Institute of Inflammation and Repair

Manchester, United Kingdom

Institute of Inflammation and Repair

Manchester, United Kingdom
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McGrath B.A.,University of Manchester | McGrath B.A.,Institute of Inflammation and Repair | Lynch K.,University of Manchester | Templeton R.,University of Manchester | And 4 more authors.
British Journal of Anaesthesia | Year: 2017

Background: Malposition of tracheostomy tubes is difficult to detect at the bedside and may contribute to eventual device misplacement. Endoscopic examination can be undertaken via tracheoscopic (T-view) or trans-laryngeal (L-view) approach, offering more precise detail regarding positioning within the airway. The aims of this study were to evaluate inter-rater agreement between bespoke T and L view scoring systems and subsequently whether T-views could predict L-views. Methods: Adult intensive care unit patients with percutaneous or surgical tracheostomies were included and paired T and L-views of their tracheostomy tube within the airway were taken on up to four occasions. Images were later scored by five independent raters using bespoke scoring systems. The primary outcome was to determine the T and L view scoring system with the best inter-rater agreement, defined by weighted kappa and intra-class correlation coefficients. The secondary outcome was to assess agreement between T and L-view scoring systems. Results: Seventy-one T-views and 43 L-views were obtained from a total of 20 patients. Images were scored by five raters, resulting in 355 T-view scores, 215 L-view scores and 215 paired T and L-view scores for comparison. There was good interrater agreement (highest T-view k = 0.84, L-view k = 0.72). There was poor agreement between T and L-view scores for each of the paired images (highest k = 0.25) although extreme-to-extreme misclassification rates remained acceptable. Conclusions: Whilst our data demonstrated good inter-rater agreement between scoring systems, it is not possible to reliably predict the T-view orientation and position of a tracheostomy tube within the airway from the paired L-view. Clinical trial registration: NCT01356719. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.

Langan E.A.,UniDersity of Luebeck | Langan E.A.,Blizard Institute | Philpott M.P.,Blizard Institute | Kloepper J.E.,UniDersity of Luebeck | And 2 more authors.
Experimental Dermatology | Year: 2015

For almost a quarter of a century, ex DiDo studies of human scalp hair follicles (HFs) haDe permitted major adDances in hair research, spanning diDerse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite this, a comprehensiDe methodological guide to serumfree human HF organ culture (HFOC) that facilitates the selection and analysis of standard HF biological parameters and points out both research opportunities and pitfalls to newcomers to the field is still lacking. The current methods reDiew aims to close an important gap in the literature and attempts to promote standardisation of human HFOC. We proDide basic information outlining the establishment of HFOC through to detailed descriptions of the analysis of standard read-out parameters alongside practical examples. The guide closes by pointing out how serum-free HFOC can be utilised optimally to obtain preDiously inaccessible insights into human HF biology and pathology that are of interest to experimental dermatologists, geneticists, deDelopmental biologists and (neuro-) endocrinologists alike and by highlighting noDel applications of the model, including gene silencing and gene expression profiling of defined, laser capture-microdissected HF compartments. © 2015 John Wiley & Sons A/S.

Burney P.G.J.,Imperial College London | Potts J.,Imperial College London | Kummeling I.,Imperial College London | Mills E.N.C.,Institute of Inflammation and Repair | And 18 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014

Background: Complaints of 'food allergy' are increasing. Standardized surveys of IgE sensitization to foods are still uncommon and multicountry surveys are rare. We have assessed IgE sensitization to food-associated allergens in different regions of Europe using a common protocol. Methods: Participants from general populations aged 20-54 years in eight European centres (Zurich, Madrid, Utrecht, Lodz, Sophia, Athens, Reykjavik and Vilnius) were asked whether they had allergic symptoms associated with specific foods. Weighted samples of those with and without allergic symptoms then completed a longer questionnaire and donated serum for IgE analysis by ImmunoCAP for 24 foods, 6 aeroallergens and, by allergen microarray, for 48 individual food proteins. Results: The prevalence of IgE sensitization to foods ranged from 23.6% to 6.6%. The least common IgE sensitizations were to fish (0.2%), milk (0.8%) and egg (0.9%), and the most common were to hazelnut (9.3%), peach (7.9%) and apple (6.5%). The order of prevalence of IgE sensitization against different foods was similar in each centre and correlated with the prevalence of the pollen-associated allergens Bet v 1 and Bet v 2 (r = 0.86). IgE sensitization to plant allergen components unrelated to pollen allergens was more evenly distributed and independent of pollen IgE sensitization (r = -0.10). The most common foods containing allergens not cross-reacting with pollens were sesame, shrimp and hazelnut. Discussion: IgE sensitization to foods is common, but varies widely and is predominantly related to IgE sensitization to pollen allergens. IgE sensitization to food allergens not cross-reacting with pollens is rare and more evenly distributed. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Wong R.,Institute of Inflammation and Repair | Kriel H.,The Stellenbosch Nanofiber Company LtdCape Town South Africa | Smit E.,The Stellenbosch Nanofiber Company LtdCape Town South Africa | Mcgrouther D.A.,Institute of Inflammation and Repair | Wong J.K.,Institute of Inflammation and Repair
Journal of Biomedical Materials Research - Part A | Year: 2016

The functional replacement of tendon represents an unmet clinical need in situations of tendon rupture, tendon grafting, and complex tendon reconstruction, as usually there is a finite source of healthy tendon to use as donors. The microfibrous architecture of tendon is critical to the function of tendon. This study investigates the use of electrospun poly(e(open)-caprolactone) scaffolds as potential biomaterial substitutes for tendon grafts. We assessed the performance of two electrospinning manufacturers (small- and large-scale) and the effect of two sterilization techniques-gamma irradiation and ethanol submersion-on cell response to these electrospun scaffolds after their implantation into a murine tendon model. Cell infiltration and proliferation analyses were undertaken to determine the effect on cell response within the implant over a 6-week period. Immunohistochemical analysis was performed to characterize inflammatory response and healing characteristics (proliferation, collagen deposition, myofibroblast activity, and apoptosis). Neither the sterilization techniques nor the manufacturer was observed to significantly affect the cell response to the scaffold. At each time point, cell response was similar to the autograft control. This suggests that ethanol submersion can be used for research purposes and that the scaffold can be easily reproduced by a large-scale manufacturer. These results further imply that this electrospun scaffold may provide an alternative to autograft, thus eliminating the need for sourcing healthy tendon tissue from a secondary site. © 2016 Wiley Periodicals, Inc.

In the first study of its kind, student Zain Habib Alhindi used different concentrations of Surgihoney, a biologically engineered honey that produces chemically reactive molecules containing oxygen, to test how effective it could be in destroying the fungus Fusarium, which is found on plants and in soil and can cause devastating infections in vulnerable people. Zain discovered even the lowest concentrations had a significant effect in breaking down the cell wall of the fungus, demonstrating its potential as a future treatment for patients. She said: "Chronic infections, such as those found in long-lasting wounds comprise about 60-80 per cent of infectious diseases in humans and the way fungi invades wounds is associated with the use of broad-spectrum antibiotics. "However, we know that biofilms - thin layers of microorganisms, which group together - contribute to the severity and delayed healing of chronic wounds. "Through my research I wanted to show the potential for honey as a healing agent to break through these biofilms and in doing so increase the process of healing. What I found amazing is that honey actually works better than some antifungals." Zain (29) from Saudi Arabia is one of only handful of students who have completed The University's new master's degree course in Medical Mycology which runs for just one year instead of the customary two, making it a world first. Because of the way the course is structured Zain was able to spend almost a third of her time in the lab working on experiments to test her theory under the supervision of Dr Riina Rautemaa-Richardson, Senior Lecturer in Infectious Diseases in The University's Institute of Inflammation and Repair. Dr Rautemaa-Richardson believes its this intensive, hands-on approach, which appeals to her students and equips them for a career in specialised medicine or research. She said: "This dynamic course provides a solid foundation to the scientific, practical and clinical aspects of fungal diseases, which allows clinically relevant research like this. In the world of increasing antimicrobial resistance new approaches to the management of infections, sparing the real antibiotics, are highly relevant and important." Professor Malcolm Richardson, Professor of Medical Mycology at The University of Manchester added: "Honey has been used since ancient times for the treatment of several diseases. Only a limited number of investigations have looked at its effect on pathogenic fungi. "This opens an exciting door for further work on the application of honey for many fungal infections and allows researchers to adopt different options for treating a range of superficial infections." Surgihoney is proving highly effective at treating infected wounds and superbugs. The honey works by killing the bugs, by producing hydrogen peroxide ROS, removing dead tissue and pus, and then providing a moisture barrier as well as local nutrition. This work confirms previous research on the clinical efficacy of Surgihoney RO in chronic wounds and in the prophylaxis of surgical site infection. Honey contains vitamins, minerals, enzymes and sugars – all of which help in the healing of wounds. Manuka is generally regarded as the most potent honey, but it relies upon nectar from a particular tree in New Zealand, limiting its supply. That is precisely the problem that has been solved by the developers of Surgihoney. They have created a product that can be made from organic honey from any floral source. They hope it will ultimately become a global wound-care product.

Abdullah S.U.,UK Institute of Food Research | Alexeev Y.,UK Institute of Food Research | Alexeev Y.,Argonne National Laboratory | Johnson P.E.,UK Institute of Food Research | And 7 more authors.
Scientific Reports | Year: 2016

Non-specific lipid transfer proteins (LTPs) are a family of lipid-binding molecules that are widely distributed across flowering plant species, many of which have been identified as allergens. They are highly resistant to simulated gastroduodenal proteolysis, a property that may play a role in determining their allergenicity and it has been suggested that lipid binding may further increase stability to proteolysis. It is demonstrated that LTPs from wheat and peach bind a range of lipids in a variety of conditions, including those found in the gastroduodenal tract. Both LTPs are initially cleaved during gastroduodenal proteolysis at three major sites between residues 39-40, 56-57 and 79-80, with wheat LTP being more resistant to cleavage than its peach ortholog. The susceptibility of wheat LTP to proteolyic cleavage increases significantly upon lipid binding. This enhanced digestibility is likely to be due to the displacement of Tyr79 and surrounding residues from the internal hydrophobic cavity upon ligand binding to the solvent exposed exterior of the LTP, facilitating proteolysis. Such knowledge contributes to our understanding as to how resistance to digestion can be used in allergenicity risk assessment of novel food proteins, including GMOs.

