Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome

Acknowledgments The authors thank the Edinburgh Imaging Facility. Sources of Funding This work and T. Singh, S. Joshi, and Drs Dweck and Newby are supported by the British Heart Foundation (grants FS/17/19/32641, CS/17/1/32445, RG/16/10/32375, RE/18/5/34216, FS/ICRF/20/26002, and FS/SCRF/21/32010). T. Singh is supported by the Medical Research Council (grant MR/T029153/1). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr McCann is supported by an NIHR Research Professorship (08-2017-ST2-007). The Edinburgh Clinical Research Facilities and Edinburgh Imaging Facility are supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board.Peer reviewe

Effects of a balanced translocation between chromosomes 1 and 11 disrupting the DISC1 locus on white matter integrity

Objective Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). Method Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). Results We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. Conclusions We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Quantification techniques to minimize the effects of native T(1) variation and B(1) inhomogeneity in dynamic contrast-enhanced MRI of the breast at 3 T.

The variation of the native T(1) (T(10) ) of different tissues and B(1) transmission-field inhomogeneity at 3 T are major contributors of errors in the quantification of breast dynamic contrast-enhanced MRI. To address these issues, we have introduced new enhancement indices derived from saturation-recovery snapshot-FLASH (SRSF) images. The stability of the new indices, i.e., the SRSF enhancement factor (EF(SRSF) ) and its simplified version (EF'(SRSF) ) with respect to differences in T(10) and B(1) inhomogeneity was compared against a typical index used in breast dynamic contrast-enhanced MRI, i.e., the enhancement ratio (ER), by using computer simulations. Imaging experiments with Gd-DTPA-doped gel phantoms and a female volunteer were also performed. A lower error was observed in the new indices compared to enhancement ratio in the presence of typical T(10) variation and B(1) inhomogeneity. At changes of relaxation rate (ΔR(1) ) of 8 s(-1) , the differences between a T(10) of 1266 and 566 ms are <1, 12, and 58%, respectively, for EF(SRSF) , EF'(SRSF) , and ER, whereas differences of 20, 8, and 51%, respectively, result from a 50% B(1) field reduction at the same ΔR(1) . These quantification techniques may be a solution to minimize the effect of T(10) variation and B(1) inhomogeneity on dynamic contrast-enhanced MRI of the breast at 3 T. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc

The accuracy of pharmacokinetic parameter measurement in DCE-MRI of the breast at 3 T

The purpose of this work is to quantify the accuracy of pharmacokinetic parameter measurement in DCE-MRI of breast cancer at 3 T in relation to three sources of error. Individually, T1 measurement error, temporal resolution and transmitted RF field inhomogeneity are considered. Dynamic contrast enhancement curves were simulated using standard acquisition parameters of a DCE-MRI protocol. Errors on pre-contrast T1 due to incorrect RF spoiling were considered. Flip angle errors were measured and introduced into the fitting routine, and temporal resolution was also varied. The error in fitted pharmacokinetic parameters, K(trans) and v(e), was calculated. Flip angles were found to be reduced by up to 55% of the expected value. The resultant errors in our range of K(trans) and v(e) were found to be up to 66% and 74%, respectively. Incorrect T1 estimation results in K(trans) and v(e) errors up to 531% and 233%, respectively. When the temporal resolution is reduced from 10 to 70 s K(trans) drops by up to 48%, while v(e) shows negligible variation. In combination, uncertainties in tissue T1 map and applied flip angle were shown to contribute to errors of up to 88% in K(trans) and 73% in v(e). These results demonstrate the importance of high temporal resolution, accurate T1 measurement and good B1 homogeneity

Novel laccase from Xylaria polymorpha and its efficiency in the biotransformation of pharmaceuticals:Optimization of operational conditions, comparative effect of redox-mediators and toxicity studies

The promising potentials of biocatalytic treatment processes in the removal of micropollutants whilst eliminating health and environmental hazards have attracted great attention in recent years. This current work investigated the biotransformation efficiency of a novel laccase from Xylaria polymorpha (XPL) in comparison with commercial laccases from Trametes versicolor (TVL) and Aspergillus sp. (ASL). XPL exhibited better oxidation performance (95.7%) on AMX than TVL (92.8%) and ASL (90.5%). Optimization of operational conditions revealed that AMX was best oxidized at pH 5, temperature (30 °C), and concentration (1.0 mg L −1). The investigation carried out to determine the effect of redox mediators revealed violuric acid (VLA) as the best redox mediator. The laccase stability experiments elucidated that the oxidation of AMX is time and mediator concentration dependent with ABTS exhibiting highest deactivation of XPL active sites. Two metabolic products; amoxicillin penilloic acid and 5-hydroxy-6-(4-hydroxyphenyl)− 3-(1,3-thiazolidin-2-yl)piperazin-2-one of AMX were obtained through Liquid Chromatography-Mass Spectrometry (LC-MS) analyses. The toxicity assessments carried out after oxidation of AMX by XPL showed 94% and 97% reduced toxicity on Artemia salina and Aliivibrio fischeri respectively. The study further underscored the efficiency of biocatalytic-mediator technology in the transformation of complex micropollutants into less toxic substances in an eco-friendly way