90 research outputs found

    Nasoseptal chondroprogenitors isolated through fibronectin-adherence confer no biological advantage for cartilage tissue engineering compared to nasoseptal chondrocytes.

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    The ability to bioprint facial cartilages could revolutionise reconstructive surgery, but identifying the optimum cell source remains one of the great challenges of tissue engineering. Tissue specific stem cells: chondroprogenitors, have been extracted previously using preferential adhesion to fibronectin based on the expression of CD49e: a perceived chondroprogenitor stem cell marker present on <1% of cartilage cells. This study sought to determine whether these fibronectin-adherent chondroprogenitor cells could be exploited for cartilage tissue engineering applications in isolation, or combined with differentiated chondrocytes. Nasoseptal cartilage samples from 20 patients (10 male, 10 female) were digested to liberate cartilage-derived cells (CDCs) from extracellular matrix. Total cell number was counted using the Trypan Blue exclusion assay and added to fibronectin coated plates for 20 min, to determine the proportion of fibronectin-adherent (FAC) and non-adherent cells (NFACs). All populations underwent flow cytometry to detect mesenchymal stem/progenitor cell markers and were cultured in osteogenic, chondrogenic and adipogenic media to determine trilineage differentiation potential. Cell adherence and growth kinetics of the different populations were compared using iCELLigence growth assays. Chondrogenic gene expression was assessed using RT-qPCR for Type 2 collagen, aggrecan and SOX9 genes. Varying proportions of NFAC and FACs were cultured in alginate beads to assess tissue engineering potential. 52.6% of cells were fibronectin adherent in males and 57.7% in females, yet on flow cytometrical analysis, only 0.19% of cells expressed CD49e. Moreover, all cells (CDC, FAC and NFACs) demonstrated an affinity for trilineage differentiation by first passage and the expression of stem/progenitor cell markers increased significantly from digest to first passage (CD29, 44, 49e, 73 and 90, p < 0.0001). No significant differences were seen in adhesion or growth rates. Collagen and aggrecan gene expression was higher in FACs than CDCs (2-fold higher, p = 0.008 and 0.012 respectively), but no differences in chondrogenic potential were seen in any cell mixtures in 3D culture models. The fibronectin adhesion assay does not appear to reliably isolate a chondroprogenitor cell population from nasoseptal cartilage, and these cells confer no advantageous properties for cartilage tissue engineering. Refinement of cell isolation methods and chondroprogenitor markers is warranted for future nasoseptal cartilage tissue engineering efforts. [Abstract copyright: Copyright © 2024 Jovic, Thomson, Jones, Thornton, Doak and Whitaker.

    Scotland's Draft Interim Constitution:Clear-Sighted and Sensible, or an SNP Power-Play?

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    The Scottish Government recently published The Scottish Independence Bill: A Consultation on an Interim Constitution for Scotland, the document which would form the basis of the constitutional arrangements for Scotland in the event of a ‘Yes’ vote in the forthcoming independence referendum. Democratic Audit asked expert constitutional thinkers to give their views on whether the document is fit for purpose

    Myocardial Approximate Spin-lock Dispersion Mapping using a Simultaneous T2 and TRAFF2 Mapping at 3T MRI

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    Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Myocardial infarction (MI) represents a third of all IHD cases, and cardiac magnetic resonance imaging (MRI) is often used to assess its damage to myocardial viability. Late gadolinium enhancement (LGE) is the current gold standard, but the use of gadolinium-based agents limits the clinical applicability in some patients. Spin-lock (SL) dispersion has recently been proposed as a promising non-contrast biomarker for the assessment of MI. However, at 3T, the required range of SL preparations acquired at different amplitudes suffers from specific absorption rate (SAR) limitations and off-resonance artifacts. Relaxation Along a Fictitious Field (RAFF) is an alternative to SL preparations with lower SAR requirements, while still sampling relaxation in the rotating frame. In this study, a single breath-hold simultaneous TRAFF2 and T2 mapping sequence is proposed for SL dispersion mapping at 3T. Excellent reproducibility (coefficient of variations lower than 10%) was achieved in phantom experiments, indicating good intrascan repeatability. The average myocardial TRAFF2, T2, and SL dispersion obtained with the proposed sequence (68.0±10.7 ms, 44.0±4.0 ms, and 0.4±0.2 ×10-4 s2, respectively) were comparable to the reference methods (62.7±11.7 ms, 41.2±2.4 ms, and 0.3±0.2x 10-4s2, respectively). High visual map quality, free of B0 and B1+ related artifacts, for T2, TRAFF2, and SL dispersion maps were obtained in phantoms and in vivo, suggesting promise in clinical use at 3T. Clinical relevance - and imaging promises non-contrast assessment of scar and focal fibrosis in a single breath-hold using approximate spin-lock dispersion mapping

    Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters

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    PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 T1 {\mathrm{T}}_1 relaxation time ( T 1 , B T1,B {\mathrm{T}}_{1,B} ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B T1,B {\mathrm{T}}_{1,B} values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 R2 {R}^2 >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 R2 {R}^2 >0.59) was observed which was reduced when calculating MBF with individual T 1 , B T1,B {\mathrm{T}}_{1,B} . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B T1,B {\mathrm{T}}_{1,B} and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters

    Review: Improving the impact of plant science on urban planning and design

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    Urban planning is a vital process in determining the functionality of future cities. It is predicted that at least two thirds of the world’s citizens will reside in towns and cities by the middle of this century, up from one third in the middle of the previous century. Not only is it essential to provide space for work and dwelling, but also for their well-being. Well-being is inextricably linked with the surrounding environment, and natural landscapes have a potent positive effect. For this reason, the inclusion and management of urban green infrastructure has become a topic of increasing scientific interest. Elements of this infrastructure, including green roofs and façades are of growing importance to operators in each stage of the planning, design and construction process in urban areas. Currently, there is a strong recognition that “green is good”. Despite the positive recognition of urban greenery, and the concerted efforts to include more of it in cities, greater scientific attention is needed to better understand its role in the urban environment. For example, many solutions are cleverly engineered without giving sufficient consideration to the biology of the vegetation that is used. This review contends that whilst “green is good” is a positive mantra to promote the inclusion of urban greenery, there is a significant opportunity to increase the contribution of plant science to the process of urban planning through both green infrastructure, and biomimicry

    Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study

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    Objective: To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. Design: International multicentre prospective study. Setting: Six large hospitals in Europe, North America, Asia, and Oceania. Participants: 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. Main outcome measures: Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. Results: The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P&lt;0.001). A Glasgow Blatchford score of ≀1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P&lt;0.001). A Glasgow Blatchford score of ≄7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P&lt;0.001). Score thresholds of ≄4 for PNED, ≄2 for AIMS65, ≄4 for admission Rockall, and ≄5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. Conclusions: The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≀1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited. Trial registration: Current Controlled Trials ISRCTN16235737
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