Parker B.,Institute of Inflammation and Repair | Al-Husain A.,Institute of Inflammation and Repair | Pemberton P.,University of Manchester | Yates A.P.,University of Manchester | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2014

Background In a prospective observational study, we investigated whether patients with active systemic lupus erythematosus (SLE) had higher indices of endothelial damage and dysfunction than healthy controls and whether improved disease control was associated with improvement in these indices. Methods: Twenty-seven patients with active SLE (four or more American College of Rheumatology (ACR) criteria) and 22 age-matched controls were assessed. Endothelial microparticles (EMPs; CD31+/annexin V+/CD42b-) were quantified using flow cytometry. Brachial artery flow-mediated dilatation (FMD) was measured using automated edge-tracking software. Twenty-two patients had a second assessment at a median (IQR) of 20 (16, 22) weeks after initiating new immunosuppressive therapy. Results: SLE patients had a median (IQR) baseline global British Isles Lupus Assessment Group Disease Activity Index (BILAG-2004) score of 14 (12, 22). CD31+/annexin V+/CD42b- EMPs were higher (157 548/ml (59 906, 272 643) vs 41 025(30 179, 98 082); p=0.003) and endothelial-dependent FMD was lower (1.63% (-1.22, 5.32) vs 5.40% (3.02, 8.57); p=0.05) in SLE patients than controls. CD31+/annexin V+/CD42b- EMPs correlated inversely with FMD (%) (r2 -0.40; p=0.006). At follow-up, the median (IQR) change in global BILAG- 2004 score was -11 (-18, -3). CD31+/annexin V +/CD42b- EMP levels were reduced (166 982/ml (59 906, 278 775 vs 55 655(29 475, 188 659; p=0.02) and FMD had improved (0.33% (-2.31, 4.1) vs 3.19% (0.98, 5.09); p=0.1) at the second visit. Conclusions: Active SLE is associated with evidence of increased endothelial damage and endothelial dysfunction, which improved with suppression of inflammation. Better control of active inflammatory disease may contribute to improved cardiovascular risk in patients with SLE.

Grimshaw K.E.C.,Clinical and Experimental science Academic Unit | Maskell J.,University of Southampton | Oliver E.M.,Clinical and Experimental science Academic Unit | Morris R.C.G.,University of Southampton | And 4 more authors.
Pediatrics | Year: 2013

OBJECTIVES: To address questions regarding breastfeeding, complementary feeding, allergy development, and current infant-feeding recommendations. METHODS: This was a nested, case-control within a cohort study in which mothers of 41 infants diagnosed with food allergy by the age of 2 years (according to double-blind, placebo-controlled food challenge) and their 82 age-matched controls kept prospective food diaries of how their infants were fed in the first year of life. RESULTS: Infants who were diagnosed with food allergy by the time they were 2 years of age were introduced to solids earlier (≤16 weeks of age) and were less likely to be receiving breast milk when cow's milk protein was first introduced into their diet. CONCLUSIONS: This study supports the current American Academy of Pediatrics' allergy prevention recommendations and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommendations on complementary feeding to not introduce solids before 4 to 6 months of age. It also supports the American Academy of Pediatrics' breastfeeding recommendations that breastfeeding should continue while solids are introduced into the diet and that breastfeeding should continue for 1 year, or longer, as mutually desired by mother and infant. © 2013 by the American Academy of Pediatrics.

PubMed | Institute of Inflammation and Repair
Type: Journal Article | Journal: The British journal of dermatology | Year: 2013

Psoriasis is associated with considerable physical and psychological morbidity. Optimal use of psoriasis treatments can limit the physical manifestations of psoriasis and help improve quality of life, but nonadherence is common. Smoking, obesity and excessive alcohol consumption are prevalent in this population. A systematic review of adherence to medication and recommendations for lifestyle change in psoriasis was undertaken, with a critical appraisal of the quality of the selected studies. Electronic searches from inception to March 2012 (PubMed, Web of Science and Embase) were conducted. Twenty-nine studies were included; however, none examined adherence to advice about lifestyle change. Studies using a dichotomous classification of adherence tended to report suboptimal adherence, with 216-666% of patients classed as adherent. No consistent pattern of results emerged for sociodemographical, disease and lifestyle factors as determinants of adherence. However, some treatment factors were associated with adherence. While mixed findings were reported for quality of life as a determinant of adherence, psychological factors (psychological distress and patient satisfaction with care and therapy) were associated with adherence. Only tentative conclusions can be made for determinants of adherence because the methodological quality of many of the included studies limits conclusions. There is a need for improved quality of research and reporting in this area, and this review provides a platform from which future research within this area should progress, along with suggested research recommendations.

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