostic. If effective, the trial may highlight the health economic burden on tertiary-referral hepatology clinics imposed by unnecessary consultations and invasive diagnostic investigations, and demonstrate that including LiverMultiScan as a NAFLD diagnostic test may be cost-effective compared to liver-related hospital consultations or liver biopsies. TRIAL REGISTRATION: ClinicalTrials.gov NCT03289897 https://clinicaltrials.gov/ct2/show/NCT03289897. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19189.status: publishe

Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance

In the present study, we have investigated the in vitro polymerization of human plasma AGT (angiotensinogen), a non-inhibitory member of the serpin (SERine Protease INhibitor) family. Polymerization of AGT is thought to contribute to a high molecular mass form of the protein in plasma that is increased in pregnancy and pregnancy-associated hypertension. The results of the present study demonstrate that the polymerization of AGT occurs through a novel mechanism which is primarily dependent on non-covalent linkages, while additional disulfide linkages formed after prolonged incubation are not essential for either formation or stability of polymers. We present the first analyses of AGT polymers by electron microscopy, CD spectroscopy, stability assays and sensitivity to proteinases and we conclude that their structure differs from the `loop-sheet¿ polymers typical of inhibitory serpins. Histidine residues within the unique N-terminal extension of AGT appear to influence polymer formation, although polymer formation can still take place after their removal by renin. At a functional level, we show that AGT polymers are not substrates for renin, so polymerization of AGT in plasma would predictably lead to decreased formation of AngI (angiotensin I) with blood pressure lowering. Polymerization may therefore be an appropriate response to hypertension. The ability of AGT to protect its renin cleavage site through polymerization may explain why the AngI decapeptide has remained linked to the large and apparently inactive serpin body throughout evolution

PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography

BACKGROUND: Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS/DESIGN: PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION: This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE